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As there is currently a lack of consensus on the most appropriate dose and duration of peginterferon alfa-2a (PEG-IFNa-2a) therapy in hepatitis B e antigen (HBeAg)-positive patients, the efficacy and safety of either 24 or 48 weeks' duration and 90 lg/week or 180 lg/week doses were compared. HBeAg-positive patients (n 5 544; 34% genotype B, 51% genotype C) were randomized to receive PEG-IFNa-2a (2 3 2 factorial design) for 24 or 48 weeks and at 90 lg/week or 180 lg/week and included in the per-protocol population. The primary efficacy endpoint of the noninferiority study was HBeAg seroconversion 6 months posttreatment. The prespecified odds ratio (OR) noninferiority margin was 1.88 with a one-sided significance level of 0.025. The highest rates of HBeAg seroconversion 6 months posttreatment were in the 180/48 arm (36.2% versus 14.1%-25.8% in the other arms). When the dose and duration arms were pooled, the OR for noninferiority of 24 weeks versus 48 weeks was 2.17 (95% confidence interval [CI] 1.43, 3.31; P 5 0.749) and for 90 lg versus 180 lg was 1.79 (95% CI 1.18, 2.72; P 5 0.410). As the upper limit of the 95% CI of the ORs were >1.88, 24 weeks were inferior to 48 weeks and 90 lg/week was inferior to 180 lg/week. The highest rates of response in the 180/48 arm were achieved by patients with HBsAg <1,500 IU/mL at Week 12 (58%) or Week 24 (57%), whereas patients with HBsAg >20,000 IU/mL did not respond. Adverse events were typical of those associated with PEG-IFNa-2a. Conclusion: Compared with lower doses and shorter durations, the licensed PEG-IFNa-2a treatment regimen (180lg/ 48 weeks) was the most efficacious and beneficial for HBeAg-positive patients predominantly infected with hepatitis B virus genotypes B or C. (HEPATOLOGY 2011;54:1591-1599 P eginterferon alfa-2a (40 kD; PEG-IFNa-2a) has proven efficacy in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) 1 and is one of the first-line drugs recommended for CHB by all international treatment guidelines. 2-4Although the licensed dose and duration of PEG-IFNa-2a is 180 lg/week for 48 weeks, there is currently a lack of consensus on the most appropriate dose and duration, which is reflected in varying recommendations in international guidelines. The European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD) guidelines recommend 48 weeks of treatment, but EASL guidelines do not provide dose information for any of the antiviral agents recommended 2 ; Asian Pacific Association for the Study of the Liver (APASL) guidelines recommend 90-

Chronic hepatitis B and its life-threatening sequelae are highly prevalent in China. There is a need for effective new therapies to suppress hepatitis B virus (HBV) replication and ameliorate liver disease. In this study, we compared the efficacy of telbivudine, a nucleoside analogue, with lamivudine in Chinese patients. In this phase III, double-blind, multicenter trial conducted in China, 332 patients with compensated hepatitis B e antigen (HBeAg)-positive or HBeAg-negative chronic hepatitis B were randomly assigned to treatment with 600 mg of telbivudine or 100 mg of lamivudine daily for 104 weeks. The primary efficacy endpoint was reduction in serum HBV DNA levels at week 52 of treatment. Secondary endpoints included clearance of HBV DNA to undetectable levels, HBeAg loss and seroconversion, therapeutic response, and alanine aminotransferase (ALT) normalization. Viral resistance and safety were assessed. At week 52, among 290 HBeAg-positive patients, mean reductions of serum HBV DNA were significantly greater in telbivudine recipients than lamivudine recipients (6.3 log 10 versus 5.5 log 10 , P < 0.001), and HBV DNA was polymerase chain reaction-negative in significantly more telbivudine recipients than lamivudine recipients (67% versus 38%, P < 0.001). ALT normalization (87% versus 75%, P ‫؍‬ 0.007), therapeutic response (85% versus 62%, P ‫؍‬ 0.001), and HBeAg loss (31% versus 20%, P ‫؍‬ 0.047) were also significantly more common in the telbivudine group. Treatment effects showed similar patterns in the smaller HBeAg-negative group (n ‫؍‬ 42). Viral resistance in telbivudine recipients was approximately half that observed with lamivudine; however, this difference was not statistically significant. Clinical adverse events were similar in the two treatment groups. Conclusion: In Chinese patients with chronic hepatitis B, telbivudine treatment for 52 weeks provided greater antiviral and clinical efficacy than lamivudine, with less resistance. (

ObjectiveThe investigation regarding the clinical significance of quantitative hepatitis B core antibody (anti-HBc) during chronic hepatitis B (CHB) treatment is limited. The aim of this study was to determine the performance of anti-HBc as a predictor for hepatitis B e antigen (HBeAg) seroconversion in HBeAg-positive CHB patients treated with peginterferon (Peg-IFN) or nucleos(t)ide analogues (NUCs), respectively.DesignThis was a retrospective cohort study consisting of 231 and 560 patients enrolled in two phase IV, multicentre, randomised, controlled trials treated with Peg-IFN or NUC-based therapy for up to 2 years, respectively. Quantitative anti-HBc evaluation was conducted for all the available samples in the two trials by using a newly developed double-sandwich anti-HBc immunoassay.ResultsAt the end of trials, 99 (42.9%) and 137 (24.5%) patients achieved HBeAg seroconversion in the Peg-IFN and NUC cohorts, respectively. We defined 4.4 log10 IU/mL, with a maximum sum of sensitivity and specificity, as the optimal cut-off value of baseline anti-HBc level to predict HBeAg seroconversion for both Peg-IFN and NUC. Patients with baseline anti-HBc ≥4.4 log10 IU/mL and baseline HBV DNA <9 log10 copies/mL had 65.8% (50/76) and 37.1% (52/140) rates of HBeAg seroconversion in the Peg-IFN and NUC cohorts, respectively. In pooled analysis, other than treatment strategy, the baseline anti-HBc level was the best independent predictor for HBeAg seroconversion (OR 2.178; 95% CI 1.577 to 3.009; p<0.001).ConclusionsBaseline anti-HBc titre is a useful predictor of Peg-IFN and NUC therapy efficacy in HBeAg-positive CHB patients, which could be used for optimising the antiviral therapy of CHB.

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