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Objectives: Chronic hepatitis B virus infection is a major cause of morbidity and mortality. The aim of the study is to describe the hepatic histology in children chronically infected with hepatitis B virus living in the United States and Canada., Methods: Liver biopsies of 134 treatment-naïve children with chronic hepatitis B virus infection were scored for inflammation, fibrosis, and other histological features, and correlated with clinical and laboratory data., Results: Sixty percentage of subjects acquired the infection vertically, 51% were male, and 69% were hepatitis B e antigen-positive at the time of the biopsy. Hepatitis B DNA levels were generally high (mean 7.70 log IU/mL), as was serum alanine aminotransferase (median 120 U/L). Using the Ishak-modified histology activity index scoring system, interface hepatitis was mild in 31%, moderate in 61%, and severe in 6%. Lobular inflammation was mild in 54%, moderate in 29%, and marked in 7%. Portal inflammation was mild in 38% and moderate in 62% of subjects. Eighteen percentage had no fibrosis, 59% had portal expansion without bridging fibrosis, 19% had bridging fibrosis, and 4% had cirrhosis. Alanine aminotransferase positively correlated with inflammation and fibrosis. Neither age, duration of infection, nor Hepatitis B virus DNA levels correlated with fibrosis. Fibrosis-4 index did not correlate with fibrosis but correlated with inflammation. Aspartate aminotransferase/platelet ratio index correlated with both inflammation and fibrosis., Conclusions: Chronic hepatitis B virus infection results in significant inflammation and fibrosis during childhood. Serum alanine aminotransferase is a strong indicator of the severity and extent of hepatic inflammation and fibrosis.

Monotherapy with interferon or nucleoside analog is generally not recommended during the immune-tolerant (IT) phase of chronic hepatitis B virus (HBV) infection. Recognition that high HBV DNA levels are associated with hepatocellular carcinoma has increased interest in treating HBV in the IT phase. Small pediatric studies reported efficacy with combination nucleoside analog and interferon therapy. The aim of this study was to evaluate the safety and efficacy of the combination of entecavir and peginterferon in adults in the IT phase of chronic HBV infection. Hepatitis B e antigen (HBeAg)-positive adults with HBV DNA > 10 7 IU/mL and alanine aminotransferase (ALT) ≤ 1.5 times the upper limit of normal (ULN) (male: ≤ 45, female: ≤ 30 U/L) received entecavir 0.5 mg daily for 8 weeks followed by the addition of peginterferon alfa-2a 180 µg/week to entecavir for an additional 40 weeks. The primary endpoint was HBeAg loss and HBV DNA ≤ 1,000 IU/mL 48 weeks after end of treatment (EOT). Among 28 participants from 11 sites, the median age was 37.2 (range: 22-61) years, 54% were male, and 96% were Asian. Nearly all were infected with genotype C (64%) or B (32%). Median baseline HBV DNA was 8.2 log 10 IU/mL, and ALT was 0.9 times the ULN. Although one (4%) participant cleared HBeAg, none met the primary endpoint of both HBeAg loss AND HBV DNA ≤ 1,000 IU/mL 48 weeks post-EOT. ALT elevations > 5 times the ULN occurred in eight (29%) participants, and none were associated with icterus. Forty-eight weeks posttreatment, HBV DNA rebounded to baseline levels in all participants, including the participant who lost HBeAg, and ALT values returned to near baseline levels in all but four participants. Conclusion: A lead-in strategy of 8 weeks of entecavir followed by combination peginterferon and entecavir therapy for 40 weeks had limited efficacy in adults in the IT phase of chronic HBV infection and cannot be recommended., (© 2018 by the American Association for the Study of Liver Diseases.)

Background & Aims: Chronic hepatitis B virus (HBV) infection is an important cause of cirrhosis and hepatocellular carcinoma worldwide; populations that migrate to the United States and Canada might be affected disproportionately. 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 the 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 men, and the median 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%); 74% 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 alanine aminotransferase levels higher than the normal range., Conclusions: The HBRN cohort is 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., (Published by Elsevier Inc.)