Will Pass

Antireflux lifestyle factors may significantly reduce the risk of gastroesophageal reflux disease (GERD), according to an analysis involving almost 43,000 women.

Tharakorn/Getty Images

Even alongside therapy with a proton-pump inhibitor (PPI) and/or a histamine-receptor antagonist (H2RA), adherence to five antireflux lifestyle factors had a meaningful impact on risk for GERD symptoms, possibly preventing nearly 40% of cases with weekly GERD symptoms, reported lead author Raaj S. Mehta, MD, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues.

“Clinicians recommend dietary and lifestyle modifications to prevent GERD symptoms, but no prospective data are available to inform these recommendations,” Dr. Mehta and colleagues wrote in JAMA Internal Medicine.

To address this gap, the investigators turned to the Nurses’ Health Study II, a nationwide, prospective study involving 116,671 women. The study, which has a follow-up rate exceeding 90%, began in 1989 and is ongoing. Participants complete biennial questionnaires that include a variety of health and lifestyle factors. In 2005, 2009, 2013, and 2017, the questionnaire inquired about heartburn or acid reflux.

The present analysis included data from 42,955 women aged 42-62 years. Participants were excluded at baseline if they had cancer, lacked dietary data, were lost to follow-up, already had GERD symptoms at least weekly, or used a PPI and/or H2RA on a regular basis. The final dataset included 392,215 person-years of follow-up, with 9,291 incident cases of GERD symptoms.

For each participant, the presence of five possible antireflux lifestyle factors were added together for a score ranging from 0 to 5: no more than two cups of soda, tea, or coffee per day; never smoking; normal body weight (BMI ≥18.5 and <25.0 kg/m²); “prudent” diet, based on top 40% of dietary pattern score; and at least 30 minutes of moderate to vigorous physical activity each day.

Multivariate logistic regression modeling showed that women who reported all five antireflux lifestyle factors had a 50% decreased risk of GERD symptoms (hazard ratio, 0.50; 95% confidence interval, 0.42-0.59), compared with women who adhered to none of them. Further analysis suggested that the collective effect of all five factors could reduce GERD symptom case volume by 37% (95% CI, 28%-46%).

Nonadherence to each antireflux lifestyle factor was independently associated with an increased risk of GERD symptoms. After mutual adjustment for other variables, BMI was associated with the highest population-attributable risk (19%), followed by physical activity (8%), food intake (7%), beverage intake (4%), and nonsmoker status (3%).

Dr. Mehta and colleagues also explored the relationship between GERD symptoms, antireflux medications, and lifestyle factors. Presence of all five antireflux factors was associated with a 53% decreased risk of GERD symptoms or initiation of PPI and/or H2RA therapy (HR, 0.47; 95% CI, 0.41-0.54). Among a group of 3,625 women who reported regular use of a PPI and/or H2RA and were free of GERD symptoms at baseline, adherence to all five lifestyle factors reduced risk of GERD symptoms by 68% (HR, 0.32; 95% CI, 0.18-0.57).

One limitation of the study was that its population was primarily White women; however, the authors noted a study suggesting GERD is more common in White women aged 30-60 years.

“Adherence to an antireflux lifestyle, even among regular users of PPIs and/or H2RAs, was associated with a decreased risk of GERD symptoms,” the investigators concluded.

Lifestyle matters

According to Ronnie Fass, MD, medical director of the Digestive Health Center at Case Western Reserve University, Cleveland, “This is the first study to show the incremental effect and thus the benefit of lifestyle factors in reducing the risk of GERD symptoms. While only five lifestyle factors were assessed in this study, potentially others may further decrease the risk for symptoms.”

Dr. Fass suggested that the nature of the data, which was self-reported, and the entirely female patient population, should inform interpretation of the findings.

“While nonerosive reflux disease is relatively more common in women, erosive esophagitis and Barrett’s esophagus are more common in men,” he said. “Furthermore, male gender is associated with more severe GERD and GERD complications.”

Yet Dr. Fass concluded by again emphasizing the merit of the analysis: “This is an important study that further supports the value of certain lifestyle factors in reducing the risk of GERD symptoms,” he said. “What is challenging for practicing physicians is to get patients to follow these lifestyle factors long term.”

The study was funded by the National Institutes of Health and by a Stuart and Suzanne Steele Massachusetts General Hospital Research Scholar Award. The investigators and Dr. Fass disclosed no conflicts of interest.

Antireflux lifestyle factors may significantly reduce the risk of gastroesophageal reflux disease (GERD), according to an analysis involving almost 43,000 women.

Tharakorn/Getty Images

Even alongside therapy with a proton-pump inhibitor (PPI) and/or a histamine-receptor antagonist (H2RA), adherence to five antireflux lifestyle factors had a meaningful impact on risk for GERD symptoms, possibly preventing nearly 40% of cases with weekly GERD symptoms, reported lead author Raaj S. Mehta, MD, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues.

“Clinicians recommend dietary and lifestyle modifications to prevent GERD symptoms, but no prospective data are available to inform these recommendations,” Dr. Mehta and colleagues wrote in JAMA Internal Medicine.

To address this gap, the investigators turned to the Nurses’ Health Study II, a nationwide, prospective study involving 116,671 women. The study, which has a follow-up rate exceeding 90%, began in 1989 and is ongoing. Participants complete biennial questionnaires that include a variety of health and lifestyle factors. In 2005, 2009, 2013, and 2017, the questionnaire inquired about heartburn or acid reflux.

The present analysis included data from 42,955 women aged 42-62 years. Participants were excluded at baseline if they had cancer, lacked dietary data, were lost to follow-up, already had GERD symptoms at least weekly, or used a PPI and/or H2RA on a regular basis. The final dataset included 392,215 person-years of follow-up, with 9,291 incident cases of GERD symptoms.

For each participant, the presence of five possible antireflux lifestyle factors were added together for a score ranging from 0 to 5: no more than two cups of soda, tea, or coffee per day; never smoking; normal body weight (BMI ≥18.5 and <25.0 kg/m²); “prudent” diet, based on top 40% of dietary pattern score; and at least 30 minutes of moderate to vigorous physical activity each day.

Multivariate logistic regression modeling showed that women who reported all five antireflux lifestyle factors had a 50% decreased risk of GERD symptoms (hazard ratio, 0.50; 95% confidence interval, 0.42-0.59), compared with women who adhered to none of them. Further analysis suggested that the collective effect of all five factors could reduce GERD symptom case volume by 37% (95% CI, 28%-46%).

Nonadherence to each antireflux lifestyle factor was independently associated with an increased risk of GERD symptoms. After mutual adjustment for other variables, BMI was associated with the highest population-attributable risk (19%), followed by physical activity (8%), food intake (7%), beverage intake (4%), and nonsmoker status (3%).

Dr. Mehta and colleagues also explored the relationship between GERD symptoms, antireflux medications, and lifestyle factors. Presence of all five antireflux factors was associated with a 53% decreased risk of GERD symptoms or initiation of PPI and/or H2RA therapy (HR, 0.47; 95% CI, 0.41-0.54). Among a group of 3,625 women who reported regular use of a PPI and/or H2RA and were free of GERD symptoms at baseline, adherence to all five lifestyle factors reduced risk of GERD symptoms by 68% (HR, 0.32; 95% CI, 0.18-0.57).

One limitation of the study was that its population was primarily White women; however, the authors noted a study suggesting GERD is more common in White women aged 30-60 years.

“Adherence to an antireflux lifestyle, even among regular users of PPIs and/or H2RAs, was associated with a decreased risk of GERD symptoms,” the investigators concluded.

Lifestyle matters

According to Ronnie Fass, MD, medical director of the Digestive Health Center at Case Western Reserve University, Cleveland, “This is the first study to show the incremental effect and thus the benefit of lifestyle factors in reducing the risk of GERD symptoms. While only five lifestyle factors were assessed in this study, potentially others may further decrease the risk for symptoms.”

Dr. Fass suggested that the nature of the data, which was self-reported, and the entirely female patient population, should inform interpretation of the findings.

“While nonerosive reflux disease is relatively more common in women, erosive esophagitis and Barrett’s esophagus are more common in men,” he said. “Furthermore, male gender is associated with more severe GERD and GERD complications.”

Yet Dr. Fass concluded by again emphasizing the merit of the analysis: “This is an important study that further supports the value of certain lifestyle factors in reducing the risk of GERD symptoms,” he said. “What is challenging for practicing physicians is to get patients to follow these lifestyle factors long term.”

The study was funded by the National Institutes of Health and by a Stuart and Suzanne Steele Massachusetts General Hospital Research Scholar Award. The investigators and Dr. Fass disclosed no conflicts of interest.

Antireflux lifestyle factors may significantly reduce the risk of gastroesophageal reflux disease (GERD), according to an analysis involving almost 43,000 women.

Tharakorn/Getty Images

Even alongside therapy with a proton-pump inhibitor (PPI) and/or a histamine-receptor antagonist (H2RA), adherence to five antireflux lifestyle factors had a meaningful impact on risk for GERD symptoms, possibly preventing nearly 40% of cases with weekly GERD symptoms, reported lead author Raaj S. Mehta, MD, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues.

“Clinicians recommend dietary and lifestyle modifications to prevent GERD symptoms, but no prospective data are available to inform these recommendations,” Dr. Mehta and colleagues wrote in JAMA Internal Medicine.

To address this gap, the investigators turned to the Nurses’ Health Study II, a nationwide, prospective study involving 116,671 women. The study, which has a follow-up rate exceeding 90%, began in 1989 and is ongoing. Participants complete biennial questionnaires that include a variety of health and lifestyle factors. In 2005, 2009, 2013, and 2017, the questionnaire inquired about heartburn or acid reflux.

The present analysis included data from 42,955 women aged 42-62 years. Participants were excluded at baseline if they had cancer, lacked dietary data, were lost to follow-up, already had GERD symptoms at least weekly, or used a PPI and/or H2RA on a regular basis. The final dataset included 392,215 person-years of follow-up, with 9,291 incident cases of GERD symptoms.

For each participant, the presence of five possible antireflux lifestyle factors were added together for a score ranging from 0 to 5: no more than two cups of soda, tea, or coffee per day; never smoking; normal body weight (BMI ≥18.5 and <25.0 kg/m²); “prudent” diet, based on top 40% of dietary pattern score; and at least 30 minutes of moderate to vigorous physical activity each day.

Multivariate logistic regression modeling showed that women who reported all five antireflux lifestyle factors had a 50% decreased risk of GERD symptoms (hazard ratio, 0.50; 95% confidence interval, 0.42-0.59), compared with women who adhered to none of them. Further analysis suggested that the collective effect of all five factors could reduce GERD symptom case volume by 37% (95% CI, 28%-46%).

Nonadherence to each antireflux lifestyle factor was independently associated with an increased risk of GERD symptoms. After mutual adjustment for other variables, BMI was associated with the highest population-attributable risk (19%), followed by physical activity (8%), food intake (7%), beverage intake (4%), and nonsmoker status (3%).

Dr. Mehta and colleagues also explored the relationship between GERD symptoms, antireflux medications, and lifestyle factors. Presence of all five antireflux factors was associated with a 53% decreased risk of GERD symptoms or initiation of PPI and/or H2RA therapy (HR, 0.47; 95% CI, 0.41-0.54). Among a group of 3,625 women who reported regular use of a PPI and/or H2RA and were free of GERD symptoms at baseline, adherence to all five lifestyle factors reduced risk of GERD symptoms by 68% (HR, 0.32; 95% CI, 0.18-0.57).

One limitation of the study was that its population was primarily White women; however, the authors noted a study suggesting GERD is more common in White women aged 30-60 years.

“Adherence to an antireflux lifestyle, even among regular users of PPIs and/or H2RAs, was associated with a decreased risk of GERD symptoms,” the investigators concluded.

Lifestyle matters

According to Ronnie Fass, MD, medical director of the Digestive Health Center at Case Western Reserve University, Cleveland, “This is the first study to show the incremental effect and thus the benefit of lifestyle factors in reducing the risk of GERD symptoms. While only five lifestyle factors were assessed in this study, potentially others may further decrease the risk for symptoms.”

Dr. Fass suggested that the nature of the data, which was self-reported, and the entirely female patient population, should inform interpretation of the findings.

“While nonerosive reflux disease is relatively more common in women, erosive esophagitis and Barrett’s esophagus are more common in men,” he said. “Furthermore, male gender is associated with more severe GERD and GERD complications.”

Yet Dr. Fass concluded by again emphasizing the merit of the analysis: “This is an important study that further supports the value of certain lifestyle factors in reducing the risk of GERD symptoms,” he said. “What is challenging for practicing physicians is to get patients to follow these lifestyle factors long term.”

The study was funded by the National Institutes of Health and by a Stuart and Suzanne Steele Massachusetts General Hospital Research Scholar Award. The investigators and Dr. Fass disclosed no conflicts of interest.

The American Academy of Pediatrics recently issued five recommendations for the most common dermatologic problems in primary care pediatrics.

Topics include diagnostic and management strategies for a variety of conditions, including atopic dermatitis, fungal infections, and autoimmune conditions.

The AAP Section on Dermatology created the recommendations, which were then reviewed and approved by “more than a dozen relevant AAP committees, councils, and sections,” before final approval by the AAP executive committee and board of directors.

The final list represents a collaborative effort with the Choosing Wisely initiative of the American Board of Internal Medicine Foundation, which aims “to promote conversations between clinicians and patients by helping patients choose care that is supported by evidence, not duplicative of other tests or procedures already received, free from harm, [and] truly necessary.”

Lawrence Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, and chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego, said that the recommendations are “a fine set of suggestions to help health care providers with some of their pediatric dermatology issues.”

• To begin, the AAP recommended against use of combination topical steroid antifungals for candida skin infections, diaper dermatitis, and tinea corporis, despite approvals for these indications.

“Many providers are unaware that the combination products contain a relatively high-potency topical steroid,” the AAP wrote, noting that “combination products are also often expensive and not covered by pharmacy plans.”

Diaper dermatitis responds best to barrier creams and ointments alone, according to the AAP. If needed, a topical, low-potency steroid may be used no more than twice a day, and tapered with improvement. Similarly, the AAP recommended a separate, low-potency steroid for tinea corporis if pruritus is severe.

• In contrast with this call for minimal treatment intensity, the AAP recommended a more intensive approach to tinea capitis, advising against topical medications alone.

“Topical treatments cannot penetrate the hair shaft itself, which is where the infection lies; thus, monotherapy with topical medications is insufficient to effectively treat the infection,” the AAP wrote. “This insufficient treatment can lead to increased health care costs resulting from multiple visits and the prescribing of ineffective medications.”

While medicated shampoos may still be used as adjunctive treatments for tinea capitis, the AAP recommended primary therapy with either griseofulvin or terbinafine, slightly favoring terbinafine because of adequate efficacy, lesser expense, and shorter regimen.

According to Dr. Eichenfield, a more thorough workup should also be considered.

“Consider culturing possible tinea capitis, so that oral antifungals can be used judiciously and not used for other scaling scalp diagnoses,” he said.

• For most cases of atopic dermatitis, the AAP advised against oral or injected corticosteroids, despite rapid efficacy, because of potential for adverse events, such as adrenal suppression, growth retardation, and disease worsening upon discontinuation. Instead, they recommended topical therapies, “good skin care practices,” and if necessary, “phototherapy and/or steroid-sparing systemic agents.”

“Systemic corticosteroids should only be prescribed for severe flares once all other treatment options have been exhausted and should be limited to a short course for the purpose of bridging to a steroid-sparing agent,” the AAP wrote.

Dr. Eichenfield emphasized this point, noting that new therapies have expanded treatment options.

“Be aware of the advances in atopic dermatitis,” he said, “with newer topical medications and with a new systemic biologic agent approved for moderate to severe refractory atopic dermatitis for ages 6 and older.”

• Turning to diagnostic strategies, the AAP recommended against routine laboratory testing for associated autoimmune diseases among patients with vitiligo, unless clinical signs and/or symptoms of such diseases are present.

“There is no convincing evidence that extensive workups in the absence of specific clinical suspicion improves outcomes for patients and may in fact beget additional costs and harms,” the AAP wrote. “Although many studies suggest ordering these tests, it is based largely on the increased cosegregation of vitiligo and thyroid disease and not on improved outcomes from having identified an abnormal laboratory test result.”

• Similarly, the AAP advised practitioners to avoid routinely testing patients with alopecia areata for other diseases if relevant symptoms and signs aren’t present.

“As in the case of vitiligo, it is more common to find thyroid autoantibodies or subclinical hypothyroidism than overt thyroid disease, unless there are clinically suspicious findings,” the AAP wrote. “Patients identified as having subclinical hypothyroidism are not currently treated and may even have resolution of the abnormal TSH.”

Before drawing blood, Dr. Eichenfield suggested that clinicians first ask the right questions.

“Be comfortable with screening questions about growth, weight, or activity changes to assist with decisions for thyroid screening in a patient with vitiligo or alopecia areata,” he said.

Choosing Wisely is an initiative of the American Board of Internal Medicine. The AAP and Dr. Eichenfield reported no conflicts of interest.

The American Academy of Pediatrics recently issued five recommendations for the most common dermatologic problems in primary care pediatrics.

Topics include diagnostic and management strategies for a variety of conditions, including atopic dermatitis, fungal infections, and autoimmune conditions.

The AAP Section on Dermatology created the recommendations, which were then reviewed and approved by “more than a dozen relevant AAP committees, councils, and sections,” before final approval by the AAP executive committee and board of directors.

The final list represents a collaborative effort with the Choosing Wisely initiative of the American Board of Internal Medicine Foundation, which aims “to promote conversations between clinicians and patients by helping patients choose care that is supported by evidence, not duplicative of other tests or procedures already received, free from harm, [and] truly necessary.”

Lawrence Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, and chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego, said that the recommendations are “a fine set of suggestions to help health care providers with some of their pediatric dermatology issues.”

• To begin, the AAP recommended against use of combination topical steroid antifungals for candida skin infections, diaper dermatitis, and tinea corporis, despite approvals for these indications.

“Many providers are unaware that the combination products contain a relatively high-potency topical steroid,” the AAP wrote, noting that “combination products are also often expensive and not covered by pharmacy plans.”

Diaper dermatitis responds best to barrier creams and ointments alone, according to the AAP. If needed, a topical, low-potency steroid may be used no more than twice a day, and tapered with improvement. Similarly, the AAP recommended a separate, low-potency steroid for tinea corporis if pruritus is severe.

• In contrast with this call for minimal treatment intensity, the AAP recommended a more intensive approach to tinea capitis, advising against topical medications alone.

“Topical treatments cannot penetrate the hair shaft itself, which is where the infection lies; thus, monotherapy with topical medications is insufficient to effectively treat the infection,” the AAP wrote. “This insufficient treatment can lead to increased health care costs resulting from multiple visits and the prescribing of ineffective medications.”

While medicated shampoos may still be used as adjunctive treatments for tinea capitis, the AAP recommended primary therapy with either griseofulvin or terbinafine, slightly favoring terbinafine because of adequate efficacy, lesser expense, and shorter regimen.

According to Dr. Eichenfield, a more thorough workup should also be considered.

“Consider culturing possible tinea capitis, so that oral antifungals can be used judiciously and not used for other scaling scalp diagnoses,” he said.

• For most cases of atopic dermatitis, the AAP advised against oral or injected corticosteroids, despite rapid efficacy, because of potential for adverse events, such as adrenal suppression, growth retardation, and disease worsening upon discontinuation. Instead, they recommended topical therapies, “good skin care practices,” and if necessary, “phototherapy and/or steroid-sparing systemic agents.”

“Systemic corticosteroids should only be prescribed for severe flares once all other treatment options have been exhausted and should be limited to a short course for the purpose of bridging to a steroid-sparing agent,” the AAP wrote.

Dr. Eichenfield emphasized this point, noting that new therapies have expanded treatment options.

“Be aware of the advances in atopic dermatitis,” he said, “with newer topical medications and with a new systemic biologic agent approved for moderate to severe refractory atopic dermatitis for ages 6 and older.”

• Turning to diagnostic strategies, the AAP recommended against routine laboratory testing for associated autoimmune diseases among patients with vitiligo, unless clinical signs and/or symptoms of such diseases are present.

“There is no convincing evidence that extensive workups in the absence of specific clinical suspicion improves outcomes for patients and may in fact beget additional costs and harms,” the AAP wrote. “Although many studies suggest ordering these tests, it is based largely on the increased cosegregation of vitiligo and thyroid disease and not on improved outcomes from having identified an abnormal laboratory test result.”

• Similarly, the AAP advised practitioners to avoid routinely testing patients with alopecia areata for other diseases if relevant symptoms and signs aren’t present.

“As in the case of vitiligo, it is more common to find thyroid autoantibodies or subclinical hypothyroidism than overt thyroid disease, unless there are clinically suspicious findings,” the AAP wrote. “Patients identified as having subclinical hypothyroidism are not currently treated and may even have resolution of the abnormal TSH.”

Before drawing blood, Dr. Eichenfield suggested that clinicians first ask the right questions.

“Be comfortable with screening questions about growth, weight, or activity changes to assist with decisions for thyroid screening in a patient with vitiligo or alopecia areata,” he said.

Choosing Wisely is an initiative of the American Board of Internal Medicine. The AAP and Dr. Eichenfield reported no conflicts of interest.

The American Academy of Pediatrics recently issued five recommendations for the most common dermatologic problems in primary care pediatrics.

Topics include diagnostic and management strategies for a variety of conditions, including atopic dermatitis, fungal infections, and autoimmune conditions.

The AAP Section on Dermatology created the recommendations, which were then reviewed and approved by “more than a dozen relevant AAP committees, councils, and sections,” before final approval by the AAP executive committee and board of directors.

The final list represents a collaborative effort with the Choosing Wisely initiative of the American Board of Internal Medicine Foundation, which aims “to promote conversations between clinicians and patients by helping patients choose care that is supported by evidence, not duplicative of other tests or procedures already received, free from harm, [and] truly necessary.”

Lawrence Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, and chief of pediatric and adolescent dermatology at Rady Children’s Hospital, San Diego, said that the recommendations are “a fine set of suggestions to help health care providers with some of their pediatric dermatology issues.”

• To begin, the AAP recommended against use of combination topical steroid antifungals for candida skin infections, diaper dermatitis, and tinea corporis, despite approvals for these indications.

“Many providers are unaware that the combination products contain a relatively high-potency topical steroid,” the AAP wrote, noting that “combination products are also often expensive and not covered by pharmacy plans.”

Diaper dermatitis responds best to barrier creams and ointments alone, according to the AAP. If needed, a topical, low-potency steroid may be used no more than twice a day, and tapered with improvement. Similarly, the AAP recommended a separate, low-potency steroid for tinea corporis if pruritus is severe.

• In contrast with this call for minimal treatment intensity, the AAP recommended a more intensive approach to tinea capitis, advising against topical medications alone.

“Topical treatments cannot penetrate the hair shaft itself, which is where the infection lies; thus, monotherapy with topical medications is insufficient to effectively treat the infection,” the AAP wrote. “This insufficient treatment can lead to increased health care costs resulting from multiple visits and the prescribing of ineffective medications.”

While medicated shampoos may still be used as adjunctive treatments for tinea capitis, the AAP recommended primary therapy with either griseofulvin or terbinafine, slightly favoring terbinafine because of adequate efficacy, lesser expense, and shorter regimen.

According to Dr. Eichenfield, a more thorough workup should also be considered.

“Consider culturing possible tinea capitis, so that oral antifungals can be used judiciously and not used for other scaling scalp diagnoses,” he said.

• For most cases of atopic dermatitis, the AAP advised against oral or injected corticosteroids, despite rapid efficacy, because of potential for adverse events, such as adrenal suppression, growth retardation, and disease worsening upon discontinuation. Instead, they recommended topical therapies, “good skin care practices,” and if necessary, “phototherapy and/or steroid-sparing systemic agents.”

“Systemic corticosteroids should only be prescribed for severe flares once all other treatment options have been exhausted and should be limited to a short course for the purpose of bridging to a steroid-sparing agent,” the AAP wrote.

Dr. Eichenfield emphasized this point, noting that new therapies have expanded treatment options.

“Be aware of the advances in atopic dermatitis,” he said, “with newer topical medications and with a new systemic biologic agent approved for moderate to severe refractory atopic dermatitis for ages 6 and older.”

• Turning to diagnostic strategies, the AAP recommended against routine laboratory testing for associated autoimmune diseases among patients with vitiligo, unless clinical signs and/or symptoms of such diseases are present.

“There is no convincing evidence that extensive workups in the absence of specific clinical suspicion improves outcomes for patients and may in fact beget additional costs and harms,” the AAP wrote. “Although many studies suggest ordering these tests, it is based largely on the increased cosegregation of vitiligo and thyroid disease and not on improved outcomes from having identified an abnormal laboratory test result.”

• Similarly, the AAP advised practitioners to avoid routinely testing patients with alopecia areata for other diseases if relevant symptoms and signs aren’t present.

“As in the case of vitiligo, it is more common to find thyroid autoantibodies or subclinical hypothyroidism than overt thyroid disease, unless there are clinically suspicious findings,” the AAP wrote. “Patients identified as having subclinical hypothyroidism are not currently treated and may even have resolution of the abnormal TSH.”

Before drawing blood, Dr. Eichenfield suggested that clinicians first ask the right questions.

“Be comfortable with screening questions about growth, weight, or activity changes to assist with decisions for thyroid screening in a patient with vitiligo or alopecia areata,” he said.

Choosing Wisely is an initiative of the American Board of Internal Medicine. The AAP and Dr. Eichenfield reported no conflicts of interest.

Among patients with nonalcoholic fatty liver disease (NAFLD) and compensated advanced chronic liver disease, liver stiffness measurements (LSMs) are associated with risks of hepatic events, according to a retrospective analysis of more than 1,000 patients.

“[N]oninvasive markers that can predict liver disease severity and outcomes in patients with NAFLD and advanced fibrosis are a major unmet need,” wrote lead author Salvatore Petta, MD, of the University of Palermo, Italy, and colleagues. Their report is in Clinical Gastroenterology and Hepatology. “Data about the accuracy of LSM in the prediction of events in NAFLD, and especially in patients with NAFLD and F3-F4 fibrosis, are scarce.”

To address this knowledge gap, the investigators retrospectively analyzed data from 1,039 consecutive patients with NAFLD who had baseline LSMs of more than 10 kPa and/or histologically diagnosed F3-F4 fibrosis. Patients were prospectively recruited at 10 centers in 6 countries, then followed for a median of 35 months, ranging from 19 to 63 months.

All patients had their liver stiffness measured with an M or XL probe at baseline. In addition, approximately half of the patients (n = 533) had a follow-up measurement using the same method, generating a subgroup with changes in liver stiffness. “Improved” liver stiffness was defined as a decrease in LSM greater than 20% from baseline, “impaired” liver stiffness was defined as an increase in LSM greater than 20% from baseline, and “stable” liver stiffness was defined as a change falling between 20% lower and 20% higher than baseline.

At baseline, mean LSM was 17.6 kPa. Cox regression analysis revealed that baseline LSM was independently associated with HCC (hazard ratio, 1.03; 95% confidence interval, 1.00-1.04; P = .003), liver decompensation (HR, 1.03; 95% CI, 1.02-1.04; P < .001), and liver-related death (HR, 1.02; 95% CI, 1.00-1.03; P = .005), but not extrahepatic events.

According to the investigators, the association between LSM at baseline and risk of liver decompensation was maintained after adjustment for the severity of liver disease and for surrogate markers of portal hypertension, they noted. Furthermore, patients with a baseline LSM of at least 21 kPa – which indicates high risk of clinically significant portal hypertension (CSPH) – were at greater risk of liver decompensation than were those with an LSM less than 21 kPa (HR, 3.71; 95% CI, 1.89-6.78; P = .04).

In the subgroup with follow-up measurements, approximately half of the patients had an improved LSM (53.3%), while 27.2% had a stable LSM, and 19.5% had an impaired LSM, a pattern that was significantly associated with diabetes at baseline (P = .01).

“These data agree with the available literature identifying diabetes as a risk factor for liver disease progression and liver-related complications,” the investigators wrote.

Cox regression showed that, among those with follow-up LSM, changes in LSM were independently associated with HCC (HR, 1.72; 95% CI, 1.01-3.02; P = .04), liver decompensation (HR, 1.56; 95% CI, 1.05-2.51; P = . 04), liver-related mortality (HR, 1.96; 95% CI, 1.10-3.38; P = .02), and mortality of any cause (HR, 1.73; 95% CI, 1.11-2.69; P = .01).

These risks could be further stratified by level of change in liver stiffness, with greater impairment predicting greater risk: The crude rate of liver decompensation was 14.4% among those with impaired LSM, compared with 6.2% among those with stable LSM and 3.8% among those with LSM improvement. That said, the categories of changes in LSM were not predictive of decompensation among patients with high risk of CSPH at baseline; however, they remained predictive among those with low risk of CSPH at baseline.

“[T]his study … showed that an integrated assessment of baseline LSM or [changes in LSM] can help in stratifying the risk of development of liver-related complications and of both hepatic and overall mortality,” the investigators concluded. “These data, if further validated, could help personalize prognosis and follow-up in NAFLD with [compensated advanced chronic liver disease].”

The investigators disclosed relationships with AbbVie, Novo Nordisk, Gilead, and others.

Among patients with nonalcoholic fatty liver disease (NAFLD) and compensated advanced chronic liver disease, liver stiffness measurements (LSMs) are associated with risks of hepatic events, according to a retrospective analysis of more than 1,000 patients.

“[N]oninvasive markers that can predict liver disease severity and outcomes in patients with NAFLD and advanced fibrosis are a major unmet need,” wrote lead author Salvatore Petta, MD, of the University of Palermo, Italy, and colleagues. Their report is in Clinical Gastroenterology and Hepatology. “Data about the accuracy of LSM in the prediction of events in NAFLD, and especially in patients with NAFLD and F3-F4 fibrosis, are scarce.”

To address this knowledge gap, the investigators retrospectively analyzed data from 1,039 consecutive patients with NAFLD who had baseline LSMs of more than 10 kPa and/or histologically diagnosed F3-F4 fibrosis. Patients were prospectively recruited at 10 centers in 6 countries, then followed for a median of 35 months, ranging from 19 to 63 months.

All patients had their liver stiffness measured with an M or XL probe at baseline. In addition, approximately half of the patients (n = 533) had a follow-up measurement using the same method, generating a subgroup with changes in liver stiffness. “Improved” liver stiffness was defined as a decrease in LSM greater than 20% from baseline, “impaired” liver stiffness was defined as an increase in LSM greater than 20% from baseline, and “stable” liver stiffness was defined as a change falling between 20% lower and 20% higher than baseline.

At baseline, mean LSM was 17.6 kPa. Cox regression analysis revealed that baseline LSM was independently associated with HCC (hazard ratio, 1.03; 95% confidence interval, 1.00-1.04; P = .003), liver decompensation (HR, 1.03; 95% CI, 1.02-1.04; P < .001), and liver-related death (HR, 1.02; 95% CI, 1.00-1.03; P = .005), but not extrahepatic events.

According to the investigators, the association between LSM at baseline and risk of liver decompensation was maintained after adjustment for the severity of liver disease and for surrogate markers of portal hypertension, they noted. Furthermore, patients with a baseline LSM of at least 21 kPa – which indicates high risk of clinically significant portal hypertension (CSPH) – were at greater risk of liver decompensation than were those with an LSM less than 21 kPa (HR, 3.71; 95% CI, 1.89-6.78; P = .04).

In the subgroup with follow-up measurements, approximately half of the patients had an improved LSM (53.3%), while 27.2% had a stable LSM, and 19.5% had an impaired LSM, a pattern that was significantly associated with diabetes at baseline (P = .01).

“These data agree with the available literature identifying diabetes as a risk factor for liver disease progression and liver-related complications,” the investigators wrote.

Cox regression showed that, among those with follow-up LSM, changes in LSM were independently associated with HCC (HR, 1.72; 95% CI, 1.01-3.02; P = .04), liver decompensation (HR, 1.56; 95% CI, 1.05-2.51; P = . 04), liver-related mortality (HR, 1.96; 95% CI, 1.10-3.38; P = .02), and mortality of any cause (HR, 1.73; 95% CI, 1.11-2.69; P = .01).

These risks could be further stratified by level of change in liver stiffness, with greater impairment predicting greater risk: The crude rate of liver decompensation was 14.4% among those with impaired LSM, compared with 6.2% among those with stable LSM and 3.8% among those with LSM improvement. That said, the categories of changes in LSM were not predictive of decompensation among patients with high risk of CSPH at baseline; however, they remained predictive among those with low risk of CSPH at baseline.

“[T]his study … showed that an integrated assessment of baseline LSM or [changes in LSM] can help in stratifying the risk of development of liver-related complications and of both hepatic and overall mortality,” the investigators concluded. “These data, if further validated, could help personalize prognosis and follow-up in NAFLD with [compensated advanced chronic liver disease].”

The investigators disclosed relationships with AbbVie, Novo Nordisk, Gilead, and others.

Among patients with nonalcoholic fatty liver disease (NAFLD) and compensated advanced chronic liver disease, liver stiffness measurements (LSMs) are associated with risks of hepatic events, according to a retrospective analysis of more than 1,000 patients.

“[N]oninvasive markers that can predict liver disease severity and outcomes in patients with NAFLD and advanced fibrosis are a major unmet need,” wrote lead author Salvatore Petta, MD, of the University of Palermo, Italy, and colleagues. Their report is in Clinical Gastroenterology and Hepatology. “Data about the accuracy of LSM in the prediction of events in NAFLD, and especially in patients with NAFLD and F3-F4 fibrosis, are scarce.”

To address this knowledge gap, the investigators retrospectively analyzed data from 1,039 consecutive patients with NAFLD who had baseline LSMs of more than 10 kPa and/or histologically diagnosed F3-F4 fibrosis. Patients were prospectively recruited at 10 centers in 6 countries, then followed for a median of 35 months, ranging from 19 to 63 months.

All patients had their liver stiffness measured with an M or XL probe at baseline. In addition, approximately half of the patients (n = 533) had a follow-up measurement using the same method, generating a subgroup with changes in liver stiffness. “Improved” liver stiffness was defined as a decrease in LSM greater than 20% from baseline, “impaired” liver stiffness was defined as an increase in LSM greater than 20% from baseline, and “stable” liver stiffness was defined as a change falling between 20% lower and 20% higher than baseline.

At baseline, mean LSM was 17.6 kPa. Cox regression analysis revealed that baseline LSM was independently associated with HCC (hazard ratio, 1.03; 95% confidence interval, 1.00-1.04; P = .003), liver decompensation (HR, 1.03; 95% CI, 1.02-1.04; P < .001), and liver-related death (HR, 1.02; 95% CI, 1.00-1.03; P = .005), but not extrahepatic events.

According to the investigators, the association between LSM at baseline and risk of liver decompensation was maintained after adjustment for the severity of liver disease and for surrogate markers of portal hypertension, they noted. Furthermore, patients with a baseline LSM of at least 21 kPa – which indicates high risk of clinically significant portal hypertension (CSPH) – were at greater risk of liver decompensation than were those with an LSM less than 21 kPa (HR, 3.71; 95% CI, 1.89-6.78; P = .04).

In the subgroup with follow-up measurements, approximately half of the patients had an improved LSM (53.3%), while 27.2% had a stable LSM, and 19.5% had an impaired LSM, a pattern that was significantly associated with diabetes at baseline (P = .01).

“These data agree with the available literature identifying diabetes as a risk factor for liver disease progression and liver-related complications,” the investigators wrote.

Cox regression showed that, among those with follow-up LSM, changes in LSM were independently associated with HCC (HR, 1.72; 95% CI, 1.01-3.02; P = .04), liver decompensation (HR, 1.56; 95% CI, 1.05-2.51; P = . 04), liver-related mortality (HR, 1.96; 95% CI, 1.10-3.38; P = .02), and mortality of any cause (HR, 1.73; 95% CI, 1.11-2.69; P = .01).

These risks could be further stratified by level of change in liver stiffness, with greater impairment predicting greater risk: The crude rate of liver decompensation was 14.4% among those with impaired LSM, compared with 6.2% among those with stable LSM and 3.8% among those with LSM improvement. That said, the categories of changes in LSM were not predictive of decompensation among patients with high risk of CSPH at baseline; however, they remained predictive among those with low risk of CSPH at baseline.

“[T]his study … showed that an integrated assessment of baseline LSM or [changes in LSM] can help in stratifying the risk of development of liver-related complications and of both hepatic and overall mortality,” the investigators concluded. “These data, if further validated, could help personalize prognosis and follow-up in NAFLD with [compensated advanced chronic liver disease].”

The investigators disclosed relationships with AbbVie, Novo Nordisk, Gilead, and others.

Among patients with nonalcoholic fatty liver disease (NAFLD) and compensated advanced chronic liver disease, liver stiffness measurements (LSMs) are associated with risks of hepatic events, according to a retrospective analysis of more than 1,000 patients.

“[N]oninvasive markers that can predict liver disease severity and outcomes in patients with NAFLD and advanced fibrosis are a major unmet need,” wrote lead author Salvatore Petta, MD, of the University of Palermo, Italy, and colleagues. Their report is in Clinical Gastroenterology and Hepatology. “Data about the accuracy of LSM in the prediction of events in NAFLD, and especially in patients with NAFLD and F3-F4 fibrosis, are scarce.”

To address this knowledge gap, the investigators retrospectively analyzed data from 1,039 consecutive patients with NAFLD who had baseline LSMs of more than 10 kPa and/or histologically diagnosed F3-F4 fibrosis. Patients were prospectively recruited at 10 centers in 6 countries, then followed for a median of 35 months, ranging from 19 to 63 months.

All patients had their liver stiffness measured with an M or XL probe at baseline. In addition, approximately half of the patients (n = 533) had a follow-up measurement using the same method, generating a subgroup with changes in liver stiffness. “Improved” liver stiffness was defined as a decrease in LSM greater than 20% from baseline, “impaired” liver stiffness was defined as an increase in LSM greater than 20% from baseline, and “stable” liver stiffness was defined as a change falling between 20% lower and 20% higher than baseline.

At baseline, mean LSM was 17.6 kPa. Cox regression analysis revealed that baseline LSM was independently associated with HCC (hazard ratio, 1.03; 95% confidence interval, 1.00-1.04; P = .003), liver decompensation (HR, 1.03; 95% CI, 1.02-1.04; P < .001), and liver-related death (HR, 1.02; 95% CI, 1.00-1.03; P = .005), but not extrahepatic events.

According to the investigators, the association between LSM at baseline and risk of liver decompensation was maintained after adjustment for the severity of liver disease and for surrogate markers of portal hypertension, they noted. Furthermore, patients with a baseline LSM of at least 21 kPa – which indicates high risk of clinically significant portal hypertension (CSPH) – were at greater risk of liver decompensation than were those with an LSM less than 21 kPa (HR, 3.71; 95% CI, 1.89-6.78; P = .04).

In the subgroup with follow-up measurements, approximately half of the patients had an improved LSM (53.3%), while 27.2% had a stable LSM, and 19.5% had an impaired LSM, a pattern that was significantly associated with diabetes at baseline (P = .01).

“These data agree with the available literature identifying diabetes as a risk factor for liver disease progression and liver-related complications,” the investigators wrote.

Cox regression showed that, among those with follow-up LSM, changes in LSM were independently associated with HCC (HR, 1.72; 95% CI, 1.01-3.02; P = .04), liver decompensation (HR, 1.56; 95% CI, 1.05-2.51; P = . 04), liver-related mortality (HR, 1.96; 95% CI, 1.10-3.38; P = .02), and mortality of any cause (HR, 1.73; 95% CI, 1.11-2.69; P = .01).

These risks could be further stratified by level of change in liver stiffness, with greater impairment predicting greater risk: The crude rate of liver decompensation was 14.4% among those with impaired LSM, compared with 6.2% among those with stable LSM and 3.8% among those with LSM improvement. That said, the categories of changes in LSM were not predictive of decompensation among patients with high risk of CSPH at baseline; however, they remained predictive among those with low risk of CSPH at baseline.

“[T]his study … showed that an integrated assessment of baseline LSM or [changes in LSM] can help in stratifying the risk of development of liver-related complications and of both hepatic and overall mortality,” the investigators concluded. “These data, if further validated, could help personalize prognosis and follow-up in NAFLD with [compensated advanced chronic liver disease].”

The investigators disclosed relationships with AbbVie, Novo Nordisk, Gilead, and others.

Among patients with nonalcoholic fatty liver disease (NAFLD) and compensated advanced chronic liver disease, liver stiffness measurements (LSMs) are associated with risks of hepatic events, according to a retrospective analysis of more than 1,000 patients.

“[N]oninvasive markers that can predict liver disease severity and outcomes in patients with NAFLD and advanced fibrosis are a major unmet need,” wrote lead author Salvatore Petta, MD, of the University of Palermo, Italy, and colleagues. Their report is in Clinical Gastroenterology and Hepatology. “Data about the accuracy of LSM in the prediction of events in NAFLD, and especially in patients with NAFLD and F3-F4 fibrosis, are scarce.”

To address this knowledge gap, the investigators retrospectively analyzed data from 1,039 consecutive patients with NAFLD who had baseline LSMs of more than 10 kPa and/or histologically diagnosed F3-F4 fibrosis. Patients were prospectively recruited at 10 centers in 6 countries, then followed for a median of 35 months, ranging from 19 to 63 months.

All patients had their liver stiffness measured with an M or XL probe at baseline. In addition, approximately half of the patients (n = 533) had a follow-up measurement using the same method, generating a subgroup with changes in liver stiffness. “Improved” liver stiffness was defined as a decrease in LSM greater than 20% from baseline, “impaired” liver stiffness was defined as an increase in LSM greater than 20% from baseline, and “stable” liver stiffness was defined as a change falling between 20% lower and 20% higher than baseline.

At baseline, mean LSM was 17.6 kPa. Cox regression analysis revealed that baseline LSM was independently associated with HCC (hazard ratio, 1.03; 95% confidence interval, 1.00-1.04; P = .003), liver decompensation (HR, 1.03; 95% CI, 1.02-1.04; P < .001), and liver-related death (HR, 1.02; 95% CI, 1.00-1.03; P = .005), but not extrahepatic events.

According to the investigators, the association between LSM at baseline and risk of liver decompensation was maintained after adjustment for the severity of liver disease and for surrogate markers of portal hypertension, they noted. Furthermore, patients with a baseline LSM of at least 21 kPa – which indicates high risk of clinically significant portal hypertension (CSPH) – were at greater risk of liver decompensation than were those with an LSM less than 21 kPa (HR, 3.71; 95% CI, 1.89-6.78; P = .04).

In the subgroup with follow-up measurements, approximately half of the patients had an improved LSM (53.3%), while 27.2% had a stable LSM, and 19.5% had an impaired LSM, a pattern that was significantly associated with diabetes at baseline (P = .01).

“These data agree with the available literature identifying diabetes as a risk factor for liver disease progression and liver-related complications,” the investigators wrote.

Cox regression showed that, among those with follow-up LSM, changes in LSM were independently associated with HCC (HR, 1.72; 95% CI, 1.01-3.02; P = .04), liver decompensation (HR, 1.56; 95% CI, 1.05-2.51; P = . 04), liver-related mortality (HR, 1.96; 95% CI, 1.10-3.38; P = .02), and mortality of any cause (HR, 1.73; 95% CI, 1.11-2.69; P = .01).

These risks could be further stratified by level of change in liver stiffness, with greater impairment predicting greater risk: The crude rate of liver decompensation was 14.4% among those with impaired LSM, compared with 6.2% among those with stable LSM and 3.8% among those with LSM improvement. That said, the categories of changes in LSM were not predictive of decompensation among patients with high risk of CSPH at baseline; however, they remained predictive among those with low risk of CSPH at baseline.

“[T]his study … showed that an integrated assessment of baseline LSM or [changes in LSM] can help in stratifying the risk of development of liver-related complications and of both hepatic and overall mortality,” the investigators concluded. “These data, if further validated, could help personalize prognosis and follow-up in NAFLD with [compensated advanced chronic liver disease].”

The investigators disclosed relationships with AbbVie, Novo Nordisk, Gilead, and others.

Among patients with nonalcoholic fatty liver disease (NAFLD) and compensated advanced chronic liver disease, liver stiffness measurements (LSMs) are associated with risks of hepatic events, according to a retrospective analysis of more than 1,000 patients.

“[N]oninvasive markers that can predict liver disease severity and outcomes in patients with NAFLD and advanced fibrosis are a major unmet need,” wrote lead author Salvatore Petta, MD, of the University of Palermo, Italy, and colleagues. Their report is in Clinical Gastroenterology and Hepatology. “Data about the accuracy of LSM in the prediction of events in NAFLD, and especially in patients with NAFLD and F3-F4 fibrosis, are scarce.”

To address this knowledge gap, the investigators retrospectively analyzed data from 1,039 consecutive patients with NAFLD who had baseline LSMs of more than 10 kPa and/or histologically diagnosed F3-F4 fibrosis. Patients were prospectively recruited at 10 centers in 6 countries, then followed for a median of 35 months, ranging from 19 to 63 months.

All patients had their liver stiffness measured with an M or XL probe at baseline. In addition, approximately half of the patients (n = 533) had a follow-up measurement using the same method, generating a subgroup with changes in liver stiffness. “Improved” liver stiffness was defined as a decrease in LSM greater than 20% from baseline, “impaired” liver stiffness was defined as an increase in LSM greater than 20% from baseline, and “stable” liver stiffness was defined as a change falling between 20% lower and 20% higher than baseline.

At baseline, mean LSM was 17.6 kPa. Cox regression analysis revealed that baseline LSM was independently associated with HCC (hazard ratio, 1.03; 95% confidence interval, 1.00-1.04; P = .003), liver decompensation (HR, 1.03; 95% CI, 1.02-1.04; P < .001), and liver-related death (HR, 1.02; 95% CI, 1.00-1.03; P = .005), but not extrahepatic events.

According to the investigators, the association between LSM at baseline and risk of liver decompensation was maintained after adjustment for the severity of liver disease and for surrogate markers of portal hypertension, they noted. Furthermore, patients with a baseline LSM of at least 21 kPa – which indicates high risk of clinically significant portal hypertension (CSPH) – were at greater risk of liver decompensation than were those with an LSM less than 21 kPa (HR, 3.71; 95% CI, 1.89-6.78; P = .04).

In the subgroup with follow-up measurements, approximately half of the patients had an improved LSM (53.3%), while 27.2% had a stable LSM, and 19.5% had an impaired LSM, a pattern that was significantly associated with diabetes at baseline (P = .01).

“These data agree with the available literature identifying diabetes as a risk factor for liver disease progression and liver-related complications,” the investigators wrote.

Cox regression showed that, among those with follow-up LSM, changes in LSM were independently associated with HCC (HR, 1.72; 95% CI, 1.01-3.02; P = .04), liver decompensation (HR, 1.56; 95% CI, 1.05-2.51; P = . 04), liver-related mortality (HR, 1.96; 95% CI, 1.10-3.38; P = .02), and mortality of any cause (HR, 1.73; 95% CI, 1.11-2.69; P = .01).

These risks could be further stratified by level of change in liver stiffness, with greater impairment predicting greater risk: The crude rate of liver decompensation was 14.4% among those with impaired LSM, compared with 6.2% among those with stable LSM and 3.8% among those with LSM improvement. That said, the categories of changes in LSM were not predictive of decompensation among patients with high risk of CSPH at baseline; however, they remained predictive among those with low risk of CSPH at baseline.

“[T]his study … showed that an integrated assessment of baseline LSM or [changes in LSM] can help in stratifying the risk of development of liver-related complications and of both hepatic and overall mortality,” the investigators concluded. “These data, if further validated, could help personalize prognosis and follow-up in NAFLD with [compensated advanced chronic liver disease].”

The investigators disclosed relationships with AbbVie, Novo Nordisk, Gilead, and others.

A mitochondrial DNA variant may increase the risk of gallstone disease more than fourfold, according to investigators.

wir0man/GettyImages

Mitochondrial DNA 827A>G disrupts mitochondrial function and leads to abnormal cholesterol transport, which increases gallstone development, reported Dayan Sun, of Fudan University, Shanghai, China, and colleagues.

The investigators noted that the findings add support to a genetic role in gallstone development, which could allow for identification of at-risk individuals and implementation of preventive measures.

“The etiology of gallstone disease is multifactorial; age, sex, pregnancy, diet (macronutrients, alcohol, and coffee), and other factors are involved,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology. “Moreover, the significant familial predisposition and ethnic differences in prevalence of this disease indicate the potential influences of genetic factors.”

In 2002, Nakeeb and colleagues reported that at least 30% of gallstone disease cases stemmed from genetic factors. And genetics may play an even greater role in certain populations, such as Native Americans, among whom more than 70% of women have gallstone disease, based on a study by Everhart and colleagues.

According to Ms. Sun and colleagues, a variety of genetic drivers of gallstone disease have been identified, such as ABCG8, identified as the most common genetic risk factor by at least one study, along with a list of other rare mutations, such as one affecting CFTR that leads to altered bile composition.

Based on previous research that linked mitochondrial DNA variants with metabolic defects and, more specifically, aberrations in lipid metabolism, as well as an observed “maternal bias in the maternal transmission of gallstone disease” that suggest mitochondrial influence, the investigators looked for patterns specifically in mitochondrial DNA variants among patients with gallstones.

The study enrolled 104 probands with confirmed gallstone disease and 300 unrelated controls. After collecting DNA samples from all participants, the investigators sequenced mitochondrial DNA HVS1 regions. A comparison of haplogroups showed that B4b’d’e’j was more common among patients with gallstone disease than among controls (odds ratio, 4.428; P = .00012), and further analysis pinpointed 827A>G, a variant in 12S ribosomal RNA.

“During the evolutionary history of modern humans, haplogroup B4 might have originated in East Asia approximately 40,000 years ago,” the investigators wrote, noting that B2, a subhaplogroup of B4, “was a founder haplogroup and expanded in the Americas after the Last Glacial Maximum (approximately 20,000 years ago).”

According to the investigators, this may explain why Native Americans have a higher prevalence of gallstones than East Asians (14%-35% vs. 3%-12%) because they are more often carriers of B4 (14%-44% vs. 2%-8%).

The investigators sought to characterize the impact that the 827A>G variant has on mitochondrial function and found effects ranging from lower respiratory chain complex activity, diminished mitochondrial function, activated mitochondrial protein quality control and retrograde signaling pathways, abnormal lipid metabolism, and abnormal cholesterol transport processes.

For example, the investigators investigated respiratory chain complex activity by creating two sister branch haplogroup cell models, including six cybrids for 827A and six more for 827G, which is how they detected the lower activity. Another step the investigators took was corroborating this finding by detecting OXPHOS function in the 827A and 827G cybrids to determine mitochondrial function.

“In summary, our study demonstrates a potential link between mitochondrial DNA 827A>G and gallstone disease,” the investigators wrote. “Our findings provide a significant biological basis for the clinical diagnosis and prevention of gallstone disease in the future.”

The study was funded by the National Natural Science Foundation of China, the 111 Project, the Shanghai Municipal Science and Technology Major Project, the Scientific and Technology Committee of Shanghai Municipality, and the CAMS Innovation Fund for Medical Sciences. The investigators reported no conflicts of interest.

A mitochondrial DNA variant may increase the risk of gallstone disease more than fourfold, according to investigators.

wir0man/GettyImages

Mitochondrial DNA 827A>G disrupts mitochondrial function and leads to abnormal cholesterol transport, which increases gallstone development, reported Dayan Sun, of Fudan University, Shanghai, China, and colleagues.

The investigators noted that the findings add support to a genetic role in gallstone development, which could allow for identification of at-risk individuals and implementation of preventive measures.

“The etiology of gallstone disease is multifactorial; age, sex, pregnancy, diet (macronutrients, alcohol, and coffee), and other factors are involved,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology. “Moreover, the significant familial predisposition and ethnic differences in prevalence of this disease indicate the potential influences of genetic factors.”

In 2002, Nakeeb and colleagues reported that at least 30% of gallstone disease cases stemmed from genetic factors. And genetics may play an even greater role in certain populations, such as Native Americans, among whom more than 70% of women have gallstone disease, based on a study by Everhart and colleagues.

According to Ms. Sun and colleagues, a variety of genetic drivers of gallstone disease have been identified, such as ABCG8, identified as the most common genetic risk factor by at least one study, along with a list of other rare mutations, such as one affecting CFTR that leads to altered bile composition.

Based on previous research that linked mitochondrial DNA variants with metabolic defects and, more specifically, aberrations in lipid metabolism, as well as an observed “maternal bias in the maternal transmission of gallstone disease” that suggest mitochondrial influence, the investigators looked for patterns specifically in mitochondrial DNA variants among patients with gallstones.

The study enrolled 104 probands with confirmed gallstone disease and 300 unrelated controls. After collecting DNA samples from all participants, the investigators sequenced mitochondrial DNA HVS1 regions. A comparison of haplogroups showed that B4b’d’e’j was more common among patients with gallstone disease than among controls (odds ratio, 4.428; P = .00012), and further analysis pinpointed 827A>G, a variant in 12S ribosomal RNA.

“During the evolutionary history of modern humans, haplogroup B4 might have originated in East Asia approximately 40,000 years ago,” the investigators wrote, noting that B2, a subhaplogroup of B4, “was a founder haplogroup and expanded in the Americas after the Last Glacial Maximum (approximately 20,000 years ago).”

According to the investigators, this may explain why Native Americans have a higher prevalence of gallstones than East Asians (14%-35% vs. 3%-12%) because they are more often carriers of B4 (14%-44% vs. 2%-8%).

The investigators sought to characterize the impact that the 827A>G variant has on mitochondrial function and found effects ranging from lower respiratory chain complex activity, diminished mitochondrial function, activated mitochondrial protein quality control and retrograde signaling pathways, abnormal lipid metabolism, and abnormal cholesterol transport processes.

For example, the investigators investigated respiratory chain complex activity by creating two sister branch haplogroup cell models, including six cybrids for 827A and six more for 827G, which is how they detected the lower activity. Another step the investigators took was corroborating this finding by detecting OXPHOS function in the 827A and 827G cybrids to determine mitochondrial function.

“In summary, our study demonstrates a potential link between mitochondrial DNA 827A>G and gallstone disease,” the investigators wrote. “Our findings provide a significant biological basis for the clinical diagnosis and prevention of gallstone disease in the future.”

The study was funded by the National Natural Science Foundation of China, the 111 Project, the Shanghai Municipal Science and Technology Major Project, the Scientific and Technology Committee of Shanghai Municipality, and the CAMS Innovation Fund for Medical Sciences. The investigators reported no conflicts of interest.

A mitochondrial DNA variant may increase the risk of gallstone disease more than fourfold, according to investigators.

wir0man/GettyImages

Mitochondrial DNA 827A>G disrupts mitochondrial function and leads to abnormal cholesterol transport, which increases gallstone development, reported Dayan Sun, of Fudan University, Shanghai, China, and colleagues.

The investigators noted that the findings add support to a genetic role in gallstone development, which could allow for identification of at-risk individuals and implementation of preventive measures.

“The etiology of gallstone disease is multifactorial; age, sex, pregnancy, diet (macronutrients, alcohol, and coffee), and other factors are involved,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology. “Moreover, the significant familial predisposition and ethnic differences in prevalence of this disease indicate the potential influences of genetic factors.”

In 2002, Nakeeb and colleagues reported that at least 30% of gallstone disease cases stemmed from genetic factors. And genetics may play an even greater role in certain populations, such as Native Americans, among whom more than 70% of women have gallstone disease, based on a study by Everhart and colleagues.

According to Ms. Sun and colleagues, a variety of genetic drivers of gallstone disease have been identified, such as ABCG8, identified as the most common genetic risk factor by at least one study, along with a list of other rare mutations, such as one affecting CFTR that leads to altered bile composition.

Based on previous research that linked mitochondrial DNA variants with metabolic defects and, more specifically, aberrations in lipid metabolism, as well as an observed “maternal bias in the maternal transmission of gallstone disease” that suggest mitochondrial influence, the investigators looked for patterns specifically in mitochondrial DNA variants among patients with gallstones.

The study enrolled 104 probands with confirmed gallstone disease and 300 unrelated controls. After collecting DNA samples from all participants, the investigators sequenced mitochondrial DNA HVS1 regions. A comparison of haplogroups showed that B4b’d’e’j was more common among patients with gallstone disease than among controls (odds ratio, 4.428; P = .00012), and further analysis pinpointed 827A>G, a variant in 12S ribosomal RNA.

“During the evolutionary history of modern humans, haplogroup B4 might have originated in East Asia approximately 40,000 years ago,” the investigators wrote, noting that B2, a subhaplogroup of B4, “was a founder haplogroup and expanded in the Americas after the Last Glacial Maximum (approximately 20,000 years ago).”

According to the investigators, this may explain why Native Americans have a higher prevalence of gallstones than East Asians (14%-35% vs. 3%-12%) because they are more often carriers of B4 (14%-44% vs. 2%-8%).

The investigators sought to characterize the impact that the 827A>G variant has on mitochondrial function and found effects ranging from lower respiratory chain complex activity, diminished mitochondrial function, activated mitochondrial protein quality control and retrograde signaling pathways, abnormal lipid metabolism, and abnormal cholesterol transport processes.

For example, the investigators investigated respiratory chain complex activity by creating two sister branch haplogroup cell models, including six cybrids for 827A and six more for 827G, which is how they detected the lower activity. Another step the investigators took was corroborating this finding by detecting OXPHOS function in the 827A and 827G cybrids to determine mitochondrial function.

“In summary, our study demonstrates a potential link between mitochondrial DNA 827A>G and gallstone disease,” the investigators wrote. “Our findings provide a significant biological basis for the clinical diagnosis and prevention of gallstone disease in the future.”

The study was funded by the National Natural Science Foundation of China, the 111 Project, the Shanghai Municipal Science and Technology Major Project, the Scientific and Technology Committee of Shanghai Municipality, and the CAMS Innovation Fund for Medical Sciences. The investigators reported no conflicts of interest.

Non-Hispanic Black and Hispanic patients are underrepresented on many liver transplant waiting lists, whereas non-Hispanic White patients are often overrepresented, according to data from 109 centers.

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While racial disparities “greatly diminished” after placement on a waiting list, which suggests recent progress in the field, pre–wait-listing disparities may be more challenging to overcome, reported lead author Curtis Warren, MPH, CPH, of the University of Florida, Gainesville, and colleagues.

“In 2020, the Organ Procurement and Transplantation Network implemented a new allocation system for liver transplantation based on concentric circles of geographic proximity rather than somewhat arbitrarily delineated Donor Service Areas (DSAs),” the investigators wrote in Journal of the American College of Surgeons. “Although this was a step toward improving and equalizing access to lifesaving organs for those on the liver transplant wait list, the listing process determining which patients will be considered for transplantation has continued to be a significant hurdle.”

The process is “rife with impediments to equal access to listing,” according to Dr. Warren and colleagues; getting on a waiting list can be affected by factors such as inequitable access to primary care, lack of private health insurance, and subjective selection by transplant centers.

To better characterize these impediments, the investigators gathered center-specific data from the Scientific Registry of Transplant Recipients and the U.S. Census Bureau. The final dataset included 30,353 patients from treated at 109 transplant centers, each of which performed more than 250 transplants between January 2013 and December 2018. The investigators compared waiting list data for each center with demographics from its DSA. Primary variables included race/ethnicity, education level, poverty, and insurance coverage.

Multiple logistic regression analysis was used to compare expected waiting list demographics with observed waiting list demographics with the aid of observed/expected ratios for each race/ethnicity. Univariate and multivariate analyses were used to identify significant predictors, including covariates such as age at listing, distance traveled to transplant center, and center type.

On an adjusted basis, the observed/expected ratios showed that non-Hispanic Black patients were underrepresented on waiting lists at 88 out of 109 centers (81%) and Hispanic patients were underrepresented at 68 centers (62%). In contrast, non-Hispanic White patients were overrepresented on waiting lists at 65 centers (58%). Non-Hispanic White patients were underrepresented on waiting lists at 49 centers, or 45%. Minority underrepresentation was further supported by mean MELD (Model for End-Stage Liver Disease) scores, which were significantly higher among non-Hispanic Black patients (20.2) and Hispanic patients (19.4), compared with non-Hispanic White patients (18.7) (P < .0001 for all) at the time of wait-listing.

Based on the multivariate model, underrepresentation among Black patients was most common in areas with a higher proportion of Black individuals in the population, longer travel distances to transplant centers, and a higher rate of private insurance among transplant recipients. For Hispanic patients, rates of private insurance alone predicted underrepresentation.

Once patients were listed, however, these disparities faded. Non-Hispanic Black patients accounted for 9.8% of all transplants across all hospitals, compared with 7.9% of wait-listed individuals (P < .0001). At approximately two out of three hospitals (65%), the transplanted percentage of Black patients exceeded the wait-listed percentage (P = .002).

“Data from this study show that the wait lists at many transplant centers in the United States underrepresent minority populations, compared with what would be expected based on their service areas,” the investigators concluded. “Future work will need to be devoted to increasing awareness of these trends to promote equitable access to listing for liver transplantation.”

Looking at social determinants of health

According to Lauren D. Nephew, MD, MSc, MAE, of Indiana University, Indianapolis, “The question of access to care is particularly important at this juncture as we examine the inequities that COVID-19 exposed in access to care for racial minorities, and as we prepare for potential changes to health insurance coverage with the new administration.”

Dr. Nephew noted that the reported racial disparities stem from social determinants of health, such as proximity to transplant centers and type of insurance coverage.

“Another striking finding was that the disparity in wait-listing non-Hispanic Black patients increased with the percentage of non-Hispanic Black patients living in the area, further highlighting barriers in access to care in majority Black neighborhoods,” she said. “Inequities such as these are unacceptable, given our mandate to distribute organs in a fair and equitable fashion, and they require prospective studies for further examination.”
 

Identifying discrimination

Lanla Conteh, MD, MPH, of the Ohio State University Wexner Medical Center, Columbus, described how these inequities are magnified through bias in patient selection.

“Often times two very similar patients may present with the same medical profile and social circumstances; however, one is turned down,” she said. “Often the patient turned down is the non-Hispanic Black patient while the non-Hispanic White patient is given a pass.”

Dr. Conteh suggested that the first step in fixing this bias is recognizing that it is a problem and calling it by its proper name.

“As transplant centers, in order to address and change these significant disparities, we must first be willing to acknowledge that they do exist,” she said. “Only then can we move to the next step of developing awareness and methods to actively combat what we should label as systemic discrimination in medicine. Transplantation is a lifesaving treatment for many patients with decompensated liver disease or liver cancer. Ensuring equitable access for all patients and populations is of paramount importance.”

The study was supported by a Health Resources and Services Administration contract, as well as grants from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases. The investigators and interviewees reported no conflicts of interest.

AGA applauds researchers who are working to raise our awareness of health disparities in digestive diseases. AGA is committed to addressing this important societal issue head on. Learn more about AGA’s commitment through the AGA Equity Project.

This article was updated Mar. 12, 2021.

Non-Hispanic Black and Hispanic patients are underrepresented on many liver transplant waiting lists, whereas non-Hispanic White patients are often overrepresented, according to data from 109 centers.

pixelheadphoto/Thinkstock

While racial disparities “greatly diminished” after placement on a waiting list, which suggests recent progress in the field, pre–wait-listing disparities may be more challenging to overcome, reported lead author Curtis Warren, MPH, CPH, of the University of Florida, Gainesville, and colleagues.

“In 2020, the Organ Procurement and Transplantation Network implemented a new allocation system for liver transplantation based on concentric circles of geographic proximity rather than somewhat arbitrarily delineated Donor Service Areas (DSAs),” the investigators wrote in Journal of the American College of Surgeons. “Although this was a step toward improving and equalizing access to lifesaving organs for those on the liver transplant wait list, the listing process determining which patients will be considered for transplantation has continued to be a significant hurdle.”

The process is “rife with impediments to equal access to listing,” according to Dr. Warren and colleagues; getting on a waiting list can be affected by factors such as inequitable access to primary care, lack of private health insurance, and subjective selection by transplant centers.

To better characterize these impediments, the investigators gathered center-specific data from the Scientific Registry of Transplant Recipients and the U.S. Census Bureau. The final dataset included 30,353 patients from treated at 109 transplant centers, each of which performed more than 250 transplants between January 2013 and December 2018. The investigators compared waiting list data for each center with demographics from its DSA. Primary variables included race/ethnicity, education level, poverty, and insurance coverage.

Multiple logistic regression analysis was used to compare expected waiting list demographics with observed waiting list demographics with the aid of observed/expected ratios for each race/ethnicity. Univariate and multivariate analyses were used to identify significant predictors, including covariates such as age at listing, distance traveled to transplant center, and center type.

On an adjusted basis, the observed/expected ratios showed that non-Hispanic Black patients were underrepresented on waiting lists at 88 out of 109 centers (81%) and Hispanic patients were underrepresented at 68 centers (62%). In contrast, non-Hispanic White patients were overrepresented on waiting lists at 65 centers (58%). Non-Hispanic White patients were underrepresented on waiting lists at 49 centers, or 45%. Minority underrepresentation was further supported by mean MELD (Model for End-Stage Liver Disease) scores, which were significantly higher among non-Hispanic Black patients (20.2) and Hispanic patients (19.4), compared with non-Hispanic White patients (18.7) (P < .0001 for all) at the time of wait-listing.

Based on the multivariate model, underrepresentation among Black patients was most common in areas with a higher proportion of Black individuals in the population, longer travel distances to transplant centers, and a higher rate of private insurance among transplant recipients. For Hispanic patients, rates of private insurance alone predicted underrepresentation.

Once patients were listed, however, these disparities faded. Non-Hispanic Black patients accounted for 9.8% of all transplants across all hospitals, compared with 7.9% of wait-listed individuals (P < .0001). At approximately two out of three hospitals (65%), the transplanted percentage of Black patients exceeded the wait-listed percentage (P = .002).

“Data from this study show that the wait lists at many transplant centers in the United States underrepresent minority populations, compared with what would be expected based on their service areas,” the investigators concluded. “Future work will need to be devoted to increasing awareness of these trends to promote equitable access to listing for liver transplantation.”

Looking at social determinants of health

According to Lauren D. Nephew, MD, MSc, MAE, of Indiana University, Indianapolis, “The question of access to care is particularly important at this juncture as we examine the inequities that COVID-19 exposed in access to care for racial minorities, and as we prepare for potential changes to health insurance coverage with the new administration.”

Dr. Nephew noted that the reported racial disparities stem from social determinants of health, such as proximity to transplant centers and type of insurance coverage.

“Another striking finding was that the disparity in wait-listing non-Hispanic Black patients increased with the percentage of non-Hispanic Black patients living in the area, further highlighting barriers in access to care in majority Black neighborhoods,” she said. “Inequities such as these are unacceptable, given our mandate to distribute organs in a fair and equitable fashion, and they require prospective studies for further examination.”
 

Identifying discrimination

Lanla Conteh, MD, MPH, of the Ohio State University Wexner Medical Center, Columbus, described how these inequities are magnified through bias in patient selection.

“Often times two very similar patients may present with the same medical profile and social circumstances; however, one is turned down,” she said. “Often the patient turned down is the non-Hispanic Black patient while the non-Hispanic White patient is given a pass.”

Dr. Conteh suggested that the first step in fixing this bias is recognizing that it is a problem and calling it by its proper name.

“As transplant centers, in order to address and change these significant disparities, we must first be willing to acknowledge that they do exist,” she said. “Only then can we move to the next step of developing awareness and methods to actively combat what we should label as systemic discrimination in medicine. Transplantation is a lifesaving treatment for many patients with decompensated liver disease or liver cancer. Ensuring equitable access for all patients and populations is of paramount importance.”

The study was supported by a Health Resources and Services Administration contract, as well as grants from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases. The investigators and interviewees reported no conflicts of interest.

AGA applauds researchers who are working to raise our awareness of health disparities in digestive diseases. AGA is committed to addressing this important societal issue head on. Learn more about AGA’s commitment through the AGA Equity Project.

This article was updated Mar. 12, 2021.

Non-Hispanic Black and Hispanic patients are underrepresented on many liver transplant waiting lists, whereas non-Hispanic White patients are often overrepresented, according to data from 109 centers.

pixelheadphoto/Thinkstock

While racial disparities “greatly diminished” after placement on a waiting list, which suggests recent progress in the field, pre–wait-listing disparities may be more challenging to overcome, reported lead author Curtis Warren, MPH, CPH, of the University of Florida, Gainesville, and colleagues.

“In 2020, the Organ Procurement and Transplantation Network implemented a new allocation system for liver transplantation based on concentric circles of geographic proximity rather than somewhat arbitrarily delineated Donor Service Areas (DSAs),” the investigators wrote in Journal of the American College of Surgeons. “Although this was a step toward improving and equalizing access to lifesaving organs for those on the liver transplant wait list, the listing process determining which patients will be considered for transplantation has continued to be a significant hurdle.”

The process is “rife with impediments to equal access to listing,” according to Dr. Warren and colleagues; getting on a waiting list can be affected by factors such as inequitable access to primary care, lack of private health insurance, and subjective selection by transplant centers.

To better characterize these impediments, the investigators gathered center-specific data from the Scientific Registry of Transplant Recipients and the U.S. Census Bureau. The final dataset included 30,353 patients from treated at 109 transplant centers, each of which performed more than 250 transplants between January 2013 and December 2018. The investigators compared waiting list data for each center with demographics from its DSA. Primary variables included race/ethnicity, education level, poverty, and insurance coverage.

Multiple logistic regression analysis was used to compare expected waiting list demographics with observed waiting list demographics with the aid of observed/expected ratios for each race/ethnicity. Univariate and multivariate analyses were used to identify significant predictors, including covariates such as age at listing, distance traveled to transplant center, and center type.

On an adjusted basis, the observed/expected ratios showed that non-Hispanic Black patients were underrepresented on waiting lists at 88 out of 109 centers (81%) and Hispanic patients were underrepresented at 68 centers (62%). In contrast, non-Hispanic White patients were overrepresented on waiting lists at 65 centers (58%). Non-Hispanic White patients were underrepresented on waiting lists at 49 centers, or 45%. Minority underrepresentation was further supported by mean MELD (Model for End-Stage Liver Disease) scores, which were significantly higher among non-Hispanic Black patients (20.2) and Hispanic patients (19.4), compared with non-Hispanic White patients (18.7) (P < .0001 for all) at the time of wait-listing.

Based on the multivariate model, underrepresentation among Black patients was most common in areas with a higher proportion of Black individuals in the population, longer travel distances to transplant centers, and a higher rate of private insurance among transplant recipients. For Hispanic patients, rates of private insurance alone predicted underrepresentation.

Once patients were listed, however, these disparities faded. Non-Hispanic Black patients accounted for 9.8% of all transplants across all hospitals, compared with 7.9% of wait-listed individuals (P < .0001). At approximately two out of three hospitals (65%), the transplanted percentage of Black patients exceeded the wait-listed percentage (P = .002).

“Data from this study show that the wait lists at many transplant centers in the United States underrepresent minority populations, compared with what would be expected based on their service areas,” the investigators concluded. “Future work will need to be devoted to increasing awareness of these trends to promote equitable access to listing for liver transplantation.”

Looking at social determinants of health

According to Lauren D. Nephew, MD, MSc, MAE, of Indiana University, Indianapolis, “The question of access to care is particularly important at this juncture as we examine the inequities that COVID-19 exposed in access to care for racial minorities, and as we prepare for potential changes to health insurance coverage with the new administration.”

Dr. Nephew noted that the reported racial disparities stem from social determinants of health, such as proximity to transplant centers and type of insurance coverage.

“Another striking finding was that the disparity in wait-listing non-Hispanic Black patients increased with the percentage of non-Hispanic Black patients living in the area, further highlighting barriers in access to care in majority Black neighborhoods,” she said. “Inequities such as these are unacceptable, given our mandate to distribute organs in a fair and equitable fashion, and they require prospective studies for further examination.”
 

Identifying discrimination

Lanla Conteh, MD, MPH, of the Ohio State University Wexner Medical Center, Columbus, described how these inequities are magnified through bias in patient selection.

“Often times two very similar patients may present with the same medical profile and social circumstances; however, one is turned down,” she said. “Often the patient turned down is the non-Hispanic Black patient while the non-Hispanic White patient is given a pass.”

Dr. Conteh suggested that the first step in fixing this bias is recognizing that it is a problem and calling it by its proper name.

“As transplant centers, in order to address and change these significant disparities, we must first be willing to acknowledge that they do exist,” she said. “Only then can we move to the next step of developing awareness and methods to actively combat what we should label as systemic discrimination in medicine. Transplantation is a lifesaving treatment for many patients with decompensated liver disease or liver cancer. Ensuring equitable access for all patients and populations is of paramount importance.”

The study was supported by a Health Resources and Services Administration contract, as well as grants from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases. The investigators and interviewees reported no conflicts of interest.

AGA applauds researchers who are working to raise our awareness of health disparities in digestive diseases. AGA is committed to addressing this important societal issue head on. Learn more about AGA’s commitment through the AGA Equity Project.

This article was updated Mar. 12, 2021.

A mitochondrial DNA variant may increase the risk of gallstone disease more than fourfold, according to investigators.

wir0man/GettyImages

Mitochondrial DNA 827A>G disrupts mitochondrial function and leads to abnormal cholesterol transport, which increases gallstone development, reported Dayan Sun, of Fudan University, Shanghai, China, and colleagues.

The investigators noted that the findings add support to a genetic role in gallstone development, which could allow for identification of at-risk individuals and implementation of preventive measures.

“The etiology of gallstone disease is multifactorial; age, sex, pregnancy, diet (macronutrients, alcohol, and coffee), and other factors are involved,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology. “Moreover, the significant familial predisposition and ethnic differences in prevalence of this disease indicate the potential influences of genetic factors.”

In 2002, Nakeeb and colleagues reported that at least 30% of gallstone disease cases stemmed from genetic factors. And genetics may play an even greater role in certain populations, such as Native Americans, among whom more than 70% of women have gallstone disease, based on a study by Everhart and colleagues.

According to Ms. Sun and colleagues, a variety of genetic drivers of gallstone disease have been identified, such as ABCG8, identified as the most common genetic risk factor by at least one study, along with a list of other rare mutations, such as one affecting CFTR that leads to altered bile composition.

Based on previous research that linked mitochondrial DNA variants with metabolic defects and, more specifically, aberrations in lipid metabolism, as well as an observed “maternal bias in the maternal transmission of gallstone disease” that suggest mitochondrial influence, the investigators looked for patterns specifically in mitochondrial DNA variants among patients with gallstones.

The study enrolled 104 probands with confirmed gallstone disease and 300 unrelated controls. After collecting DNA samples from all participants, the investigators sequenced mitochondrial DNA HVS1 regions. A comparison of haplogroups showed that B4b’d’e’j was more common among patients with gallstone disease than among controls (odds ratio, 4.428; P = .00012), and further analysis pinpointed 827A>G, a variant in 12S rRNA.

“During the evolutionary history of modern humans, haplogroup B4 might have originated in East Asia approximately 40,000 years ago,” the investigators wrote, noting that B2, a subhaplogroup of B4, “was a founder haplogroup and expanded in the Americas after the Last Glacial Maximum (approximately 20,000 years ago).”

According to the investigators, this may explain why Native Americans have a higher prevalence of gallstones than East Asians (14%-35% vs. 3%-12%) because they are more often carriers of B4 (14%-44% vs. 2%-8%).

The investigators sought to characterize the impact that the 827A>G variant has on mitochondrial function and found effects ranging from lower respiratory chain complex activity, diminished mitochondrial function, activated mitochondrial protein quality control and retrograde signaling pathways, abnormal lipid metabolism, and abnormal cholesterol transport processes.

For example, the investigators investigated respiratory chain complex activity by creating two sister branch haplogroup cell models, including six cybrids for 827A and six more for 827G, which is how they detected the lower activity. Another step the investigators took was corroborating this finding by detecting OXPHOS function in the 827A and 827G cybrids to determine mitochondrial function.

“In summary, our study demonstrates a potential link between mitochondrial DNA 827A>G and gallstone disease,” the investigators wrote. “Our findings provide a significant biological basis for the clinical diagnosis and prevention of gallstone disease in the future.”

The study was funded by the National Natural Science Foundation of China, the 111 Project, the Shanghai Municipal Science and Technology Major Project, the Scientific and Technology Committee of Shanghai Municipality, and the CAMS Innovation Fund for Medical Sciences. The investigators reported no conflicts of interest.

A mitochondrial DNA variant may increase the risk of gallstone disease more than fourfold, according to investigators.

wir0man/GettyImages

Mitochondrial DNA 827A>G disrupts mitochondrial function and leads to abnormal cholesterol transport, which increases gallstone development, reported Dayan Sun, of Fudan University, Shanghai, China, and colleagues.

The investigators noted that the findings add support to a genetic role in gallstone development, which could allow for identification of at-risk individuals and implementation of preventive measures.

“The etiology of gallstone disease is multifactorial; age, sex, pregnancy, diet (macronutrients, alcohol, and coffee), and other factors are involved,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology. “Moreover, the significant familial predisposition and ethnic differences in prevalence of this disease indicate the potential influences of genetic factors.”

In 2002, Nakeeb and colleagues reported that at least 30% of gallstone disease cases stemmed from genetic factors. And genetics may play an even greater role in certain populations, such as Native Americans, among whom more than 70% of women have gallstone disease, based on a study by Everhart and colleagues.

According to Ms. Sun and colleagues, a variety of genetic drivers of gallstone disease have been identified, such as ABCG8, identified as the most common genetic risk factor by at least one study, along with a list of other rare mutations, such as one affecting CFTR that leads to altered bile composition.

Based on previous research that linked mitochondrial DNA variants with metabolic defects and, more specifically, aberrations in lipid metabolism, as well as an observed “maternal bias in the maternal transmission of gallstone disease” that suggest mitochondrial influence, the investigators looked for patterns specifically in mitochondrial DNA variants among patients with gallstones.

The study enrolled 104 probands with confirmed gallstone disease and 300 unrelated controls. After collecting DNA samples from all participants, the investigators sequenced mitochondrial DNA HVS1 regions. A comparison of haplogroups showed that B4b’d’e’j was more common among patients with gallstone disease than among controls (odds ratio, 4.428; P = .00012), and further analysis pinpointed 827A>G, a variant in 12S rRNA.

“During the evolutionary history of modern humans, haplogroup B4 might have originated in East Asia approximately 40,000 years ago,” the investigators wrote, noting that B2, a subhaplogroup of B4, “was a founder haplogroup and expanded in the Americas after the Last Glacial Maximum (approximately 20,000 years ago).”

According to the investigators, this may explain why Native Americans have a higher prevalence of gallstones than East Asians (14%-35% vs. 3%-12%) because they are more often carriers of B4 (14%-44% vs. 2%-8%).

The investigators sought to characterize the impact that the 827A>G variant has on mitochondrial function and found effects ranging from lower respiratory chain complex activity, diminished mitochondrial function, activated mitochondrial protein quality control and retrograde signaling pathways, abnormal lipid metabolism, and abnormal cholesterol transport processes.

For example, the investigators investigated respiratory chain complex activity by creating two sister branch haplogroup cell models, including six cybrids for 827A and six more for 827G, which is how they detected the lower activity. Another step the investigators took was corroborating this finding by detecting OXPHOS function in the 827A and 827G cybrids to determine mitochondrial function.

“In summary, our study demonstrates a potential link between mitochondrial DNA 827A>G and gallstone disease,” the investigators wrote. “Our findings provide a significant biological basis for the clinical diagnosis and prevention of gallstone disease in the future.”

The study was funded by the National Natural Science Foundation of China, the 111 Project, the Shanghai Municipal Science and Technology Major Project, the Scientific and Technology Committee of Shanghai Municipality, and the CAMS Innovation Fund for Medical Sciences. The investigators reported no conflicts of interest.

A mitochondrial DNA variant may increase the risk of gallstone disease more than fourfold, according to investigators.

wir0man/GettyImages

Mitochondrial DNA 827A>G disrupts mitochondrial function and leads to abnormal cholesterol transport, which increases gallstone development, reported Dayan Sun, of Fudan University, Shanghai, China, and colleagues.

The investigators noted that the findings add support to a genetic role in gallstone development, which could allow for identification of at-risk individuals and implementation of preventive measures.

“The etiology of gallstone disease is multifactorial; age, sex, pregnancy, diet (macronutrients, alcohol, and coffee), and other factors are involved,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology. “Moreover, the significant familial predisposition and ethnic differences in prevalence of this disease indicate the potential influences of genetic factors.”

In 2002, Nakeeb and colleagues reported that at least 30% of gallstone disease cases stemmed from genetic factors. And genetics may play an even greater role in certain populations, such as Native Americans, among whom more than 70% of women have gallstone disease, based on a study by Everhart and colleagues.

According to Ms. Sun and colleagues, a variety of genetic drivers of gallstone disease have been identified, such as ABCG8, identified as the most common genetic risk factor by at least one study, along with a list of other rare mutations, such as one affecting CFTR that leads to altered bile composition.

Based on previous research that linked mitochondrial DNA variants with metabolic defects and, more specifically, aberrations in lipid metabolism, as well as an observed “maternal bias in the maternal transmission of gallstone disease” that suggest mitochondrial influence, the investigators looked for patterns specifically in mitochondrial DNA variants among patients with gallstones.

The study enrolled 104 probands with confirmed gallstone disease and 300 unrelated controls. After collecting DNA samples from all participants, the investigators sequenced mitochondrial DNA HVS1 regions. A comparison of haplogroups showed that B4b’d’e’j was more common among patients with gallstone disease than among controls (odds ratio, 4.428; P = .00012), and further analysis pinpointed 827A>G, a variant in 12S rRNA.

“During the evolutionary history of modern humans, haplogroup B4 might have originated in East Asia approximately 40,000 years ago,” the investigators wrote, noting that B2, a subhaplogroup of B4, “was a founder haplogroup and expanded in the Americas after the Last Glacial Maximum (approximately 20,000 years ago).”

According to the investigators, this may explain why Native Americans have a higher prevalence of gallstones than East Asians (14%-35% vs. 3%-12%) because they are more often carriers of B4 (14%-44% vs. 2%-8%).

The investigators sought to characterize the impact that the 827A>G variant has on mitochondrial function and found effects ranging from lower respiratory chain complex activity, diminished mitochondrial function, activated mitochondrial protein quality control and retrograde signaling pathways, abnormal lipid metabolism, and abnormal cholesterol transport processes.

For example, the investigators investigated respiratory chain complex activity by creating two sister branch haplogroup cell models, including six cybrids for 827A and six more for 827G, which is how they detected the lower activity. Another step the investigators took was corroborating this finding by detecting OXPHOS function in the 827A and 827G cybrids to determine mitochondrial function.

“In summary, our study demonstrates a potential link between mitochondrial DNA 827A>G and gallstone disease,” the investigators wrote. “Our findings provide a significant biological basis for the clinical diagnosis and prevention of gallstone disease in the future.”

The study was funded by the National Natural Science Foundation of China, the 111 Project, the Shanghai Municipal Science and Technology Major Project, the Scientific and Technology Committee of Shanghai Municipality, and the CAMS Innovation Fund for Medical Sciences. The investigators reported no conflicts of interest.

Proton pump inhibitors (PPIs) improve functional dyspepsia (FD) by reducing duodenal eosinophils and mast cells, according to a prospective study.

This suggests that the anti-inflammatory effects of PPIs are responsible for symptom improvement, and not barrier-protective or acid-suppressive effects, a finding that may guide future therapies and biomarkers, reported lead author Lucas Wauters, PhD, of University Hospitals Leuven (Belgium), and colleagues reported in Gastroenterology.

“FD is a common and unexplained disorder with unknown pathophysiology, hampering a conclusive diagnosis and the development of effective drugs,” the investigators wrote.

Although PPIs are currently used as first-line FD therapy, ostensibly for acid suppression, “the exact mechanism of action of PPIs in FD is unknown,” the investigators noted.

According to Dr. Wauters and colleagues, previous FD studies, such as a 2020 study published in Gut, have reported a variety of pathophysiological findings in the duodenum, including increased eosinophils and mast cells, as well as activation of duodenogastric reflexes, which suggests “a primary role for duodenal pathology in FD symptom generation.” Several drivers of this pathology have been proposed. Some, such as aberrations in bile salts and acidity, point to local, luminal changes, whereas others, such as dysregulated hypothalamic-pituitary-adrenal axis responsiveness and psychosocial factors, implicate a broader set of drivers, the investigators wrote.

The present study explored this landscape through a prospective trial that enrolled 30 healthy volunteers and 47 patients with FD (2 patients with FD did not complete the study).

Patients with FD were subgrouped into “FD-starters” who had not taken PPIs and/or acid suppression for at least 3 months leading up to the trial (n = 28) and “FD-stoppers” who had refractory symptoms after at least 1 month of daily PPI usage (n = 19). Among participants with FD, 25 had postprandial distress syndrome (PDS), 9 had epigastric pain syndrome (EPS), and 13 had subtype overlap.

For the trial, FD-starters and healthy volunteers took 4 weeks of pantoprazole 40 mg once daily, whereas FD-stoppers ceased PPI therapy for 8 weeks. Before and after these respective periods, certain study procedures were conducted, including duodenal biopsy collection, duodenal fluid aspiration, and questionnaires for symptoms and stress. The study also included use of Ussing chambers for biopsies, immunohistochemistry, and bile salt measurements.

FD-starters were significantly more symptomatic than healthy volunteers were at baseline. After starting PPIs, those with FD had symptom improvements, confirming “clinical efficacy of a standard course of PPIs in all FD subtypes,” whereas healthy volunteers showed no significant change in symptoms.

Similarly, baseline duodenal eosinophil counts were higher in FD-starters than in healthy volunteers. On starting PPIs, however, eosinophil counts in these two groups moved in opposite directions: FD-starters’ counts dropped from a mean of 331 to 183 eosinophils/mm², whereas healthy volunteers’ counts rose from a mean of 115 to 229 eosinophils/mm² (P < .0001). Changes in mast cells and paracellular passage followed the same pattern, falling in FD-starters and rising in healthy volunteers. On the other hand, symptoms actually improved in the FD-stoppers after they went off PPIs, although they did not reach symptom levels of the healthy volunteers.

“Differential effects of PPIs in healthy volunteers point to the role of luminal changes in determining low-grade mucosal immune activation in the duodenum, which can also occur in FD after long-term use and provide arguments against continued use in refractory patients,” the investigators wrote.

Dr. Wauters and colleagues suggested that their findings could guide future approaches to FD management.

“Our results suggest that quantification of duodenal eosinophils has the potential to become part of diagnostic workup and guide therapeutic decisions in FD,” they wrote. “Additional study of the underlying mediators might lead to the discovery of new potential biomarkers or novel therapeutic targets, potentially allowing the identification of subgroups responding to biologically targeted rather than symptom-based treatments.”

The study was supported by the clinical research fund of the University Hospitals Leuven. The investigators reported no conflicts of interest.

Proton pump inhibitors (PPIs) improve functional dyspepsia (FD) by reducing duodenal eosinophils and mast cells, according to a prospective study.

This suggests that the anti-inflammatory effects of PPIs are responsible for symptom improvement, and not barrier-protective or acid-suppressive effects, a finding that may guide future therapies and biomarkers, reported lead author Lucas Wauters, PhD, of University Hospitals Leuven (Belgium), and colleagues reported in Gastroenterology.

“FD is a common and unexplained disorder with unknown pathophysiology, hampering a conclusive diagnosis and the development of effective drugs,” the investigators wrote.

Although PPIs are currently used as first-line FD therapy, ostensibly for acid suppression, “the exact mechanism of action of PPIs in FD is unknown,” the investigators noted.

According to Dr. Wauters and colleagues, previous FD studies, such as a 2020 study published in Gut, have reported a variety of pathophysiological findings in the duodenum, including increased eosinophils and mast cells, as well as activation of duodenogastric reflexes, which suggests “a primary role for duodenal pathology in FD symptom generation.” Several drivers of this pathology have been proposed. Some, such as aberrations in bile salts and acidity, point to local, luminal changes, whereas others, such as dysregulated hypothalamic-pituitary-adrenal axis responsiveness and psychosocial factors, implicate a broader set of drivers, the investigators wrote.

The present study explored this landscape through a prospective trial that enrolled 30 healthy volunteers and 47 patients with FD (2 patients with FD did not complete the study).

Patients with FD were subgrouped into “FD-starters” who had not taken PPIs and/or acid suppression for at least 3 months leading up to the trial (n = 28) and “FD-stoppers” who had refractory symptoms after at least 1 month of daily PPI usage (n = 19). Among participants with FD, 25 had postprandial distress syndrome (PDS), 9 had epigastric pain syndrome (EPS), and 13 had subtype overlap.

For the trial, FD-starters and healthy volunteers took 4 weeks of pantoprazole 40 mg once daily, whereas FD-stoppers ceased PPI therapy for 8 weeks. Before and after these respective periods, certain study procedures were conducted, including duodenal biopsy collection, duodenal fluid aspiration, and questionnaires for symptoms and stress. The study also included use of Ussing chambers for biopsies, immunohistochemistry, and bile salt measurements.

FD-starters were significantly more symptomatic than healthy volunteers were at baseline. After starting PPIs, those with FD had symptom improvements, confirming “clinical efficacy of a standard course of PPIs in all FD subtypes,” whereas healthy volunteers showed no significant change in symptoms.

Similarly, baseline duodenal eosinophil counts were higher in FD-starters than in healthy volunteers. On starting PPIs, however, eosinophil counts in these two groups moved in opposite directions: FD-starters’ counts dropped from a mean of 331 to 183 eosinophils/mm², whereas healthy volunteers’ counts rose from a mean of 115 to 229 eosinophils/mm² (P < .0001). Changes in mast cells and paracellular passage followed the same pattern, falling in FD-starters and rising in healthy volunteers. On the other hand, symptoms actually improved in the FD-stoppers after they went off PPIs, although they did not reach symptom levels of the healthy volunteers.

“Differential effects of PPIs in healthy volunteers point to the role of luminal changes in determining low-grade mucosal immune activation in the duodenum, which can also occur in FD after long-term use and provide arguments against continued use in refractory patients,” the investigators wrote.

Dr. Wauters and colleagues suggested that their findings could guide future approaches to FD management.

“Our results suggest that quantification of duodenal eosinophils has the potential to become part of diagnostic workup and guide therapeutic decisions in FD,” they wrote. “Additional study of the underlying mediators might lead to the discovery of new potential biomarkers or novel therapeutic targets, potentially allowing the identification of subgroups responding to biologically targeted rather than symptom-based treatments.”

The study was supported by the clinical research fund of the University Hospitals Leuven. The investigators reported no conflicts of interest.

Proton pump inhibitors (PPIs) improve functional dyspepsia (FD) by reducing duodenal eosinophils and mast cells, according to a prospective study.

This suggests that the anti-inflammatory effects of PPIs are responsible for symptom improvement, and not barrier-protective or acid-suppressive effects, a finding that may guide future therapies and biomarkers, reported lead author Lucas Wauters, PhD, of University Hospitals Leuven (Belgium), and colleagues reported in Gastroenterology.

“FD is a common and unexplained disorder with unknown pathophysiology, hampering a conclusive diagnosis and the development of effective drugs,” the investigators wrote.

Although PPIs are currently used as first-line FD therapy, ostensibly for acid suppression, “the exact mechanism of action of PPIs in FD is unknown,” the investigators noted.

According to Dr. Wauters and colleagues, previous FD studies, such as a 2020 study published in Gut, have reported a variety of pathophysiological findings in the duodenum, including increased eosinophils and mast cells, as well as activation of duodenogastric reflexes, which suggests “a primary role for duodenal pathology in FD symptom generation.” Several drivers of this pathology have been proposed. Some, such as aberrations in bile salts and acidity, point to local, luminal changes, whereas others, such as dysregulated hypothalamic-pituitary-adrenal axis responsiveness and psychosocial factors, implicate a broader set of drivers, the investigators wrote.

The present study explored this landscape through a prospective trial that enrolled 30 healthy volunteers and 47 patients with FD (2 patients with FD did not complete the study).

Patients with FD were subgrouped into “FD-starters” who had not taken PPIs and/or acid suppression for at least 3 months leading up to the trial (n = 28) and “FD-stoppers” who had refractory symptoms after at least 1 month of daily PPI usage (n = 19). Among participants with FD, 25 had postprandial distress syndrome (PDS), 9 had epigastric pain syndrome (EPS), and 13 had subtype overlap.

For the trial, FD-starters and healthy volunteers took 4 weeks of pantoprazole 40 mg once daily, whereas FD-stoppers ceased PPI therapy for 8 weeks. Before and after these respective periods, certain study procedures were conducted, including duodenal biopsy collection, duodenal fluid aspiration, and questionnaires for symptoms and stress. The study also included use of Ussing chambers for biopsies, immunohistochemistry, and bile salt measurements.

FD-starters were significantly more symptomatic than healthy volunteers were at baseline. After starting PPIs, those with FD had symptom improvements, confirming “clinical efficacy of a standard course of PPIs in all FD subtypes,” whereas healthy volunteers showed no significant change in symptoms.

Similarly, baseline duodenal eosinophil counts were higher in FD-starters than in healthy volunteers. On starting PPIs, however, eosinophil counts in these two groups moved in opposite directions: FD-starters’ counts dropped from a mean of 331 to 183 eosinophils/mm², whereas healthy volunteers’ counts rose from a mean of 115 to 229 eosinophils/mm² (P < .0001). Changes in mast cells and paracellular passage followed the same pattern, falling in FD-starters and rising in healthy volunteers. On the other hand, symptoms actually improved in the FD-stoppers after they went off PPIs, although they did not reach symptom levels of the healthy volunteers.

“Differential effects of PPIs in healthy volunteers point to the role of luminal changes in determining low-grade mucosal immune activation in the duodenum, which can also occur in FD after long-term use and provide arguments against continued use in refractory patients,” the investigators wrote.

Dr. Wauters and colleagues suggested that their findings could guide future approaches to FD management.

“Our results suggest that quantification of duodenal eosinophils has the potential to become part of diagnostic workup and guide therapeutic decisions in FD,” they wrote. “Additional study of the underlying mediators might lead to the discovery of new potential biomarkers or novel therapeutic targets, potentially allowing the identification of subgroups responding to biologically targeted rather than symptom-based treatments.”

The study was supported by the clinical research fund of the University Hospitals Leuven. The investigators reported no conflicts of interest.

Proton pump inhibitors (PPIs) improve functional dyspepsia (FD) by reducing duodenal eosinophils and mast cells, according to a prospective study.

This suggests that the anti-inflammatory effects of PPIs are responsible for symptom improvement, and not barrier-protective or acid-suppressive effects, a finding that may guide future therapies and biomarkers, reported lead author Lucas Wauters, PhD, of University Hospitals Leuven (Belgium), and colleagues reported in Gastroenterology.

“FD is a common and unexplained disorder with unknown pathophysiology, hampering a conclusive diagnosis and the development of effective drugs,” the investigators wrote.

Although PPIs are currently used as first-line FD therapy, ostensibly for acid suppression, “the exact mechanism of action of PPIs in FD is unknown,” the investigators noted.

According to Dr. Wauters and colleagues, previous FD studies, such as a 2020 study published in Gut, have reported a variety of pathophysiological findings in the duodenum, including increased eosinophils and mast cells, as well as activation of duodenogastric reflexes, which suggests “a primary role for duodenal pathology in FD symptom generation.” Several drivers of this pathology have been proposed. Some, such as aberrations in bile salts and acidity, point to local, luminal changes, whereas others, such as dysregulated hypothalamic-pituitary-adrenal axis responsiveness and psychosocial factors, implicate a broader set of drivers, the investigators wrote.

The present study explored this landscape through a prospective trial that enrolled 30 healthy volunteers and 47 patients with FD (2 patients with FD did not complete the study).

Patients with FD were subgrouped into “FD-starters” who had not taken PPIs and/or acid suppression for at least 3 months leading up to the trial (n = 28) and “FD-stoppers” who had refractory symptoms after at least 1 month of daily PPI usage (n = 19). Among participants with FD, 25 had postprandial distress syndrome (PDS), 9 had epigastric pain syndrome (EPS), and 13 had subtype overlap.

For the trial, FD-starters and healthy volunteers took 4 weeks of pantoprazole 40 mg once daily, whereas FD-stoppers ceased PPI therapy for 8 weeks. Before and after these respective periods, certain study procedures were conducted, including duodenal biopsy collection, duodenal fluid aspiration, and questionnaires for symptoms and stress. The study also included use of Ussing chambers for biopsies, immunohistochemistry, and bile salt measurements.

FD-starters were significantly more symptomatic than healthy volunteers were at baseline. After starting PPIs, those with FD had symptom improvements, confirming “clinical efficacy of a standard course of PPIs in all FD subtypes,” whereas healthy volunteers showed no significant change in symptoms.

Similarly, baseline duodenal eosinophil counts were higher in FD-starters than in healthy volunteers. On starting PPIs, however, eosinophil counts in these two groups moved in opposite directions: FD-starters’ counts dropped from a mean of 331 to 183 eosinophils/mm², whereas healthy volunteers’ counts rose from a mean of 115 to 229 eosinophils/mm² (P < .0001). Changes in mast cells and paracellular passage followed the same pattern, falling in FD-starters and rising in healthy volunteers. On the other hand, symptoms actually improved in the FD-stoppers after they went off PPIs, although they did not reach symptom levels of the healthy volunteers.

“Differential effects of PPIs in healthy volunteers point to the role of luminal changes in determining low-grade mucosal immune activation in the duodenum, which can also occur in FD after long-term use and provide arguments against continued use in refractory patients,” the investigators wrote.

Dr. Wauters and colleagues suggested that their findings could guide future approaches to FD management.

“Our results suggest that quantification of duodenal eosinophils has the potential to become part of diagnostic workup and guide therapeutic decisions in FD,” they wrote. “Additional study of the underlying mediators might lead to the discovery of new potential biomarkers or novel therapeutic targets, potentially allowing the identification of subgroups responding to biologically targeted rather than symptom-based treatments.”

The study was supported by the clinical research fund of the University Hospitals Leuven. The investigators reported no conflicts of interest.

Proton pump inhibitors (PPIs) improve functional dyspepsia (FD) by reducing duodenal eosinophils and mast cells, according to a prospective study.

This suggests that the anti-inflammatory effects of PPIs are responsible for symptom improvement, and not barrier-protective or acid-suppressive effects, a finding that may guide future therapies and biomarkers, reported lead author Lucas Wauters, PhD, of University Hospitals Leuven (Belgium), and colleagues reported in Gastroenterology.

“FD is a common and unexplained disorder with unknown pathophysiology, hampering a conclusive diagnosis and the development of effective drugs,” the investigators wrote.

Although PPIs are currently used as first-line FD therapy, ostensibly for acid suppression, “the exact mechanism of action of PPIs in FD is unknown,” the investigators noted.

According to Dr. Wauters and colleagues, previous FD studies, such as a 2020 study published in Gut, have reported a variety of pathophysiological findings in the duodenum, including increased eosinophils and mast cells, as well as activation of duodenogastric reflexes, which suggests “a primary role for duodenal pathology in FD symptom generation.” Several drivers of this pathology have been proposed. Some, such as aberrations in bile salts and acidity, point to local, luminal changes, whereas others, such as dysregulated hypothalamic-pituitary-adrenal axis responsiveness and psychosocial factors, implicate a broader set of drivers, the investigators wrote.

The present study explored this landscape through a prospective trial that enrolled 30 healthy volunteers and 47 patients with FD (2 patients with FD did not complete the study).

Patients with FD were subgrouped into “FD-starters” who had not taken PPIs and/or acid suppression for at least 3 months leading up to the trial (n = 28) and “FD-stoppers” who had refractory symptoms after at least 1 month of daily PPI usage (n = 19). Among participants with FD, 25 had postprandial distress syndrome (PDS), 9 had epigastric pain syndrome (EPS), and 13 had subtype overlap.

For the trial, FD-starters and healthy volunteers took 4 weeks of pantoprazole 40 mg once daily, whereas FD-stoppers ceased PPI therapy for 8 weeks. Before and after these respective periods, certain study procedures were conducted, including duodenal biopsy collection, duodenal fluid aspiration, and questionnaires for symptoms and stress. The study also included use of Ussing chambers for biopsies, immunohistochemistry, and bile salt measurements.

FD-starters were significantly more symptomatic than healthy volunteers were at baseline. After starting PPIs, those with FD had symptom improvements, confirming “clinical efficacy of a standard course of PPIs in all FD subtypes,” whereas healthy volunteers showed no significant change in symptoms.

Similarly, baseline duodenal eosinophil counts were higher in FD-starters than in healthy volunteers. On starting PPIs, however, eosinophil counts in these two groups moved in opposite directions: FD-starters’ counts dropped from a mean of 331 to 183 eosinophils/mm², whereas healthy volunteers’ counts rose from a mean of 115 to 229 eosinophils/mm² (P < .0001). Changes in mast cells and paracellular passage followed the same pattern, falling in FD-starters and rising in healthy volunteers. On the other hand, symptoms actually improved in the FD-stoppers after they went off PPIs, although they did not reach symptom levels of the healthy volunteers.

“Differential effects of PPIs in healthy volunteers point to the role of luminal changes in determining low-grade mucosal immune activation in the duodenum, which can also occur in FD after long-term use and provide arguments against continued use in refractory patients,” the investigators wrote.

Dr. Wauters and colleagues suggested that their findings could guide future approaches to FD management.

“Our results suggest that quantification of duodenal eosinophils has the potential to become part of diagnostic workup and guide therapeutic decisions in FD,” they wrote. “Additional study of the underlying mediators might lead to the discovery of new potential biomarkers or novel therapeutic targets, potentially allowing the identification of subgroups responding to biologically targeted rather than symptom-based treatments.”

The study was supported by the clinical research fund of the University Hospitals Leuven. The investigators reported no conflicts of interest.

Proton pump inhibitors (PPIs) improve functional dyspepsia (FD) by reducing duodenal eosinophils and mast cells, according to a prospective study.

This suggests that the anti-inflammatory effects of PPIs are responsible for symptom improvement, and not barrier-protective or acid-suppressive effects, a finding that may guide future therapies and biomarkers, reported lead author Lucas Wauters, PhD, of University Hospitals Leuven (Belgium), and colleagues reported in Gastroenterology.

“FD is a common and unexplained disorder with unknown pathophysiology, hampering a conclusive diagnosis and the development of effective drugs,” the investigators wrote.

Although PPIs are currently used as first-line FD therapy, ostensibly for acid suppression, “the exact mechanism of action of PPIs in FD is unknown,” the investigators noted.

According to Dr. Wauters and colleagues, previous FD studies, such as a 2020 study published in Gut, have reported a variety of pathophysiological findings in the duodenum, including increased eosinophils and mast cells, as well as activation of duodenogastric reflexes, which suggests “a primary role for duodenal pathology in FD symptom generation.” Several drivers of this pathology have been proposed. Some, such as aberrations in bile salts and acidity, point to local, luminal changes, whereas others, such as dysregulated hypothalamic-pituitary-adrenal axis responsiveness and psychosocial factors, implicate a broader set of drivers, the investigators wrote.

The present study explored this landscape through a prospective trial that enrolled 30 healthy volunteers and 47 patients with FD (2 patients with FD did not complete the study).

Patients with FD were subgrouped into “FD-starters” who had not taken PPIs and/or acid suppression for at least 3 months leading up to the trial (n = 28) and “FD-stoppers” who had refractory symptoms after at least 1 month of daily PPI usage (n = 19). Among participants with FD, 25 had postprandial distress syndrome (PDS), 9 had epigastric pain syndrome (EPS), and 13 had subtype overlap.

For the trial, FD-starters and healthy volunteers took 4 weeks of pantoprazole 40 mg once daily, whereas FD-stoppers ceased PPI therapy for 8 weeks. Before and after these respective periods, certain study procedures were conducted, including duodenal biopsy collection, duodenal fluid aspiration, and questionnaires for symptoms and stress. The study also included use of Ussing chambers for biopsies, immunohistochemistry, and bile salt measurements.

FD-starters were significantly more symptomatic than healthy volunteers were at baseline. After starting PPIs, those with FD had symptom improvements, confirming “clinical efficacy of a standard course of PPIs in all FD subtypes,” whereas healthy volunteers showed no significant change in symptoms.

Similarly, baseline duodenal eosinophil counts were higher in FD-starters than in healthy volunteers. On starting PPIs, however, eosinophil counts in these two groups moved in opposite directions: FD-starters’ counts dropped from a mean of 331 to 183 eosinophils/mm², whereas healthy volunteers’ counts rose from a mean of 115 to 229 eosinophils/mm² (P < .0001). Changes in mast cells and paracellular passage followed the same pattern, falling in FD-starters and rising in healthy volunteers. On the other hand, symptoms actually improved in the FD-stoppers after they went off PPIs, although they did not reach symptom levels of the healthy volunteers.

“Differential effects of PPIs in healthy volunteers point to the role of luminal changes in determining low-grade mucosal immune activation in the duodenum, which can also occur in FD after long-term use and provide arguments against continued use in refractory patients,” the investigators wrote.

Dr. Wauters and colleagues suggested that their findings could guide future approaches to FD management.

“Our results suggest that quantification of duodenal eosinophils has the potential to become part of diagnostic workup and guide therapeutic decisions in FD,” they wrote. “Additional study of the underlying mediators might lead to the discovery of new potential biomarkers or novel therapeutic targets, potentially allowing the identification of subgroups responding to biologically targeted rather than symptom-based treatments.”

The study was supported by the clinical research fund of the University Hospitals Leuven. The investigators reported no conflicts of interest.

Modified endoscopy documentation software can automatically generate endoscopic retrograde cholangiopancreatography (ERCP) quality metrics, based on a trial at two referral centers.

Providers were prompted during procedures, and inputting any missed data took providers less than 30 additional seconds per patient. The approach led to highly accurate quality reports, lead author Gregory A. Coté, MD, MS, of the Medical University of South Carolina, Charleston, and colleagues wrote in Techniques and Innovations in Gastrointestinal Endoscopy.

The investigators suggested that these findings may lead to the kind of quality reports already used for colonoscopy, which are easier to produce. Such reports are important, they wrote, as the U.S. health care system shifts to value-based reimbursement models, which in turn puts greater scrutiny on the quality of endoscopic procedures. However, doing so with ERCP isn’t entirely straightforward.

“Measuring adherence to ERCP quality indicators is especially challenging given: variance in indications, intraprocedural maneuvers, potential outcomes of a complex procedure, and variability in physician report documentation,” Dr. Coté and colleagues wrote. “In order to operationalize robust tracking of clinically relevant adherence to ERCP quality indicators in clinical practice – that is, to provide real-time feedback to providers, health systems, payors, and patients – an automated system of measurement must be developed.”

The quality indicators used in the study were largely drawn from an American Society for Gastrointestinal Endoscopy/American College of Gastroenterology task force document, with exclusion of those that were subjective or required systematic follow-up. The investigators modified existing endoscopy documentation software at two referral centers to include mandatory, structured data fields, principally with inclusion of quality improvements deemed high priority by the society consensus document, study authors, or both. For instance, providers were obligated to select a specific indication instead of various, synonymous terms (for example, “biliary stricture” vs. “common bile duct stricture”). Examples of quality indicators included successful cannulation of the desired duct, successful retrieval of stone less than 10 mm, or successful placement of a bile duct stent when indicated. Endoscopists were also required to note the presence of postoperative foregut anatomy or presence of existing sphincterotomy, variables which serve to stratefy the quality indicator outcome for degree of difficulty and allow appropriate comparisons of data. In addition, the study authors included inquiries about use of rectal indomethacin, use of prophylactic pancreatic duct stent, and documentation of need for repeat ERCP, follow-up x-ray, or both.

After 9 months, the system recorded 1,376 ERCP procedures conducted by eight providers, with a median annualized volume of 237 procedures (range, 37-336). Almost one-third (29%) of the patients had not had prior sphincterotomy.

Automated reporting of ERCP was compared with manual record review, which confirmed high (98%-100%) accuracy. This high level of accuracy “obviates the need for manual adjudication of medical records,” the investigators wrote.

They used data from one provider to create a template report card, and while exact comparisons across providers and institutions were not published, an example report card that was published with the study showed how such comparisons could be generated in the real world.

“The tool presented in this study allows for an objective assessment of ERCP performance which can provide explicit feedback to providers and allow transparent assessment of quality outcomes; it has the potential to improve the quality of ERCP akin to what has been demonstrated using colonoscopy report cards,” the investigators wrote. “Importantly, this can be achieved with minimal alteration to providers’ routine procedure documentation.”

Dr. Coté and colleagues also noted that the software modifications “can be implemented in other endoscopy units using the same or similar software.”

Taking the project to the next level would require widespread collaboration, according to the investigators.

“A key next step is to operationalize the transfer of data across multiple institutions, allowing for the creation of interim, standard-quality indicator reports that could be disseminated to providers, health systems, and payors,” they wrote. “If applied to a national cohort, this tool could accurately assess the current landscape of ERCP quality and provide tremendous opportunities for systematic improvement.”

One author disclosed a relationship with Provation Medical, but the remaining authors declared no relevant conflicts.

Modified endoscopy documentation software can automatically generate endoscopic retrograde cholangiopancreatography (ERCP) quality metrics, based on a trial at two referral centers.

Providers were prompted during procedures, and inputting any missed data took providers less than 30 additional seconds per patient. The approach led to highly accurate quality reports, lead author Gregory A. Coté, MD, MS, of the Medical University of South Carolina, Charleston, and colleagues wrote in Techniques and Innovations in Gastrointestinal Endoscopy.

The investigators suggested that these findings may lead to the kind of quality reports already used for colonoscopy, which are easier to produce. Such reports are important, they wrote, as the U.S. health care system shifts to value-based reimbursement models, which in turn puts greater scrutiny on the quality of endoscopic procedures. However, doing so with ERCP isn’t entirely straightforward.

“Measuring adherence to ERCP quality indicators is especially challenging given: variance in indications, intraprocedural maneuvers, potential outcomes of a complex procedure, and variability in physician report documentation,” Dr. Coté and colleagues wrote. “In order to operationalize robust tracking of clinically relevant adherence to ERCP quality indicators in clinical practice – that is, to provide real-time feedback to providers, health systems, payors, and patients – an automated system of measurement must be developed.”

The quality indicators used in the study were largely drawn from an American Society for Gastrointestinal Endoscopy/American College of Gastroenterology task force document, with exclusion of those that were subjective or required systematic follow-up. The investigators modified existing endoscopy documentation software at two referral centers to include mandatory, structured data fields, principally with inclusion of quality improvements deemed high priority by the society consensus document, study authors, or both. For instance, providers were obligated to select a specific indication instead of various, synonymous terms (for example, “biliary stricture” vs. “common bile duct stricture”). Examples of quality indicators included successful cannulation of the desired duct, successful retrieval of stone less than 10 mm, or successful placement of a bile duct stent when indicated. Endoscopists were also required to note the presence of postoperative foregut anatomy or presence of existing sphincterotomy, variables which serve to stratefy the quality indicator outcome for degree of difficulty and allow appropriate comparisons of data. In addition, the study authors included inquiries about use of rectal indomethacin, use of prophylactic pancreatic duct stent, and documentation of need for repeat ERCP, follow-up x-ray, or both.

After 9 months, the system recorded 1,376 ERCP procedures conducted by eight providers, with a median annualized volume of 237 procedures (range, 37-336). Almost one-third (29%) of the patients had not had prior sphincterotomy.

Automated reporting of ERCP was compared with manual record review, which confirmed high (98%-100%) accuracy. This high level of accuracy “obviates the need for manual adjudication of medical records,” the investigators wrote.

They used data from one provider to create a template report card, and while exact comparisons across providers and institutions were not published, an example report card that was published with the study showed how such comparisons could be generated in the real world.

“The tool presented in this study allows for an objective assessment of ERCP performance which can provide explicit feedback to providers and allow transparent assessment of quality outcomes; it has the potential to improve the quality of ERCP akin to what has been demonstrated using colonoscopy report cards,” the investigators wrote. “Importantly, this can be achieved with minimal alteration to providers’ routine procedure documentation.”

Dr. Coté and colleagues also noted that the software modifications “can be implemented in other endoscopy units using the same or similar software.”

Taking the project to the next level would require widespread collaboration, according to the investigators.

“A key next step is to operationalize the transfer of data across multiple institutions, allowing for the creation of interim, standard-quality indicator reports that could be disseminated to providers, health systems, and payors,” they wrote. “If applied to a national cohort, this tool could accurately assess the current landscape of ERCP quality and provide tremendous opportunities for systematic improvement.”

One author disclosed a relationship with Provation Medical, but the remaining authors declared no relevant conflicts.

Modified endoscopy documentation software can automatically generate endoscopic retrograde cholangiopancreatography (ERCP) quality metrics, based on a trial at two referral centers.

Providers were prompted during procedures, and inputting any missed data took providers less than 30 additional seconds per patient. The approach led to highly accurate quality reports, lead author Gregory A. Coté, MD, MS, of the Medical University of South Carolina, Charleston, and colleagues wrote in Techniques and Innovations in Gastrointestinal Endoscopy.

The investigators suggested that these findings may lead to the kind of quality reports already used for colonoscopy, which are easier to produce. Such reports are important, they wrote, as the U.S. health care system shifts to value-based reimbursement models, which in turn puts greater scrutiny on the quality of endoscopic procedures. However, doing so with ERCP isn’t entirely straightforward.

“Measuring adherence to ERCP quality indicators is especially challenging given: variance in indications, intraprocedural maneuvers, potential outcomes of a complex procedure, and variability in physician report documentation,” Dr. Coté and colleagues wrote. “In order to operationalize robust tracking of clinically relevant adherence to ERCP quality indicators in clinical practice – that is, to provide real-time feedback to providers, health systems, payors, and patients – an automated system of measurement must be developed.”

The quality indicators used in the study were largely drawn from an American Society for Gastrointestinal Endoscopy/American College of Gastroenterology task force document, with exclusion of those that were subjective or required systematic follow-up. The investigators modified existing endoscopy documentation software at two referral centers to include mandatory, structured data fields, principally with inclusion of quality improvements deemed high priority by the society consensus document, study authors, or both. For instance, providers were obligated to select a specific indication instead of various, synonymous terms (for example, “biliary stricture” vs. “common bile duct stricture”). Examples of quality indicators included successful cannulation of the desired duct, successful retrieval of stone less than 10 mm, or successful placement of a bile duct stent when indicated. Endoscopists were also required to note the presence of postoperative foregut anatomy or presence of existing sphincterotomy, variables which serve to stratefy the quality indicator outcome for degree of difficulty and allow appropriate comparisons of data. In addition, the study authors included inquiries about use of rectal indomethacin, use of prophylactic pancreatic duct stent, and documentation of need for repeat ERCP, follow-up x-ray, or both.

After 9 months, the system recorded 1,376 ERCP procedures conducted by eight providers, with a median annualized volume of 237 procedures (range, 37-336). Almost one-third (29%) of the patients had not had prior sphincterotomy.

Automated reporting of ERCP was compared with manual record review, which confirmed high (98%-100%) accuracy. This high level of accuracy “obviates the need for manual adjudication of medical records,” the investigators wrote.

They used data from one provider to create a template report card, and while exact comparisons across providers and institutions were not published, an example report card that was published with the study showed how such comparisons could be generated in the real world.

“The tool presented in this study allows for an objective assessment of ERCP performance which can provide explicit feedback to providers and allow transparent assessment of quality outcomes; it has the potential to improve the quality of ERCP akin to what has been demonstrated using colonoscopy report cards,” the investigators wrote. “Importantly, this can be achieved with minimal alteration to providers’ routine procedure documentation.”

Dr. Coté and colleagues also noted that the software modifications “can be implemented in other endoscopy units using the same or similar software.”

Taking the project to the next level would require widespread collaboration, according to the investigators.

“A key next step is to operationalize the transfer of data across multiple institutions, allowing for the creation of interim, standard-quality indicator reports that could be disseminated to providers, health systems, and payors,” they wrote. “If applied to a national cohort, this tool could accurately assess the current landscape of ERCP quality and provide tremendous opportunities for systematic improvement.”

One author disclosed a relationship with Provation Medical, but the remaining authors declared no relevant conflicts.