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Facial Temperature Can Reveal Age and Disease
This transcript has been edited for clarity.
My oldest daughter is at sleepaway camp for a couple of weeks, and the camp has a photographer who goes around all day taking pictures of the kids, which get uploaded to a private Facebook group. In the past, I would go online every day (or, okay, several times a day) and scroll through all those pictures looking for one that features my kid.
I don’t have to do that anymore. This year, I simply uploaded a picture of my daughter to an app and artificial intelligence (AI) takes care of the rest, recognizing her face amidst the sea of smiling children, and flagging just those photos for me to peruse. It’s amazing, really. And a bit scary.
The fact that facial recognition has penetrated the summer camp market should tell you that the tech is truly ubiquitous. But today we’re going to think a bit more about what AI can do with a picture of your face, because the power of facial recognition is not just skin deep.
What’s got me hot and bothered about facial images is this paper, appearing in Cell Metabolism, which adds a new layer to the standard facial-analysis playbook: facial temperature.
To understand this paper, you need to understand a whole field of research that is developing various different “clocks” for age.
It turns out that age really is just a number. Our cells, our proteins, our biochemistry can be analyzed to give different numbers. These “clocks,” as distinct from the calendar we usually use to measure our age, might have more predictive power than the number itself.
There are numerous molecular clocks, such as telomere length, that not only correlate with calendar age but are superior to calendar age in predicting age-related complications. Testing telomere length typically requires a blood sample — and remains costly. But we can use other sources to estimate age; how about a photo?
I mean, we do this all the time when we meet someone new or, as a physician, when we meet a new patient. I have often written that a patient “appears younger than their stated age,” and we’ve all had the experience of hearing how old someone is and being shocked. I mean, have you seen Sharon Stone recently? She’s 66 years old. Okay — to be fair, there might be some outside help there. But you get the point.
Back to the Cell Metabolism paper. Researchers report on multiple algorithms to obtain an “age” from a picture of an individual’s face.
The first algorithm is pretty straightforward. Researchers collected 2811 images, all of Han Chinese individuals ranging in age from 20 to 90 years, and reconstructed a 3D facial map from those. 
They then trained a convolutional neural network to predict the individuals’ ages from the pictures. It was quite accurate, as you can see here.
In the AI age, this may not seem that impressive. A brief search online turned up dozens of apps that promised to guess my age from a photo.
I sent this rather unflattering picture of myself to ChatGPT which, after initially demurring and saying it was not designed to guess ages, pegged me at somewhere between 35 and 45, which I am taking as a major victory.
But the Cell Metabolism paper goes deeper. Literally. 
And this is where things start to get interesting. Because sure, the visible part of your face can change depending on makeup, expression, plastic surgery, and the like. But the temperature? That’s harder to fake.
It turns out that the temperature distribution in your face changes as you get older. There is a cooling of the nose and the cheeks, for example.
And the researchers could combine all this temperature data to guess someone’s calendar age fairly accurately, though notably not as accurately as the model that just looks at the pictures.
But guessing your age is not really the interesting part of thermal imaging of the face. It’s guessing — or, rather, predicting — the state of your metabolism. All these study participants had extensive metabolic testing performed, as well as detailed analysis of their lifestyle behaviors. And facial images could be used to predict those factors.
For example, the 3D reconstruction of the faces could predict who ate seafood (they tend to look younger than their actual age) compared with who ate poultry and meat (they tend to look older). The thermal imaging could predict who got more sleep (they look younger from a temperature perspective) and who ate more yogurt (also younger-appearing, temperature-wise). Facial temperature patterns could identify those with higher BMI, higher blood pressure, higher fasting glucose.
The researchers used the difference between actual and predicted age as a metric to measure illness as well. You can see here how, on average, individuals with hypertension, diabetes, and even liver cysts are “older,” at least by face temperature.
It may even be possible to use facial temperature as biofeedback. In a small study, the researchers measured the difference between facial temperature age and real age before and after 2 weeks of jump-roping. It turns out that 2 weeks of jump-roping can make you look about 5 years younger, at least as judged by a thermal camera. Or like the Predator.
Okay, this is all very cool, but I’m not saying we’ll all be doing facial temperature tests in the near future. No; what this study highlights for me is how much information about ourselves is available to those who know how to decode it. Maybe those data come from the wrinkles in our faces, or the angles of our smiles, or the speed with which we type, or the temperature of our elbows. The data have always been there, actually, but we’ve never had the tools powerful enough to analyze them until now.
When I was a kid, I was obsessed with Star Trek — I know, you’re shocked — and, of course, the famous tricorder, a scanner that could tell everything about someone’s state of health in 5 seconds from 3 feet away. That’s how I thought medicine really would be in the future. Once I got to medical school, I was disabused of that notion. But the age of data, the age of AI, may mean the tricorder age is not actually that far away.
Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
My oldest daughter is at sleepaway camp for a couple of weeks, and the camp has a photographer who goes around all day taking pictures of the kids, which get uploaded to a private Facebook group. In the past, I would go online every day (or, okay, several times a day) and scroll through all those pictures looking for one that features my kid.
I don’t have to do that anymore. This year, I simply uploaded a picture of my daughter to an app and artificial intelligence (AI) takes care of the rest, recognizing her face amidst the sea of smiling children, and flagging just those photos for me to peruse. It’s amazing, really. And a bit scary.
The fact that facial recognition has penetrated the summer camp market should tell you that the tech is truly ubiquitous. But today we’re going to think a bit more about what AI can do with a picture of your face, because the power of facial recognition is not just skin deep.
What’s got me hot and bothered about facial images is this paper, appearing in Cell Metabolism, which adds a new layer to the standard facial-analysis playbook: facial temperature.
To understand this paper, you need to understand a whole field of research that is developing various different “clocks” for age.
It turns out that age really is just a number. Our cells, our proteins, our biochemistry can be analyzed to give different numbers. These “clocks,” as distinct from the calendar we usually use to measure our age, might have more predictive power than the number itself.
There are numerous molecular clocks, such as telomere length, that not only correlate with calendar age but are superior to calendar age in predicting age-related complications. Testing telomere length typically requires a blood sample — and remains costly. But we can use other sources to estimate age; how about a photo?
I mean, we do this all the time when we meet someone new or, as a physician, when we meet a new patient. I have often written that a patient “appears younger than their stated age,” and we’ve all had the experience of hearing how old someone is and being shocked. I mean, have you seen Sharon Stone recently? She’s 66 years old. Okay — to be fair, there might be some outside help there. But you get the point.
Back to the Cell Metabolism paper. Researchers report on multiple algorithms to obtain an “age” from a picture of an individual’s face.
The first algorithm is pretty straightforward. Researchers collected 2811 images, all of Han Chinese individuals ranging in age from 20 to 90 years, and reconstructed a 3D facial map from those.
They then trained a convolutional neural network to predict the individuals’ ages from the pictures. It was quite accurate, as you can see here.
In the AI age, this may not seem that impressive. A brief search online turned up dozens of apps that promised to guess my age from a photo.
I sent this rather unflattering picture of myself to ChatGPT which, after initially demurring and saying it was not designed to guess ages, pegged me at somewhere between 35 and 45, which I am taking as a major victory.
But the Cell Metabolism paper goes deeper. Literally.
And this is where things start to get interesting. Because sure, the visible part of your face can change depending on makeup, expression, plastic surgery, and the like. But the temperature? That’s harder to fake.
It turns out that the temperature distribution in your face changes as you get older. There is a cooling of the nose and the cheeks, for example.
And the researchers could combine all this temperature data to guess someone’s calendar age fairly accurately, though notably not as accurately as the model that just looks at the pictures.
But guessing your age is not really the interesting part of thermal imaging of the face. It’s guessing — or, rather, predicting — the state of your metabolism. All these study participants had extensive metabolic testing performed, as well as detailed analysis of their lifestyle behaviors. And facial images could be used to predict those factors.
For example, the 3D reconstruction of the faces could predict who ate seafood (they tend to look younger than their actual age) compared with who ate poultry and meat (they tend to look older). The thermal imaging could predict who got more sleep (they look younger from a temperature perspective) and who ate more yogurt (also younger-appearing, temperature-wise). Facial temperature patterns could identify those with higher BMI, higher blood pressure, higher fasting glucose.
The researchers used the difference between actual and predicted age as a metric to measure illness as well. You can see here how, on average, individuals with hypertension, diabetes, and even liver cysts are “older,” at least by face temperature.
It may even be possible to use facial temperature as biofeedback. In a small study, the researchers measured the difference between facial temperature age and real age before and after 2 weeks of jump-roping. It turns out that 2 weeks of jump-roping can make you look about 5 years younger, at least as judged by a thermal camera. Or like the Predator.
Okay, this is all very cool, but I’m not saying we’ll all be doing facial temperature tests in the near future. No; what this study highlights for me is how much information about ourselves is available to those who know how to decode it. Maybe those data come from the wrinkles in our faces, or the angles of our smiles, or the speed with which we type, or the temperature of our elbows. The data have always been there, actually, but we’ve never had the tools powerful enough to analyze them until now.
When I was a kid, I was obsessed with Star Trek — I know, you’re shocked — and, of course, the famous tricorder, a scanner that could tell everything about someone’s state of health in 5 seconds from 3 feet away. That’s how I thought medicine really would be in the future. Once I got to medical school, I was disabused of that notion. But the age of data, the age of AI, may mean the tricorder age is not actually that far away.
Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
My oldest daughter is at sleepaway camp for a couple of weeks, and the camp has a photographer who goes around all day taking pictures of the kids, which get uploaded to a private Facebook group. In the past, I would go online every day (or, okay, several times a day) and scroll through all those pictures looking for one that features my kid.
I don’t have to do that anymore. This year, I simply uploaded a picture of my daughter to an app and artificial intelligence (AI) takes care of the rest, recognizing her face amidst the sea of smiling children, and flagging just those photos for me to peruse. It’s amazing, really. And a bit scary.
The fact that facial recognition has penetrated the summer camp market should tell you that the tech is truly ubiquitous. But today we’re going to think a bit more about what AI can do with a picture of your face, because the power of facial recognition is not just skin deep.
What’s got me hot and bothered about facial images is this paper, appearing in Cell Metabolism, which adds a new layer to the standard facial-analysis playbook: facial temperature.
To understand this paper, you need to understand a whole field of research that is developing various different “clocks” for age.
It turns out that age really is just a number. Our cells, our proteins, our biochemistry can be analyzed to give different numbers. These “clocks,” as distinct from the calendar we usually use to measure our age, might have more predictive power than the number itself.
There are numerous molecular clocks, such as telomere length, that not only correlate with calendar age but are superior to calendar age in predicting age-related complications. Testing telomere length typically requires a blood sample — and remains costly. But we can use other sources to estimate age; how about a photo?
I mean, we do this all the time when we meet someone new or, as a physician, when we meet a new patient. I have often written that a patient “appears younger than their stated age,” and we’ve all had the experience of hearing how old someone is and being shocked. I mean, have you seen Sharon Stone recently? She’s 66 years old. Okay — to be fair, there might be some outside help there. But you get the point.
Back to the Cell Metabolism paper. Researchers report on multiple algorithms to obtain an “age” from a picture of an individual’s face.
The first algorithm is pretty straightforward. Researchers collected 2811 images, all of Han Chinese individuals ranging in age from 20 to 90 years, and reconstructed a 3D facial map from those.
They then trained a convolutional neural network to predict the individuals’ ages from the pictures. It was quite accurate, as you can see here.
In the AI age, this may not seem that impressive. A brief search online turned up dozens of apps that promised to guess my age from a photo.
I sent this rather unflattering picture of myself to ChatGPT which, after initially demurring and saying it was not designed to guess ages, pegged me at somewhere between 35 and 45, which I am taking as a major victory.
But the Cell Metabolism paper goes deeper. Literally.
And this is where things start to get interesting. Because sure, the visible part of your face can change depending on makeup, expression, plastic surgery, and the like. But the temperature? That’s harder to fake.
It turns out that the temperature distribution in your face changes as you get older. There is a cooling of the nose and the cheeks, for example.
And the researchers could combine all this temperature data to guess someone’s calendar age fairly accurately, though notably not as accurately as the model that just looks at the pictures.
But guessing your age is not really the interesting part of thermal imaging of the face. It’s guessing — or, rather, predicting — the state of your metabolism. All these study participants had extensive metabolic testing performed, as well as detailed analysis of their lifestyle behaviors. And facial images could be used to predict those factors.
For example, the 3D reconstruction of the faces could predict who ate seafood (they tend to look younger than their actual age) compared with who ate poultry and meat (they tend to look older). The thermal imaging could predict who got more sleep (they look younger from a temperature perspective) and who ate more yogurt (also younger-appearing, temperature-wise). Facial temperature patterns could identify those with higher BMI, higher blood pressure, higher fasting glucose.
The researchers used the difference between actual and predicted age as a metric to measure illness as well. You can see here how, on average, individuals with hypertension, diabetes, and even liver cysts are “older,” at least by face temperature.
It may even be possible to use facial temperature as biofeedback. In a small study, the researchers measured the difference between facial temperature age and real age before and after 2 weeks of jump-roping. It turns out that 2 weeks of jump-roping can make you look about 5 years younger, at least as judged by a thermal camera. Or like the Predator.
Okay, this is all very cool, but I’m not saying we’ll all be doing facial temperature tests in the near future. No; what this study highlights for me is how much information about ourselves is available to those who know how to decode it. Maybe those data come from the wrinkles in our faces, or the angles of our smiles, or the speed with which we type, or the temperature of our elbows. The data have always been there, actually, but we’ve never had the tools powerful enough to analyze them until now.
When I was a kid, I was obsessed with Star Trek — I know, you’re shocked — and, of course, the famous tricorder, a scanner that could tell everything about someone’s state of health in 5 seconds from 3 feet away. That’s how I thought medicine really would be in the future. Once I got to medical school, I was disabused of that notion. But the age of data, the age of AI, may mean the tricorder age is not actually that far away.
Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Sex Hormones Linked to Fatty Liver in Men With T2D
TOPLINE:
In men with type 2 diabetes (T2D), higher serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were associated with a lower risk for metabolic dysfunction–associated fatty liver disease (MAFLD), whereas higher progesterone levels were associated with a higher risk. In women with T2D, sex- or thyroid-related hormones were not independently associated with the risk for MAFLD.
METHODOLOGY:
- People with T2D may have FLD, and this study explored the link between sex-related and thyroid-related hormone levels and MAFLD to explore and confirm risk factors.
- The researchers used a 2020 definition of MAFLD, now defined in patients as both hepatic steatosis and the presence of overweight/obesity, T2D, or evidence of metabolic dysfunction in lean individuals.
- This cross-sectional study conducted in one hospital in China included 432 patients hospitalized because of T2D and its complications from January 2018 to April 2020 (median T2D duration, 6 years; mean age, 55.8 years; 247 men and 185 postmenopausal women).
- Researchers measured and later adjusted for potential confounding factors, including weight, height, waist circumference, arterial blood pressure, glycemic parameters, liver function, and lipid profiles.
- They assessed blood levels of sex and thyroid hormones by chemiluminescent immunoassays; MAFLD was diagnosed by either ultrasonography findings of hepatic steatosis or a high liver fat index score (fatty liver index > 60).
TAKEAWAY:
- Overall, 275 (63.7%) patients were diagnosed with MAFLD; after adjusting for potential confounding factors, none of the sex- and thyroid-related hormones were independently associated with the risk for MAFLD in all patients with T2D.
- In men with T2D, higher serum levels of FSH (adjusted odds ratio [aOR], 0.919; P = .019) and LH (aOR, 0.888; P = .022) were associated with a reduced risk for MAFLD.
- Higher serum levels of progesterone were associated with an increased risk for MAFLD in men with T2D (aOR, 8.069; P = .003).
- In women with T2D, sex hormones and thyroid hormones were not significantly linked to the risk of developing MAFLD.
IN PRACTICE:
“Our findings could be used to imply that screening for MAFLD and monitoring sex-related hormones are important for T2D patients, especially in men,” the authors wrote.
SOURCE:
This study was led by Weihong Lu, Xiamen Clinical Research Center for Cancer Therapy, Xiamen, China; Shangjian Li, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China; and Yuhua Li, China University of Mining & Technology-Beijing, Beijing, and was published online in BMC Endocrine Disorders.
LIMITATIONS:
Temporal sequences of the associations between sex-related and thyroid-related hormones and MAFLD were not evaluated because of the cross-sectional nature of the study. The small sample size from a single institution may have introduced selection bias. Serum levels of sex hormone-binding globulin and free testosterone were not assessed. The postmenopausal status of women in the study may have affected the ability to find sex-hormone related associations. The findings can only be limitedly extrapolated to similar patients with T2D but not the general population.
DISCLOSURES:
The study was supported by the Fujian Province Nature Science Foundations, China, and the Guiding Project on Medicine and Health in Xiamen, China. The authors declared no conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
In men with type 2 diabetes (T2D), higher serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were associated with a lower risk for metabolic dysfunction–associated fatty liver disease (MAFLD), whereas higher progesterone levels were associated with a higher risk. In women with T2D, sex- or thyroid-related hormones were not independently associated with the risk for MAFLD.
METHODOLOGY:
- People with T2D may have FLD, and this study explored the link between sex-related and thyroid-related hormone levels and MAFLD to explore and confirm risk factors.
- The researchers used a 2020 definition of MAFLD, now defined in patients as both hepatic steatosis and the presence of overweight/obesity, T2D, or evidence of metabolic dysfunction in lean individuals.
- This cross-sectional study conducted in one hospital in China included 432 patients hospitalized because of T2D and its complications from January 2018 to April 2020 (median T2D duration, 6 years; mean age, 55.8 years; 247 men and 185 postmenopausal women).
- Researchers measured and later adjusted for potential confounding factors, including weight, height, waist circumference, arterial blood pressure, glycemic parameters, liver function, and lipid profiles.
- They assessed blood levels of sex and thyroid hormones by chemiluminescent immunoassays; MAFLD was diagnosed by either ultrasonography findings of hepatic steatosis or a high liver fat index score (fatty liver index > 60).
TAKEAWAY:
- Overall, 275 (63.7%) patients were diagnosed with MAFLD; after adjusting for potential confounding factors, none of the sex- and thyroid-related hormones were independently associated with the risk for MAFLD in all patients with T2D.
- In men with T2D, higher serum levels of FSH (adjusted odds ratio [aOR], 0.919; P = .019) and LH (aOR, 0.888; P = .022) were associated with a reduced risk for MAFLD.
- Higher serum levels of progesterone were associated with an increased risk for MAFLD in men with T2D (aOR, 8.069; P = .003).
- In women with T2D, sex hormones and thyroid hormones were not significantly linked to the risk of developing MAFLD.
IN PRACTICE:
“Our findings could be used to imply that screening for MAFLD and monitoring sex-related hormones are important for T2D patients, especially in men,” the authors wrote.
SOURCE:
This study was led by Weihong Lu, Xiamen Clinical Research Center for Cancer Therapy, Xiamen, China; Shangjian Li, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China; and Yuhua Li, China University of Mining & Technology-Beijing, Beijing, and was published online in BMC Endocrine Disorders.
LIMITATIONS:
Temporal sequences of the associations between sex-related and thyroid-related hormones and MAFLD were not evaluated because of the cross-sectional nature of the study. The small sample size from a single institution may have introduced selection bias. Serum levels of sex hormone-binding globulin and free testosterone were not assessed. The postmenopausal status of women in the study may have affected the ability to find sex-hormone related associations. The findings can only be limitedly extrapolated to similar patients with T2D but not the general population.
DISCLOSURES:
The study was supported by the Fujian Province Nature Science Foundations, China, and the Guiding Project on Medicine and Health in Xiamen, China. The authors declared no conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
In men with type 2 diabetes (T2D), higher serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were associated with a lower risk for metabolic dysfunction–associated fatty liver disease (MAFLD), whereas higher progesterone levels were associated with a higher risk. In women with T2D, sex- or thyroid-related hormones were not independently associated with the risk for MAFLD.
METHODOLOGY:
- People with T2D may have FLD, and this study explored the link between sex-related and thyroid-related hormone levels and MAFLD to explore and confirm risk factors.
- The researchers used a 2020 definition of MAFLD, now defined in patients as both hepatic steatosis and the presence of overweight/obesity, T2D, or evidence of metabolic dysfunction in lean individuals.
- This cross-sectional study conducted in one hospital in China included 432 patients hospitalized because of T2D and its complications from January 2018 to April 2020 (median T2D duration, 6 years; mean age, 55.8 years; 247 men and 185 postmenopausal women).
- Researchers measured and later adjusted for potential confounding factors, including weight, height, waist circumference, arterial blood pressure, glycemic parameters, liver function, and lipid profiles.
- They assessed blood levels of sex and thyroid hormones by chemiluminescent immunoassays; MAFLD was diagnosed by either ultrasonography findings of hepatic steatosis or a high liver fat index score (fatty liver index > 60).
TAKEAWAY:
- Overall, 275 (63.7%) patients were diagnosed with MAFLD; after adjusting for potential confounding factors, none of the sex- and thyroid-related hormones were independently associated with the risk for MAFLD in all patients with T2D.
- In men with T2D, higher serum levels of FSH (adjusted odds ratio [aOR], 0.919; P = .019) and LH (aOR, 0.888; P = .022) were associated with a reduced risk for MAFLD.
- Higher serum levels of progesterone were associated with an increased risk for MAFLD in men with T2D (aOR, 8.069; P = .003).
- In women with T2D, sex hormones and thyroid hormones were not significantly linked to the risk of developing MAFLD.
IN PRACTICE:
“Our findings could be used to imply that screening for MAFLD and monitoring sex-related hormones are important for T2D patients, especially in men,” the authors wrote.
SOURCE:
This study was led by Weihong Lu, Xiamen Clinical Research Center for Cancer Therapy, Xiamen, China; Shangjian Li, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China; and Yuhua Li, China University of Mining & Technology-Beijing, Beijing, and was published online in BMC Endocrine Disorders.
LIMITATIONS:
Temporal sequences of the associations between sex-related and thyroid-related hormones and MAFLD were not evaluated because of the cross-sectional nature of the study. The small sample size from a single institution may have introduced selection bias. Serum levels of sex hormone-binding globulin and free testosterone were not assessed. The postmenopausal status of women in the study may have affected the ability to find sex-hormone related associations. The findings can only be limitedly extrapolated to similar patients with T2D but not the general population.
DISCLOSURES:
The study was supported by the Fujian Province Nature Science Foundations, China, and the Guiding Project on Medicine and Health in Xiamen, China. The authors declared no conflicts of interest.
A version of this article first appeared on Medscape.com.
Women with Autoimmune Liver Diseases Still Face Increased CVD Risks
WASHINGTON – , according to a study presented at the annual Digestive Disease Week® (DDW).
In particular, women with autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) appear to have higher risks than women without AIH or PBC. Those with primary sclerosing cholangitis (PSC) don’t seem to have increased risks.
“We know that cardiovascular disease remains the number one cause of death, but the mortality rate for women over the last decade has plateaued, whereas in men it’s actually declining due to interventions,” said lead author Rachel Redfield, MD, a transplant hepatology fellow at Thomas Jefferson University Hospital in Philadelphia.
“This is likely because we don’t have adequate risk stratification, especially for women,” she said. “We know that immune-mediated diseases — such as rheumatoid arthritis and psoriasis — carry a higher risk of cardiovascular disease, but there’s not a lot of data on our autoimmune liver disease patients.”
Although being a female can offer protection against some CVD risks, the atherosclerotic cardiovascular disease (ASCVD) 10-year risk score calculator recommended by the American College of Cardiology doesn’t include chronic inflammatory diseases associated with increased CVD risk, including AILD.
Dr. Redfield and colleagues conducted a multicenter, retrospective cohort study of patients with AIH, PBC, and PSC from 1999-2019. Using TriNetX data, the researchers looked at women with AILD who also had diabetes mellitus, hypertension, and hyperlipidemia, as well as a control group of men and women with these same disorders, excluding those who used biologics, immune modulators, and steroids or had other autoimmune disorders.
The research team used 1:1 propensity-score matching for women in the study group and in the control group based on age, race, ethnicity, ASCVD risk factors, and tobacco use. Women in the study group and men in the control group were matched for age, race, ethnicity, and tobacco use.
The primary outcome was summative cardiovascular risk, including unstable angina, acute myocardial infarction, presence of coronary angioplasty implant, coronary artery bypass, percutaneous coronary intervention, and cerebral infarction.
Overall, women with AIH had a significantly higher cardiovascular risk compared to women without AIH, at 25.4% versus 20.6% (P = .0007).
Specifically, women with PBC had a significantly higher cardiovascular risk compared to women without PBC, at 27.05% versus 20.9% (P < .0001).
There wasn’t a significant difference in risk between women with and without PSC, at 27.5% versus 21.8% (P = .27).
When compared to men without disease, women with AIH didn’t have a statistically significant higher risk, at 25.3% versus 24.2% (P = .44). Similarly, there didn’t appear to be a significant difference between women with PBC and men without PBC, at 26.9% versus 25.9% (P = .52), or between women with PSC and men without PSC, at 27.7% versus 26.2% (P = .78).
Dr. Redfield and colleagues then compared the ASCVD-calculated risk versus database risk, finding that in each group of women with AILD — including AIH, PBC, and PSC — the ASCVD-calculated risk was around 11%, compared with database risk scores of 25% for AIH, 27% for PBC, and 28% for PSC. These database risks appeared similar to both the ASCVD and database risk percentages for men.
“So potentially there’s an oversight in women with any kind of inflammatory disease, but specifically here, autoimmune liver diseases,” she said. “We really need to enhance our risk assessment strategies to take into account their risk and optimize patient outcomes.”
Dr. Redfield noted the limitations with using TriNetX data, including coding consistency among providers and healthcare organizations, unknown patient follow-up dates, and the inability to capture various inflammatory disease phenotypes, such as autoimmune hepatitis with multiple flares, which may be associated with higher cardiovascular risks.
As an attendee of the DDW session, Kenneth Kelson, MD, a gastroenterologist with Fremont Medical Group and Washington Hospital Healthcare System in Fremont, California, noted the importance of investigating the effects of different types of statins in these patients. Although the research team looked at top-level differences among statin users, finding that women with AILD were more likely to be on a statin, they didn’t incorporate statin therapy in the propensity-score matching model.
“Lipid-soluble statins are known to cause more liver trouble, even though it’s pretty low,” Dr. Kelson said. “Whereas the water-soluble statins have a lower incidence of liver issues.”
Dr. Redfield and Dr. Kelson reported no relevant disclosures.
WASHINGTON – , according to a study presented at the annual Digestive Disease Week® (DDW).
In particular, women with autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) appear to have higher risks than women without AIH or PBC. Those with primary sclerosing cholangitis (PSC) don’t seem to have increased risks.
“We know that cardiovascular disease remains the number one cause of death, but the mortality rate for women over the last decade has plateaued, whereas in men it’s actually declining due to interventions,” said lead author Rachel Redfield, MD, a transplant hepatology fellow at Thomas Jefferson University Hospital in Philadelphia.
“This is likely because we don’t have adequate risk stratification, especially for women,” she said. “We know that immune-mediated diseases — such as rheumatoid arthritis and psoriasis — carry a higher risk of cardiovascular disease, but there’s not a lot of data on our autoimmune liver disease patients.”
Although being a female can offer protection against some CVD risks, the atherosclerotic cardiovascular disease (ASCVD) 10-year risk score calculator recommended by the American College of Cardiology doesn’t include chronic inflammatory diseases associated with increased CVD risk, including AILD.
Dr. Redfield and colleagues conducted a multicenter, retrospective cohort study of patients with AIH, PBC, and PSC from 1999-2019. Using TriNetX data, the researchers looked at women with AILD who also had diabetes mellitus, hypertension, and hyperlipidemia, as well as a control group of men and women with these same disorders, excluding those who used biologics, immune modulators, and steroids or had other autoimmune disorders.
The research team used 1:1 propensity-score matching for women in the study group and in the control group based on age, race, ethnicity, ASCVD risk factors, and tobacco use. Women in the study group and men in the control group were matched for age, race, ethnicity, and tobacco use.
The primary outcome was summative cardiovascular risk, including unstable angina, acute myocardial infarction, presence of coronary angioplasty implant, coronary artery bypass, percutaneous coronary intervention, and cerebral infarction.
Overall, women with AIH had a significantly higher cardiovascular risk compared to women without AIH, at 25.4% versus 20.6% (P = .0007).
Specifically, women with PBC had a significantly higher cardiovascular risk compared to women without PBC, at 27.05% versus 20.9% (P < .0001).
There wasn’t a significant difference in risk between women with and without PSC, at 27.5% versus 21.8% (P = .27).
When compared to men without disease, women with AIH didn’t have a statistically significant higher risk, at 25.3% versus 24.2% (P = .44). Similarly, there didn’t appear to be a significant difference between women with PBC and men without PBC, at 26.9% versus 25.9% (P = .52), or between women with PSC and men without PSC, at 27.7% versus 26.2% (P = .78).
Dr. Redfield and colleagues then compared the ASCVD-calculated risk versus database risk, finding that in each group of women with AILD — including AIH, PBC, and PSC — the ASCVD-calculated risk was around 11%, compared with database risk scores of 25% for AIH, 27% for PBC, and 28% for PSC. These database risks appeared similar to both the ASCVD and database risk percentages for men.
“So potentially there’s an oversight in women with any kind of inflammatory disease, but specifically here, autoimmune liver diseases,” she said. “We really need to enhance our risk assessment strategies to take into account their risk and optimize patient outcomes.”
Dr. Redfield noted the limitations with using TriNetX data, including coding consistency among providers and healthcare organizations, unknown patient follow-up dates, and the inability to capture various inflammatory disease phenotypes, such as autoimmune hepatitis with multiple flares, which may be associated with higher cardiovascular risks.
As an attendee of the DDW session, Kenneth Kelson, MD, a gastroenterologist with Fremont Medical Group and Washington Hospital Healthcare System in Fremont, California, noted the importance of investigating the effects of different types of statins in these patients. Although the research team looked at top-level differences among statin users, finding that women with AILD were more likely to be on a statin, they didn’t incorporate statin therapy in the propensity-score matching model.
“Lipid-soluble statins are known to cause more liver trouble, even though it’s pretty low,” Dr. Kelson said. “Whereas the water-soluble statins have a lower incidence of liver issues.”
Dr. Redfield and Dr. Kelson reported no relevant disclosures.
WASHINGTON – , according to a study presented at the annual Digestive Disease Week® (DDW).
In particular, women with autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) appear to have higher risks than women without AIH or PBC. Those with primary sclerosing cholangitis (PSC) don’t seem to have increased risks.
“We know that cardiovascular disease remains the number one cause of death, but the mortality rate for women over the last decade has plateaued, whereas in men it’s actually declining due to interventions,” said lead author Rachel Redfield, MD, a transplant hepatology fellow at Thomas Jefferson University Hospital in Philadelphia.
“This is likely because we don’t have adequate risk stratification, especially for women,” she said. “We know that immune-mediated diseases — such as rheumatoid arthritis and psoriasis — carry a higher risk of cardiovascular disease, but there’s not a lot of data on our autoimmune liver disease patients.”
Although being a female can offer protection against some CVD risks, the atherosclerotic cardiovascular disease (ASCVD) 10-year risk score calculator recommended by the American College of Cardiology doesn’t include chronic inflammatory diseases associated with increased CVD risk, including AILD.
Dr. Redfield and colleagues conducted a multicenter, retrospective cohort study of patients with AIH, PBC, and PSC from 1999-2019. Using TriNetX data, the researchers looked at women with AILD who also had diabetes mellitus, hypertension, and hyperlipidemia, as well as a control group of men and women with these same disorders, excluding those who used biologics, immune modulators, and steroids or had other autoimmune disorders.
The research team used 1:1 propensity-score matching for women in the study group and in the control group based on age, race, ethnicity, ASCVD risk factors, and tobacco use. Women in the study group and men in the control group were matched for age, race, ethnicity, and tobacco use.
The primary outcome was summative cardiovascular risk, including unstable angina, acute myocardial infarction, presence of coronary angioplasty implant, coronary artery bypass, percutaneous coronary intervention, and cerebral infarction.
Overall, women with AIH had a significantly higher cardiovascular risk compared to women without AIH, at 25.4% versus 20.6% (P = .0007).
Specifically, women with PBC had a significantly higher cardiovascular risk compared to women without PBC, at 27.05% versus 20.9% (P < .0001).
There wasn’t a significant difference in risk between women with and without PSC, at 27.5% versus 21.8% (P = .27).
When compared to men without disease, women with AIH didn’t have a statistically significant higher risk, at 25.3% versus 24.2% (P = .44). Similarly, there didn’t appear to be a significant difference between women with PBC and men without PBC, at 26.9% versus 25.9% (P = .52), or between women with PSC and men without PSC, at 27.7% versus 26.2% (P = .78).
Dr. Redfield and colleagues then compared the ASCVD-calculated risk versus database risk, finding that in each group of women with AILD — including AIH, PBC, and PSC — the ASCVD-calculated risk was around 11%, compared with database risk scores of 25% for AIH, 27% for PBC, and 28% for PSC. These database risks appeared similar to both the ASCVD and database risk percentages for men.
“So potentially there’s an oversight in women with any kind of inflammatory disease, but specifically here, autoimmune liver diseases,” she said. “We really need to enhance our risk assessment strategies to take into account their risk and optimize patient outcomes.”
Dr. Redfield noted the limitations with using TriNetX data, including coding consistency among providers and healthcare organizations, unknown patient follow-up dates, and the inability to capture various inflammatory disease phenotypes, such as autoimmune hepatitis with multiple flares, which may be associated with higher cardiovascular risks.
As an attendee of the DDW session, Kenneth Kelson, MD, a gastroenterologist with Fremont Medical Group and Washington Hospital Healthcare System in Fremont, California, noted the importance of investigating the effects of different types of statins in these patients. Although the research team looked at top-level differences among statin users, finding that women with AILD were more likely to be on a statin, they didn’t incorporate statin therapy in the propensity-score matching model.
“Lipid-soluble statins are known to cause more liver trouble, even though it’s pretty low,” Dr. Kelson said. “Whereas the water-soluble statins have a lower incidence of liver issues.”
Dr. Redfield and Dr. Kelson reported no relevant disclosures.
FROM DDW 2024
Intelligent Liver Function Testing Helps Detect, Diagnose Chronic Liver Disease
TOPLINE:
, new data show.
METHODOLOGY:
- At the European Association for the Study of the Liver (EASL) Congress 2024, researchers presented 5-year, real-world data of the iLFT platform from its use in NHS Tayside in Dundee, Scotland, which serves a population of 400,000. The platform has been available since 2018.
- The iLFT platform uses an automated algorithm that analyzes standard liver function test results.
- Abnormal results prompt the system to initiate further fibrosis scoring and relevant etiologic testing to determine the cause of liver dysfunction.
- The results of these tests combined with practitioner-entered clinical information produce a probable diagnosis and recommend a patient-management strategy.
TAKEAWAY:
- Of the 26,459 iLFT tests performed between 2018 and 2023, 68.3% (18,079) required further testing beyond the initial liver function test, whereas 31.7% (8380) did not.
- Further testing generated 20,895 outcomes, of which, isolated abnormal alanine transaminase (ALT) without fibrosis was most frequent (23.7%). Abnormal ALT was found to be most likely due to metabolic dysfunction–associated steatotic liver disease (MASLD).
- Overall, half of cascaded samples had a positive etiologic diagnosis. Alcoholic liver disease (ALD) and MASLD were the most common etiologic outcomes identified.
- In addition, 20% of cascaded tests identified potentially significant liver fibrosis.
- A total of 69.9% of outcomes recommended that patients could be safely managed in primary care. The inclusion of automatic Enhanced Liver Fibrosis (ELF) testing in 2020 further reduced the requirement for referral to secondary care by 34%.
IN PRACTICE:
“Without this algorithm, the 18,000 patients who had algorithm-directed further testing would have had to go back to the [primary care practitioner] to obtain the additional tests, and the [primary care practitioner] would need to interpret them too,” said Damien Leith, MD, trainee hepatologist at Ninewells Hospital, Dundee, Scotland, who presented the findings. “iLFTs ensure the right patients get automated, appropriate follow-up testing and subsequent recommendation of referral to secondary care if necessary, and importantly iLFT helps the primary care practitioner identify the cause of chronic liver disease.”
SOURCE:
This study was presented on June 6, 2024 at the EASL Congress 2024 (abstract OS-007-YI).
LIMITATIONS:
Limitations include the need for further refinement of the algorithm to increase the proportion of positive etiologic iLFT outcomes. More analysis is needed to optimize the cost-effectiveness of iLFT.
DISCLOSURES:
Dr. Leith reports no relevant financial relationships.
A version of this article appeared on Medscape.com.
TOPLINE:
, new data show.
METHODOLOGY:
- At the European Association for the Study of the Liver (EASL) Congress 2024, researchers presented 5-year, real-world data of the iLFT platform from its use in NHS Tayside in Dundee, Scotland, which serves a population of 400,000. The platform has been available since 2018.
- The iLFT platform uses an automated algorithm that analyzes standard liver function test results.
- Abnormal results prompt the system to initiate further fibrosis scoring and relevant etiologic testing to determine the cause of liver dysfunction.
- The results of these tests combined with practitioner-entered clinical information produce a probable diagnosis and recommend a patient-management strategy.
TAKEAWAY:
- Of the 26,459 iLFT tests performed between 2018 and 2023, 68.3% (18,079) required further testing beyond the initial liver function test, whereas 31.7% (8380) did not.
- Further testing generated 20,895 outcomes, of which, isolated abnormal alanine transaminase (ALT) without fibrosis was most frequent (23.7%). Abnormal ALT was found to be most likely due to metabolic dysfunction–associated steatotic liver disease (MASLD).
- Overall, half of cascaded samples had a positive etiologic diagnosis. Alcoholic liver disease (ALD) and MASLD were the most common etiologic outcomes identified.
- In addition, 20% of cascaded tests identified potentially significant liver fibrosis.
- A total of 69.9% of outcomes recommended that patients could be safely managed in primary care. The inclusion of automatic Enhanced Liver Fibrosis (ELF) testing in 2020 further reduced the requirement for referral to secondary care by 34%.
IN PRACTICE:
“Without this algorithm, the 18,000 patients who had algorithm-directed further testing would have had to go back to the [primary care practitioner] to obtain the additional tests, and the [primary care practitioner] would need to interpret them too,” said Damien Leith, MD, trainee hepatologist at Ninewells Hospital, Dundee, Scotland, who presented the findings. “iLFTs ensure the right patients get automated, appropriate follow-up testing and subsequent recommendation of referral to secondary care if necessary, and importantly iLFT helps the primary care practitioner identify the cause of chronic liver disease.”
SOURCE:
This study was presented on June 6, 2024 at the EASL Congress 2024 (abstract OS-007-YI).
LIMITATIONS:
Limitations include the need for further refinement of the algorithm to increase the proportion of positive etiologic iLFT outcomes. More analysis is needed to optimize the cost-effectiveness of iLFT.
DISCLOSURES:
Dr. Leith reports no relevant financial relationships.
A version of this article appeared on Medscape.com.
TOPLINE:
, new data show.
METHODOLOGY:
- At the European Association for the Study of the Liver (EASL) Congress 2024, researchers presented 5-year, real-world data of the iLFT platform from its use in NHS Tayside in Dundee, Scotland, which serves a population of 400,000. The platform has been available since 2018.
- The iLFT platform uses an automated algorithm that analyzes standard liver function test results.
- Abnormal results prompt the system to initiate further fibrosis scoring and relevant etiologic testing to determine the cause of liver dysfunction.
- The results of these tests combined with practitioner-entered clinical information produce a probable diagnosis and recommend a patient-management strategy.
TAKEAWAY:
- Of the 26,459 iLFT tests performed between 2018 and 2023, 68.3% (18,079) required further testing beyond the initial liver function test, whereas 31.7% (8380) did not.
- Further testing generated 20,895 outcomes, of which, isolated abnormal alanine transaminase (ALT) without fibrosis was most frequent (23.7%). Abnormal ALT was found to be most likely due to metabolic dysfunction–associated steatotic liver disease (MASLD).
- Overall, half of cascaded samples had a positive etiologic diagnosis. Alcoholic liver disease (ALD) and MASLD were the most common etiologic outcomes identified.
- In addition, 20% of cascaded tests identified potentially significant liver fibrosis.
- A total of 69.9% of outcomes recommended that patients could be safely managed in primary care. The inclusion of automatic Enhanced Liver Fibrosis (ELF) testing in 2020 further reduced the requirement for referral to secondary care by 34%.
IN PRACTICE:
“Without this algorithm, the 18,000 patients who had algorithm-directed further testing would have had to go back to the [primary care practitioner] to obtain the additional tests, and the [primary care practitioner] would need to interpret them too,” said Damien Leith, MD, trainee hepatologist at Ninewells Hospital, Dundee, Scotland, who presented the findings. “iLFTs ensure the right patients get automated, appropriate follow-up testing and subsequent recommendation of referral to secondary care if necessary, and importantly iLFT helps the primary care practitioner identify the cause of chronic liver disease.”
SOURCE:
This study was presented on June 6, 2024 at the EASL Congress 2024 (abstract OS-007-YI).
LIMITATIONS:
Limitations include the need for further refinement of the algorithm to increase the proportion of positive etiologic iLFT outcomes. More analysis is needed to optimize the cost-effectiveness of iLFT.
DISCLOSURES:
Dr. Leith reports no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM EASL 2024
FDA OKs Iqirvo, First-in-Class PPAR Treatment for Primary Biliary Cholangitis
in combination with ursodeoxycholic acid (UDCA) in adults who do not respond adequately to UDCA or as monotherapy in patients unable to tolerate UDCA.
PBC is a rare, chronic cholestatic liver disease that destroys interlobular bile ducts and leads to cholestasis and liver fibrosis. Left untreated, the disease can worsen over time, leading to cirrhosis and liver transplant and, in some cases, premature death. PBC also harms quality of life, with patients often experiencing severe fatigue and pruritus.
Iqirvo, an oral dual peroxisome proliferator–activated receptor (PPAR) alpha and delta agonist, is the first new drug approved in nearly a decade for treatment of PBC.
Accelerated approval of Iqirvo for PBC was based on data from the phase 3 ELATIVE trial published last year in The New England Journal of Medicine.
The trial randomly assigned patients with PBC who had an inadequate response to or unacceptable side effects with UDCA to receive either once-daily elafibranor (80 mg) or placebo.
The primary endpoint was a biochemical response, defined as an alkaline phosphatase (ALP) level < 1.67 times the upper limit of the normal range, with a reduction ≥ 15% from baseline, as well as normal total bilirubin levels.
Among 161 patients, a biochemical response was seen in 55 of 108 (51%) who received elafibranor vs 2 of 53 (4%) who received placebo.
At week 52, the ALP level normalized in 15% of patients in the elafibranor group and none of the patients in the placebo group.
In a news release announcing approval of Iqirvo, the company notes that improvement in survival and prevention of liver decompensation events have not been demonstrated and that continued approval for PBC may be contingent upon verification and description of clinical benefit in confirmatory trials.
The most common adverse effects with Iqirvo, reported in ≥ 10% of study participants, were weight gain, abdominal pain, diarrhea, nausea, and vomiting. Iqirvo is not recommended for people who have or develop decompensated cirrhosis. Full prescribing information is available online.
The data show that Iqirvo is “an effective second-line treatment for patients with PBC with favorable benefit and risk data,” Kris Kowdley, MD, AGAF, director of the Liver Institute Northwest in Seattle, Washington, and a primary investigator on the ELATIVE study, said in the news release.
The approval of Iqirvo “will allow healthcare providers in the US to address an unmet need with the potential to significantly reduce ALP levels for our patients with PBC,” Dr. Kowdley said.
A version of this article appeared on Medscape.com.
in combination with ursodeoxycholic acid (UDCA) in adults who do not respond adequately to UDCA or as monotherapy in patients unable to tolerate UDCA.
PBC is a rare, chronic cholestatic liver disease that destroys interlobular bile ducts and leads to cholestasis and liver fibrosis. Left untreated, the disease can worsen over time, leading to cirrhosis and liver transplant and, in some cases, premature death. PBC also harms quality of life, with patients often experiencing severe fatigue and pruritus.
Iqirvo, an oral dual peroxisome proliferator–activated receptor (PPAR) alpha and delta agonist, is the first new drug approved in nearly a decade for treatment of PBC.
Accelerated approval of Iqirvo for PBC was based on data from the phase 3 ELATIVE trial published last year in The New England Journal of Medicine.
The trial randomly assigned patients with PBC who had an inadequate response to or unacceptable side effects with UDCA to receive either once-daily elafibranor (80 mg) or placebo.
The primary endpoint was a biochemical response, defined as an alkaline phosphatase (ALP) level < 1.67 times the upper limit of the normal range, with a reduction ≥ 15% from baseline, as well as normal total bilirubin levels.
Among 161 patients, a biochemical response was seen in 55 of 108 (51%) who received elafibranor vs 2 of 53 (4%) who received placebo.
At week 52, the ALP level normalized in 15% of patients in the elafibranor group and none of the patients in the placebo group.
In a news release announcing approval of Iqirvo, the company notes that improvement in survival and prevention of liver decompensation events have not been demonstrated and that continued approval for PBC may be contingent upon verification and description of clinical benefit in confirmatory trials.
The most common adverse effects with Iqirvo, reported in ≥ 10% of study participants, were weight gain, abdominal pain, diarrhea, nausea, and vomiting. Iqirvo is not recommended for people who have or develop decompensated cirrhosis. Full prescribing information is available online.
The data show that Iqirvo is “an effective second-line treatment for patients with PBC with favorable benefit and risk data,” Kris Kowdley, MD, AGAF, director of the Liver Institute Northwest in Seattle, Washington, and a primary investigator on the ELATIVE study, said in the news release.
The approval of Iqirvo “will allow healthcare providers in the US to address an unmet need with the potential to significantly reduce ALP levels for our patients with PBC,” Dr. Kowdley said.
A version of this article appeared on Medscape.com.
in combination with ursodeoxycholic acid (UDCA) in adults who do not respond adequately to UDCA or as monotherapy in patients unable to tolerate UDCA.
PBC is a rare, chronic cholestatic liver disease that destroys interlobular bile ducts and leads to cholestasis and liver fibrosis. Left untreated, the disease can worsen over time, leading to cirrhosis and liver transplant and, in some cases, premature death. PBC also harms quality of life, with patients often experiencing severe fatigue and pruritus.
Iqirvo, an oral dual peroxisome proliferator–activated receptor (PPAR) alpha and delta agonist, is the first new drug approved in nearly a decade for treatment of PBC.
Accelerated approval of Iqirvo for PBC was based on data from the phase 3 ELATIVE trial published last year in The New England Journal of Medicine.
The trial randomly assigned patients with PBC who had an inadequate response to or unacceptable side effects with UDCA to receive either once-daily elafibranor (80 mg) or placebo.
The primary endpoint was a biochemical response, defined as an alkaline phosphatase (ALP) level < 1.67 times the upper limit of the normal range, with a reduction ≥ 15% from baseline, as well as normal total bilirubin levels.
Among 161 patients, a biochemical response was seen in 55 of 108 (51%) who received elafibranor vs 2 of 53 (4%) who received placebo.
At week 52, the ALP level normalized in 15% of patients in the elafibranor group and none of the patients in the placebo group.
In a news release announcing approval of Iqirvo, the company notes that improvement in survival and prevention of liver decompensation events have not been demonstrated and that continued approval for PBC may be contingent upon verification and description of clinical benefit in confirmatory trials.
The most common adverse effects with Iqirvo, reported in ≥ 10% of study participants, were weight gain, abdominal pain, diarrhea, nausea, and vomiting. Iqirvo is not recommended for people who have or develop decompensated cirrhosis. Full prescribing information is available online.
The data show that Iqirvo is “an effective second-line treatment for patients with PBC with favorable benefit and risk data,” Kris Kowdley, MD, AGAF, director of the Liver Institute Northwest in Seattle, Washington, and a primary investigator on the ELATIVE study, said in the news release.
The approval of Iqirvo “will allow healthcare providers in the US to address an unmet need with the potential to significantly reduce ALP levels for our patients with PBC,” Dr. Kowdley said.
A version of this article appeared on Medscape.com.
FMT Could Prevent Recurrence of Hepatic Encephalopathy in Patients With Cirrhosis
MILAN — , results of a phase 2 randomized controlled trial show.
“Not only was FMT more beneficial, but also it didn’t matter which route of administration was used — oral or enema — which is good because people don’t really like enemas,” said Jasmohan S. Bajaj, MD, AGAF, professor, School of Medicine, Virginia Commonwealth University, Richmond, and hepatologist at Richmond VA Medical Center.
Donor background (including vegan or omnivore) and dose range also did not affect the efficacy of FMT, Dr. Bajaj said.
Dr. Bajaj presented the findings (Abstract GS-001) at the opening session of the annual European Association for the Study of the Liver (EASL) Congress 2024.
Hepatic encephalopathy is a complication of advanced liver disease that causes a dementia-like state. Standard treatment with lactulose and rifaximin often results in a lack of patient response, meaning the patient is constantly being readmitted to the hospital, Dr. Bajaj said.
“This is a burden for the family as well as the patients,” and is very difficult to manage from a clinical and psychosocial perspective, he said in an interview.
With FMT, “we are transferring an ecosystem of good microbes,” which modifies the gut microbiome in patients with advanced liver disease and reduces associated brain toxicity, Dr. Bajaj explained.
Resetting the Gut
The double-blind, randomized, placebo-controlled trial enrolled a total of 60 patients with cirrhosis who had experienced hepatic encephalopathy. Aged 61-65 years, participants had Model for End-Stage Liver Disease (MELD) scores of 12-13, all were taking lactulose and rifaximin, and all had experienced their last hepatic encephalopathy episode 8-13 months prior.
Participants had similar baseline cognition, Sickness Impact Profile (SIP), and cirrhosis severity. Those with recent infections, taking other antibiotics, with a MELD score > 22, had received a transplant, or were immunosuppressed were excluded.
Study participants were divided into four dose administration groups (n = 15 each): oral and enema active FMT therapy (group 1), oral active FMT and enema placebo (group 2), oral placebo and enema active FMT (group 3), and oral and enema placebo (group 4).
The range of FMT dose frequency was zero (all placebo), or one, two, or three FMT administrations, each given 1 month apart.
Two thirds of those receiving active FMT were given omnivore-donor FMT, and one third were given vegan-donor FMT, in addition to receiving standard of care.
“Colony-forming units were standard and the same whether given via oral capsule or enema,” Dr. Bajaj said. This is “similar to what we used in our phase 1 study.”
Intent-to-treat (ITT) analysis was performed with 6-month data. The primary outcomes were safety and hepatic encephalopathy recurrence defined as ≥ grade 2 on West-Haven criteria. Secondary outcomes included other adverse events, changes in infections, severity of cirrhosis and cognition, and patient-reported outcomes. A statistical regression for hepatic encephalopathy recurrence was also performed. Patients were followed for 6 months or until death.
One Dose of FMT Better Than None
Hepatic encephalopathy recurrence was highest (40%) in group 4 patients, compared with those in group 1 (13%), group 2 (13%), and group 3 (0%), as were liver-related hospitalizations (47% vs 7%-20%).
SIP total/physical and psych scores improved with FMT (P = .003).
When all patients were included in the analysis, the hepatic encephalopathy recurrence was related to dose number (odds radio [OR], 0.27; 95% CI, 0.10-0.79; P = .02), male sex (OR, 0.16; 95% CI, 0.03-0.89; P = .04), and physical SIP (OR, 1.05; 95% CI, 1.01-1.10, P = .05). However, when analyzing results from FMT recipients only, FMT dose, route of administration, and donor source were not found to affect recurrence.
Of those on placebo alone, six patients (40%) had a recurrence, compared with four on FMT (8.8%) in the combined FMT groups.
“As long as a patient received at least one FMT dose, they had a better response than a patient who had none,” Dr. Bajaj said.
Six patients dropped out; two in group 1 died after hepatic encephalopathy and falls, and one in group 2 died after a seizure. Three others did not return for follow-up visits. Four patients developed infections, including spontaneous bacterial peritonitis, cholecystitis, and cellulitis, all unrelated to FMT.
“I think many patients in Western countries are underserved because apart from lactulose and rifaximin, there is little else to give them,” Dr. Bajaj said. “The assumption is because rifaximin kills everything, we shouldn’t give FMT. But here, we administered it to a harsh and hostile wasteland of microbiota, and it still got a toehold and generated a reduction in hepatic encephalopathy.”
He pointed out that in smaller prior studies, the effects lasted up to 1 year.
Setting the Stage for Phase 3 Trials
Dr. Bajaj noted that this phase 2 study sets the stage for larger phase 3 trials in patients not responding to first-line therapy.
“Given how well-tolerated and effective FMT appears to be in these patients, if the larger phase 3 trial shows similar results, I can imagine FMT becoming a standard therapy,” said Colleen R. Kelly, MD, AGAF, gastroenterologist at Brigham and Women’s Hospital and Harvard Medical School, Boston, who was not involved in the study.
This study was built on Dr. Bajaj’s prior work that established the safety of FMT by enema, she added, stressing that this new research was incredibly important in these immunocompromised patients who are at higher risk for infection transmission.
That the administration route doesn’t matter is also an important finding as oral administration is much more feasible than enema, said Dr. Kelly, who went on to point out the importance of finding an alternative to rifaximin and lactulose, which are often poorly tolerated.
The study highlights the central role played by the gut microbiota in dysbiosis in the pathophysiology of hepatic encephalopathy, Dr. Kelly said. “It is another exciting example of how gut microbiota can be manipulated to treat disease.”
Dr. Bajaj and Dr. Kelly report no relevant financial relationships to this study.
A version of this article appeared on Medscape.com.
MILAN — , results of a phase 2 randomized controlled trial show.
“Not only was FMT more beneficial, but also it didn’t matter which route of administration was used — oral or enema — which is good because people don’t really like enemas,” said Jasmohan S. Bajaj, MD, AGAF, professor, School of Medicine, Virginia Commonwealth University, Richmond, and hepatologist at Richmond VA Medical Center.
Donor background (including vegan or omnivore) and dose range also did not affect the efficacy of FMT, Dr. Bajaj said.
Dr. Bajaj presented the findings (Abstract GS-001) at the opening session of the annual European Association for the Study of the Liver (EASL) Congress 2024.
Hepatic encephalopathy is a complication of advanced liver disease that causes a dementia-like state. Standard treatment with lactulose and rifaximin often results in a lack of patient response, meaning the patient is constantly being readmitted to the hospital, Dr. Bajaj said.
“This is a burden for the family as well as the patients,” and is very difficult to manage from a clinical and psychosocial perspective, he said in an interview.
With FMT, “we are transferring an ecosystem of good microbes,” which modifies the gut microbiome in patients with advanced liver disease and reduces associated brain toxicity, Dr. Bajaj explained.
Resetting the Gut
The double-blind, randomized, placebo-controlled trial enrolled a total of 60 patients with cirrhosis who had experienced hepatic encephalopathy. Aged 61-65 years, participants had Model for End-Stage Liver Disease (MELD) scores of 12-13, all were taking lactulose and rifaximin, and all had experienced their last hepatic encephalopathy episode 8-13 months prior.
Participants had similar baseline cognition, Sickness Impact Profile (SIP), and cirrhosis severity. Those with recent infections, taking other antibiotics, with a MELD score > 22, had received a transplant, or were immunosuppressed were excluded.
Study participants were divided into four dose administration groups (n = 15 each): oral and enema active FMT therapy (group 1), oral active FMT and enema placebo (group 2), oral placebo and enema active FMT (group 3), and oral and enema placebo (group 4).
The range of FMT dose frequency was zero (all placebo), or one, two, or three FMT administrations, each given 1 month apart.
Two thirds of those receiving active FMT were given omnivore-donor FMT, and one third were given vegan-donor FMT, in addition to receiving standard of care.
“Colony-forming units were standard and the same whether given via oral capsule or enema,” Dr. Bajaj said. This is “similar to what we used in our phase 1 study.”
Intent-to-treat (ITT) analysis was performed with 6-month data. The primary outcomes were safety and hepatic encephalopathy recurrence defined as ≥ grade 2 on West-Haven criteria. Secondary outcomes included other adverse events, changes in infections, severity of cirrhosis and cognition, and patient-reported outcomes. A statistical regression for hepatic encephalopathy recurrence was also performed. Patients were followed for 6 months or until death.
One Dose of FMT Better Than None
Hepatic encephalopathy recurrence was highest (40%) in group 4 patients, compared with those in group 1 (13%), group 2 (13%), and group 3 (0%), as were liver-related hospitalizations (47% vs 7%-20%).
SIP total/physical and psych scores improved with FMT (P = .003).
When all patients were included in the analysis, the hepatic encephalopathy recurrence was related to dose number (odds radio [OR], 0.27; 95% CI, 0.10-0.79; P = .02), male sex (OR, 0.16; 95% CI, 0.03-0.89; P = .04), and physical SIP (OR, 1.05; 95% CI, 1.01-1.10, P = .05). However, when analyzing results from FMT recipients only, FMT dose, route of administration, and donor source were not found to affect recurrence.
Of those on placebo alone, six patients (40%) had a recurrence, compared with four on FMT (8.8%) in the combined FMT groups.
“As long as a patient received at least one FMT dose, they had a better response than a patient who had none,” Dr. Bajaj said.
Six patients dropped out; two in group 1 died after hepatic encephalopathy and falls, and one in group 2 died after a seizure. Three others did not return for follow-up visits. Four patients developed infections, including spontaneous bacterial peritonitis, cholecystitis, and cellulitis, all unrelated to FMT.
“I think many patients in Western countries are underserved because apart from lactulose and rifaximin, there is little else to give them,” Dr. Bajaj said. “The assumption is because rifaximin kills everything, we shouldn’t give FMT. But here, we administered it to a harsh and hostile wasteland of microbiota, and it still got a toehold and generated a reduction in hepatic encephalopathy.”
He pointed out that in smaller prior studies, the effects lasted up to 1 year.
Setting the Stage for Phase 3 Trials
Dr. Bajaj noted that this phase 2 study sets the stage for larger phase 3 trials in patients not responding to first-line therapy.
“Given how well-tolerated and effective FMT appears to be in these patients, if the larger phase 3 trial shows similar results, I can imagine FMT becoming a standard therapy,” said Colleen R. Kelly, MD, AGAF, gastroenterologist at Brigham and Women’s Hospital and Harvard Medical School, Boston, who was not involved in the study.
This study was built on Dr. Bajaj’s prior work that established the safety of FMT by enema, she added, stressing that this new research was incredibly important in these immunocompromised patients who are at higher risk for infection transmission.
That the administration route doesn’t matter is also an important finding as oral administration is much more feasible than enema, said Dr. Kelly, who went on to point out the importance of finding an alternative to rifaximin and lactulose, which are often poorly tolerated.
The study highlights the central role played by the gut microbiota in dysbiosis in the pathophysiology of hepatic encephalopathy, Dr. Kelly said. “It is another exciting example of how gut microbiota can be manipulated to treat disease.”
Dr. Bajaj and Dr. Kelly report no relevant financial relationships to this study.
A version of this article appeared on Medscape.com.
MILAN — , results of a phase 2 randomized controlled trial show.
“Not only was FMT more beneficial, but also it didn’t matter which route of administration was used — oral or enema — which is good because people don’t really like enemas,” said Jasmohan S. Bajaj, MD, AGAF, professor, School of Medicine, Virginia Commonwealth University, Richmond, and hepatologist at Richmond VA Medical Center.
Donor background (including vegan or omnivore) and dose range also did not affect the efficacy of FMT, Dr. Bajaj said.
Dr. Bajaj presented the findings (Abstract GS-001) at the opening session of the annual European Association for the Study of the Liver (EASL) Congress 2024.
Hepatic encephalopathy is a complication of advanced liver disease that causes a dementia-like state. Standard treatment with lactulose and rifaximin often results in a lack of patient response, meaning the patient is constantly being readmitted to the hospital, Dr. Bajaj said.
“This is a burden for the family as well as the patients,” and is very difficult to manage from a clinical and psychosocial perspective, he said in an interview.
With FMT, “we are transferring an ecosystem of good microbes,” which modifies the gut microbiome in patients with advanced liver disease and reduces associated brain toxicity, Dr. Bajaj explained.
Resetting the Gut
The double-blind, randomized, placebo-controlled trial enrolled a total of 60 patients with cirrhosis who had experienced hepatic encephalopathy. Aged 61-65 years, participants had Model for End-Stage Liver Disease (MELD) scores of 12-13, all were taking lactulose and rifaximin, and all had experienced their last hepatic encephalopathy episode 8-13 months prior.
Participants had similar baseline cognition, Sickness Impact Profile (SIP), and cirrhosis severity. Those with recent infections, taking other antibiotics, with a MELD score > 22, had received a transplant, or were immunosuppressed were excluded.
Study participants were divided into four dose administration groups (n = 15 each): oral and enema active FMT therapy (group 1), oral active FMT and enema placebo (group 2), oral placebo and enema active FMT (group 3), and oral and enema placebo (group 4).
The range of FMT dose frequency was zero (all placebo), or one, two, or three FMT administrations, each given 1 month apart.
Two thirds of those receiving active FMT were given omnivore-donor FMT, and one third were given vegan-donor FMT, in addition to receiving standard of care.
“Colony-forming units were standard and the same whether given via oral capsule or enema,” Dr. Bajaj said. This is “similar to what we used in our phase 1 study.”
Intent-to-treat (ITT) analysis was performed with 6-month data. The primary outcomes were safety and hepatic encephalopathy recurrence defined as ≥ grade 2 on West-Haven criteria. Secondary outcomes included other adverse events, changes in infections, severity of cirrhosis and cognition, and patient-reported outcomes. A statistical regression for hepatic encephalopathy recurrence was also performed. Patients were followed for 6 months or until death.
One Dose of FMT Better Than None
Hepatic encephalopathy recurrence was highest (40%) in group 4 patients, compared with those in group 1 (13%), group 2 (13%), and group 3 (0%), as were liver-related hospitalizations (47% vs 7%-20%).
SIP total/physical and psych scores improved with FMT (P = .003).
When all patients were included in the analysis, the hepatic encephalopathy recurrence was related to dose number (odds radio [OR], 0.27; 95% CI, 0.10-0.79; P = .02), male sex (OR, 0.16; 95% CI, 0.03-0.89; P = .04), and physical SIP (OR, 1.05; 95% CI, 1.01-1.10, P = .05). However, when analyzing results from FMT recipients only, FMT dose, route of administration, and donor source were not found to affect recurrence.
Of those on placebo alone, six patients (40%) had a recurrence, compared with four on FMT (8.8%) in the combined FMT groups.
“As long as a patient received at least one FMT dose, they had a better response than a patient who had none,” Dr. Bajaj said.
Six patients dropped out; two in group 1 died after hepatic encephalopathy and falls, and one in group 2 died after a seizure. Three others did not return for follow-up visits. Four patients developed infections, including spontaneous bacterial peritonitis, cholecystitis, and cellulitis, all unrelated to FMT.
“I think many patients in Western countries are underserved because apart from lactulose and rifaximin, there is little else to give them,” Dr. Bajaj said. “The assumption is because rifaximin kills everything, we shouldn’t give FMT. But here, we administered it to a harsh and hostile wasteland of microbiota, and it still got a toehold and generated a reduction in hepatic encephalopathy.”
He pointed out that in smaller prior studies, the effects lasted up to 1 year.
Setting the Stage for Phase 3 Trials
Dr. Bajaj noted that this phase 2 study sets the stage for larger phase 3 trials in patients not responding to first-line therapy.
“Given how well-tolerated and effective FMT appears to be in these patients, if the larger phase 3 trial shows similar results, I can imagine FMT becoming a standard therapy,” said Colleen R. Kelly, MD, AGAF, gastroenterologist at Brigham and Women’s Hospital and Harvard Medical School, Boston, who was not involved in the study.
This study was built on Dr. Bajaj’s prior work that established the safety of FMT by enema, she added, stressing that this new research was incredibly important in these immunocompromised patients who are at higher risk for infection transmission.
That the administration route doesn’t matter is also an important finding as oral administration is much more feasible than enema, said Dr. Kelly, who went on to point out the importance of finding an alternative to rifaximin and lactulose, which are often poorly tolerated.
The study highlights the central role played by the gut microbiota in dysbiosis in the pathophysiology of hepatic encephalopathy, Dr. Kelly said. “It is another exciting example of how gut microbiota can be manipulated to treat disease.”
Dr. Bajaj and Dr. Kelly report no relevant financial relationships to this study.
A version of this article appeared on Medscape.com.
FROM EASL 2024
Emerging Evidence Supports Dietary Management of MASLD Through Gut-Liver Axis
WASHINGTON — , according to a study presented at the annual Digestive Disease Week® (DDW).
For instance, patients with MASLD had lower intake of fiber and omega-3 fatty acids but higher consumption of added sugars and ultraprocessed foods, which correlated with the associated bacterial species and functional pathways.
“MASLD is an escalating concern globally, which highlights the need for innovative targets for disease prevention and management,” said lead author Georgina Williams, PhD, a postdoctoral researcher in diet and gastroenterology at the University of Newcastle, Australia.
“Therapeutic options often rely on lifestyle modifications, with a focus on weight loss,” she said. “Diet is considered a key component of disease management.”
Although calorie restriction with a 3%-5% fat loss is associated with hepatic benefits in MASLD, Dr. Williams noted, researchers have considered whole dietary patterns and the best fit for patients. Aspects of the Mediterranean diet may be effective, as reflected in recommendations from the American Association for the Study of Liver Disease (AASLD), which highlight dietary components such as limited carbohydrates and saturated fat, along with high fiber and unsaturated fats. The gut microbiome may be essential to consider as well, she said, given MASLD-associated differences in bile acid metabolism, inflammation, and ethanol production.
Dr. Williams and colleagues conducted a retrospective case-control study in an outpatient liver clinic to understand diet and dysbiosis in MASLD, looking at differences in diet, gut microbiota composition, and functional pathways in those with and without MASLD. The researchers investigated daily average intake, serum, and stool samples among 50 people (25 per group) matched for age and gender, comparing fibrosis-4, MASLD severity scores, macronutrients, micronutrients, food groups, metagenomic sequencing, and inflammatory markers such as interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, cytokeratin (CK)-18, and high-sensitivity C-reactive protein (hsCRP).
Dietary Characteristics
At baseline, the groups differed by ethnicity, prescription medication use, and body mass index (BMI), where the MASLD group had greater ethnic diversity, medication use, and BMI. In addition, the MASLD group had a zero to mild score of fibrosis.
Overall, energy intake didn’t differ significantly between the two groups. The control group had higher alcohol intake, likely since the MASLD group was recommended to reduce alcohol intake, though the difference was about 5 grams per day. The MASLD group also had less caffeine intake than the control group, as well as slightly lower protein intake, though the differences weren’t statistically significant.
While consumption of total carbohydrates didn’t differ significantly between the groups, participants with MASLD consumed more calories from carbohydrates than did the controls. The MASLD group consumed more calories from added and free sugars and didn’t meet recommendations for dietary fiber.
With particular food groups, participants with MASLD ate significantly fewer whole grains, red and orange fruits, and leafy green vegetables. When consuming fruit, those with MASLD were more likely to drink juice than eat whole fruit. These findings could be relevant when considering high sugar intake and low dietary fiber, Dr. Williams said.
With dietary fat, there were no differences in total fat between the groups, but the fat profiles differed. The control group was significantly more likely to consume omega-3 fatty acids, including alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). The MASLD group was less likely to consume seafood, nuts, seeds, avocado, and olive oil.
With inflammatory markers, hsCRP and CK-18 were increased in MASLD, while IL-1ß was increased in controls, which was consistently associated with higher alcohol intake among the control group. IL-6 and TNF-α didn’t differ between the groups.
Notably, dietary fats were most consistently associated with inflammatory markers, Dr. Williams said, with inflammation being positively associated with saturated fats and negatively associated with unsaturated fats.
Looking at microbiota, the alpha diversity was no different, but the beta diversity was across 162 taxa. Per bacterial species, there was an inverse relationship between MASLD and associations with unsaturated fat, as well as positive indicators of high sugar and fructose intake and low unsaturated fat and dietary fiber intake.
Beyond that, the functional pathways enriched in MASLD were associated with increased sugar and carbohydrates, reduced fiber, and reduced unsaturated fat. Lower butyrate production in MASLD was associated with low intake of nuts, seeds, and unsaturated fat.
In Clinical Practice
Dr. Williams suggested reinforcing AASLD guidelines and looking at diet quality, not just diet quantity. Although an energy deficit remains relevant in MASLD, macronutrient consumption matters across dietary fats, fibers, and sugars.
Future avenues for research include metabolomic pathways related to bile acids and fatty acids, she said, as well as disentangling metabolic syndrome from MASLD outcomes.
Session moderator Olivier Barbier, PhD, professor of pharmacy at Laval University in Quebec, Canada, asked about microbiome differences across countries. Dr. Williams noted the limitations in this study of looking at differences across geography and ethnicity, particularly in Australia, but said the species identified were consistent with those found in most literature globally.
In response to other questions after the presentation, Dr. Williams said supplements (such as omega-3 fatty acids) were included in total intake, and those taking prebiotics or probiotics were excluded from the study. In an upcoming clinical trial, she and colleagues plan to control for household microbiomes as well.
“The premise is that microbiomes are shared between households, so when you’re doing these sorts of large-scale clinical studies, if you’re going to look at the microbiome, then you should control for one of the major confounding variables,” said Mark Sundrud, PhD, professor of medicine at the Dartmouth Center for Digestive Health in Lebanon, New Hampshire. Dr. Sundrud, who wasn’t involved with this study, presented on the role of bile acids in mucosal immune cell function at DDW.
“We’ve done a collaborative study looking at microbiomes and bile acids in inflammatory bowel disease (IBD) patients versus controls,” which included consideration of households, he said. “We were able to see more intrinsic disease-specific changes.”
Dr. Williams declared no relevant disclosures. Dr. Sundrud has served as a scientific adviser to Sage Therapeutics.
WASHINGTON — , according to a study presented at the annual Digestive Disease Week® (DDW).
For instance, patients with MASLD had lower intake of fiber and omega-3 fatty acids but higher consumption of added sugars and ultraprocessed foods, which correlated with the associated bacterial species and functional pathways.
“MASLD is an escalating concern globally, which highlights the need for innovative targets for disease prevention and management,” said lead author Georgina Williams, PhD, a postdoctoral researcher in diet and gastroenterology at the University of Newcastle, Australia.
“Therapeutic options often rely on lifestyle modifications, with a focus on weight loss,” she said. “Diet is considered a key component of disease management.”
Although calorie restriction with a 3%-5% fat loss is associated with hepatic benefits in MASLD, Dr. Williams noted, researchers have considered whole dietary patterns and the best fit for patients. Aspects of the Mediterranean diet may be effective, as reflected in recommendations from the American Association for the Study of Liver Disease (AASLD), which highlight dietary components such as limited carbohydrates and saturated fat, along with high fiber and unsaturated fats. The gut microbiome may be essential to consider as well, she said, given MASLD-associated differences in bile acid metabolism, inflammation, and ethanol production.
Dr. Williams and colleagues conducted a retrospective case-control study in an outpatient liver clinic to understand diet and dysbiosis in MASLD, looking at differences in diet, gut microbiota composition, and functional pathways in those with and without MASLD. The researchers investigated daily average intake, serum, and stool samples among 50 people (25 per group) matched for age and gender, comparing fibrosis-4, MASLD severity scores, macronutrients, micronutrients, food groups, metagenomic sequencing, and inflammatory markers such as interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, cytokeratin (CK)-18, and high-sensitivity C-reactive protein (hsCRP).
Dietary Characteristics
At baseline, the groups differed by ethnicity, prescription medication use, and body mass index (BMI), where the MASLD group had greater ethnic diversity, medication use, and BMI. In addition, the MASLD group had a zero to mild score of fibrosis.
Overall, energy intake didn’t differ significantly between the two groups. The control group had higher alcohol intake, likely since the MASLD group was recommended to reduce alcohol intake, though the difference was about 5 grams per day. The MASLD group also had less caffeine intake than the control group, as well as slightly lower protein intake, though the differences weren’t statistically significant.
While consumption of total carbohydrates didn’t differ significantly between the groups, participants with MASLD consumed more calories from carbohydrates than did the controls. The MASLD group consumed more calories from added and free sugars and didn’t meet recommendations for dietary fiber.
With particular food groups, participants with MASLD ate significantly fewer whole grains, red and orange fruits, and leafy green vegetables. When consuming fruit, those with MASLD were more likely to drink juice than eat whole fruit. These findings could be relevant when considering high sugar intake and low dietary fiber, Dr. Williams said.
With dietary fat, there were no differences in total fat between the groups, but the fat profiles differed. The control group was significantly more likely to consume omega-3 fatty acids, including alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). The MASLD group was less likely to consume seafood, nuts, seeds, avocado, and olive oil.
With inflammatory markers, hsCRP and CK-18 were increased in MASLD, while IL-1ß was increased in controls, which was consistently associated with higher alcohol intake among the control group. IL-6 and TNF-α didn’t differ between the groups.
Notably, dietary fats were most consistently associated with inflammatory markers, Dr. Williams said, with inflammation being positively associated with saturated fats and negatively associated with unsaturated fats.
Looking at microbiota, the alpha diversity was no different, but the beta diversity was across 162 taxa. Per bacterial species, there was an inverse relationship between MASLD and associations with unsaturated fat, as well as positive indicators of high sugar and fructose intake and low unsaturated fat and dietary fiber intake.
Beyond that, the functional pathways enriched in MASLD were associated with increased sugar and carbohydrates, reduced fiber, and reduced unsaturated fat. Lower butyrate production in MASLD was associated with low intake of nuts, seeds, and unsaturated fat.
In Clinical Practice
Dr. Williams suggested reinforcing AASLD guidelines and looking at diet quality, not just diet quantity. Although an energy deficit remains relevant in MASLD, macronutrient consumption matters across dietary fats, fibers, and sugars.
Future avenues for research include metabolomic pathways related to bile acids and fatty acids, she said, as well as disentangling metabolic syndrome from MASLD outcomes.
Session moderator Olivier Barbier, PhD, professor of pharmacy at Laval University in Quebec, Canada, asked about microbiome differences across countries. Dr. Williams noted the limitations in this study of looking at differences across geography and ethnicity, particularly in Australia, but said the species identified were consistent with those found in most literature globally.
In response to other questions after the presentation, Dr. Williams said supplements (such as omega-3 fatty acids) were included in total intake, and those taking prebiotics or probiotics were excluded from the study. In an upcoming clinical trial, she and colleagues plan to control for household microbiomes as well.
“The premise is that microbiomes are shared between households, so when you’re doing these sorts of large-scale clinical studies, if you’re going to look at the microbiome, then you should control for one of the major confounding variables,” said Mark Sundrud, PhD, professor of medicine at the Dartmouth Center for Digestive Health in Lebanon, New Hampshire. Dr. Sundrud, who wasn’t involved with this study, presented on the role of bile acids in mucosal immune cell function at DDW.
“We’ve done a collaborative study looking at microbiomes and bile acids in inflammatory bowel disease (IBD) patients versus controls,” which included consideration of households, he said. “We were able to see more intrinsic disease-specific changes.”
Dr. Williams declared no relevant disclosures. Dr. Sundrud has served as a scientific adviser to Sage Therapeutics.
WASHINGTON — , according to a study presented at the annual Digestive Disease Week® (DDW).
For instance, patients with MASLD had lower intake of fiber and omega-3 fatty acids but higher consumption of added sugars and ultraprocessed foods, which correlated with the associated bacterial species and functional pathways.
“MASLD is an escalating concern globally, which highlights the need for innovative targets for disease prevention and management,” said lead author Georgina Williams, PhD, a postdoctoral researcher in diet and gastroenterology at the University of Newcastle, Australia.
“Therapeutic options often rely on lifestyle modifications, with a focus on weight loss,” she said. “Diet is considered a key component of disease management.”
Although calorie restriction with a 3%-5% fat loss is associated with hepatic benefits in MASLD, Dr. Williams noted, researchers have considered whole dietary patterns and the best fit for patients. Aspects of the Mediterranean diet may be effective, as reflected in recommendations from the American Association for the Study of Liver Disease (AASLD), which highlight dietary components such as limited carbohydrates and saturated fat, along with high fiber and unsaturated fats. The gut microbiome may be essential to consider as well, she said, given MASLD-associated differences in bile acid metabolism, inflammation, and ethanol production.
Dr. Williams and colleagues conducted a retrospective case-control study in an outpatient liver clinic to understand diet and dysbiosis in MASLD, looking at differences in diet, gut microbiota composition, and functional pathways in those with and without MASLD. The researchers investigated daily average intake, serum, and stool samples among 50 people (25 per group) matched for age and gender, comparing fibrosis-4, MASLD severity scores, macronutrients, micronutrients, food groups, metagenomic sequencing, and inflammatory markers such as interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, cytokeratin (CK)-18, and high-sensitivity C-reactive protein (hsCRP).
Dietary Characteristics
At baseline, the groups differed by ethnicity, prescription medication use, and body mass index (BMI), where the MASLD group had greater ethnic diversity, medication use, and BMI. In addition, the MASLD group had a zero to mild score of fibrosis.
Overall, energy intake didn’t differ significantly between the two groups. The control group had higher alcohol intake, likely since the MASLD group was recommended to reduce alcohol intake, though the difference was about 5 grams per day. The MASLD group also had less caffeine intake than the control group, as well as slightly lower protein intake, though the differences weren’t statistically significant.
While consumption of total carbohydrates didn’t differ significantly between the groups, participants with MASLD consumed more calories from carbohydrates than did the controls. The MASLD group consumed more calories from added and free sugars and didn’t meet recommendations for dietary fiber.
With particular food groups, participants with MASLD ate significantly fewer whole grains, red and orange fruits, and leafy green vegetables. When consuming fruit, those with MASLD were more likely to drink juice than eat whole fruit. These findings could be relevant when considering high sugar intake and low dietary fiber, Dr. Williams said.
With dietary fat, there were no differences in total fat between the groups, but the fat profiles differed. The control group was significantly more likely to consume omega-3 fatty acids, including alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). The MASLD group was less likely to consume seafood, nuts, seeds, avocado, and olive oil.
With inflammatory markers, hsCRP and CK-18 were increased in MASLD, while IL-1ß was increased in controls, which was consistently associated with higher alcohol intake among the control group. IL-6 and TNF-α didn’t differ between the groups.
Notably, dietary fats were most consistently associated with inflammatory markers, Dr. Williams said, with inflammation being positively associated with saturated fats and negatively associated with unsaturated fats.
Looking at microbiota, the alpha diversity was no different, but the beta diversity was across 162 taxa. Per bacterial species, there was an inverse relationship between MASLD and associations with unsaturated fat, as well as positive indicators of high sugar and fructose intake and low unsaturated fat and dietary fiber intake.
Beyond that, the functional pathways enriched in MASLD were associated with increased sugar and carbohydrates, reduced fiber, and reduced unsaturated fat. Lower butyrate production in MASLD was associated with low intake of nuts, seeds, and unsaturated fat.
In Clinical Practice
Dr. Williams suggested reinforcing AASLD guidelines and looking at diet quality, not just diet quantity. Although an energy deficit remains relevant in MASLD, macronutrient consumption matters across dietary fats, fibers, and sugars.
Future avenues for research include metabolomic pathways related to bile acids and fatty acids, she said, as well as disentangling metabolic syndrome from MASLD outcomes.
Session moderator Olivier Barbier, PhD, professor of pharmacy at Laval University in Quebec, Canada, asked about microbiome differences across countries. Dr. Williams noted the limitations in this study of looking at differences across geography and ethnicity, particularly in Australia, but said the species identified were consistent with those found in most literature globally.
In response to other questions after the presentation, Dr. Williams said supplements (such as omega-3 fatty acids) were included in total intake, and those taking prebiotics or probiotics were excluded from the study. In an upcoming clinical trial, she and colleagues plan to control for household microbiomes as well.
“The premise is that microbiomes are shared between households, so when you’re doing these sorts of large-scale clinical studies, if you’re going to look at the microbiome, then you should control for one of the major confounding variables,” said Mark Sundrud, PhD, professor of medicine at the Dartmouth Center for Digestive Health in Lebanon, New Hampshire. Dr. Sundrud, who wasn’t involved with this study, presented on the role of bile acids in mucosal immune cell function at DDW.
“We’ve done a collaborative study looking at microbiomes and bile acids in inflammatory bowel disease (IBD) patients versus controls,” which included consideration of households, he said. “We were able to see more intrinsic disease-specific changes.”
Dr. Williams declared no relevant disclosures. Dr. Sundrud has served as a scientific adviser to Sage Therapeutics.
FROM DDW 2024
New Gel Makes Alcohol 50% Less Toxic, Curbs Organ Damage
It sounds like a gimmick. Drink a couple glasses of wine and feel only half as intoxicated as you normally would — and sustain less damage to your liver and other organs.
But that’s the promise of a new gel, developed by researchers in Switzerland, that changes how the body processes alcohol. The gel has been tested in mice so far, but the researchers hope to make it available to people soon. The goal: To protect people from alcohol-related accidents and chronic disease — responsible for more than three million annual deaths worldwide.
“It is a global, urgent issue,” said study coauthor Raffaele Mezzenga, PhD, a professor at ETH Zürich, Switzerland.
The advance builds on a decades-long quest among scientists to reduce the toxicity of alcohol, said Che-Hong Chen, PhD, a molecular biologist at Stanford School of Medicine, Stanford, California, who was not involved in the study. Some probiotic-based products aim to help process alcohol’s toxic byproduct acetaldehyde in the gut, but their effects seem inconsistent from one person to another, Dr. Chen said. Intravenous infusions of natural enzyme complexes, such as those that mimic liver cells to speed up alcohol metabolism, can actually produce some acetaldehyde, mitigating their detoxifying effects.
“Our method has the potential to fill the gap of most of the approaches being explored,” Dr. Mezzenga said. “We hope and plan to move to clinical studies as soon as possible.”
Usually, the liver processes alcohol, causing the release of toxic acetaldehyde followed by less harmful acetic acid. Acetaldehyde can cause DNA damage, oxidative stress, and vascular inflammation. Too much acetaldehyde can increase the risk for cancer.
“The concentration of acetaldehyde will be decreased by a factor of more than two and so will the ‘intoxicating’ effect of the alcohol,” said Dr. Mezzenga.
Ideally, someone would ingest the gel immediately before or when consuming alcohol. It’s designed to continue working for several hours.
Some of the mice received one serving of alcohol, while others were served regularly for 10 days. The gel slashed their blood alcohol level by 40% after half an hour and by up to 56% after 5 hours compared with a control group given alcohol but not the gel. Mice that consumed the gel also had less liver and intestinal damage.
“The results, both the short-term behavior of the mice and in the long term for the preservation of organs, were way beyond our expectation,” said Dr. Mezzenga.
Casual drinkers could benefit from the gel. However, the gel could also lead people to consume more alcohol than they would normally to feel intoxicated, Dr. Chen said.
Bypassing a Problematic Pathway
A liver enzyme called alcohol dehydrogenase (ADH) converts alcohol to acetaldehyde before a second enzyme called aldehyde dehydrogenase (ALDH2) helps process acetaldehyde into acetic acid. But with the gel, alcohol transforms directly to acetic acid in the digestive tract.
“This chemical reaction seems to bypass the known biological pathway of alcohol metabolism. That’s new to me,” said Dr. Chen, a senior research scientist at Stanford and country director at the Center for Asian Health Research and Education Center. The processing of alcohol before it passes through the mucous membrane of the digestive tract is “another novel aspect,”Dr. Chen said.
To make the gel, the researchers boil whey proteins — also found in milk — to produce stringy fibrils. Next, they add salt and water to cause the fibrils to crosslink, forming a gel. The gel gets infused with iron atoms, which catalyze the conversion of alcohol into acetic acid. That conversion relies on hydrogen peroxide, the byproduct of a reaction between gold and glucose, both of which are also added to the gel.
A previous version of the technology used iron nanoparticles, which needed to be “digested down to ionic form by the acidic pH in the stomach,” said Dr. Mezzenga. That process took too long, giving alcohol more time to cross into the bloodstream. By “decorating” the protein fibrils with single iron atoms, the researchers were able to “increase their catalytic efficiency,” he added.
What’s Next?
With animal studies completed, human clinical studies are next. How soon that could happen will depend on ethical clearance and financial support, the researchers said.
An “interesting next step,” said Dr. Chen, would be to give the gel to mice with a genetic mutation in ALDH2. The mutation makes it harder to process acetaldehyde, often causing facial redness. Prevalent among East Asian populations, the mutation affects about 560 million people and has been linked to Alzheimer’s disease. Dr. Chen’s lab found a chemical compound that can increase the activity of ADH2, which is expected to begin phase 2 clinical trials this year.
A version of this article appeared on Medscape.com.
It sounds like a gimmick. Drink a couple glasses of wine and feel only half as intoxicated as you normally would — and sustain less damage to your liver and other organs.
But that’s the promise of a new gel, developed by researchers in Switzerland, that changes how the body processes alcohol. The gel has been tested in mice so far, but the researchers hope to make it available to people soon. The goal: To protect people from alcohol-related accidents and chronic disease — responsible for more than three million annual deaths worldwide.
“It is a global, urgent issue,” said study coauthor Raffaele Mezzenga, PhD, a professor at ETH Zürich, Switzerland.
The advance builds on a decades-long quest among scientists to reduce the toxicity of alcohol, said Che-Hong Chen, PhD, a molecular biologist at Stanford School of Medicine, Stanford, California, who was not involved in the study. Some probiotic-based products aim to help process alcohol’s toxic byproduct acetaldehyde in the gut, but their effects seem inconsistent from one person to another, Dr. Chen said. Intravenous infusions of natural enzyme complexes, such as those that mimic liver cells to speed up alcohol metabolism, can actually produce some acetaldehyde, mitigating their detoxifying effects.
“Our method has the potential to fill the gap of most of the approaches being explored,” Dr. Mezzenga said. “We hope and plan to move to clinical studies as soon as possible.”
Usually, the liver processes alcohol, causing the release of toxic acetaldehyde followed by less harmful acetic acid. Acetaldehyde can cause DNA damage, oxidative stress, and vascular inflammation. Too much acetaldehyde can increase the risk for cancer.
“The concentration of acetaldehyde will be decreased by a factor of more than two and so will the ‘intoxicating’ effect of the alcohol,” said Dr. Mezzenga.
Ideally, someone would ingest the gel immediately before or when consuming alcohol. It’s designed to continue working for several hours.
Some of the mice received one serving of alcohol, while others were served regularly for 10 days. The gel slashed their blood alcohol level by 40% after half an hour and by up to 56% after 5 hours compared with a control group given alcohol but not the gel. Mice that consumed the gel also had less liver and intestinal damage.
“The results, both the short-term behavior of the mice and in the long term for the preservation of organs, were way beyond our expectation,” said Dr. Mezzenga.
Casual drinkers could benefit from the gel. However, the gel could also lead people to consume more alcohol than they would normally to feel intoxicated, Dr. Chen said.
Bypassing a Problematic Pathway
A liver enzyme called alcohol dehydrogenase (ADH) converts alcohol to acetaldehyde before a second enzyme called aldehyde dehydrogenase (ALDH2) helps process acetaldehyde into acetic acid. But with the gel, alcohol transforms directly to acetic acid in the digestive tract.
“This chemical reaction seems to bypass the known biological pathway of alcohol metabolism. That’s new to me,” said Dr. Chen, a senior research scientist at Stanford and country director at the Center for Asian Health Research and Education Center. The processing of alcohol before it passes through the mucous membrane of the digestive tract is “another novel aspect,”Dr. Chen said.
To make the gel, the researchers boil whey proteins — also found in milk — to produce stringy fibrils. Next, they add salt and water to cause the fibrils to crosslink, forming a gel. The gel gets infused with iron atoms, which catalyze the conversion of alcohol into acetic acid. That conversion relies on hydrogen peroxide, the byproduct of a reaction between gold and glucose, both of which are also added to the gel.
A previous version of the technology used iron nanoparticles, which needed to be “digested down to ionic form by the acidic pH in the stomach,” said Dr. Mezzenga. That process took too long, giving alcohol more time to cross into the bloodstream. By “decorating” the protein fibrils with single iron atoms, the researchers were able to “increase their catalytic efficiency,” he added.
What’s Next?
With animal studies completed, human clinical studies are next. How soon that could happen will depend on ethical clearance and financial support, the researchers said.
An “interesting next step,” said Dr. Chen, would be to give the gel to mice with a genetic mutation in ALDH2. The mutation makes it harder to process acetaldehyde, often causing facial redness. Prevalent among East Asian populations, the mutation affects about 560 million people and has been linked to Alzheimer’s disease. Dr. Chen’s lab found a chemical compound that can increase the activity of ADH2, which is expected to begin phase 2 clinical trials this year.
A version of this article appeared on Medscape.com.
It sounds like a gimmick. Drink a couple glasses of wine and feel only half as intoxicated as you normally would — and sustain less damage to your liver and other organs.
But that’s the promise of a new gel, developed by researchers in Switzerland, that changes how the body processes alcohol. The gel has been tested in mice so far, but the researchers hope to make it available to people soon. The goal: To protect people from alcohol-related accidents and chronic disease — responsible for more than three million annual deaths worldwide.
“It is a global, urgent issue,” said study coauthor Raffaele Mezzenga, PhD, a professor at ETH Zürich, Switzerland.
The advance builds on a decades-long quest among scientists to reduce the toxicity of alcohol, said Che-Hong Chen, PhD, a molecular biologist at Stanford School of Medicine, Stanford, California, who was not involved in the study. Some probiotic-based products aim to help process alcohol’s toxic byproduct acetaldehyde in the gut, but their effects seem inconsistent from one person to another, Dr. Chen said. Intravenous infusions of natural enzyme complexes, such as those that mimic liver cells to speed up alcohol metabolism, can actually produce some acetaldehyde, mitigating their detoxifying effects.
“Our method has the potential to fill the gap of most of the approaches being explored,” Dr. Mezzenga said. “We hope and plan to move to clinical studies as soon as possible.”
Usually, the liver processes alcohol, causing the release of toxic acetaldehyde followed by less harmful acetic acid. Acetaldehyde can cause DNA damage, oxidative stress, and vascular inflammation. Too much acetaldehyde can increase the risk for cancer.
“The concentration of acetaldehyde will be decreased by a factor of more than two and so will the ‘intoxicating’ effect of the alcohol,” said Dr. Mezzenga.
Ideally, someone would ingest the gel immediately before or when consuming alcohol. It’s designed to continue working for several hours.
Some of the mice received one serving of alcohol, while others were served regularly for 10 days. The gel slashed their blood alcohol level by 40% after half an hour and by up to 56% after 5 hours compared with a control group given alcohol but not the gel. Mice that consumed the gel also had less liver and intestinal damage.
“The results, both the short-term behavior of the mice and in the long term for the preservation of organs, were way beyond our expectation,” said Dr. Mezzenga.
Casual drinkers could benefit from the gel. However, the gel could also lead people to consume more alcohol than they would normally to feel intoxicated, Dr. Chen said.
Bypassing a Problematic Pathway
A liver enzyme called alcohol dehydrogenase (ADH) converts alcohol to acetaldehyde before a second enzyme called aldehyde dehydrogenase (ALDH2) helps process acetaldehyde into acetic acid. But with the gel, alcohol transforms directly to acetic acid in the digestive tract.
“This chemical reaction seems to bypass the known biological pathway of alcohol metabolism. That’s new to me,” said Dr. Chen, a senior research scientist at Stanford and country director at the Center for Asian Health Research and Education Center. The processing of alcohol before it passes through the mucous membrane of the digestive tract is “another novel aspect,”Dr. Chen said.
To make the gel, the researchers boil whey proteins — also found in milk — to produce stringy fibrils. Next, they add salt and water to cause the fibrils to crosslink, forming a gel. The gel gets infused with iron atoms, which catalyze the conversion of alcohol into acetic acid. That conversion relies on hydrogen peroxide, the byproduct of a reaction between gold and glucose, both of which are also added to the gel.
A previous version of the technology used iron nanoparticles, which needed to be “digested down to ionic form by the acidic pH in the stomach,” said Dr. Mezzenga. That process took too long, giving alcohol more time to cross into the bloodstream. By “decorating” the protein fibrils with single iron atoms, the researchers were able to “increase their catalytic efficiency,” he added.
What’s Next?
With animal studies completed, human clinical studies are next. How soon that could happen will depend on ethical clearance and financial support, the researchers said.
An “interesting next step,” said Dr. Chen, would be to give the gel to mice with a genetic mutation in ALDH2. The mutation makes it harder to process acetaldehyde, often causing facial redness. Prevalent among East Asian populations, the mutation affects about 560 million people and has been linked to Alzheimer’s disease. Dr. Chen’s lab found a chemical compound that can increase the activity of ADH2, which is expected to begin phase 2 clinical trials this year.
A version of this article appeared on Medscape.com.
A Single Meatless Meal Can Benefit Patients With Cirrhosis
Replacing meat with plant-based proteins for just one meal reduced ammonia levels in patients with cirrhosis, a proof-of-concept study showed.
, according to Jasmohan Bajaj, MD, a gastroenterologist at Virginia Commonwealth University School of Medicine and the Richmond VA Medical Center, Richmond, Virginia, and colleagues.
However, changing from meat-based to non–meat-based meals is difficult to do over a long period.
“Previous studies have changed people’s diets completely, expecting them to be on a meatless or vegetarian diet with a similar amount of protein when they’ve been eating meat their entire life,” Dr. Bajaj told this news organization. “That’s not really sustainable in the long run.”
“Our hope is that occasional meal substitutions would be beneficial,” he said. “This study is a first step toward seeing if that works.”
The study was published online on May 2 in Clinical and Translational Gastroenterology.
Meal Type Affects Ammonia Levels Differently
The researchers randomized 30 men with cirrhosis and on a traditional Western meat-based diet into three groups, where they received a pork/beef burger, a vegetarian bean burger, or a burger made of vegan meat substitute. The burgers provided 20 g of protein each, and all meals contained low-fat potato chips, a whole-grain bun, water, and no condiments.
The participants’ median age was 66 years in the meat and vegetarian arms and 71 years in the vegan arm. About half had diabetes, and half had prior HE and were evenly distributed across the treatment arms. Cirrhosis etiologies included hepatitis C virus infection, alcohol, and metabolic-associated steatohepatitis.
Stool microbiome characteristics, changes in ammonia, and metabolomics were compared between and within groups.
In the 3 days prior to the intervention, participants had similar intakes of red meat, poultry, fish, eggs, bread, cheese, rice, fruits, vegetables, yogurt, coffee, tea, and carbonated caffeinated and decaffeinated beverages.
Blood for metabolomics and ammonia was drawn at baseline and hourly for 3 hours post-meal while patients were under observation. All participants completed the entire meal, as shown subsequently by markers of food consumption, and none developed HE symptoms during the observation period.
The composition of the stool microbiome was similar at baseline across groups and remained unchanged. However, serum ammonia increased from baseline in the meat group but not in the vegetarian or vegan groups. The serum microbiome was not analyzed because of the low yield.
Serum metabolomics showed beneficial changes over time associated with branched-chain amino acid metabolism and urea cycle, phospholipid, and acylcarnitine levels in the vegetarian and vegan meal groups compared with the meat-based group.
In contrast, alterations in lipid profiles (higher sphingomyelins and lower lysophospholipids) were seen in the meat group.
The study was limited by its relatively small sample size, focus on the impact of only one meal, and lack of clinical outcomes, sarcopenia assessment, cognitive testing, or urine collection.
“Intermittent meat substitution with vegan or vegetarian alternatives could be helpful in reducing ammonia generation in cirrhosis,” the authors concluded.
The next step “is to substitute one meal two or three times a week, so we can move forward with this analysis and eventually be able to show that the liver is in better shape,” Dr. Bajaj said.
Meanwhile, clinicians should encourage patients with liver disease who eat meat regularly to try to substitute it with protein from plant or dairy sources, at least occasionally, he said. When doing so, “clinicians should ask their patients’ preferences before assuming that they will do everything that you ask them to do because nutrition in cirrhosis is really critical — not only what they eat but also when they eat. Working with a dietitian, like we did in our study, is critical, or at least having access to one if you don’t have one in your practice.”
Positive Results From a Simple Change
Commenting on the study, Nancy S. Reau, MD, section chief, hepatology and associate director of organ transplantation at Rush Medical College in Chicago, said, “My biggest concern is making sure patients are ingesting enough quality protein and calories because anorexia is a common complication in cirrhosis, and sarcopenia is associated with poor outcomes.
“You don’t want to suggest a change that will result in eating less or skipping a meal,” she said. So, “it is encouraging to see that suggesting a small change, just one meal a day, that may not impact calorie intake could have positive results.”
Dr. Reau added that “it is great to see evidence that this small change also could be a way of decreasing the risk of HE while not compromising on patient nutrition.”
Larger studies with outcome data showing that this approach could prevent readmission in patients hospitalized for HE would be helpful, she said.
The study was partly supported by the ACG Clinical Research Award, VA Merit Review 2I01CX001076, I01CX002472, and NIAAA RO1AA29398. Dr. Bajaj and Dr. Reau reported no conflicts of interest.
A version of this article appeared on Medscape.com.
Replacing meat with plant-based proteins for just one meal reduced ammonia levels in patients with cirrhosis, a proof-of-concept study showed.
, according to Jasmohan Bajaj, MD, a gastroenterologist at Virginia Commonwealth University School of Medicine and the Richmond VA Medical Center, Richmond, Virginia, and colleagues.
However, changing from meat-based to non–meat-based meals is difficult to do over a long period.
“Previous studies have changed people’s diets completely, expecting them to be on a meatless or vegetarian diet with a similar amount of protein when they’ve been eating meat their entire life,” Dr. Bajaj told this news organization. “That’s not really sustainable in the long run.”
“Our hope is that occasional meal substitutions would be beneficial,” he said. “This study is a first step toward seeing if that works.”
The study was published online on May 2 in Clinical and Translational Gastroenterology.
Meal Type Affects Ammonia Levels Differently
The researchers randomized 30 men with cirrhosis and on a traditional Western meat-based diet into three groups, where they received a pork/beef burger, a vegetarian bean burger, or a burger made of vegan meat substitute. The burgers provided 20 g of protein each, and all meals contained low-fat potato chips, a whole-grain bun, water, and no condiments.
The participants’ median age was 66 years in the meat and vegetarian arms and 71 years in the vegan arm. About half had diabetes, and half had prior HE and were evenly distributed across the treatment arms. Cirrhosis etiologies included hepatitis C virus infection, alcohol, and metabolic-associated steatohepatitis.
Stool microbiome characteristics, changes in ammonia, and metabolomics were compared between and within groups.
In the 3 days prior to the intervention, participants had similar intakes of red meat, poultry, fish, eggs, bread, cheese, rice, fruits, vegetables, yogurt, coffee, tea, and carbonated caffeinated and decaffeinated beverages.
Blood for metabolomics and ammonia was drawn at baseline and hourly for 3 hours post-meal while patients were under observation. All participants completed the entire meal, as shown subsequently by markers of food consumption, and none developed HE symptoms during the observation period.
The composition of the stool microbiome was similar at baseline across groups and remained unchanged. However, serum ammonia increased from baseline in the meat group but not in the vegetarian or vegan groups. The serum microbiome was not analyzed because of the low yield.
Serum metabolomics showed beneficial changes over time associated with branched-chain amino acid metabolism and urea cycle, phospholipid, and acylcarnitine levels in the vegetarian and vegan meal groups compared with the meat-based group.
In contrast, alterations in lipid profiles (higher sphingomyelins and lower lysophospholipids) were seen in the meat group.
The study was limited by its relatively small sample size, focus on the impact of only one meal, and lack of clinical outcomes, sarcopenia assessment, cognitive testing, or urine collection.
“Intermittent meat substitution with vegan or vegetarian alternatives could be helpful in reducing ammonia generation in cirrhosis,” the authors concluded.
The next step “is to substitute one meal two or three times a week, so we can move forward with this analysis and eventually be able to show that the liver is in better shape,” Dr. Bajaj said.
Meanwhile, clinicians should encourage patients with liver disease who eat meat regularly to try to substitute it with protein from plant or dairy sources, at least occasionally, he said. When doing so, “clinicians should ask their patients’ preferences before assuming that they will do everything that you ask them to do because nutrition in cirrhosis is really critical — not only what they eat but also when they eat. Working with a dietitian, like we did in our study, is critical, or at least having access to one if you don’t have one in your practice.”
Positive Results From a Simple Change
Commenting on the study, Nancy S. Reau, MD, section chief, hepatology and associate director of organ transplantation at Rush Medical College in Chicago, said, “My biggest concern is making sure patients are ingesting enough quality protein and calories because anorexia is a common complication in cirrhosis, and sarcopenia is associated with poor outcomes.
“You don’t want to suggest a change that will result in eating less or skipping a meal,” she said. So, “it is encouraging to see that suggesting a small change, just one meal a day, that may not impact calorie intake could have positive results.”
Dr. Reau added that “it is great to see evidence that this small change also could be a way of decreasing the risk of HE while not compromising on patient nutrition.”
Larger studies with outcome data showing that this approach could prevent readmission in patients hospitalized for HE would be helpful, she said.
The study was partly supported by the ACG Clinical Research Award, VA Merit Review 2I01CX001076, I01CX002472, and NIAAA RO1AA29398. Dr. Bajaj and Dr. Reau reported no conflicts of interest.
A version of this article appeared on Medscape.com.
Replacing meat with plant-based proteins for just one meal reduced ammonia levels in patients with cirrhosis, a proof-of-concept study showed.
, according to Jasmohan Bajaj, MD, a gastroenterologist at Virginia Commonwealth University School of Medicine and the Richmond VA Medical Center, Richmond, Virginia, and colleagues.
However, changing from meat-based to non–meat-based meals is difficult to do over a long period.
“Previous studies have changed people’s diets completely, expecting them to be on a meatless or vegetarian diet with a similar amount of protein when they’ve been eating meat their entire life,” Dr. Bajaj told this news organization. “That’s not really sustainable in the long run.”
“Our hope is that occasional meal substitutions would be beneficial,” he said. “This study is a first step toward seeing if that works.”
The study was published online on May 2 in Clinical and Translational Gastroenterology.
Meal Type Affects Ammonia Levels Differently
The researchers randomized 30 men with cirrhosis and on a traditional Western meat-based diet into three groups, where they received a pork/beef burger, a vegetarian bean burger, or a burger made of vegan meat substitute. The burgers provided 20 g of protein each, and all meals contained low-fat potato chips, a whole-grain bun, water, and no condiments.
The participants’ median age was 66 years in the meat and vegetarian arms and 71 years in the vegan arm. About half had diabetes, and half had prior HE and were evenly distributed across the treatment arms. Cirrhosis etiologies included hepatitis C virus infection, alcohol, and metabolic-associated steatohepatitis.
Stool microbiome characteristics, changes in ammonia, and metabolomics were compared between and within groups.
In the 3 days prior to the intervention, participants had similar intakes of red meat, poultry, fish, eggs, bread, cheese, rice, fruits, vegetables, yogurt, coffee, tea, and carbonated caffeinated and decaffeinated beverages.
Blood for metabolomics and ammonia was drawn at baseline and hourly for 3 hours post-meal while patients were under observation. All participants completed the entire meal, as shown subsequently by markers of food consumption, and none developed HE symptoms during the observation period.
The composition of the stool microbiome was similar at baseline across groups and remained unchanged. However, serum ammonia increased from baseline in the meat group but not in the vegetarian or vegan groups. The serum microbiome was not analyzed because of the low yield.
Serum metabolomics showed beneficial changes over time associated with branched-chain amino acid metabolism and urea cycle, phospholipid, and acylcarnitine levels in the vegetarian and vegan meal groups compared with the meat-based group.
In contrast, alterations in lipid profiles (higher sphingomyelins and lower lysophospholipids) were seen in the meat group.
The study was limited by its relatively small sample size, focus on the impact of only one meal, and lack of clinical outcomes, sarcopenia assessment, cognitive testing, or urine collection.
“Intermittent meat substitution with vegan or vegetarian alternatives could be helpful in reducing ammonia generation in cirrhosis,” the authors concluded.
The next step “is to substitute one meal two or three times a week, so we can move forward with this analysis and eventually be able to show that the liver is in better shape,” Dr. Bajaj said.
Meanwhile, clinicians should encourage patients with liver disease who eat meat regularly to try to substitute it with protein from plant or dairy sources, at least occasionally, he said. When doing so, “clinicians should ask their patients’ preferences before assuming that they will do everything that you ask them to do because nutrition in cirrhosis is really critical — not only what they eat but also when they eat. Working with a dietitian, like we did in our study, is critical, or at least having access to one if you don’t have one in your practice.”
Positive Results From a Simple Change
Commenting on the study, Nancy S. Reau, MD, section chief, hepatology and associate director of organ transplantation at Rush Medical College in Chicago, said, “My biggest concern is making sure patients are ingesting enough quality protein and calories because anorexia is a common complication in cirrhosis, and sarcopenia is associated with poor outcomes.
“You don’t want to suggest a change that will result in eating less or skipping a meal,” she said. So, “it is encouraging to see that suggesting a small change, just one meal a day, that may not impact calorie intake could have positive results.”
Dr. Reau added that “it is great to see evidence that this small change also could be a way of decreasing the risk of HE while not compromising on patient nutrition.”
Larger studies with outcome data showing that this approach could prevent readmission in patients hospitalized for HE would be helpful, she said.
The study was partly supported by the ACG Clinical Research Award, VA Merit Review 2I01CX001076, I01CX002472, and NIAAA RO1AA29398. Dr. Bajaj and Dr. Reau reported no conflicts of interest.
A version of this article appeared on Medscape.com.
New Contraindications to Coadministration of Atazanavir
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) this week recommended new contraindications on the coadministration of the protease inhibitor atazanavir (Reyataz, Bristol-Myers Squibb) with antineoplastic agents encorafenib and ivosidenib (atazanavir may significantly increase blood levels and thus side effects), and with the anticonvulsants carbamazepine, phenobarbital, and phenytoin (which may decrease serum levels of atazanavir).
The new rules alter sections 4.3 and 4.5 of the summary of product characteristics (SmPC) to reclassify drug–drug interactions with the new contraindications.
Atazanavir is an orally administered drug, used in combination with low-dose ritonavir (Norvir) to boost its pharmacokinetics. It is indicated for the treatment of HIV-1 infected adults and pediatric patients 3 months of age and older in combination with other antiretroviral medicinal products. A combination preparation boosted with cobicistat (Evotaz) is also available.
The drug is an azapeptide HIV-1 protease inhibitor (PI) that selectively inhibits the virus-specific processing of viral Gag-Pol proteins in HIV-1 infected cells, thus preventing formation of mature virions and infection of other cells. This prevents the virus from multiplying and slows the spread of infection. Based on available virological and clinical data from adult patients, no benefit is expected in patients with HIV strains resistant to multiple protease inhibitors (four or more PI mutations).
Therapy with atazanavir is intended to be initiated by a physician experienced in the management of HIV infection, with the choice of atazanavir in treatment-experienced adult and pediatric patients based on individual viral resistance testing and the patient’s treatment history. The standard dose is 300 mg atazanavir taken with 100 mg ritonavir once daily with food.
Atazanavir is already contraindicated in combination or coadministration with a wide variety of other agents:
- Coadministration with simvastatin or lovastatin [statins – risk of increased blood levels with atazanavir].
- Combination with the anti-TB antibiotic rifampicin.
- Combination with the PDE5 inhibitor sildenafil when used for the treatment of pulmonary arterial hypertension only.
- Coadministration with substrates of the CYP3A4 isoform of cytochrome P450 that have narrow therapeutic windows (eg, quetiapine, lurasidone, alfuzosin, astemizole, terfenadine, cisapride, pimozide, quinidine, bepridil, triazolam, oral midazolam, lomitapide, and ergot alkaloids).
- Coadministration with grazoprevir-containing products, including elbasvir/grazoprevir fixed dose combination (hepatitis C drug combination; atazanavir increases its blood levels).
- Coadministration with glecaprevir/pibrentasvir fixed dose combination (hepatitis C drug combination; increased hepatotoxicity due to increased bilirubin concentration).
- Coadministration with products containing St. John’s wort (Hypericum perforatum).
The EMA said detailed recommendations for the use of atazanavir will be described in the updated SmPC, which will be published in the revised European public assessment report after a decision on this change to the marketing authorization has been granted by the European Commission.
A version of this article appeared on Medscape.com.
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) this week recommended new contraindications on the coadministration of the protease inhibitor atazanavir (Reyataz, Bristol-Myers Squibb) with antineoplastic agents encorafenib and ivosidenib (atazanavir may significantly increase blood levels and thus side effects), and with the anticonvulsants carbamazepine, phenobarbital, and phenytoin (which may decrease serum levels of atazanavir).
The new rules alter sections 4.3 and 4.5 of the summary of product characteristics (SmPC) to reclassify drug–drug interactions with the new contraindications.
Atazanavir is an orally administered drug, used in combination with low-dose ritonavir (Norvir) to boost its pharmacokinetics. It is indicated for the treatment of HIV-1 infected adults and pediatric patients 3 months of age and older in combination with other antiretroviral medicinal products. A combination preparation boosted with cobicistat (Evotaz) is also available.
The drug is an azapeptide HIV-1 protease inhibitor (PI) that selectively inhibits the virus-specific processing of viral Gag-Pol proteins in HIV-1 infected cells, thus preventing formation of mature virions and infection of other cells. This prevents the virus from multiplying and slows the spread of infection. Based on available virological and clinical data from adult patients, no benefit is expected in patients with HIV strains resistant to multiple protease inhibitors (four or more PI mutations).
Therapy with atazanavir is intended to be initiated by a physician experienced in the management of HIV infection, with the choice of atazanavir in treatment-experienced adult and pediatric patients based on individual viral resistance testing and the patient’s treatment history. The standard dose is 300 mg atazanavir taken with 100 mg ritonavir once daily with food.
Atazanavir is already contraindicated in combination or coadministration with a wide variety of other agents:
- Coadministration with simvastatin or lovastatin [statins – risk of increased blood levels with atazanavir].
- Combination with the anti-TB antibiotic rifampicin.
- Combination with the PDE5 inhibitor sildenafil when used for the treatment of pulmonary arterial hypertension only.
- Coadministration with substrates of the CYP3A4 isoform of cytochrome P450 that have narrow therapeutic windows (eg, quetiapine, lurasidone, alfuzosin, astemizole, terfenadine, cisapride, pimozide, quinidine, bepridil, triazolam, oral midazolam, lomitapide, and ergot alkaloids).
- Coadministration with grazoprevir-containing products, including elbasvir/grazoprevir fixed dose combination (hepatitis C drug combination; atazanavir increases its blood levels).
- Coadministration with glecaprevir/pibrentasvir fixed dose combination (hepatitis C drug combination; increased hepatotoxicity due to increased bilirubin concentration).
- Coadministration with products containing St. John’s wort (Hypericum perforatum).
The EMA said detailed recommendations for the use of atazanavir will be described in the updated SmPC, which will be published in the revised European public assessment report after a decision on this change to the marketing authorization has been granted by the European Commission.
A version of this article appeared on Medscape.com.
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) this week recommended new contraindications on the coadministration of the protease inhibitor atazanavir (Reyataz, Bristol-Myers Squibb) with antineoplastic agents encorafenib and ivosidenib (atazanavir may significantly increase blood levels and thus side effects), and with the anticonvulsants carbamazepine, phenobarbital, and phenytoin (which may decrease serum levels of atazanavir).
The new rules alter sections 4.3 and 4.5 of the summary of product characteristics (SmPC) to reclassify drug–drug interactions with the new contraindications.
Atazanavir is an orally administered drug, used in combination with low-dose ritonavir (Norvir) to boost its pharmacokinetics. It is indicated for the treatment of HIV-1 infected adults and pediatric patients 3 months of age and older in combination with other antiretroviral medicinal products. A combination preparation boosted with cobicistat (Evotaz) is also available.
The drug is an azapeptide HIV-1 protease inhibitor (PI) that selectively inhibits the virus-specific processing of viral Gag-Pol proteins in HIV-1 infected cells, thus preventing formation of mature virions and infection of other cells. This prevents the virus from multiplying and slows the spread of infection. Based on available virological and clinical data from adult patients, no benefit is expected in patients with HIV strains resistant to multiple protease inhibitors (four or more PI mutations).
Therapy with atazanavir is intended to be initiated by a physician experienced in the management of HIV infection, with the choice of atazanavir in treatment-experienced adult and pediatric patients based on individual viral resistance testing and the patient’s treatment history. The standard dose is 300 mg atazanavir taken with 100 mg ritonavir once daily with food.
Atazanavir is already contraindicated in combination or coadministration with a wide variety of other agents:
- Coadministration with simvastatin or lovastatin [statins – risk of increased blood levels with atazanavir].
- Combination with the anti-TB antibiotic rifampicin.
- Combination with the PDE5 inhibitor sildenafil when used for the treatment of pulmonary arterial hypertension only.
- Coadministration with substrates of the CYP3A4 isoform of cytochrome P450 that have narrow therapeutic windows (eg, quetiapine, lurasidone, alfuzosin, astemizole, terfenadine, cisapride, pimozide, quinidine, bepridil, triazolam, oral midazolam, lomitapide, and ergot alkaloids).
- Coadministration with grazoprevir-containing products, including elbasvir/grazoprevir fixed dose combination (hepatitis C drug combination; atazanavir increases its blood levels).
- Coadministration with glecaprevir/pibrentasvir fixed dose combination (hepatitis C drug combination; increased hepatotoxicity due to increased bilirubin concentration).
- Coadministration with products containing St. John’s wort (Hypericum perforatum).
The EMA said detailed recommendations for the use of atazanavir will be described in the updated SmPC, which will be published in the revised European public assessment report after a decision on this change to the marketing authorization has been granted by the European Commission.
A version of this article appeared on Medscape.com.