HBsAg Level as Predictor of Liver Fibrosis in HBeAg Positive Patients With Chronic Hepatitis B Virus Infection.

BACKGROUND AND AIMS: Preliminary data suggests lower serum hepatitis B surface antigen level is associated with more severe liver fibrosis in HBeAg positive patients. We evaluated the association of HBsAg level with biochemical, virological, and histological features in asymptomatic patients with chronic HBV infection. METHODS: HBsAg levels were measured at baseline in 481 asymptomatic, treatment naive patients with chronic HBV infection. Subjects were followed-up prospectively (median, 12; range, 8-36 months). Phases of HBV infection were defined after regular monitoring of HBV-DNA and transaminases. Liver histology was scored using the METAVIR system. RESULTS: HBeAg positive (n, 126) patients were significantly younger than HBeAg negative (n, 355), median age 26 vs 30 years; P < 0.01. HBV genotype could be determined in 350 patients, 240 (68.57%) had genotype D and 100 (28.57%) had genotype A. HBsAg level had modest correlation with serum HBV DNA(r = 0.6 vs 0.4 in eAg positive & negative respectively). HBeAg + ve patients with fibrosis score ≥ F2 showed significantly lower median serum HBsAg levels and serum HBV DNA levels compared with patients with F0-F1 score (median, range; 4.51, 2.99-6.10 vs 5.06, 4.13-5.89, P < 0.01) and (8.39, 3.85-10.60, P < 0.01) respectively. Significant inverse correlation of HBsAg level was found with liver fibrosis in eAg positive group (r = -0.76; P < 0.001). HBsAg level cut off value 4.7 log10 IU/ml predicted moderate to advance fibrosis (F ≥ 2) with 92% sensitivity, 85% specificity & 91% negative predictive value. CONCLUSION: Lower HBsAg level might reflect the status of advanced liver fibrosis in HBeAg positive chronic hepatitis B subjects.

Prolonged use of tenofovir and entecavir in hepatitis B virus-related cirrhosis.

BACKGROUND AND AIMS: Limited data is available from India on outcome and efficacy of tenofovir and entecavir in hepatitis B virus (HBV)-related cirrhosis when used for prolonged time. We report the long-term efficacy and outcome of these antiviral drugs in patients with chronic HBV infection, with compensated or decompensated cirrhosis. METHODS: We retrospectively analyzed laboratory and clinical data of 400 HBV-related cirrhotic patients without access to liver transplantation, who were treated with tenofovir/entecavir therapy, from January 2007 to January 2014. Two hundred and ten (52.5 %) patients had at least one of the components of decompensation at baseline. Two hundred and twenty (55 %) and 180 (45 %) patients were initiated tenofovir and entecavir, respectively. Follow up period was 45 (12-68) months for tenofovir and 36 (11-60) months for entecavir. RESULTS: At the end of 1 year, levels of HBV DNA <20 IU/mL were achieved in 91.8 % and 88.8 % of patients, and alanine aminotransferase normalized in 54.5 % and 55.5 % of patients who received tenofovir and entecavir, respectively. At the last visit, Child-Turcotte-Pugh scores improved among 29.5 % of patients who received tenofovir, 25 % of those who received entecavir, and remained stable in 61.9 % and 65 % patients, respectively, in both groups. The 5-year cumulative rate of liver decompensation, hepatocellular carcinoma, and cirrhosis-related complications were 3.1 %, 1.9 %, and 2.1 % with an annual incidence of 0.8 %, 0.3 %, and 0.5 % per person-year, respectively. CONCLUSION: Tenofovir and entecavir were effective and potent drugs for prolonged treatment of HBV cirrhosis and improved the overall clinical course.

Role of proinflammatory cytokines (interferon gamma) and anti-inflammatory cytokine (interleukin-10) gene polymorphisms in chronic hepatitis B infection: an Indian scenario.

Immune-mediated mechanisms have been found to play an important role in the progression of hepatitis B virus (HBV) infection. The outcomes of infection do not appear to be determined by viral strains. Instead, allelic variants in human genome are likely to affect the disease progression. Allelic variation of proinflammatory cytokines such as interferon gamma (IFN-γ) participates in the elimination of HBV, and interleukin-10 (IL-10) helps in inhibition of Th1 effector mechanisms for host defense. The aim of this study was to determine the influence of host genetic factors in chronic HBV infection and gene promoter polymorphism or single-nucleotide polymorphism analysis of IFN-γ+874 and IL-10 (-1082, -592, and -819) on disease progression and persistence. A total of 232 patients along with 76 healthy controls were included. Allele-specific primers for IFN-γ and restriction fragment length polymorphism for IL-10 were used. The study indicated that low IFN-γ expression probably impairs host immune response to HBV, rendering these subjects more prone to HBV infection. No significant differences were detected between the 2 groups in the distributions of IL-10 genotype at the -1082, -819, and -592 positions. Odds ratio indicated that heterozygosity of genotypes -819 CT and -592 AC was more strongly associated with liver chronicity. Significantly, AA homozygous genotype was dominant in chronic hepatitis B cases in IFN-γ+874 and IL-10 (-1082 and -592) and is associated with increased risk of persistent infection.