The prevalence of cirrhosis is higher than previously estimated. Many cases may be undiagnosed, and more than half are potentially preventable by controlling diabetes, alcohol abuse, and viral hepatitis. Public health efforts are needed to reduce this disease burden, particularly among racial/ethnic minorities and individuals at lower socioeconomic status.

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§ Drs. Murphy and Parikh contributed equally and are co-senior authors Author contributions: Dr. Singal had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design (Singal and Parikh); Acquisition, analysis and interpretation of the data (all authors); Drafting of the manuscript (Singal); Critical revision of the manuscript for important intellectual content (all authors); Obtained funding (Singal, Parikh); Administrative, technical, and material support (Singal and Parikh); Study supervision (Singal) Conflicts of Interest: Amit Singal was on speakers bureau for Gilead, Bayer, and Bristol Meyers Squibb. He has served on advisory boards for Gilead, Abbvie, Bayer, Eisai, Wako Diagnostics, Roche, and Exact Sciences. He serves as a consultant to Bayer, Eisai, Roche, and Glycotest. He has received research funding from Gilead and Abbvie. Neil Mehta has received research funding from Wako Diagnostics. Anjana Pillai serves as a consultant and is on speakers bureau for Eisai and BTG. Jordan Feld has received research support from Gilead, Abbvie, Merck, and Janssen. Binu John has served on advisory boards for Eisai. Catherine Frenette is on speakers bureaus for Bayer, Bristol Meyers Squibb, Gilead, Merck, Abbvie, and Eisai. She served on advisory boards for Gilead, Eisai, and Wako. She served as a consultant for Bayer and Gilead. She received research funding from Bayer. Parvez Mantry is on speakers bureaus and served on advisory boards for Gilead, Abbvie, Bayer, BMS, Eisai, Merck, and BTG. He has received research funding from Gilead and Sirtex. Michael Leise has received research funding from Abbvie. Kalyan Ram Bhamidimarri serves as scientific advisory board member for Gilead, Merck, and Abbvie. He has received research funding from Gilead. Laura Kulik is on speakers bureau for Eisai, Gilead, and Dova. She serves as an advisory board member for BMS, Eisai, Bayer, Exelixis Reena Salgia is on speakers bureau for Bayer. She has served on advisory boards for Bayer, Eisai, and Exelixis. Sanjaya Satapathy has received research support from Gilead and Bayer.He has served on advisory boards or as a consultant for Abbvie and Gilead.

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Hepatocellular carcinoma screening is associated with increased early tumor detection and improved survival; however, a minority of hepatocellular carcinoma patients are detected by screening. Interventions to increase screening use in patients with cirrhosis may help curb hepatocellular carcinoma mortality rates.

Patients with decompensated cirrhosis have high rates of hospitalization and frequently experience an early readmission. An early readmission to an acute care hospital is an independent predictor of mortality in patients with decompensated cirrhosis for at least 1 year following initial hospitalization.

Acute hepatitis E virus (HEV) infection is a leading cause of acute liver failure (ALF) in many developing countries yet rarely identified in Western countries. Since antibody testing for HEV infection is not routinely obtained, we hypothesized that HEV-related ALF might be present and unrecognized in North American ALF patients. Serum samples of 681 adults enrolled in the US ALF Study Group were tested for anti-HEV IgM and anti-HEV IgG levels. Subjects with a detectable anti-HEV IgM also underwent testing for HEV-RNA. Mean patient age was 41.8 years, 32.9% male, and ALF etiologies included acetaminophen hepatotoxicity (29%), indeterminate ALF (23%), idiosyncratic DILI (22%), acute HBV infection (12%), autoimmune hepatitis (12%) and pregnancy related ALF (2%). Three men ages 36, 39, and 70 demonstrated repeatedly detectable anti-HEV IgM but all were HEV RNA negative and had other putative diagnoses. The latter two subjects died within 3 and 11 days of enrollment while the 36 year old underwent emergency liver transplantation on study day 2. At admission, 294 (43.4%) of the ALF patients were anti-HEV IgG positive with the seroprevalence being highest in those from the Midwest (50%) and lowest in those from the Southeast (28%). Anti-HEV IgG + subjects were significantly older, less likely to have APAP overdose, and had a lower overall 3 week survival compared to anti-HEV IgG − subjects (63% vs 70%, p= 0.018). CONCLUSIONS Acute HEV infection is very rare in adult Americans with ALF (i.e., 0.4%) and could not be implicated in any indeterminate, autoimmune, or pregnancy-related ALF cases. Prior exposure to HEV with detectable anti-HEV IgG was significantly more common in the ALF patients compared to the general US population.

OBJECTIVES:Data from the United States are lacking regarding the impact of entecavir (ETV) on the risk of hepatocellular carcinoma (HCC). Our aim is to determine whether treatment with ETV is associated with a reduced HCC risk by calculating the expected HCC incidence based on the Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B (REACH-B) model and comparing it with the observed HCC incidence. METHODS:The incidence of HCC in US patients treated with ETV between 2005 and 2013 in a retrospective cohort was obtained. The predicted HCC incidence was calculated using the REACH-B model. The standardized incidence ratios (SIRs) were calculated as a ratio of observed over predicted HCC cases. RESULTS:Of 841 patients, 646 (65% male, 84% Asian, median age 47 years, 36% hepatitis B e antigen positive, 9.4% with cirrhosis) met the inclusion criteria. Over a median follow-up of 4 years, 17 (2.6%) cases of HCC were diagnosed, including 8 out of 61 (13.1%) patients with cirrhosis and 9 out of 585 (1.5%) without cirrhosis. Compared with those without HCC, the 17 patients with HCC were older at 53 years vs. 47 years and more likely to have cirrhosis at 47.1% vs. 8.4%. Among patients without cirrhosis, the observed HCC incidence was signifi cantly lower than predicted by the fourth year (SIR, 0.37; 95% confi dence interval: 0.166-0.82). A sensitivity analysis that comprised all patients, including those with cirrhosis, showed that at the maximum follow-up time of 8.2 years, a signifi cantly lower than predicted HCC incidence was noted with an SIR of 0.56 (95% confi dence interval: 0.35-0.905).CONCLUSIONS: Based on the REACH-B model, long-term ETV therapy was associated with a lower than predicted HCC incidence. However, the risk of HCC persisted, and careful HCC surveillance remains warranted despite the anti-viral treatment.SUPPLEMENTARY MATERIAL is linked to the online version of the paper at