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Background Little is known about cause and intervention for alanine aminotransferase (ALT) elevation after complete viral suppression in patients with chronic hepatitis B (CHB). Methods In this prospective cohort study, patients with CHB who were treated with nucleos(t)ide analogs and maintained undetectable levels of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) for at least 6 months were enrolled. Patients were followed up at 6-month intervals, and anthropometric, biochemical, and virological assessments were performed. Results Of 1965 patients with median follow-up of 18.36 months, one third of patients experienced ALT elevation. Baseline high body mass index ([BMI] defined as ≥25 kg/m2), younger age, and liver cirrhosis independently increased the risk of longitudinal ALT elevation. At the end of follow-up, 89 (4.8%) patients reverted to low BMI, and 92 (5.0%) developed to high BMI. Compared with persistent high BMI, reversion to low BMI reduced the risk of ALT elevation (adjusted odds ratio [aOR], 0.38; 95% confidence interval [CI], 0.19–0.77); compared with persistent low BMI, onset of high BMI increased the risk of ALT elevation (aOR, 1.78; 95% CI, 1.02–3.11). Conclusions High BMI is an independent predictor for ALT elevation after complete HBV DNA suppression. Improvement of BMI may have a beneficial effect on ALT normalization and even long-term outcomes. [ABSTRACT FROM AUTHOR]

Toll-like receptor 2 (TLR2) plays an important role in the immunopathogenesis of hepatitis B virus (HBV) infection. The relationship between TLR2 expression and clinical outcome of chronic HBV infection is not yet elucidated in details so far. Here, we employed clinical cohorts to investigate TLR2 expression and function in different phases of HBV infection and dynamic changes of TLR2 expression in HBeAg-positive chronic hepatitis B (CHB) patients during antiviral therapy. TLR2 was mainly expressed in monocytes and its ligand stimulation resulted in TNF-α, IL-6 and IL-10 production. Serum soluble TLR2 (sTLR2) levels were negatively correlated with TLR2 mRNA in PBMCs. As compared with immunotolerant carriers and inactive carriers, CHB patients showed an elevated TLR2 expression and TNF-α, IL-6 induction in PBMC, but had a decreased level of sTLR2 in serum. However, TLR2 expression and TNF-α induction in monocytes of CHB patients remained lower than healthy controls. Furthermore, higher TLR2 expression in PBMCs and lower level of sTLR2 in serum at baseline were predictive of a complete response to 52 weeks of telbivudine (LdT) therapy. Temporal dynamic analysis showed that TLR2 expression was restored with viral suppression and ALT normalization from week 12 to 24. However, peg-IFN-α-2a therapy induced a slightly decline in TLR2 expression. In conclusion, TLR2 expression and function in monocytes were impaired by chronic HBV infection. Higher TLR2 expression in PBMC and lower level of sTLR2 in serum at baseline were associated with a complete response to LdT therapy, and dynamic TLR2 expression was differently regulated by LdT and peg-IFN-α-2a therapy. [ABSTRACT FROM AUTHOR]