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Background and Aim: Besifovir dipivoxil maleate (BSV) was reported to have comparable antiviral efficacy and superior renal and bone safety to tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) patients. The present study aims to evaluate changes of liver histology and intrahepatic covalently closed circular DNA (cccDNA) levels by BSV treatment in comparison with TDF therapy. Methods: This is a subset study of the phase 3 trial comparing BSV with TDF. Among them, only CHB patients willing to participate in a histologic evaluation study were enrolled. Liver histologic examination and intrahepatic cccDNA quantification were performed. Results: A total of 46 CHB patients received liver biopsies (BSV, n = 29; TDF, n = 17). After 48 weeks of treatment, virological response rate was comparable between the groups (P = 0.707). Follow‐up liver biopsies showed that necroinflammation was significantly improved in the both groups. However, the histological response rate defined as the proportion of subjects whose modified histologic activity index score decreased by ≥ 2 without deterioration in fibrosis was higher in the BSV group than in the TDF group (77.8% vs 36.4%, P = 0.048). The proportion of subjects with Ishak fibrosis score 3 or more decreased from 77.7% to 55.5% in the BSV and that decreased from 72.7% to 45.4% in the TDF group. The intrahepatic cccDNA significantly decreased from baseline after 48 weeks of BSV or TDF treatment (P < 0.001) without intergroup differences (P = 0.349). Conclusions: The BSV therapy improves hepatic histology and decreases intrahepatic cccDNA in CHB patients. [ABSTRACT FROM AUTHOR]

Background and Aims: Analysis of alpha-fetoprotein (AFP) levels affords limited diagnostic accuracy because of the high false-positive rates, especially in those with active chronic hepatitis B (CHB). We measured AFP levels before and after commencement of oral antiviral therapy and explored the utility of these data in terms of early detection of hepatocellular carcinoma (HCC) in patients with CHB. Methods: A total of 207 patients with CHB who were treated with an oral antiviral agent were consecutively included. Dynamic changes in AFP levels and the diagnostic utility of such changes for HCC detection during the therapy were explored. Results: The proportions of patients showing elevated AFP levels (≥ 20 ng/mL) were 22.2%, 5.5%, and 1.3% at baseline; and at 6 and 12 months after commencement of antiviral therapy, respectively. All patients who did not suffer from HCC exhibited normalization of AFP levels at 12 months. The cumulative incidence of HCC was 9.5% during 36 months of follow-up. If AFP levels were over 20 ng/mL after 12 months of antiviral treatment, the probability of HCC development approached certainty. The positive predictive value for HCC development remained at 100% in patients prescribed long-term (≥ 12 months) antiviral therapy, if AFP levels persistently or abruptly elevated more than 12 ng/mL. Conclusions: In the era of oral antiviral agents, AFP might be a useful biomarker for HCC surveillance in patients with CHB. [ABSTRACT FROM AUTHOR]

Background and Aims Although prolonged lamivudine ( LAM) therapy is associated with the emergence of LAM-resistant mutations, it is still a commonly used therapy in many Asian countries because of its established long-term safety and low cost. The aim of our study was to assess the predictors of long-term LAM treatment response and to establish an individual prediction model ( IPM) for hepatitis B virus e antigen ( HBeAg) seroconversion in HBeAg-positive chronic hepatitis B ( CHB) patients. Methods This was a multicenter analysis of 838 patients treated with LAM between January 1999 and August 2004. Of these, 748 patients were followed up for at least 24 months. Results The median age was 43.0 years (range, 19-79 years) and the mean duration of LAM monotherapy was 34.2 ± 0.7 months. In the multivariate analysis, age (odds ratio [ OR] = 0.974, P < 0.001), baseline alanine aminotransferase level ( OR = 1.001, P = 0.014), and baseline hepatitis B virus DNA level ( OR = 0.749, P < 0.001) were independent factors for HBeAg seroconversion. Based on the predictors, an IPM was established. Patients were classified into high (> 50%), intermediate (30-50%), or low (≤ 30%) response groups based on their probability of HBeAg seroconversion according to the IPM. The cumulative HBeAg seroconversion rate at 6 years for the high, intermediate, and low response groups was 66.0%, 48.5%, and 21.8%, respectively ( P < 0.001). Conclusions An IPM was developed based on predictors of HBeAg seroconversion in HBeAg-positive CHB patients on LAM monotherapy. This model will allow screening of LAM responders prior to the commencement of antiviral treatment. [ABSTRACT FROM AUTHOR]