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Liver cancer risk lower after sustained response to DAAs
Individuals with hepatitis C infection who achieved a sustained virologic response (SVR) to treatment with direct-acting antivirals had a significantly lower risk of hepatocellular carcinoma (HCC), a new study suggests.
A retrospective cohort study of 22,500 U.S. veterans with hepatitis C who had been treated with direct-acting antivirals (DAAs) found those with an SVR had a 72% lower risk of HCC, compared with those who did not achieve that response (hazard ratio, 0.28; 95% confidence interval, 0.22-0.36; P less than .0001), even after adjusting for demographics as well as clinical and health utilization factors.
“These data show that successful eradication of HCV [hepatitis C virus] confers a benefit in DAA-treated patients,” wrote Fasiha Kanwal, MD, from the Michael E. DeBakey Veterans Affairs Medical Center in Houston and her coauthors. “Although a few recent studies have raised concerns that DAA might accelerate the risk of HCC in some patients early in the course of treatment, we did not find any factors that differentiated patients with HCC that developed during DAA treatment.”
The results highlighted the importance of early treatment with antivirals, beginning well before the patients showed signs of progressing to advanced fibrosis or cirrhosis, the investigators noted.
“Delaying treatment until patients progress to cirrhosis might be associated with substantial downstream costs incurred as part of lifelong HCC surveillance and/or management of HCC,” they wrote.
Sustained virologic response to DAAs also was associated with a longer time to diagnosis, and patients who didn’t achieve it showed higher rates of cancer much earlier. The most common antivirals used were sofosbuvir (75.2%; 51.1% in combination with ledipasvir), the combination of paritaprevir/ritonavir (23.3%), daclatasvir-based treatments (0.8%), and simeprevir (0.7%).
While the patients achieved SVR that showed similarly beneficial effects on HCC risk in patients with or without cirrhosis, the authors also noted that patients with cirrhosis had a nearly fivefold greater risk of developing cancer than did those without (HR, 4.73; 95% CI, 3.34-6.68). Similarly, patients with a fibrosis score (FIB-4) greater than 3.25 had a sixfold higher risk of HCC, compared with those with a value of 1.45 or lower.
Researchers commented that, at this level of risk, surveillance for HCC in these patients may be cost effective.
“Based on these data, HCC surveillance or risk modification may be needed for all patients who have progressed to cirrhosis or advanced fibrosis (as indicated by high FIB-4) at the time of SVR,” they wrote.
Alcohol use was also associated with a significantly higher annual incidence of HCC (HR, 1.56; 95% CI, 1.11-2.18).
Among the study cohort, 39% had cirrhosis, 29.7% had advanced fibrosis, and nearly one-quarter had previously been treated for hepatitis C infection. More than 40% also had diabetes, 61.4% reported alcohol use, and 54.2% had a history of drug use.
“DAAs offer a chance of cure for all patients with HCV, including patients with advanced cirrhosis, older patients, and those with alcohol use – all characteristics independently associated with risk of HCC in HCV,” the authors explained. “These data show the treated population has changed significantly in the DAA era to include many patients with other HCC risk factors; these differences likely explain why the newer cohorts of DAA-treated patients face higher absolute HCC risk than expected, based on historic data.”
The study was partly supported by the Department of Veteran Affairs’ Center for Innovations in Quality, Effectiveness, and Safety at the Michael E. DeBakey VA Medical Center. No conflicts of interest were declared.
The availability of direct-acting antivirals (DAAs) has revolutionized treatment of hepatitis C. Sustained virologic response (SVR) can be routinely achieved in more than 95% of patients – except in those with decompensated cirrhosis – with a 12-week course of these oral drugs, which have minimal adverse effects. Thus, guidelines recommend that all patients with hepatitis C should be treated with DAAs.1 It was a shock to the medical community when the recent Cochrane review concluded there was insufficient evidence to confirm or reject an effect of DAA therapy on HCV-related morbidity or all-cause mortality.2 The authors cautioned that the lack of valid evidence for DAAs’ effectiveness and the possibility of potential harm should be considered before treating people with hepatitis C with DAAs. Their conclusion was in part based on their rejection of SVR as a valid surrogate for clinical outcome. Previous studies of interferon-based therapies showed that SVR was associated with improvement in liver histology, decreased risk of hepatocellular carcinoma (HCC), and mortality.
Treatment of hepatitis C with DAAs represents one out of a handful of cases in which we can claim that a cure for a chronic disease is possible; however, treatment must be initiated early before advanced fibrosis or cirrhosis to prevent a persistent, though greatly reduced, risk of HCC. Physicians managing patients with hepatitis C should make treatment decisions based on evidence from the entire literature – which supports claims of the DAA treatment’s benefits and refutes allegations of its harmfulness – and should not be swayed by the misguided conclusions of the Cochrane review.
References
1. AASLD-IDSA. Recommendations for testing, managing, and treating hepatitis C. www.hcvguidelines.org. Accessed on July 2, 2017.
2. Jakobsen J.C., Nielsen E.E., Feinberg J., et al. Direct-acting antivirals for chronic hepatitis C. Cochrane Database Syst Rev. 2017 Jun 6;6:CD012143.
3. Curry M.P., O’Leary J.G., Bzowej N., et al. Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. N Engl J Med. 2015;373(27):2618-28.
4. Kanwal F., Kramer J., Asch S.M., et al. Risk of hepatocellular cancer in HCV patients treated with direct acting antiviral agents. Gastroenterology. 2017 Jun 19. pii: S0016-5085(17)35797.
Anna S. Lok, MD, AGAF, FAASLD, is the Alice Lohrman Andrews Research Professor in Hepatology in the department of internal medicine at the University of Michigan Health System in Ann Arbor. She has received research grants from Bristol-Myers Squibb and Gilead through the University of Michigan.
The availability of direct-acting antivirals (DAAs) has revolutionized treatment of hepatitis C. Sustained virologic response (SVR) can be routinely achieved in more than 95% of patients – except in those with decompensated cirrhosis – with a 12-week course of these oral drugs, which have minimal adverse effects. Thus, guidelines recommend that all patients with hepatitis C should be treated with DAAs.1 It was a shock to the medical community when the recent Cochrane review concluded there was insufficient evidence to confirm or reject an effect of DAA therapy on HCV-related morbidity or all-cause mortality.2 The authors cautioned that the lack of valid evidence for DAAs’ effectiveness and the possibility of potential harm should be considered before treating people with hepatitis C with DAAs. Their conclusion was in part based on their rejection of SVR as a valid surrogate for clinical outcome. Previous studies of interferon-based therapies showed that SVR was associated with improvement in liver histology, decreased risk of hepatocellular carcinoma (HCC), and mortality.
Treatment of hepatitis C with DAAs represents one out of a handful of cases in which we can claim that a cure for a chronic disease is possible; however, treatment must be initiated early before advanced fibrosis or cirrhosis to prevent a persistent, though greatly reduced, risk of HCC. Physicians managing patients with hepatitis C should make treatment decisions based on evidence from the entire literature – which supports claims of the DAA treatment’s benefits and refutes allegations of its harmfulness – and should not be swayed by the misguided conclusions of the Cochrane review.
References
1. AASLD-IDSA. Recommendations for testing, managing, and treating hepatitis C. www.hcvguidelines.org. Accessed on July 2, 2017.
2. Jakobsen J.C., Nielsen E.E., Feinberg J., et al. Direct-acting antivirals for chronic hepatitis C. Cochrane Database Syst Rev. 2017 Jun 6;6:CD012143.
3. Curry M.P., O’Leary J.G., Bzowej N., et al. Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. N Engl J Med. 2015;373(27):2618-28.
4. Kanwal F., Kramer J., Asch S.M., et al. Risk of hepatocellular cancer in HCV patients treated with direct acting antiviral agents. Gastroenterology. 2017 Jun 19. pii: S0016-5085(17)35797.
Anna S. Lok, MD, AGAF, FAASLD, is the Alice Lohrman Andrews Research Professor in Hepatology in the department of internal medicine at the University of Michigan Health System in Ann Arbor. She has received research grants from Bristol-Myers Squibb and Gilead through the University of Michigan.
The availability of direct-acting antivirals (DAAs) has revolutionized treatment of hepatitis C. Sustained virologic response (SVR) can be routinely achieved in more than 95% of patients – except in those with decompensated cirrhosis – with a 12-week course of these oral drugs, which have minimal adverse effects. Thus, guidelines recommend that all patients with hepatitis C should be treated with DAAs.1 It was a shock to the medical community when the recent Cochrane review concluded there was insufficient evidence to confirm or reject an effect of DAA therapy on HCV-related morbidity or all-cause mortality.2 The authors cautioned that the lack of valid evidence for DAAs’ effectiveness and the possibility of potential harm should be considered before treating people with hepatitis C with DAAs. Their conclusion was in part based on their rejection of SVR as a valid surrogate for clinical outcome. Previous studies of interferon-based therapies showed that SVR was associated with improvement in liver histology, decreased risk of hepatocellular carcinoma (HCC), and mortality.
Treatment of hepatitis C with DAAs represents one out of a handful of cases in which we can claim that a cure for a chronic disease is possible; however, treatment must be initiated early before advanced fibrosis or cirrhosis to prevent a persistent, though greatly reduced, risk of HCC. Physicians managing patients with hepatitis C should make treatment decisions based on evidence from the entire literature – which supports claims of the DAA treatment’s benefits and refutes allegations of its harmfulness – and should not be swayed by the misguided conclusions of the Cochrane review.
References
1. AASLD-IDSA. Recommendations for testing, managing, and treating hepatitis C. www.hcvguidelines.org. Accessed on July 2, 2017.
2. Jakobsen J.C., Nielsen E.E., Feinberg J., et al. Direct-acting antivirals for chronic hepatitis C. Cochrane Database Syst Rev. 2017 Jun 6;6:CD012143.
3. Curry M.P., O’Leary J.G., Bzowej N., et al. Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. N Engl J Med. 2015;373(27):2618-28.
4. Kanwal F., Kramer J., Asch S.M., et al. Risk of hepatocellular cancer in HCV patients treated with direct acting antiviral agents. Gastroenterology. 2017 Jun 19. pii: S0016-5085(17)35797.
Anna S. Lok, MD, AGAF, FAASLD, is the Alice Lohrman Andrews Research Professor in Hepatology in the department of internal medicine at the University of Michigan Health System in Ann Arbor. She has received research grants from Bristol-Myers Squibb and Gilead through the University of Michigan.
Individuals with hepatitis C infection who achieved a sustained virologic response (SVR) to treatment with direct-acting antivirals had a significantly lower risk of hepatocellular carcinoma (HCC), a new study suggests.
A retrospective cohort study of 22,500 U.S. veterans with hepatitis C who had been treated with direct-acting antivirals (DAAs) found those with an SVR had a 72% lower risk of HCC, compared with those who did not achieve that response (hazard ratio, 0.28; 95% confidence interval, 0.22-0.36; P less than .0001), even after adjusting for demographics as well as clinical and health utilization factors.
“These data show that successful eradication of HCV [hepatitis C virus] confers a benefit in DAA-treated patients,” wrote Fasiha Kanwal, MD, from the Michael E. DeBakey Veterans Affairs Medical Center in Houston and her coauthors. “Although a few recent studies have raised concerns that DAA might accelerate the risk of HCC in some patients early in the course of treatment, we did not find any factors that differentiated patients with HCC that developed during DAA treatment.”
The results highlighted the importance of early treatment with antivirals, beginning well before the patients showed signs of progressing to advanced fibrosis or cirrhosis, the investigators noted.
“Delaying treatment until patients progress to cirrhosis might be associated with substantial downstream costs incurred as part of lifelong HCC surveillance and/or management of HCC,” they wrote.
Sustained virologic response to DAAs also was associated with a longer time to diagnosis, and patients who didn’t achieve it showed higher rates of cancer much earlier. The most common antivirals used were sofosbuvir (75.2%; 51.1% in combination with ledipasvir), the combination of paritaprevir/ritonavir (23.3%), daclatasvir-based treatments (0.8%), and simeprevir (0.7%).
While the patients achieved SVR that showed similarly beneficial effects on HCC risk in patients with or without cirrhosis, the authors also noted that patients with cirrhosis had a nearly fivefold greater risk of developing cancer than did those without (HR, 4.73; 95% CI, 3.34-6.68). Similarly, patients with a fibrosis score (FIB-4) greater than 3.25 had a sixfold higher risk of HCC, compared with those with a value of 1.45 or lower.
Researchers commented that, at this level of risk, surveillance for HCC in these patients may be cost effective.
“Based on these data, HCC surveillance or risk modification may be needed for all patients who have progressed to cirrhosis or advanced fibrosis (as indicated by high FIB-4) at the time of SVR,” they wrote.
Alcohol use was also associated with a significantly higher annual incidence of HCC (HR, 1.56; 95% CI, 1.11-2.18).
Among the study cohort, 39% had cirrhosis, 29.7% had advanced fibrosis, and nearly one-quarter had previously been treated for hepatitis C infection. More than 40% also had diabetes, 61.4% reported alcohol use, and 54.2% had a history of drug use.
“DAAs offer a chance of cure for all patients with HCV, including patients with advanced cirrhosis, older patients, and those with alcohol use – all characteristics independently associated with risk of HCC in HCV,” the authors explained. “These data show the treated population has changed significantly in the DAA era to include many patients with other HCC risk factors; these differences likely explain why the newer cohorts of DAA-treated patients face higher absolute HCC risk than expected, based on historic data.”
The study was partly supported by the Department of Veteran Affairs’ Center for Innovations in Quality, Effectiveness, and Safety at the Michael E. DeBakey VA Medical Center. No conflicts of interest were declared.
Individuals with hepatitis C infection who achieved a sustained virologic response (SVR) to treatment with direct-acting antivirals had a significantly lower risk of hepatocellular carcinoma (HCC), a new study suggests.
A retrospective cohort study of 22,500 U.S. veterans with hepatitis C who had been treated with direct-acting antivirals (DAAs) found those with an SVR had a 72% lower risk of HCC, compared with those who did not achieve that response (hazard ratio, 0.28; 95% confidence interval, 0.22-0.36; P less than .0001), even after adjusting for demographics as well as clinical and health utilization factors.
“These data show that successful eradication of HCV [hepatitis C virus] confers a benefit in DAA-treated patients,” wrote Fasiha Kanwal, MD, from the Michael E. DeBakey Veterans Affairs Medical Center in Houston and her coauthors. “Although a few recent studies have raised concerns that DAA might accelerate the risk of HCC in some patients early in the course of treatment, we did not find any factors that differentiated patients with HCC that developed during DAA treatment.”
The results highlighted the importance of early treatment with antivirals, beginning well before the patients showed signs of progressing to advanced fibrosis or cirrhosis, the investigators noted.
“Delaying treatment until patients progress to cirrhosis might be associated with substantial downstream costs incurred as part of lifelong HCC surveillance and/or management of HCC,” they wrote.
Sustained virologic response to DAAs also was associated with a longer time to diagnosis, and patients who didn’t achieve it showed higher rates of cancer much earlier. The most common antivirals used were sofosbuvir (75.2%; 51.1% in combination with ledipasvir), the combination of paritaprevir/ritonavir (23.3%), daclatasvir-based treatments (0.8%), and simeprevir (0.7%).
While the patients achieved SVR that showed similarly beneficial effects on HCC risk in patients with or without cirrhosis, the authors also noted that patients with cirrhosis had a nearly fivefold greater risk of developing cancer than did those without (HR, 4.73; 95% CI, 3.34-6.68). Similarly, patients with a fibrosis score (FIB-4) greater than 3.25 had a sixfold higher risk of HCC, compared with those with a value of 1.45 or lower.
Researchers commented that, at this level of risk, surveillance for HCC in these patients may be cost effective.
“Based on these data, HCC surveillance or risk modification may be needed for all patients who have progressed to cirrhosis or advanced fibrosis (as indicated by high FIB-4) at the time of SVR,” they wrote.
Alcohol use was also associated with a significantly higher annual incidence of HCC (HR, 1.56; 95% CI, 1.11-2.18).
Among the study cohort, 39% had cirrhosis, 29.7% had advanced fibrosis, and nearly one-quarter had previously been treated for hepatitis C infection. More than 40% also had diabetes, 61.4% reported alcohol use, and 54.2% had a history of drug use.
“DAAs offer a chance of cure for all patients with HCV, including patients with advanced cirrhosis, older patients, and those with alcohol use – all characteristics independently associated with risk of HCC in HCV,” the authors explained. “These data show the treated population has changed significantly in the DAA era to include many patients with other HCC risk factors; these differences likely explain why the newer cohorts of DAA-treated patients face higher absolute HCC risk than expected, based on historic data.”
The study was partly supported by the Department of Veteran Affairs’ Center for Innovations in Quality, Effectiveness, and Safety at the Michael E. DeBakey VA Medical Center. No conflicts of interest were declared.
FROM GASTROENTEROLOGY
Key clinical point:
Major finding: Individuals who achieved an SVR to antiviral treatment for hepatitis C infection had a 72% lower risk of hepatocellular carcinoma than those who do not show a sustained response.
Data source: Retrospective cohort study in 22,500 U.S. veterans with hepatitis C.
Disclosures: The study was partly supported by the Department of Veterans Affairs’ Center for Innovations in Quality, Effectiveness, and Safety at the Michael E. DeBakey VA Medical Center. No conflicts of interest were declared.
VIDEO: Autoimmune hepatitis with cirrhosis tied to hepatocellular carcinoma
The presence of cirrhosis in patients with autoimmune hepatitis markedly increased their risk of hepatocellular carcinoma, according to a systematic review and meta-analysis of 25 cohort studies and 6,528 patients.
Estimated rates of hepatocellular carcinoma (HCC) were 10.1 (6.9-14.7) cases per 1,000 person-years in these patients versus 1.1 (0.6-2.2) cases per 1,000 person-years in patients without cirrhosis at diagnosis, Aylin Tansel, MD, of Baylor College of Medicine in Houston, and associates reported in Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.02.006). Thus, surveillance for HCC “might be cost effective in this population,” they wrote. “However, patients with AIH [autoimmune hepatitis] without cirrhosis at index diagnosis, particularly those identified from general populations, are at an extremely low risk of HCC.”
Source: American Gastroenterological Association
Autoimmune hepatitis may be asymptomatic at presentation or may cause severe acute hepatitis or even fulminant liver failure. Even with immunosuppressive therapy, patients progress to cirrhosis at reported annual rates of 0.1%-8%. HCC is the fastest-growing cause of cancer mortality, and the American Association for the Study of Liver Diseases (AASLD) recommends enhanced surveillance for this disease in patients whose annual estimated risk is at least 1.5%. Although the European Association for the Study of Liver Diseases recommends screening for HCC in patients with autoimmune hepatitis and cirrhosis, AASLD makes no such recommendation, the reviewers noted. To study the risk of HCC in patients with autoimmune hepatitis, they searched PubMed, Embase, and reference lists for relevant cohort studies published through June 2016. This work yielded 20 papers and five abstracts with a pooled median follow-up period of 8 years.
The overall pooled incidence of HCC was 3.1 (95% confidence interval, 2.2-4.2) cases per 1,000 person-years, or 1.007% per year, the reviewers wrote. However, the 95% confidence interval for the annual incidence rate nearly encompassed the 1.5% cutoff recommended by AASLD, they said. Furthermore, 5 of 16 studies that investigated the risk of HCC in patients with concurrent cirrhosis reported incidence rates above 1.5%. Among 93 patients who developed HCC in the meta-analysis, only 1 did not have cirrhosis by the time autoimmune hepatitis was diagnosed.
The meta-analysis also linked HCC to older age and Asian ethnicity among patients with autoimmune hepatitis, as has been reported before. Male sex only slightly increased the risk of HCC, but the studies included only about 1,130 men, the reviewers noted. Although the severity of autoimmune hepatitis varied among studies, higher rates of relapse predicted HCC in two cohorts. Additionally, one study linked alcohol abuse to a sixfold higher risk of HCC among patients with autoimmune hepatitis. “These data support careful monitoring of patients with autoimmune hepatitis, particularly older men, patients with multiple autoimmune hepatitis relapses, and those with ongoing alcohol abuse,” the investigators wrote.
They found no evidence of publication bias, but each individual study included at most 15 cases of HCC, so pooled incidence rates were probably imprecise, especially for subgroups, they said. Studies also inconsistently reported HCC risk factors, often lacked comparison groups, and usually did not report the effects of surveillance for HCC.
Dr. Tansel reported receiving support from the National Institutes of Health. The reviewers had no conflicts of interest.
Serial imaging surveillance facilitates detection of hepatocellular carcinoma (HCC) at a stage amenable to potentially curative resection or liver transplantation. The AASLD, EASL, and APASL recommend surveillance for cirrhotic patients; however, the AASLD stipulates that the incidence of HCC exceed the threshold of cost-effectiveness of 1.5% per year. Whether HCC surveillance in cirrhotic patients with autoimmune hepatitis (AIH) is cost effective remains controversial. The systematic review and meta-analysis by Tansel et al. of 25 rigorously selected cohort studies of AIH addresses this question by calculating incidence rates of HCC per 1,000 person-years using 95% confidence intervals derived from event rates in relation to the duration of follow-up. 
John M. Vierling, MD, FACP, FAASLD, is professor of medicine and surgery, chief of hepatology, Baylor College of Medicine, Houston. He has received grant support from Taiwan J and Novartis and is on the scientific advisory board for Novartis.
Serial imaging surveillance facilitates detection of hepatocellular carcinoma (HCC) at a stage amenable to potentially curative resection or liver transplantation. The AASLD, EASL, and APASL recommend surveillance for cirrhotic patients; however, the AASLD stipulates that the incidence of HCC exceed the threshold of cost-effectiveness of 1.5% per year. Whether HCC surveillance in cirrhotic patients with autoimmune hepatitis (AIH) is cost effective remains controversial. The systematic review and meta-analysis by Tansel et al. of 25 rigorously selected cohort studies of AIH addresses this question by calculating incidence rates of HCC per 1,000 person-years using 95% confidence intervals derived from event rates in relation to the duration of follow-up.
John M. Vierling, MD, FACP, FAASLD, is professor of medicine and surgery, chief of hepatology, Baylor College of Medicine, Houston. He has received grant support from Taiwan J and Novartis and is on the scientific advisory board for Novartis.
Serial imaging surveillance facilitates detection of hepatocellular carcinoma (HCC) at a stage amenable to potentially curative resection or liver transplantation. The AASLD, EASL, and APASL recommend surveillance for cirrhotic patients; however, the AASLD stipulates that the incidence of HCC exceed the threshold of cost-effectiveness of 1.5% per year. Whether HCC surveillance in cirrhotic patients with autoimmune hepatitis (AIH) is cost effective remains controversial. The systematic review and meta-analysis by Tansel et al. of 25 rigorously selected cohort studies of AIH addresses this question by calculating incidence rates of HCC per 1,000 person-years using 95% confidence intervals derived from event rates in relation to the duration of follow-up.
John M. Vierling, MD, FACP, FAASLD, is professor of medicine and surgery, chief of hepatology, Baylor College of Medicine, Houston. He has received grant support from Taiwan J and Novartis and is on the scientific advisory board for Novartis.
The presence of cirrhosis in patients with autoimmune hepatitis markedly increased their risk of hepatocellular carcinoma, according to a systematic review and meta-analysis of 25 cohort studies and 6,528 patients.
Estimated rates of hepatocellular carcinoma (HCC) were 10.1 (6.9-14.7) cases per 1,000 person-years in these patients versus 1.1 (0.6-2.2) cases per 1,000 person-years in patients without cirrhosis at diagnosis, Aylin Tansel, MD, of Baylor College of Medicine in Houston, and associates reported in Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.02.006). Thus, surveillance for HCC “might be cost effective in this population,” they wrote. “However, patients with AIH [autoimmune hepatitis] without cirrhosis at index diagnosis, particularly those identified from general populations, are at an extremely low risk of HCC.”
Source: American Gastroenterological Association
Autoimmune hepatitis may be asymptomatic at presentation or may cause severe acute hepatitis or even fulminant liver failure. Even with immunosuppressive therapy, patients progress to cirrhosis at reported annual rates of 0.1%-8%. HCC is the fastest-growing cause of cancer mortality, and the American Association for the Study of Liver Diseases (AASLD) recommends enhanced surveillance for this disease in patients whose annual estimated risk is at least 1.5%. Although the European Association for the Study of Liver Diseases recommends screening for HCC in patients with autoimmune hepatitis and cirrhosis, AASLD makes no such recommendation, the reviewers noted. To study the risk of HCC in patients with autoimmune hepatitis, they searched PubMed, Embase, and reference lists for relevant cohort studies published through June 2016. This work yielded 20 papers and five abstracts with a pooled median follow-up period of 8 years.
The overall pooled incidence of HCC was 3.1 (95% confidence interval, 2.2-4.2) cases per 1,000 person-years, or 1.007% per year, the reviewers wrote. However, the 95% confidence interval for the annual incidence rate nearly encompassed the 1.5% cutoff recommended by AASLD, they said. Furthermore, 5 of 16 studies that investigated the risk of HCC in patients with concurrent cirrhosis reported incidence rates above 1.5%. Among 93 patients who developed HCC in the meta-analysis, only 1 did not have cirrhosis by the time autoimmune hepatitis was diagnosed.
The meta-analysis also linked HCC to older age and Asian ethnicity among patients with autoimmune hepatitis, as has been reported before. Male sex only slightly increased the risk of HCC, but the studies included only about 1,130 men, the reviewers noted. Although the severity of autoimmune hepatitis varied among studies, higher rates of relapse predicted HCC in two cohorts. Additionally, one study linked alcohol abuse to a sixfold higher risk of HCC among patients with autoimmune hepatitis. “These data support careful monitoring of patients with autoimmune hepatitis, particularly older men, patients with multiple autoimmune hepatitis relapses, and those with ongoing alcohol abuse,” the investigators wrote.
They found no evidence of publication bias, but each individual study included at most 15 cases of HCC, so pooled incidence rates were probably imprecise, especially for subgroups, they said. Studies also inconsistently reported HCC risk factors, often lacked comparison groups, and usually did not report the effects of surveillance for HCC.
Dr. Tansel reported receiving support from the National Institutes of Health. The reviewers had no conflicts of interest.
The presence of cirrhosis in patients with autoimmune hepatitis markedly increased their risk of hepatocellular carcinoma, according to a systematic review and meta-analysis of 25 cohort studies and 6,528 patients.
Estimated rates of hepatocellular carcinoma (HCC) were 10.1 (6.9-14.7) cases per 1,000 person-years in these patients versus 1.1 (0.6-2.2) cases per 1,000 person-years in patients without cirrhosis at diagnosis, Aylin Tansel, MD, of Baylor College of Medicine in Houston, and associates reported in Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.02.006). Thus, surveillance for HCC “might be cost effective in this population,” they wrote. “However, patients with AIH [autoimmune hepatitis] without cirrhosis at index diagnosis, particularly those identified from general populations, are at an extremely low risk of HCC.”
Source: American Gastroenterological Association
Autoimmune hepatitis may be asymptomatic at presentation or may cause severe acute hepatitis or even fulminant liver failure. Even with immunosuppressive therapy, patients progress to cirrhosis at reported annual rates of 0.1%-8%. HCC is the fastest-growing cause of cancer mortality, and the American Association for the Study of Liver Diseases (AASLD) recommends enhanced surveillance for this disease in patients whose annual estimated risk is at least 1.5%. Although the European Association for the Study of Liver Diseases recommends screening for HCC in patients with autoimmune hepatitis and cirrhosis, AASLD makes no such recommendation, the reviewers noted. To study the risk of HCC in patients with autoimmune hepatitis, they searched PubMed, Embase, and reference lists for relevant cohort studies published through June 2016. This work yielded 20 papers and five abstracts with a pooled median follow-up period of 8 years.
The overall pooled incidence of HCC was 3.1 (95% confidence interval, 2.2-4.2) cases per 1,000 person-years, or 1.007% per year, the reviewers wrote. However, the 95% confidence interval for the annual incidence rate nearly encompassed the 1.5% cutoff recommended by AASLD, they said. Furthermore, 5 of 16 studies that investigated the risk of HCC in patients with concurrent cirrhosis reported incidence rates above 1.5%. Among 93 patients who developed HCC in the meta-analysis, only 1 did not have cirrhosis by the time autoimmune hepatitis was diagnosed.
The meta-analysis also linked HCC to older age and Asian ethnicity among patients with autoimmune hepatitis, as has been reported before. Male sex only slightly increased the risk of HCC, but the studies included only about 1,130 men, the reviewers noted. Although the severity of autoimmune hepatitis varied among studies, higher rates of relapse predicted HCC in two cohorts. Additionally, one study linked alcohol abuse to a sixfold higher risk of HCC among patients with autoimmune hepatitis. “These data support careful monitoring of patients with autoimmune hepatitis, particularly older men, patients with multiple autoimmune hepatitis relapses, and those with ongoing alcohol abuse,” the investigators wrote.
They found no evidence of publication bias, but each individual study included at most 15 cases of HCC, so pooled incidence rates were probably imprecise, especially for subgroups, they said. Studies also inconsistently reported HCC risk factors, often lacked comparison groups, and usually did not report the effects of surveillance for HCC.
Dr. Tansel reported receiving support from the National Institutes of Health. The reviewers had no conflicts of interest.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Patients with autoimmune hepatitis and cirrhosis are at increased risk of hepatocellular carcinoma.
Major finding: For every 1,000 person-years, there were 3.1 (95% CI, 2.2-4.2) cases of hepatocellular carcinoma overall, 10.1 (6.9-14.7) cases in patients who also had cirrhosis at diagnosis, and 1.1 (0.6-2.2) cases in patients who did not have cirrhosis at diagnosis.
Data source: A systematic review and meta-analysis of 25 studies of 6,528 patients with autoimmune hepatitis.
Disclosures: Dr. Tansel reported receiving support from the National Institutes of Health. The investigators disclosed no conflicts.
VIDEO: Meta-analysis favors anticoagulation for patients with cirrhosis and portal vein thrombosis
Patients with cirrhosis and portal vein thrombosis (PVT) who received anticoagulation therapy had nearly fivefold greater odds of recanalization compared with untreated patients, and were no more likely to experience major or minor bleeding, in a pooled analysis of eight studies published in the August issue of Gastroenterology (doi: 10.1053/j.gastro.2017.04.042).
Rates of any recanalization were 71% in treated patients and 42% in untreated patients (P less than .0001), wrote Lorenzo Loffredo, MD, of Sapienza University, Rome, and his coinvestigators. Rates of complete recanalization were 53% and 33%, respectively (P = .002), rates of spontaneous variceal bleeding were 2% and 12% (P = .04), and bleeding affected 11% of patients in each group. Together, the findings “show that anticoagulants are efficacious and safe for treatment of portal vein thrombosis in cirrhotic patients,” although larger, interventional clinical trials are needed to pinpoint the clinical role of anticoagulation in cirrhotic patients with PVT, the reviewers reported.
Source: American Gastroenterological Association
Bleeding from portal hypertension is a major complication in cirrhosis, but PVT affects about 20% of patients and predicts poor outcomes, they noted. Anticoagulation in this setting can be difficult because patients often have concurrent coagulopathies that are hard to assess with standard techniques, such as PT-INR (international normalized ratio). Although some studies support anticoagulating these patients, data are limited. Therefore, the reviewers searched PubMed, the ISI Web of Science, SCOPUS, and the Cochrane database through Feb. 14, 2017, for trials comparing anticoagulation with no treatment in patients with cirrhosis and PVT.
This search yielded eight trials of 353 patients who received low-molecular-weight heparin, warfarin, or no treatment for about 6 months, with a typical follow-up period of 2 years. The reviewers found no evidence of publication bias or significant heterogeneity among the trials. Six studies evaluated complete recanalization, another set of six studies tracked progression of PVT, a third set of six studies evaluated major or minor bleeding events, and four studies evaluated spontaneous variceal bleeding. Compared with no treatment, anticoagulation was tied to a significantly greater likelihood of complete recanalization (pooled odds ratio, 3.4; 95% confidence interval, 1.5-7.4; P = .002), a significantly lower chance of PVT progressing (9% vs. 33%; pooled odds ratio, 0.14; 95% CI, 0.06-0.31; P less than .0001), no difference in bleeding rates (11% in each pooled group), and a significantly lower risk of spontaneous variceal bleeding (OR, 0.23; 95% CI, 0.06-0.94; P = .04).
“Metaregression analysis showed that duration of anticoagulation did not influence outcomes,” the reviewers wrote. “Low-molecular-weight heparin, but not warfarin, was significantly associated with a complete PVT resolution as compared to untreated patients, while both low-molecular-weight heparin and warfarin were effective in reducing PVT progression.” That finding merits careful interpretation, however, because most studies on warfarin were retrospective and lacked data on the quality of anticoagulation, they added.
“It is a challenge to treat patients with cirrhosis using anticoagulants because of the perception that the coexistent coagulopathy could promote bleeding,” the researchers wrote. Nonetheless, their analysis suggests that anticoagulation has significant benefits and does not increase bleeding risk, regardless of the severity of liver failure, they concluded.
The reviewers reported having no funding sources or conflicts of interest.
Patients with cirrhosis and portal vein thrombosis (PVT) who received anticoagulation therapy had nearly fivefold greater odds of recanalization compared with untreated patients, and were no more likely to experience major or minor bleeding, in a pooled analysis of eight studies published in the August issue of Gastroenterology (doi: 10.1053/j.gastro.2017.04.042).
Rates of any recanalization were 71% in treated patients and 42% in untreated patients (P less than .0001), wrote Lorenzo Loffredo, MD, of Sapienza University, Rome, and his coinvestigators. Rates of complete recanalization were 53% and 33%, respectively (P = .002), rates of spontaneous variceal bleeding were 2% and 12% (P = .04), and bleeding affected 11% of patients in each group. Together, the findings “show that anticoagulants are efficacious and safe for treatment of portal vein thrombosis in cirrhotic patients,” although larger, interventional clinical trials are needed to pinpoint the clinical role of anticoagulation in cirrhotic patients with PVT, the reviewers reported.
Source: American Gastroenterological Association
Bleeding from portal hypertension is a major complication in cirrhosis, but PVT affects about 20% of patients and predicts poor outcomes, they noted. Anticoagulation in this setting can be difficult because patients often have concurrent coagulopathies that are hard to assess with standard techniques, such as PT-INR (international normalized ratio). Although some studies support anticoagulating these patients, data are limited. Therefore, the reviewers searched PubMed, the ISI Web of Science, SCOPUS, and the Cochrane database through Feb. 14, 2017, for trials comparing anticoagulation with no treatment in patients with cirrhosis and PVT.
This search yielded eight trials of 353 patients who received low-molecular-weight heparin, warfarin, or no treatment for about 6 months, with a typical follow-up period of 2 years. The reviewers found no evidence of publication bias or significant heterogeneity among the trials. Six studies evaluated complete recanalization, another set of six studies tracked progression of PVT, a third set of six studies evaluated major or minor bleeding events, and four studies evaluated spontaneous variceal bleeding. Compared with no treatment, anticoagulation was tied to a significantly greater likelihood of complete recanalization (pooled odds ratio, 3.4; 95% confidence interval, 1.5-7.4; P = .002), a significantly lower chance of PVT progressing (9% vs. 33%; pooled odds ratio, 0.14; 95% CI, 0.06-0.31; P less than .0001), no difference in bleeding rates (11% in each pooled group), and a significantly lower risk of spontaneous variceal bleeding (OR, 0.23; 95% CI, 0.06-0.94; P = .04).
“Metaregression analysis showed that duration of anticoagulation did not influence outcomes,” the reviewers wrote. “Low-molecular-weight heparin, but not warfarin, was significantly associated with a complete PVT resolution as compared to untreated patients, while both low-molecular-weight heparin and warfarin were effective in reducing PVT progression.” That finding merits careful interpretation, however, because most studies on warfarin were retrospective and lacked data on the quality of anticoagulation, they added.
“It is a challenge to treat patients with cirrhosis using anticoagulants because of the perception that the coexistent coagulopathy could promote bleeding,” the researchers wrote. Nonetheless, their analysis suggests that anticoagulation has significant benefits and does not increase bleeding risk, regardless of the severity of liver failure, they concluded.
The reviewers reported having no funding sources or conflicts of interest.
Patients with cirrhosis and portal vein thrombosis (PVT) who received anticoagulation therapy had nearly fivefold greater odds of recanalization compared with untreated patients, and were no more likely to experience major or minor bleeding, in a pooled analysis of eight studies published in the August issue of Gastroenterology (doi: 10.1053/j.gastro.2017.04.042).
Rates of any recanalization were 71% in treated patients and 42% in untreated patients (P less than .0001), wrote Lorenzo Loffredo, MD, of Sapienza University, Rome, and his coinvestigators. Rates of complete recanalization were 53% and 33%, respectively (P = .002), rates of spontaneous variceal bleeding were 2% and 12% (P = .04), and bleeding affected 11% of patients in each group. Together, the findings “show that anticoagulants are efficacious and safe for treatment of portal vein thrombosis in cirrhotic patients,” although larger, interventional clinical trials are needed to pinpoint the clinical role of anticoagulation in cirrhotic patients with PVT, the reviewers reported.
Source: American Gastroenterological Association
Bleeding from portal hypertension is a major complication in cirrhosis, but PVT affects about 20% of patients and predicts poor outcomes, they noted. Anticoagulation in this setting can be difficult because patients often have concurrent coagulopathies that are hard to assess with standard techniques, such as PT-INR (international normalized ratio). Although some studies support anticoagulating these patients, data are limited. Therefore, the reviewers searched PubMed, the ISI Web of Science, SCOPUS, and the Cochrane database through Feb. 14, 2017, for trials comparing anticoagulation with no treatment in patients with cirrhosis and PVT.
This search yielded eight trials of 353 patients who received low-molecular-weight heparin, warfarin, or no treatment for about 6 months, with a typical follow-up period of 2 years. The reviewers found no evidence of publication bias or significant heterogeneity among the trials. Six studies evaluated complete recanalization, another set of six studies tracked progression of PVT, a third set of six studies evaluated major or minor bleeding events, and four studies evaluated spontaneous variceal bleeding. Compared with no treatment, anticoagulation was tied to a significantly greater likelihood of complete recanalization (pooled odds ratio, 3.4; 95% confidence interval, 1.5-7.4; P = .002), a significantly lower chance of PVT progressing (9% vs. 33%; pooled odds ratio, 0.14; 95% CI, 0.06-0.31; P less than .0001), no difference in bleeding rates (11% in each pooled group), and a significantly lower risk of spontaneous variceal bleeding (OR, 0.23; 95% CI, 0.06-0.94; P = .04).
“Metaregression analysis showed that duration of anticoagulation did not influence outcomes,” the reviewers wrote. “Low-molecular-weight heparin, but not warfarin, was significantly associated with a complete PVT resolution as compared to untreated patients, while both low-molecular-weight heparin and warfarin were effective in reducing PVT progression.” That finding merits careful interpretation, however, because most studies on warfarin were retrospective and lacked data on the quality of anticoagulation, they added.
“It is a challenge to treat patients with cirrhosis using anticoagulants because of the perception that the coexistent coagulopathy could promote bleeding,” the researchers wrote. Nonetheless, their analysis suggests that anticoagulation has significant benefits and does not increase bleeding risk, regardless of the severity of liver failure, they concluded.
The reviewers reported having no funding sources or conflicts of interest.
FROM GASTROENTEROLOGY
Key clinical point: Anticoagulation produced favorable outcomes with no increase in bleeding risk in patients with cirrhosis and portal vein thrombosis.
Major finding: Rates of any recanalization were 71% in treated patients and 42% in untreated patients (P less than .0001); rates of complete recanalization were 53% and 33%, respectively (P = .002), rates of spontaneous variceal bleeding were 2% and 12% (P = .04), and bleeding affected 11% of patients in each group.
Data source: A systematic review and meta-analysis of eight studies of 353 patients with cirrhosis and portal vein thrombosis.
Disclosures: The reviewers reported having no funding sources or conflicts of interest.
ACIP approves new hepatitis A vaccine draft recommendations
, including a focus on catch-up vaccines for adolescents and those over age 40 years.
While hepatitis A cases have dropped significantly since the vaccine’s debut – with the number of reported cases in 2015 dropping to 1,390, compared with 9,606 in 1971 – previous recommendations regarding catch-up vaccinations suggested patients should consider treatment, as opposed to catch-up vaccination.
Adult catch-up vaccines now are recommended to be considered in areas with increasing disease risks, an addition that was not part of the current recommendations but has been changed because of evidence that patients over 40 years old are more vulnerable to the virus and more likely to be hospitalized if infected, said Noele Nelson, MD, PhD, of the Division of Viral Hepatitis at the CDC.
“Increasing proportions of adults in the United States are susceptible to hepatitis A ... due to reduced exposure to virus early in life and significant serum prevalence in older adults greater and equal to 40 years,” said Dr. Nelson. “In addition, there is low two-dose vaccination coverage among adults, including high risk adults, and morbidity and mortality increases with age.”
Recommendations for pregnant women also have been updated with a more definitive message. Previous recommendations advised pregnant women to weigh the options of acquiring hepatitis A against possible adverse effects of the vaccine. But, new evidence was presented at the meeting: in a study of 139 pregnant women vaccinated between 1996 and 2015 who experienced adverse effects, only seven of the effects were considered serious, and no maternal or infant deaths were apparent. In light of this, the ACIP approved the recommendation change to advise all pregnant women to be vaccinated, if they have not already been so before pregnancy.
Updates also included recommendations for patients with chronic liver disease, who are considered to be members of a high-risk population. Newly approved recommendations include a section on epidemiology, which states that, while those with chronic liver disease are not at increased risk for hepatitis A virus infection unless they experience fecal-oral exposure to the virus, those with acute hepatitis A may be more at risk to develop more severe liver disease. Recommendations for those with chronic liver disease also include a statement advising patients to seek immunoglobulin, as well as a hepatitis A, vaccination as soon as possible after exposure.
The ACIP also approved a change in recommendations to advise all residents and caretakers of those living in a group home, specifically those caring for developmentally disabled patients, to be vaccinated because of the historically high endemic nature of such institutions.
Committee members hope these new recommendations will help the United States reach its goal of a national hepatitis A case ratio of 0.3/100,000 people and a hepatitis A vaccination rate of 85%.
If these recommendations are approved by the director of the CDC and the U.S. Health Department, as they usually are, they will be published in the CDC’s Weekly Morbidity and Mortality Report.
Members of the committee reported no relevant financial disclosures.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
, including a focus on catch-up vaccines for adolescents and those over age 40 years.
While hepatitis A cases have dropped significantly since the vaccine’s debut – with the number of reported cases in 2015 dropping to 1,390, compared with 9,606 in 1971 – previous recommendations regarding catch-up vaccinations suggested patients should consider treatment, as opposed to catch-up vaccination.
Adult catch-up vaccines now are recommended to be considered in areas with increasing disease risks, an addition that was not part of the current recommendations but has been changed because of evidence that patients over 40 years old are more vulnerable to the virus and more likely to be hospitalized if infected, said Noele Nelson, MD, PhD, of the Division of Viral Hepatitis at the CDC.
“Increasing proportions of adults in the United States are susceptible to hepatitis A ... due to reduced exposure to virus early in life and significant serum prevalence in older adults greater and equal to 40 years,” said Dr. Nelson. “In addition, there is low two-dose vaccination coverage among adults, including high risk adults, and morbidity and mortality increases with age.”
Recommendations for pregnant women also have been updated with a more definitive message. Previous recommendations advised pregnant women to weigh the options of acquiring hepatitis A against possible adverse effects of the vaccine. But, new evidence was presented at the meeting: in a study of 139 pregnant women vaccinated between 1996 and 2015 who experienced adverse effects, only seven of the effects were considered serious, and no maternal or infant deaths were apparent. In light of this, the ACIP approved the recommendation change to advise all pregnant women to be vaccinated, if they have not already been so before pregnancy.
Updates also included recommendations for patients with chronic liver disease, who are considered to be members of a high-risk population. Newly approved recommendations include a section on epidemiology, which states that, while those with chronic liver disease are not at increased risk for hepatitis A virus infection unless they experience fecal-oral exposure to the virus, those with acute hepatitis A may be more at risk to develop more severe liver disease. Recommendations for those with chronic liver disease also include a statement advising patients to seek immunoglobulin, as well as a hepatitis A, vaccination as soon as possible after exposure.
The ACIP also approved a change in recommendations to advise all residents and caretakers of those living in a group home, specifically those caring for developmentally disabled patients, to be vaccinated because of the historically high endemic nature of such institutions.
Committee members hope these new recommendations will help the United States reach its goal of a national hepatitis A case ratio of 0.3/100,000 people and a hepatitis A vaccination rate of 85%.
If these recommendations are approved by the director of the CDC and the U.S. Health Department, as they usually are, they will be published in the CDC’s Weekly Morbidity and Mortality Report.
Members of the committee reported no relevant financial disclosures.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
, including a focus on catch-up vaccines for adolescents and those over age 40 years.
While hepatitis A cases have dropped significantly since the vaccine’s debut – with the number of reported cases in 2015 dropping to 1,390, compared with 9,606 in 1971 – previous recommendations regarding catch-up vaccinations suggested patients should consider treatment, as opposed to catch-up vaccination.
Adult catch-up vaccines now are recommended to be considered in areas with increasing disease risks, an addition that was not part of the current recommendations but has been changed because of evidence that patients over 40 years old are more vulnerable to the virus and more likely to be hospitalized if infected, said Noele Nelson, MD, PhD, of the Division of Viral Hepatitis at the CDC.
“Increasing proportions of adults in the United States are susceptible to hepatitis A ... due to reduced exposure to virus early in life and significant serum prevalence in older adults greater and equal to 40 years,” said Dr. Nelson. “In addition, there is low two-dose vaccination coverage among adults, including high risk adults, and morbidity and mortality increases with age.”
Recommendations for pregnant women also have been updated with a more definitive message. Previous recommendations advised pregnant women to weigh the options of acquiring hepatitis A against possible adverse effects of the vaccine. But, new evidence was presented at the meeting: in a study of 139 pregnant women vaccinated between 1996 and 2015 who experienced adverse effects, only seven of the effects were considered serious, and no maternal or infant deaths were apparent. In light of this, the ACIP approved the recommendation change to advise all pregnant women to be vaccinated, if they have not already been so before pregnancy.
Updates also included recommendations for patients with chronic liver disease, who are considered to be members of a high-risk population. Newly approved recommendations include a section on epidemiology, which states that, while those with chronic liver disease are not at increased risk for hepatitis A virus infection unless they experience fecal-oral exposure to the virus, those with acute hepatitis A may be more at risk to develop more severe liver disease. Recommendations for those with chronic liver disease also include a statement advising patients to seek immunoglobulin, as well as a hepatitis A, vaccination as soon as possible after exposure.
The ACIP also approved a change in recommendations to advise all residents and caretakers of those living in a group home, specifically those caring for developmentally disabled patients, to be vaccinated because of the historically high endemic nature of such institutions.
Committee members hope these new recommendations will help the United States reach its goal of a national hepatitis A case ratio of 0.3/100,000 people and a hepatitis A vaccination rate of 85%.
If these recommendations are approved by the director of the CDC and the U.S. Health Department, as they usually are, they will be published in the CDC’s Weekly Morbidity and Mortality Report.
Members of the committee reported no relevant financial disclosures.
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
FROM ACIP MEETING
Liver disease doubles risk of colorectal cancer
Chronic liver disease appears to double the risk of colorectal cancer (CRC), even after patients undergo liver transplantation, according to a report published in Gastrointestinal Endoscopy.
“Strict surveillance for colorectal cancer is warranted in this patient population,” said Yuga Komaki, MD, of the section of gastroenterology, hepatology, and nutrition, University of Chicago, and associates.
One prominent chronic liver disease, primary sclerosing cholangitis, is known to raise the risk of CRC, which “is mainly attributed to the concurrence of inflammatory bowel disease.” In addition, whether liver transplantation mitigates that risk remains “controversial,” the investigators noted.
To assess whether chronic liver disease impacts CRC risk, they performed a systematic review and meta-analysis of the literature, examining data from 55 observational studies involving 55,991 participants. Case patients had a variety of chronic liver diseases, including primary sclerosing cholangitis, viral hepatitis, autoimmune hepatitis, primary biliary cirrhosis, and alcoholic liver damage.
Overall, the pooled standardized incidence ratio of CRC was 2.06 among patients with liver disease, compared with control subjects. It was highest in the subgroup of patients with primary sclerosing cholangitis at 6.70, the investigators said (Gastrointest. Endosc. 2017;86:93-104).
CRC risk appeared to be slightly higher among patients who had cirrhosis than among those who had hepatitis, “suggesting that advanced liver damage may lead to higher risks of CRC. This is not surprising because advanced liver damage can cause systemic alterations in immunity that may precipitate malignant transformation,” Dr. Komaki and associates noted.
The pooled standardized incidence ratio of CRC remained elevated at 2.16 among patients who underwent liver transplantation for a variety of causes. It is possible that their exposure to immunosuppressive therapy plays a role in elevating this risk, the researchers added.
“We propose that patients with chronic hepatitis and cirrhosis require a screening colonoscopy every 5 years, as opposed to the 10-year interval in the general population. Patients undergoing liver transplant should have a colonoscopy before the transplant and, subsequently, should undergo colonoscopy at 5-year intervals,” Dr. Komaki and associates said.
They added that the sixfold increase in CRC risk among patients with PSC “justifies the present recommendation of annual surveillance colonoscopy that should be continued after transplant.”
Chronic liver disease appears to double the risk of colorectal cancer (CRC), even after patients undergo liver transplantation, according to a report published in Gastrointestinal Endoscopy.
“Strict surveillance for colorectal cancer is warranted in this patient population,” said Yuga Komaki, MD, of the section of gastroenterology, hepatology, and nutrition, University of Chicago, and associates.
One prominent chronic liver disease, primary sclerosing cholangitis, is known to raise the risk of CRC, which “is mainly attributed to the concurrence of inflammatory bowel disease.” In addition, whether liver transplantation mitigates that risk remains “controversial,” the investigators noted.
To assess whether chronic liver disease impacts CRC risk, they performed a systematic review and meta-analysis of the literature, examining data from 55 observational studies involving 55,991 participants. Case patients had a variety of chronic liver diseases, including primary sclerosing cholangitis, viral hepatitis, autoimmune hepatitis, primary biliary cirrhosis, and alcoholic liver damage.
Overall, the pooled standardized incidence ratio of CRC was 2.06 among patients with liver disease, compared with control subjects. It was highest in the subgroup of patients with primary sclerosing cholangitis at 6.70, the investigators said (Gastrointest. Endosc. 2017;86:93-104).
CRC risk appeared to be slightly higher among patients who had cirrhosis than among those who had hepatitis, “suggesting that advanced liver damage may lead to higher risks of CRC. This is not surprising because advanced liver damage can cause systemic alterations in immunity that may precipitate malignant transformation,” Dr. Komaki and associates noted.
The pooled standardized incidence ratio of CRC remained elevated at 2.16 among patients who underwent liver transplantation for a variety of causes. It is possible that their exposure to immunosuppressive therapy plays a role in elevating this risk, the researchers added.
“We propose that patients with chronic hepatitis and cirrhosis require a screening colonoscopy every 5 years, as opposed to the 10-year interval in the general population. Patients undergoing liver transplant should have a colonoscopy before the transplant and, subsequently, should undergo colonoscopy at 5-year intervals,” Dr. Komaki and associates said.
They added that the sixfold increase in CRC risk among patients with PSC “justifies the present recommendation of annual surveillance colonoscopy that should be continued after transplant.”
Chronic liver disease appears to double the risk of colorectal cancer (CRC), even after patients undergo liver transplantation, according to a report published in Gastrointestinal Endoscopy.
“Strict surveillance for colorectal cancer is warranted in this patient population,” said Yuga Komaki, MD, of the section of gastroenterology, hepatology, and nutrition, University of Chicago, and associates.
One prominent chronic liver disease, primary sclerosing cholangitis, is known to raise the risk of CRC, which “is mainly attributed to the concurrence of inflammatory bowel disease.” In addition, whether liver transplantation mitigates that risk remains “controversial,” the investigators noted.
To assess whether chronic liver disease impacts CRC risk, they performed a systematic review and meta-analysis of the literature, examining data from 55 observational studies involving 55,991 participants. Case patients had a variety of chronic liver diseases, including primary sclerosing cholangitis, viral hepatitis, autoimmune hepatitis, primary biliary cirrhosis, and alcoholic liver damage.
Overall, the pooled standardized incidence ratio of CRC was 2.06 among patients with liver disease, compared with control subjects. It was highest in the subgroup of patients with primary sclerosing cholangitis at 6.70, the investigators said (Gastrointest. Endosc. 2017;86:93-104).
CRC risk appeared to be slightly higher among patients who had cirrhosis than among those who had hepatitis, “suggesting that advanced liver damage may lead to higher risks of CRC. This is not surprising because advanced liver damage can cause systemic alterations in immunity that may precipitate malignant transformation,” Dr. Komaki and associates noted.
The pooled standardized incidence ratio of CRC remained elevated at 2.16 among patients who underwent liver transplantation for a variety of causes. It is possible that their exposure to immunosuppressive therapy plays a role in elevating this risk, the researchers added.
“We propose that patients with chronic hepatitis and cirrhosis require a screening colonoscopy every 5 years, as opposed to the 10-year interval in the general population. Patients undergoing liver transplant should have a colonoscopy before the transplant and, subsequently, should undergo colonoscopy at 5-year intervals,” Dr. Komaki and associates said.
They added that the sixfold increase in CRC risk among patients with PSC “justifies the present recommendation of annual surveillance colonoscopy that should be continued after transplant.”
FROM GASTROINTESTINAL ENDOSCOPY
Key clinical point: Chronic liver disease appears to double the risk of colorectal cancer, even after patients undergo liver transplantation.
Major finding: The pooled standardized incidence ratio of colorectal cancer was 2.06 among patients with liver disease, compared with control subjects.
Data source: A meta-analysis of 50 observational studies (55,991 participants) that examined the rate of colorectal cancer in patients with a variety of liver diseases.
Disclosures: No specific sponsor was identified for this study. Dr. Komaki reported receiving research support from the Children’s Cancer Association of Japan. Dr. Komaki and associates reported having no other relevant financial disclosures.
HCV/HIV-coinfected teens rapidly progress to advanced liver disease
MADRID – Roughly one in four children with vertically transmitted hepatitis C virus (HCV)/HIV coinfection will progress to advanced hepatic fibrosis by age 20 years despite treatment with pegylated interferon plus ribavirin, Carolina Fernández McPhee, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
This rate was nearly five times higher than in matched children with vertically acquired HCV monoinfection in a multicenter retrospective study, according to Dr. McPhee of Hospital General Universitario Gregorio Marañón in Madrid.
She presented a multicenter retrospective study of liver disease progression in 71 HCV/HIV coinfected children and 71 age- and sex-matched HCV-monoinfected children. The coinfected children are being followed in CORISPES (the Spanish Cohort of HIV-infected Children), where they receive state-of-the-art care.
All was quiet through age 9 years, with no progression to liver fibrosis in either patient group. Among patients followed to age 20 years, however, 9 (24%) of 38 HCV/HIV-coinfected patients showed progression to advanced fibrosis, compared with just 3 (6%) of 54 patients with HCV only.
Of HCV/HIV coinfected patients, 73% were infected with the hard to treat viral genotypes 1 or 4, compared with 93% of patients with HCV-only.
In the study group, 22 patients with HCV/HIV and 52 patients with HCV-only underwent treatment with pegylated interferon and ribavirin. At the time of treatment, three coinfected patients already had cirrhosis, another eight had moderate to advanced fibrosis, and half had no or mild fibrosis. In contrast, only one patient with HCV monoinfection had cirrhosis, four had moderate to advanced fibrosis, and the rest – nearly 90% of the total group – had no or mild fibrosis.
At treatment initiation, 96% of the HCV/HIV group were on antiretroviral therapy, 86% showed suppression of HIV RNA, 44% had AIDS, and 32% had a CD4 count below 500 cells/mm3.
The sustained viral response rate was similar in the two groups of patients – 41% in the HCV/HIV group and 42% in HCV-only patients – despite the fact that the HCV monoinfected patients had a higher prevalence of the tough to treat genotypes.
Roughly 12 million people worldwide are coinfected with HCV and HIV.
Dr. McPhee reported having no relevant financial disclosures.
MADRID – Roughly one in four children with vertically transmitted hepatitis C virus (HCV)/HIV coinfection will progress to advanced hepatic fibrosis by age 20 years despite treatment with pegylated interferon plus ribavirin, Carolina Fernández McPhee, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
This rate was nearly five times higher than in matched children with vertically acquired HCV monoinfection in a multicenter retrospective study, according to Dr. McPhee of Hospital General Universitario Gregorio Marañón in Madrid.
She presented a multicenter retrospective study of liver disease progression in 71 HCV/HIV coinfected children and 71 age- and sex-matched HCV-monoinfected children. The coinfected children are being followed in CORISPES (the Spanish Cohort of HIV-infected Children), where they receive state-of-the-art care.
All was quiet through age 9 years, with no progression to liver fibrosis in either patient group. Among patients followed to age 20 years, however, 9 (24%) of 38 HCV/HIV-coinfected patients showed progression to advanced fibrosis, compared with just 3 (6%) of 54 patients with HCV only.
Of HCV/HIV coinfected patients, 73% were infected with the hard to treat viral genotypes 1 or 4, compared with 93% of patients with HCV-only.
In the study group, 22 patients with HCV/HIV and 52 patients with HCV-only underwent treatment with pegylated interferon and ribavirin. At the time of treatment, three coinfected patients already had cirrhosis, another eight had moderate to advanced fibrosis, and half had no or mild fibrosis. In contrast, only one patient with HCV monoinfection had cirrhosis, four had moderate to advanced fibrosis, and the rest – nearly 90% of the total group – had no or mild fibrosis.
At treatment initiation, 96% of the HCV/HIV group were on antiretroviral therapy, 86% showed suppression of HIV RNA, 44% had AIDS, and 32% had a CD4 count below 500 cells/mm3.
The sustained viral response rate was similar in the two groups of patients – 41% in the HCV/HIV group and 42% in HCV-only patients – despite the fact that the HCV monoinfected patients had a higher prevalence of the tough to treat genotypes.
Roughly 12 million people worldwide are coinfected with HCV and HIV.
Dr. McPhee reported having no relevant financial disclosures.
MADRID – Roughly one in four children with vertically transmitted hepatitis C virus (HCV)/HIV coinfection will progress to advanced hepatic fibrosis by age 20 years despite treatment with pegylated interferon plus ribavirin, Carolina Fernández McPhee, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
This rate was nearly five times higher than in matched children with vertically acquired HCV monoinfection in a multicenter retrospective study, according to Dr. McPhee of Hospital General Universitario Gregorio Marañón in Madrid.
She presented a multicenter retrospective study of liver disease progression in 71 HCV/HIV coinfected children and 71 age- and sex-matched HCV-monoinfected children. The coinfected children are being followed in CORISPES (the Spanish Cohort of HIV-infected Children), where they receive state-of-the-art care.
All was quiet through age 9 years, with no progression to liver fibrosis in either patient group. Among patients followed to age 20 years, however, 9 (24%) of 38 HCV/HIV-coinfected patients showed progression to advanced fibrosis, compared with just 3 (6%) of 54 patients with HCV only.
Of HCV/HIV coinfected patients, 73% were infected with the hard to treat viral genotypes 1 or 4, compared with 93% of patients with HCV-only.
In the study group, 22 patients with HCV/HIV and 52 patients with HCV-only underwent treatment with pegylated interferon and ribavirin. At the time of treatment, three coinfected patients already had cirrhosis, another eight had moderate to advanced fibrosis, and half had no or mild fibrosis. In contrast, only one patient with HCV monoinfection had cirrhosis, four had moderate to advanced fibrosis, and the rest – nearly 90% of the total group – had no or mild fibrosis.
At treatment initiation, 96% of the HCV/HIV group were on antiretroviral therapy, 86% showed suppression of HIV RNA, 44% had AIDS, and 32% had a CD4 count below 500 cells/mm3.
The sustained viral response rate was similar in the two groups of patients – 41% in the HCV/HIV group and 42% in HCV-only patients – despite the fact that the HCV monoinfected patients had a higher prevalence of the tough to treat genotypes.
Roughly 12 million people worldwide are coinfected with HCV and HIV.
Dr. McPhee reported having no relevant financial disclosures.
AT ESPID 2017
Key clinical point:
Major finding: By age 20 years, 24% of a group of patients with vertically transmitted HCV/HIV coinfection had progressed to advanced hepatic fibrosis, compared with 6% of patients with vertically transmitted HCV monoinfection.
Data source: This retrospective, multicenter, observational Spanish study included 71 children with vertically transmitted HCV/HIV coinfection and 71 with vertically transmitted HCV monoinfection.
Disclosures: Dr. McPhee reported having no relevant financial disclosures.
Relatives of NAFLD patients: 12-fold higher risk
Asymptomatic first-degree relatives of patients who have nonalcoholic fatty liver disease with cirrhosis are at a 12-fold higher risk for advanced liver fibrosis compared with the general population, according to a report published online June 19 in the Journal of Clinical Investigation.
If this preliminary but robust association is confirmed in further research, it may well change clinical practice. First-degree relatives would likely require screening for advanced fibrosis, and those found to have it would likely need continued surveillance for hepatocellular carcinoma.
They noted that previous studies have suggested a familial component to NAFLD, and decided to assess the risk of advanced fibrosis in first-degree relatives of patients who had NAFLD plus cirrhosis. The investigators used noninvasive imaging techniques – MRI-PDFF (MRI proton density fat fraction) and MRE (magnetic resonance elastography) – to quantify liver fat and liver fibrosis in 26 patients who had NAFLD plus cirrhosis, 39 of their first-degree relatives who were asymptomatic, 69 community-dwelling adults who did not have NAFLD or cirrhosis, and 69 of their first-degree relatives.
The primary outcome measure, the prevalence of advanced liver fibrosis, was 18% among first-degree relatives of patients who had NAFLD plus cirrhosis. This was markedly greater than the prevalence of advanced fibrosis among first-degree relatives of unaffected adults (1.4%).
The odds ratio of having advanced fibrosis among first-degree relatives of affected patients was 14.9, compared with the control population. When the data were adjusted to account for age, sex, body mass index, and diabetes status, the OR remained statistically and clinically significant at 12.5, Dr. Caussy and her associates said (doi.org/10.1172/JCI93465).
This study was limited in that it was a single-center investigation and used advanced MRI techniques that may not be routinely available at other centers. In addition, since it was cross-sectional in design, long-term outcomes, such as the development of hepatocellular carcinoma and survival rates, could not be assessed.
“Despite these limitations, we believe that this study provides important data that require validation in larger studies to then change clinical practice guidelines to screen first-degree relatives of patients with NAFLD with cirrhosis,” the investigators added.
The National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Environmental Health Sciences supported the study. Dr. Caussy and her associates reported having no relevant financial disclosures.
Asymptomatic first-degree relatives of patients who have nonalcoholic fatty liver disease with cirrhosis are at a 12-fold higher risk for advanced liver fibrosis compared with the general population, according to a report published online June 19 in the Journal of Clinical Investigation.
If this preliminary but robust association is confirmed in further research, it may well change clinical practice. First-degree relatives would likely require screening for advanced fibrosis, and those found to have it would likely need continued surveillance for hepatocellular carcinoma.
They noted that previous studies have suggested a familial component to NAFLD, and decided to assess the risk of advanced fibrosis in first-degree relatives of patients who had NAFLD plus cirrhosis. The investigators used noninvasive imaging techniques – MRI-PDFF (MRI proton density fat fraction) and MRE (magnetic resonance elastography) – to quantify liver fat and liver fibrosis in 26 patients who had NAFLD plus cirrhosis, 39 of their first-degree relatives who were asymptomatic, 69 community-dwelling adults who did not have NAFLD or cirrhosis, and 69 of their first-degree relatives.
The primary outcome measure, the prevalence of advanced liver fibrosis, was 18% among first-degree relatives of patients who had NAFLD plus cirrhosis. This was markedly greater than the prevalence of advanced fibrosis among first-degree relatives of unaffected adults (1.4%).
The odds ratio of having advanced fibrosis among first-degree relatives of affected patients was 14.9, compared with the control population. When the data were adjusted to account for age, sex, body mass index, and diabetes status, the OR remained statistically and clinically significant at 12.5, Dr. Caussy and her associates said (doi.org/10.1172/JCI93465).
This study was limited in that it was a single-center investigation and used advanced MRI techniques that may not be routinely available at other centers. In addition, since it was cross-sectional in design, long-term outcomes, such as the development of hepatocellular carcinoma and survival rates, could not be assessed.
“Despite these limitations, we believe that this study provides important data that require validation in larger studies to then change clinical practice guidelines to screen first-degree relatives of patients with NAFLD with cirrhosis,” the investigators added.
The National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Environmental Health Sciences supported the study. Dr. Caussy and her associates reported having no relevant financial disclosures.
Asymptomatic first-degree relatives of patients who have nonalcoholic fatty liver disease with cirrhosis are at a 12-fold higher risk for advanced liver fibrosis compared with the general population, according to a report published online June 19 in the Journal of Clinical Investigation.
If this preliminary but robust association is confirmed in further research, it may well change clinical practice. First-degree relatives would likely require screening for advanced fibrosis, and those found to have it would likely need continued surveillance for hepatocellular carcinoma.
They noted that previous studies have suggested a familial component to NAFLD, and decided to assess the risk of advanced fibrosis in first-degree relatives of patients who had NAFLD plus cirrhosis. The investigators used noninvasive imaging techniques – MRI-PDFF (MRI proton density fat fraction) and MRE (magnetic resonance elastography) – to quantify liver fat and liver fibrosis in 26 patients who had NAFLD plus cirrhosis, 39 of their first-degree relatives who were asymptomatic, 69 community-dwelling adults who did not have NAFLD or cirrhosis, and 69 of their first-degree relatives.
The primary outcome measure, the prevalence of advanced liver fibrosis, was 18% among first-degree relatives of patients who had NAFLD plus cirrhosis. This was markedly greater than the prevalence of advanced fibrosis among first-degree relatives of unaffected adults (1.4%).
The odds ratio of having advanced fibrosis among first-degree relatives of affected patients was 14.9, compared with the control population. When the data were adjusted to account for age, sex, body mass index, and diabetes status, the OR remained statistically and clinically significant at 12.5, Dr. Caussy and her associates said (doi.org/10.1172/JCI93465).
This study was limited in that it was a single-center investigation and used advanced MRI techniques that may not be routinely available at other centers. In addition, since it was cross-sectional in design, long-term outcomes, such as the development of hepatocellular carcinoma and survival rates, could not be assessed.
“Despite these limitations, we believe that this study provides important data that require validation in larger studies to then change clinical practice guidelines to screen first-degree relatives of patients with NAFLD with cirrhosis,” the investigators added.
The National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Environmental Health Sciences supported the study. Dr. Caussy and her associates reported having no relevant financial disclosures.
FROM THE JOURNAL OF CLINICAL INVESTIGATION
Key clinical point: First-degree relatives of patients who have nonalcoholic fatty liver disease with cirrhosis are at a 12-fold higher risk of advanced liver fibrosis compared with the general population.
Major finding: The adjusted odds ratio of having advanced fibrosis among first-degree relatives of affected patients was 12.5, compared with the control population.
Data source: A cross-sectional cohort study involving 25 probands with NAFLD + cirrhosis, 39 first-degree relatives, and 69 control pairs of relatives from the general population.
Disclosures: The National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Environmental Health Sciences supported the study. Dr. Caussy and her associates reported having no relevant financial disclosures.
Steatosis linked to persistent ALT increase in hepatitis B
About one in five patients with chronic hepatitis B virus (HBV) infection had persistently elevated alanine aminotransferase (ALT) levels despite long-term treatment with tenofovir disoproxil fumarate, according to data from two phase III trials reported in the July issue of Clinical Gastroenterology and Hepatology (2017. doi: 10.1016/j.cgh.2017.01.032).
“Both host and viral factors, particularly hepatic steatosis and hepatitis B e antigen [HBeAg] seropositivity, are important contributors to this phenomenon,” Ira M. Jacobson, MD, of Mount Sinai Beth Israel Medical Center, New York, wrote with his associates. “Although serum ALT may indicate significant liver injury, this association is inconsistent, suggesting that relying on serum ALT alone is not sufficient to gauge either the extent of liver injury or the impact of antiviral therapy.”
Long-term treatment with newer antivirals such as tenofovir disoproxil fumarate (TDF) achieves complete viral suppression and improves liver histology in most cases of HBV infection. Transaminase levels are used to track long-term clinical response but sometimes remain elevated in the face of complete virologic response and regression of fibrosis. To explore predictors of this outcome, the researchers analyzed data from 471 chronic HBV patients receiving TDF 300 mg once daily for 5 years as part of two ongoing phase III trials (NCT00117676 and NCT00116805). At baseline, about 25% of patients were cirrhotic (Ishak fibrosis score greater than or equal to 5) and none had decompensated cirrhosis. A central laboratory analyzed ALT levels, which were up to 10 times the upper limit of normal in both HBeAg-positive and -negative patients and were at least twice the upper limit of normal in all HBeAg-positive patients.
After 5 years of TDF, ALT levels remained elevated in 87 (18%) of patients. Patients with at least 5% (grade 1) steatosis at baseline were significantly more likely to have persistent ALT elevation than were those with less or no steatosis (odds ratio, 2.2; 95% confidence interval, 1.03-4.9; P = .04). At least grade 1 steatosis at year 5 also was associated with persistent ALT elevation (OR, 3.4; 95% CI, 1.6-7.4; P =.002). Other significant correlates included HBeAg seropositivity (OR, 3.3; 95% CI, 1.7-6.6; P less than .001) and age 40 years or younger (OR, 2.1; 95% CI, 1.01-4.3; P = .046). Strikingly, half of HBeAg-positive patients with steatosis at baseline had elevated ALT at year 5, said the investigators.
Because many patients whose ALT values fall within commercial laboratory reference ranges have chronic active necroinflammation or fibrogenesis, the researchers performed a sensitivity analysis of patients who achieved a stricter definition of ALT normalization of no more than 30 U/L for men and 19 U/L for women that has been previously recommended (Ann Intern Med. 2002;137:1-10). In this analysis, 47% of patients had persistently elevated ALT despite effective virologic suppression, and the only significant predictor of persistent ALT elevation was grade 1 or more steatosis at year 5 (OR, 6.2; 95% CI, 2.3-16.4; P less than .001). Younger age and HBeAg positivity plus age were no longer significant.
Hepatic steatosis is common overall and in chronic HBV infection and often leads to increased serum transaminases, the researchers noted. Although past work has linked a PNPLA3 single nucleotide polymorphism to obesity, metabolic syndrome, and hepatic steatosis, the presence of this single nucleotide polymorphism was not significant in their study, possibly because many patients lacked genotype data, they added. “Larger longitudinal studies are warranted to further explore this factor and its potential effect on the biochemical response to antiviral treatment in [chronic HBV] patients,” they concluded.
Gilead Sciences sponsored the study. Dr. Jacobson disclosed consultancy, honoraria, and research ties to Gilead and several other pharmaceutical companies.
Antiviral therapy for chronic hepatitis B virus in most treated patients suppresses rather than eradicates infection. Despite this, long-term treatment results in substantial histologic improvement – including regression of fibrosis and reduction in complications.
However, as Jacobson et al. report in a histologic follow-up of 471 HBV patients treated long-term, aminotransferase elevation persisted in 18%. Factors implicated on multivariate analysis in unresolved biochemical dysfunction included HBeAg seropositivity, age less than 40 years, and steatosis at entry, in addition to steatosis at 5-year follow-up. The only association with hepatic dysfunction that persisted was steatosis when modified normal ranges for aminotransferases proposed by Prati were applied, namely 30 U for men and 19 U for women. This suggests that metabolic rather than viral factors are implicated in persistent biochemical dysfunction in patients with chronic HBV infection. Steatosis is also a frequent finding on liver biopsy in patients with chronic HCV infection.
Importantly, HCV-specific mechanisms have been implicated in the accumulation of steatosis in infected patients, as the virus may interfere with host lipid metabolism. HCV genotype 3 has a marked propensity to cause fat accumulation in hepatocytes, which appears to regress with successful antiviral therapy. In the interferon era, hepatic steatosis had been identified as a predictor of nonresponse to therapy for HCV. In patients with chronic viral hepatitis, attention needs to be paid to cofactors in liver disease – notably the metabolic syndrome – particularly because successfully treated patients are now discharged from the care of specialists.
Paul S. Martin, MD, is chief, division of hepatology, professor of medicine, University of Miami Health System, Fla. He has been a consultant and investigator for Gilead, BMS, and Merck.
Antiviral therapy for chronic hepatitis B virus in most treated patients suppresses rather than eradicates infection. Despite this, long-term treatment results in substantial histologic improvement – including regression of fibrosis and reduction in complications.
However, as Jacobson et al. report in a histologic follow-up of 471 HBV patients treated long-term, aminotransferase elevation persisted in 18%. Factors implicated on multivariate analysis in unresolved biochemical dysfunction included HBeAg seropositivity, age less than 40 years, and steatosis at entry, in addition to steatosis at 5-year follow-up. The only association with hepatic dysfunction that persisted was steatosis when modified normal ranges for aminotransferases proposed by Prati were applied, namely 30 U for men and 19 U for women. This suggests that metabolic rather than viral factors are implicated in persistent biochemical dysfunction in patients with chronic HBV infection. Steatosis is also a frequent finding on liver biopsy in patients with chronic HCV infection.
Importantly, HCV-specific mechanisms have been implicated in the accumulation of steatosis in infected patients, as the virus may interfere with host lipid metabolism. HCV genotype 3 has a marked propensity to cause fat accumulation in hepatocytes, which appears to regress with successful antiviral therapy. In the interferon era, hepatic steatosis had been identified as a predictor of nonresponse to therapy for HCV. In patients with chronic viral hepatitis, attention needs to be paid to cofactors in liver disease – notably the metabolic syndrome – particularly because successfully treated patients are now discharged from the care of specialists.
Paul S. Martin, MD, is chief, division of hepatology, professor of medicine, University of Miami Health System, Fla. He has been a consultant and investigator for Gilead, BMS, and Merck.
Antiviral therapy for chronic hepatitis B virus in most treated patients suppresses rather than eradicates infection. Despite this, long-term treatment results in substantial histologic improvement – including regression of fibrosis and reduction in complications.
However, as Jacobson et al. report in a histologic follow-up of 471 HBV patients treated long-term, aminotransferase elevation persisted in 18%. Factors implicated on multivariate analysis in unresolved biochemical dysfunction included HBeAg seropositivity, age less than 40 years, and steatosis at entry, in addition to steatosis at 5-year follow-up. The only association with hepatic dysfunction that persisted was steatosis when modified normal ranges for aminotransferases proposed by Prati were applied, namely 30 U for men and 19 U for women. This suggests that metabolic rather than viral factors are implicated in persistent biochemical dysfunction in patients with chronic HBV infection. Steatosis is also a frequent finding on liver biopsy in patients with chronic HCV infection.
Importantly, HCV-specific mechanisms have been implicated in the accumulation of steatosis in infected patients, as the virus may interfere with host lipid metabolism. HCV genotype 3 has a marked propensity to cause fat accumulation in hepatocytes, which appears to regress with successful antiviral therapy. In the interferon era, hepatic steatosis had been identified as a predictor of nonresponse to therapy for HCV. In patients with chronic viral hepatitis, attention needs to be paid to cofactors in liver disease – notably the metabolic syndrome – particularly because successfully treated patients are now discharged from the care of specialists.
Paul S. Martin, MD, is chief, division of hepatology, professor of medicine, University of Miami Health System, Fla. He has been a consultant and investigator for Gilead, BMS, and Merck.
About one in five patients with chronic hepatitis B virus (HBV) infection had persistently elevated alanine aminotransferase (ALT) levels despite long-term treatment with tenofovir disoproxil fumarate, according to data from two phase III trials reported in the July issue of Clinical Gastroenterology and Hepatology (2017. doi: 10.1016/j.cgh.2017.01.032).
“Both host and viral factors, particularly hepatic steatosis and hepatitis B e antigen [HBeAg] seropositivity, are important contributors to this phenomenon,” Ira M. Jacobson, MD, of Mount Sinai Beth Israel Medical Center, New York, wrote with his associates. “Although serum ALT may indicate significant liver injury, this association is inconsistent, suggesting that relying on serum ALT alone is not sufficient to gauge either the extent of liver injury or the impact of antiviral therapy.”
Long-term treatment with newer antivirals such as tenofovir disoproxil fumarate (TDF) achieves complete viral suppression and improves liver histology in most cases of HBV infection. Transaminase levels are used to track long-term clinical response but sometimes remain elevated in the face of complete virologic response and regression of fibrosis. To explore predictors of this outcome, the researchers analyzed data from 471 chronic HBV patients receiving TDF 300 mg once daily for 5 years as part of two ongoing phase III trials (NCT00117676 and NCT00116805). At baseline, about 25% of patients were cirrhotic (Ishak fibrosis score greater than or equal to 5) and none had decompensated cirrhosis. A central laboratory analyzed ALT levels, which were up to 10 times the upper limit of normal in both HBeAg-positive and -negative patients and were at least twice the upper limit of normal in all HBeAg-positive patients.
After 5 years of TDF, ALT levels remained elevated in 87 (18%) of patients. Patients with at least 5% (grade 1) steatosis at baseline were significantly more likely to have persistent ALT elevation than were those with less or no steatosis (odds ratio, 2.2; 95% confidence interval, 1.03-4.9; P = .04). At least grade 1 steatosis at year 5 also was associated with persistent ALT elevation (OR, 3.4; 95% CI, 1.6-7.4; P =.002). Other significant correlates included HBeAg seropositivity (OR, 3.3; 95% CI, 1.7-6.6; P less than .001) and age 40 years or younger (OR, 2.1; 95% CI, 1.01-4.3; P = .046). Strikingly, half of HBeAg-positive patients with steatosis at baseline had elevated ALT at year 5, said the investigators.
Because many patients whose ALT values fall within commercial laboratory reference ranges have chronic active necroinflammation or fibrogenesis, the researchers performed a sensitivity analysis of patients who achieved a stricter definition of ALT normalization of no more than 30 U/L for men and 19 U/L for women that has been previously recommended (Ann Intern Med. 2002;137:1-10). In this analysis, 47% of patients had persistently elevated ALT despite effective virologic suppression, and the only significant predictor of persistent ALT elevation was grade 1 or more steatosis at year 5 (OR, 6.2; 95% CI, 2.3-16.4; P less than .001). Younger age and HBeAg positivity plus age were no longer significant.
Hepatic steatosis is common overall and in chronic HBV infection and often leads to increased serum transaminases, the researchers noted. Although past work has linked a PNPLA3 single nucleotide polymorphism to obesity, metabolic syndrome, and hepatic steatosis, the presence of this single nucleotide polymorphism was not significant in their study, possibly because many patients lacked genotype data, they added. “Larger longitudinal studies are warranted to further explore this factor and its potential effect on the biochemical response to antiviral treatment in [chronic HBV] patients,” they concluded.
Gilead Sciences sponsored the study. Dr. Jacobson disclosed consultancy, honoraria, and research ties to Gilead and several other pharmaceutical companies.
About one in five patients with chronic hepatitis B virus (HBV) infection had persistently elevated alanine aminotransferase (ALT) levels despite long-term treatment with tenofovir disoproxil fumarate, according to data from two phase III trials reported in the July issue of Clinical Gastroenterology and Hepatology (2017. doi: 10.1016/j.cgh.2017.01.032).
“Both host and viral factors, particularly hepatic steatosis and hepatitis B e antigen [HBeAg] seropositivity, are important contributors to this phenomenon,” Ira M. Jacobson, MD, of Mount Sinai Beth Israel Medical Center, New York, wrote with his associates. “Although serum ALT may indicate significant liver injury, this association is inconsistent, suggesting that relying on serum ALT alone is not sufficient to gauge either the extent of liver injury or the impact of antiviral therapy.”
Long-term treatment with newer antivirals such as tenofovir disoproxil fumarate (TDF) achieves complete viral suppression and improves liver histology in most cases of HBV infection. Transaminase levels are used to track long-term clinical response but sometimes remain elevated in the face of complete virologic response and regression of fibrosis. To explore predictors of this outcome, the researchers analyzed data from 471 chronic HBV patients receiving TDF 300 mg once daily for 5 years as part of two ongoing phase III trials (NCT00117676 and NCT00116805). At baseline, about 25% of patients were cirrhotic (Ishak fibrosis score greater than or equal to 5) and none had decompensated cirrhosis. A central laboratory analyzed ALT levels, which were up to 10 times the upper limit of normal in both HBeAg-positive and -negative patients and were at least twice the upper limit of normal in all HBeAg-positive patients.
After 5 years of TDF, ALT levels remained elevated in 87 (18%) of patients. Patients with at least 5% (grade 1) steatosis at baseline were significantly more likely to have persistent ALT elevation than were those with less or no steatosis (odds ratio, 2.2; 95% confidence interval, 1.03-4.9; P = .04). At least grade 1 steatosis at year 5 also was associated with persistent ALT elevation (OR, 3.4; 95% CI, 1.6-7.4; P =.002). Other significant correlates included HBeAg seropositivity (OR, 3.3; 95% CI, 1.7-6.6; P less than .001) and age 40 years or younger (OR, 2.1; 95% CI, 1.01-4.3; P = .046). Strikingly, half of HBeAg-positive patients with steatosis at baseline had elevated ALT at year 5, said the investigators.
Because many patients whose ALT values fall within commercial laboratory reference ranges have chronic active necroinflammation or fibrogenesis, the researchers performed a sensitivity analysis of patients who achieved a stricter definition of ALT normalization of no more than 30 U/L for men and 19 U/L for women that has been previously recommended (Ann Intern Med. 2002;137:1-10). In this analysis, 47% of patients had persistently elevated ALT despite effective virologic suppression, and the only significant predictor of persistent ALT elevation was grade 1 or more steatosis at year 5 (OR, 6.2; 95% CI, 2.3-16.4; P less than .001). Younger age and HBeAg positivity plus age were no longer significant.
Hepatic steatosis is common overall and in chronic HBV infection and often leads to increased serum transaminases, the researchers noted. Although past work has linked a PNPLA3 single nucleotide polymorphism to obesity, metabolic syndrome, and hepatic steatosis, the presence of this single nucleotide polymorphism was not significant in their study, possibly because many patients lacked genotype data, they added. “Larger longitudinal studies are warranted to further explore this factor and its potential effect on the biochemical response to antiviral treatment in [chronic HBV] patients,” they concluded.
Gilead Sciences sponsored the study. Dr. Jacobson disclosed consultancy, honoraria, and research ties to Gilead and several other pharmaceutical companies.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: In patients with chronic hepatitis B virus infection, steatosis was significantly associated with persistently elevated alanine aminotransferase (ALT) levels despite successful treatment with tenofovir disoproxil fumarate.
Major finding: At baseline and after 5 years of treatment, steatosis of grade 1 (5%) or more predicted persistent ALT elevation with odds ratios of 2.2 (P = .04) and 3.4 (P = .002), respectively.
Data source: Two phase III trials of tenofovir disoproxil fumarate in 471 patients with chronic hepatitis B virus infection.
Disclosures: Gilead Sciences sponsored the study. Dr. Jacobson disclosed consultancy, honoraria, and research ties to Gilead and several other pharmaceutical companies.
Cirrhosis linked to increased risk of stroke
reported online June 5 in JAMA Neurology.
Cirrhosis is known to be associated with “extrahepatic hemorrhagic and thrombotic processes, such as GI bleeding and venous thromboembolism. [But] the cerebrovascular complications of cirrhosis are comparatively less well understood.” Previous studies of the association with stroke have been small and have yielded conflicting results, with some finding a reduced incidence of stroke and others finding an increase among cirrhosis patients, said Neal S. Parikh, MD, of the Fell Family Brain and Mind Research Institute and Weill Cornell Medicine, both in New York, and his associates.
After the data were adjusted to account for stroke risk factors, relevant comorbidities, and demographic traits, the annual incidence of any type of stroke was significantly higher with cirrhosis than without cirrhosis (hazard ratio, 1.4). The association was stronger for intracranial hemorrhage (HR, 1.9) and subarachnoid hemorrhage (HR, 2.4) than for ischemic stroke (HR, 1.3).
The results of several secondary and sensitivity analyses were consistent with those of the primary analysis, regardless of whether the cirrhosis was alcohol-related or the stroke was fatal. The association was strongest among patients who had decompensated cirrhosis and was not evident at all among patients who had mild liver disease, Dr. Parikh and his associates said (JAMA Neurol. 2017 Jun 5 [doi: 10.1001/jamaneurol.2017.0923).
This study was not designed to explore the reasons for an association between cirrhosis and stroke, but the investigators noted many possible explanations. First, “cirrhosis is accompanied by a mixed coagulopathy, with potential implications for hemorrhagic and thrombotic processes.” It has been linked to many bleeding complications, including, most recently, cerebral microhemorrhages detectable on brain MRI. In addition, the underlying causes of cirrhosis, including alcohol abuse, hepatitis infection, and metabolic disease, may also contribute to stroke risk.
Alternatively, clinicians caring for patients with cirrhosis “may limit the aggressiveness of stroke prevention” – for example, by limiting antithrombotic medications or statins – because they are mindful of the patient’s increased risk of bleeding and hepatic toxicity, the investigators said.
reported online June 5 in JAMA Neurology.
Cirrhosis is known to be associated with “extrahepatic hemorrhagic and thrombotic processes, such as GI bleeding and venous thromboembolism. [But] the cerebrovascular complications of cirrhosis are comparatively less well understood.” Previous studies of the association with stroke have been small and have yielded conflicting results, with some finding a reduced incidence of stroke and others finding an increase among cirrhosis patients, said Neal S. Parikh, MD, of the Fell Family Brain and Mind Research Institute and Weill Cornell Medicine, both in New York, and his associates.
After the data were adjusted to account for stroke risk factors, relevant comorbidities, and demographic traits, the annual incidence of any type of stroke was significantly higher with cirrhosis than without cirrhosis (hazard ratio, 1.4). The association was stronger for intracranial hemorrhage (HR, 1.9) and subarachnoid hemorrhage (HR, 2.4) than for ischemic stroke (HR, 1.3).
The results of several secondary and sensitivity analyses were consistent with those of the primary analysis, regardless of whether the cirrhosis was alcohol-related or the stroke was fatal. The association was strongest among patients who had decompensated cirrhosis and was not evident at all among patients who had mild liver disease, Dr. Parikh and his associates said (JAMA Neurol. 2017 Jun 5 [doi: 10.1001/jamaneurol.2017.0923).
This study was not designed to explore the reasons for an association between cirrhosis and stroke, but the investigators noted many possible explanations. First, “cirrhosis is accompanied by a mixed coagulopathy, with potential implications for hemorrhagic and thrombotic processes.” It has been linked to many bleeding complications, including, most recently, cerebral microhemorrhages detectable on brain MRI. In addition, the underlying causes of cirrhosis, including alcohol abuse, hepatitis infection, and metabolic disease, may also contribute to stroke risk.
Alternatively, clinicians caring for patients with cirrhosis “may limit the aggressiveness of stroke prevention” – for example, by limiting antithrombotic medications or statins – because they are mindful of the patient’s increased risk of bleeding and hepatic toxicity, the investigators said.
reported online June 5 in JAMA Neurology.
Cirrhosis is known to be associated with “extrahepatic hemorrhagic and thrombotic processes, such as GI bleeding and venous thromboembolism. [But] the cerebrovascular complications of cirrhosis are comparatively less well understood.” Previous studies of the association with stroke have been small and have yielded conflicting results, with some finding a reduced incidence of stroke and others finding an increase among cirrhosis patients, said Neal S. Parikh, MD, of the Fell Family Brain and Mind Research Institute and Weill Cornell Medicine, both in New York, and his associates.
After the data were adjusted to account for stroke risk factors, relevant comorbidities, and demographic traits, the annual incidence of any type of stroke was significantly higher with cirrhosis than without cirrhosis (hazard ratio, 1.4). The association was stronger for intracranial hemorrhage (HR, 1.9) and subarachnoid hemorrhage (HR, 2.4) than for ischemic stroke (HR, 1.3).
The results of several secondary and sensitivity analyses were consistent with those of the primary analysis, regardless of whether the cirrhosis was alcohol-related or the stroke was fatal. The association was strongest among patients who had decompensated cirrhosis and was not evident at all among patients who had mild liver disease, Dr. Parikh and his associates said (JAMA Neurol. 2017 Jun 5 [doi: 10.1001/jamaneurol.2017.0923).
This study was not designed to explore the reasons for an association between cirrhosis and stroke, but the investigators noted many possible explanations. First, “cirrhosis is accompanied by a mixed coagulopathy, with potential implications for hemorrhagic and thrombotic processes.” It has been linked to many bleeding complications, including, most recently, cerebral microhemorrhages detectable on brain MRI. In addition, the underlying causes of cirrhosis, including alcohol abuse, hepatitis infection, and metabolic disease, may also contribute to stroke risk.
Alternatively, clinicians caring for patients with cirrhosis “may limit the aggressiveness of stroke prevention” – for example, by limiting antithrombotic medications or statins – because they are mindful of the patient’s increased risk of bleeding and hepatic toxicity, the investigators said.
FROM JAMA NEUROLOGY
Key clinical point: Cirrhosis was associated with an increased risk of stroke, especially hemorrhagic stroke, in a large nationally representative cohort study.
Major finding: The annual incidence of any type of stroke was significantly higher with cirrhosis than without cirrhosis (HR, 1.4), and this association was stronger for intracranial hemorrhage (HR, 1.9) and subarachnoid hemorrhage (HR, 2.4) than for ischemic stroke (HR, 1.3).
Data source: A retrospective cohort study involving a nationally representative sample of 1.6 million Medicare patients.
Disclosures: This study was supported by the National Institute of Neurological Disorders and Stroke and the Florence Gould Endowment for Discovery in Stroke. Dr. Parikh and his associates reported having no relevant financial disclosures.
Distance from transplant center predicted mortality in chronic liver disease
Living more than 150 miles from a liver transplant center was associated with a higher risk of mortality among patients with chronic liver failure, regardless of etiology, transplantation status, or whether patients had decompensated cirrhosis or hepatocellular carcinoma, according to a first-in-kind, population-based study reported in the June issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.02.023).
The findings underscore the need for accessible, specialized liver care irrespective of whether patients with chronic liver failure (CLF) are destined for transplantation, David S. Goldberg, MD, of the University of Pennsylvania, Philadelphia, wrote with his associates. The associations “do not provide cause and effect,” but underscore the need to consider “the broader impact of transplant-related policies that could decrease transplant volumes and threaten closures of smaller liver transplant centers that serve geographically isolated populations in the Southeast and Midwest,” they added.
A total of 879 (5.2%) patients lived more than 150 miles from the nearest liver transplant center, the analysis showed. Even after controlling for etiology of liver disease, this subgroup was at significantly greater risk of mortality (hazard ratio, 1.2; 95% confidence interval, 1.1-1.3; P less than .001) and of dying without undergoing transplantation (HR, 1.2; 95% CI, 1.1-1.3; P = .003) than were patients who were less geographically isolated. Distance from a transplant center also predicted overall and transplant-free mortality when modeled as a continuous variable, with hazard ratios of 1.02 (P = .02) and 1.03 (P = .04), respectively. “Although patients living more than 150 miles from a liver transplant center had fewer outpatient gastroenterologist visits, this covariate did not affect the final models,” the investigators reported. Rural locality did not predict mortality after controlling for distance from a transplant center, and neither did living in a low-income zip code, they added.
Data from the Centers for Disease Control and Prevention indicate that age-adjusted rates of death from liver disease are lowest in New York, where the entire population lives within 150 miles of a liver transplant center, the researchers noted. “By contrast, New Mexico and Wyoming have the highest age-adjusted death rates, and more than 95% of those states’ populations live more than 150 miles from a [transplant] center,” they emphasized. “The management of most patients with CLF is not centered on transplantation, but rather the spectrum of care for decompensated cirrhosis and hepatocellular carcinoma. Thus, maintaining access to specialized liver care is important for patients with CLF.”
Dr. Goldberg received support from the National Institutes of Health. The investigators had no conflicts.
Living more than 150 miles from a liver transplant center was associated with a higher risk of mortality among patients with chronic liver failure, regardless of etiology, transplantation status, or whether patients had decompensated cirrhosis or hepatocellular carcinoma, according to a first-in-kind, population-based study reported in the June issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.02.023).
The findings underscore the need for accessible, specialized liver care irrespective of whether patients with chronic liver failure (CLF) are destined for transplantation, David S. Goldberg, MD, of the University of Pennsylvania, Philadelphia, wrote with his associates. The associations “do not provide cause and effect,” but underscore the need to consider “the broader impact of transplant-related policies that could decrease transplant volumes and threaten closures of smaller liver transplant centers that serve geographically isolated populations in the Southeast and Midwest,” they added.
A total of 879 (5.2%) patients lived more than 150 miles from the nearest liver transplant center, the analysis showed. Even after controlling for etiology of liver disease, this subgroup was at significantly greater risk of mortality (hazard ratio, 1.2; 95% confidence interval, 1.1-1.3; P less than .001) and of dying without undergoing transplantation (HR, 1.2; 95% CI, 1.1-1.3; P = .003) than were patients who were less geographically isolated. Distance from a transplant center also predicted overall and transplant-free mortality when modeled as a continuous variable, with hazard ratios of 1.02 (P = .02) and 1.03 (P = .04), respectively. “Although patients living more than 150 miles from a liver transplant center had fewer outpatient gastroenterologist visits, this covariate did not affect the final models,” the investigators reported. Rural locality did not predict mortality after controlling for distance from a transplant center, and neither did living in a low-income zip code, they added.
Data from the Centers for Disease Control and Prevention indicate that age-adjusted rates of death from liver disease are lowest in New York, where the entire population lives within 150 miles of a liver transplant center, the researchers noted. “By contrast, New Mexico and Wyoming have the highest age-adjusted death rates, and more than 95% of those states’ populations live more than 150 miles from a [transplant] center,” they emphasized. “The management of most patients with CLF is not centered on transplantation, but rather the spectrum of care for decompensated cirrhosis and hepatocellular carcinoma. Thus, maintaining access to specialized liver care is important for patients with CLF.”
Dr. Goldberg received support from the National Institutes of Health. The investigators had no conflicts.
Living more than 150 miles from a liver transplant center was associated with a higher risk of mortality among patients with chronic liver failure, regardless of etiology, transplantation status, or whether patients had decompensated cirrhosis or hepatocellular carcinoma, according to a first-in-kind, population-based study reported in the June issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.02.023).
The findings underscore the need for accessible, specialized liver care irrespective of whether patients with chronic liver failure (CLF) are destined for transplantation, David S. Goldberg, MD, of the University of Pennsylvania, Philadelphia, wrote with his associates. The associations “do not provide cause and effect,” but underscore the need to consider “the broader impact of transplant-related policies that could decrease transplant volumes and threaten closures of smaller liver transplant centers that serve geographically isolated populations in the Southeast and Midwest,” they added.
A total of 879 (5.2%) patients lived more than 150 miles from the nearest liver transplant center, the analysis showed. Even after controlling for etiology of liver disease, this subgroup was at significantly greater risk of mortality (hazard ratio, 1.2; 95% confidence interval, 1.1-1.3; P less than .001) and of dying without undergoing transplantation (HR, 1.2; 95% CI, 1.1-1.3; P = .003) than were patients who were less geographically isolated. Distance from a transplant center also predicted overall and transplant-free mortality when modeled as a continuous variable, with hazard ratios of 1.02 (P = .02) and 1.03 (P = .04), respectively. “Although patients living more than 150 miles from a liver transplant center had fewer outpatient gastroenterologist visits, this covariate did not affect the final models,” the investigators reported. Rural locality did not predict mortality after controlling for distance from a transplant center, and neither did living in a low-income zip code, they added.
Data from the Centers for Disease Control and Prevention indicate that age-adjusted rates of death from liver disease are lowest in New York, where the entire population lives within 150 miles of a liver transplant center, the researchers noted. “By contrast, New Mexico and Wyoming have the highest age-adjusted death rates, and more than 95% of those states’ populations live more than 150 miles from a [transplant] center,” they emphasized. “The management of most patients with CLF is not centered on transplantation, but rather the spectrum of care for decompensated cirrhosis and hepatocellular carcinoma. Thus, maintaining access to specialized liver care is important for patients with CLF.”
Dr. Goldberg received support from the National Institutes of Health. The investigators had no conflicts.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Geographic isolation from a liver transplant center independently predicted mortality among patients with chronic liver failure.
Major finding: In adjusted analyses, patients who lived more than 150 miles from a liver transplant center were at significantly greater risk of mortality (HR, 1.2; 95% CI, 1.1-1.3; P less than .001) and of dying without undergoing transplantation (HR, 1.2; 95% CI, 1.1-1.3; P = .003) than were patients who were less geographically isolated.
Data source: A retrospective cohort study of 16,824 patients with chronic liver failure who were included in the Healthcare Integrated Research Database between 2006 and 2014.
Disclosures: Dr. Goldberg received support from the National Institutes of Health. The investigators had no conflicts.