Background and Aim Hepatitis B core-related antigen (HBcrAg) has been shown to correlate with various viral markers in chronic hepatitis B, but its role in defining natural history is not well studied. We aimed to investigate the use of HBcrAg to define different phases of chronic hepatitis B. Methods Stored residual serum samples from longitudinal cohorts of chronic hepatitis B patients in Hong Kong and Japan were studied. Viral markers were measured in three serial serum samples for each patient. Patients were divided into six groups for analysis: hepatitis B e antigen (HBeAg)-positive chronic infection (EPI), HBeAg-positive chronic hepatitis (EPH), HBeAg seroconversion (ES), HBeAg-negative chronic hepatitis (ENH), HBeAg-negative chronic infection (ENI), and HBsAg seroclearance (SS). Results In total, 166 patients followed up for 100 (76-113) months were included. HBcrAg was correlated with hepatitis B virus DNA and HBsAg levels in both HBeAg-positive and HBeAg-negative patients. HBcrAg cut-off of >= 6.0 log U/mL could best differentiate HBeAg-positive from HBeAg-negative patients (area under receiver operating characteristic curve of 0.99, P < 0.001). HBcrAg could not differentiate patients in EPI and EPH phases, but HBcrAg declined dramatically at HBeAg seroconversion. In HBeAg-negative patients, HBcrAg >= 4.0 log U/mL could best differentiate ENH from ENI (area under receiver operating characteristic curve of 0.81; P < 0.001), with high specificity (81.6%) but only moderate sensitivity (65.7%) at baseline. Undetectable HBcrAg was found in 17%, 63%, and 89% patients in ENH, ENI, and SS groups at the last visit, respectively. Conclusions HBcrAg provides useful information to stage the natural history of chronic hepatitis B, particularly identifying HBeAg-positive patients and HBeAg-negative patients with active disease.

Introduction and aim: Occult hepatitis B virus infection (OBI) is characterized by the presence of replication-competent hepatitis B virus (HBV) DNA in the liver and/or serum of patients with undetectable levels of the HBV surface antigen (HBsAg). Due to the shared infection routes HIV positive patients are at higher risk of developing OBI, thus, the aim of this study was to determine the frequency of OBI in Mexican HIV-infected patients and to identify mutations in the HBV S gene that could be associated to the development of OBI. Materials and methods: Plasma samples from 50 HIV-infected patients with undetectable levels of the HBsAg were obtained and analyzed. The Core, PreS and S genes were amplified by nested PCR and sequenced by the Sanger method. To analyze HBV diversity in the OBI-positive patients, ten sequences of 762 bp from the HBV S gene were selected, cloned, and subsequently sequenced for mutational analyses. Results: OBI infection was found with a frequency of 36% (18/50). All the HBV sequences corresponded to the H genotype. The most common mutations were: C19Y, Q129H, E164D, and I195M, with a frequency of 44%, 36%, 39% and 48% respectively. Conclusions: In this study, we report the presence of OBI in a cohort of Mexican HIV-infected patients with an overall prevalence of 36%. Mutational analyses revealed that four non-silent mutations were frequent in different regions of the HBsAg gene, suggesting that they might be associated to the development of OBI in this population, nevertheless, further studies are required to determine their role in the pathogenesis of OBI. (C) 2020 Fundacion Clinica Medica Sur, A.C. Published by Elsevier Espana, S.L.U.