Background & Aims Chronic hepatitis B virus (HBV) infection is an important cause of cirrhosis and hepatocellular carcinoma worldwide; populations that migrate to the US and Canada might be disproportionately affected. The Hepatitis B Research Network (HBRN) is a cooperative network of investigators from the United States and Canada, created to facilitate clinical, therapeutic, and translational research in adults and children with hepatitis B. We describe the structure of the network and baseline characteristics of adults with hepatitis B enrolled in the network. Methods The HBRN collected data on clinical characteristics of 1625 adults with chronic HBV infection who are not receiving antiviral therapy from 21 clinical centers in North America. Results Half of the subjects in the HBRN are male, and the mean age is 42 years; 72% are Asian, 15% are Black, and 11% are White, with 82% born outside of North America. The most common HBV genotype was B (39%); 745 of subjects were negative for the hepatitis B e antigen. The median serum level of HBV DNA when the study began was 3.6 log10 IU/mL; 68% of male subjects and 67% of female subjects had levels of alanine aminotransferase above the normal range. Conclusions The HBRN cohort will be used to address important clinical and therapeutic questions for North Americans infected with chronic HBV and to guide health policies on HBV prevention and management in North America.

Disease burden is an important indicator of the state of health of a population. It can be measured as the frequency (e.g. incidence and prevalence) of a condition or its effects including: fatal and non-fatal health loss from disease (e.g. disability-adjusted life years (DALYs)) as well as the financial costs (e.g. direct health care costs and indirect health care expenditures related to lost income due to premature death). Accurate disease burden information is essential for policy-making such as prioritization of health interventions and allocation of resources. Chronic Liver Disease (CLD) causes substantial health and economic burden in the US, where nearly two million deaths annually are attributable to CLD. In the recent past, overall mortality rate of CLD has been increasing. Viral hepatitis and alcoholic liver disease are thought to be the most common etiologies of chronic liver diseases. More recently, the prevalence of non-alcoholic steatohepatitis (NAFLD) is rapidly increasing and non-alcoholic steatohepatitis (NASH) has become a leading indication for liver transplantation. In this work, we assemble available data on the burden of CLD in the United States, focusing on non-malignant complications, whereas the impact on mortality and healthcare expenses of hepatocellular carcinoma (HCC), an important consequence of CLD is discussed elsewhere.

Background and Aims Cirrhosis from hepatitis C virus (HCV) infection is a major cause of end-stage liver disease and hepatocellular carcinoma worldwide. We determine the prevalence of cirrhosis among HCV-infected American adults including those unaware of their infection. Methods Using the National Health and Nutrition Examination Survey (NHANES) data, we identified participants aged≥20 years with detectable serum HCV RNA. The prevalence of advanced fibrosis and cirrhosis was determined for Eras 1 (1988-94), 2 (1999-2006) and 3 (2007-12) by using FIB-4 > 3.25 and APRI > 2.0, respectively. Results Out of 52,644 NHANES examinees, 49,429 were tested for HCV, of whom 725 met the inclusion criteria (positive HCV RNA with available data for FIB-4 and APRI). Based on APRI, 6.6% (95% confidence interval [CI]:2.2-11.0) of HCV-infected adults in Era 1, 7.6% (95%CI:3.4-11.8) in Era 2 and 17.0% (95%CI:8.0-26.0) in Era 3 had cirrhosis. In the multivariable regression analysis, this era effect was attributable to increasing age (odds ratio [OR]:1.04, 95%CI:1.02-1.07), diabetes (OR:2.33, 95%CI:1.01-5.40) and obesity (OR:2.96, 95%CI:1.15-7.57). Cirrhosis was as common among respondents who were unaware of their infection as those who were aware (both 11%). Results were identical when FIB-4 was used. Conclusions Among HCV-infected American adults, the proportion with cirrhosis has increased rapidly. Cirrhosis prevalence remains high in individuals unaware of their HCV infection. These data highlight the urgency for HCV screening regardless of symptoms, systematic assessment for liver fibrosis in those with HCV infection and institution of antivirals to prevent advanced liver disease.

Non-selective beta-blockers have played an important role in the prevention of portal hypertensive bleeding in cirrhotic patients. However, recent studies have suggested that non-selective beta-blockers may be harmful in some patients with end-stage liver disease. To evaluate the association between use of non-selective beta-blocker and the incidence of acute kidney injury (AKI). We conducted a nested case-control study in a cohort of liver transplant waitlist registrants. Each patient with AKI was matched to a control by the model for end-stage liver disease (MELD)-Na score, age, serum creatinine, and follow-up duration. Out of a total of 2,361 waitlist registrants, 205 patients developed AKI after a median follow-up duration of 18.2 months. When compared to matched controls, ascites (79.0% versus 51.7%) and non-Caucasian race (16.6% versus 7.8%) were more common among the cases. The frequency of non-selective beta-blocker use was higher among the cases than controls, albeit insignificantly (45.9% versus 37.1%, P = .08). In multivariable analyses, the impact of non-selective beta-blockade on the development of AKI was dependent upon the presence of ascites: non-selective beta-blockade in patients with ascites significantly increased the risk of AKI (hazard ratio [HR], 3.31; 95% confidence interval [CI], 1.57-6.95), while in patients without ascites, non-selective beta-blocker use reduced it (HR, 0.19; 95% CI, 0.06-0.60). Potential benefits and harms of a non-selective beta-blocker in terms of AKI depend on the presence of ascites in liver transplant candidates. Non-selective beta-blocker therapy in cirrhotic patients may need to be individualized.