The Drug-Induced Liver Injury Network (DILIN) studies hepatotoxicity caused by conventional medications as well as herbals and dietary supplements (HDS). To characterize hepatotoxicity and its outcomes from HDS versus medications, patients with hepatotoxicity attributed to medications or HDS were enrolled prospectively between 2004 and 2013. The study took place among eight U.S. referral centers that are part of the DILIN. Consecutive patients with liver injury referred to a DILIN center were eligible. The final sample comprised 130 (15.5%) of all subjects enrolled (839) who were judged to have experienced liver injury caused by HDS. Hepatotoxicity caused by HDS was evaluated by expert opinion. Demographic and clinical characteristics and outcome assessments, including death and liver transplantation (LT), were ascertained. Cases were stratified and compared according to the type of agent implicated in liver injury; 45 had injury caused by bodybuilding HDS, 85 by nonbodybuilding HDS, and 709 by medications. Liver injury caused by HDS increased from 7% to 20% (P < 0.001) during the study period. Bodybuilding HDS caused prolonged jaundice (median, 91 days) in young men, but did not result in any fatalities or LT. The remaining HDS cases presented as hepatocellular injury, predominantly in middle-aged women, and, more frequently, led to death or transplantation, compared to injury from medications (13% vs. 3%; P < 0.05). Conclusions: The proportion of liver injury cases attributed to HDS in DILIN has increased significantly. Liver injury from nonbodybuilding HDS is more severe than from bodybuilding HDS or medications, as evidenced by differences in unfavorable outcomes (death and transplantation). (Hepatology 2014;60:1399–1408)

Patients with hepatitis C virus (HCV) infection and cirrhosis are underrepresented in clinical trials of interferon‐free regimens of direct‐acting antiviral agents, making it difficult to optimize therapy. We performed a post‐hoc analysis of data from seven clinical trials to evaluate the efficacy and safety of the fixed‐dose combination of ledipasvir (LDV) and sofosbuvir (SOF), with and without ribavirin (RBV), in 513 treatment‐naïve and previously treated patients with genotype 1 HCV and compensated cirrhosis. All patients received LDV‐SOF for 12 or 24 weeks with or without RBV. We determined the rates of sustained virological response (SVR) 12 weeks after treatment (SVR12) overall and for subgroups. Of the 513 patients analyzed, 69% were previously treated and 47% had failed previous treatment with a protease‐inhibitor regimen. Overall, 493 patients (96%; 95% confidence interval [CI]: 94%‐98%) achieved SVR12, 98% of treatment‐naïve and 95% of previously treated patients. SVR12 rates did not vary greatly by treatment duration (95% of patients receiving 12 weeks and 98% of patients receiving 24 weeks of treatment), nor by addition of RBV (95% of patients receiving LDV‐SOF alone and 97% of those who received LDV‐SOF plus RBV), although previously treated patients receiving 12 weeks of LDV‐SOF without RBV had an SVR12 rate of 90%. One patient discontinued LDV‐SOF because of an adverse event (AE). The most common AEs were headache (23%), fatigue (16%‐19%), and asthenia (14%‐16%). One patient (<1%) of those receiving LDV‐SOF alone, and 4 (2%) of those receiving LDV‐SOF plus RBV had treatment‐related serious AEs. Conclusions: This analysis suggests that 12 weeks of LDV‐SOF is safe and effective for treatment‐naïve patients with HCV genotype 1 and compensated cirrhosis. The relatively lower SVR in treatment‐experienced patients treated with 12 weeks of LDV‐SOF raises the question of whether these patients would benefit from adding RBV or extending treatment duration to 24 weeks. (Hepatology 2015;62:79‐86)

Summary: Background: Malnutrition/sarcopenia and frailty are common in patients with cirrhosis and are associated with poor outcomes.Aim: To provide an overview of data on the importance, assessment and management of malnutrition/sarcopenia and frailty in cirrhosis.Methods: A literature search was conducted in PubMed and other sources, using the search terms “sarcopenia,” “muscle,” “malnutrition,” “cirrhosis,” “liver” and “frailty” from inception to April 2019, to identify the relevant studies and international guidelines.Results: The prevalence of malnutrition/sarcopenia in cirrhosis is 23%‐60%. Frailty generally overlaps with malnutrition/sarcopenia in cirrhosis, leading to increased morbidity and mortality. Rapid nutritional screening assessment should be performed in all patients with cirrhosis, and more specific tests for sarcopenia should be performed in those at high risk. The pathogenesis of malnutrition/sarcopenia in cirrhosis is complex/multifactorial and not just reduction in protein/calorie intake. Hyperammonemia appears to be the main driver of sarcopenia in cirrhosis through several molecular signalling pathways. Nutritional management in malnourished patients with cirrhosis should be undertaken by a multidisciplinary team to achieve adequate protein/calorie intake. While the role of branched‐chained amino acids remains somewhat contentious in achieving a global benefit of decreasing mortality‐ and liver‐related events, they, and vitamin supplements, are recommended for those with advanced liver disease. Novel strategies to reverse sarcopenia such as hormone supplementation, long‐term ammonia‐lowering agents and myostatin antagonists, are currently under investigation.Conclusions: Malnutrition/sarcopenia and frailty are unique, inter‐related and multi‐dimensional problems in cirrhosis which require special attention, prompt assessment and appropriate management as they significantly impact morbidity and mortality.