Effects of telbivudine and entecavir for HBeAg-positive chronic hepatitis B: A meta-analysis

AIM:To compare the effects of telbivudine (LDT) and entecavir (ETV) in treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B by meta-analysis. METHODS:We conducted a literature search using PubMed, MEDLINE, EMBASE, the China National Knowledge Infrastructure, the VIP database, the Wanfang database and the Cochrane Controlled Trial Register for all relevant articles published before April 1, 2012. Randomized controlled trials (RCTs) comparing LDT with ETV for treatment of HBeAg-positive chronic hepatitis B were included. The data was analyzed with Review Manager Software 5.0. We used relative risk (RR) as an effect measure, and reported its 95% CI. Meta-analysis was performed using either a fixedeffect or random-effect model, based on the absence or presence of significant heterogeneity. Two reviewers assessed the risk of bias and extracted data indepen- dently and in duplicate. The analysis was executed using the main outcome parameters including hepatitis B virus (HBV) DNA undetectability, alanine aminotransferase (ALT) normalization, HBeAg loss, HBeAg seroconversion, drug-resistance, and adverse reactions. Meta-analysis of the included trials and subgroup analyses were conducted to examine the association between pre-specified characteristics with the therapeutic effects of the two agents. RESULTS:Thirteen eligible trials (3925 patients in total) were included and evaluated for methodological quality and heterogeneity. In various treatment durations of 4 wk, 8 wk, 12 wk, 24 wk, 36 wk, 48 wk, 52 wk, 60 wk and 72 wk, the rates of HBV DNA undetectability and ALT normalization in the two groups were similar, without statistical significance. At 4 wk and 8 wk of the treatment, no statistical differences were found in the rate of HBeAg loss between the two groups, while the rate in the LDT group was higher than in the ETV group at 12 wk, 24 wk, 48 wk and 52 wk, respectively (RR 2.28, 95% CI 1.16, 7.03, P = 0.02; RR 1.45, 95% CI 1.16, 1.82, P = 0.001; RR 1.45, 95% CI 1.11, 1.89, P = 0.006; and RR 1.86, 95% CI 1.04, 3.32, P = 0.04). At 4 wk, 8 wk, 60 wk and 72 wk of the treatment, there were no significant differences in the rate of HBeAg seroconversion between the two groups, while at 12 wk, 24 wk, 48 wk and 52 wk, the rate in the LDT group was higher than in the ETV group (RR 2.10, 95% CI 1.36, 3.24, P = 0.0008; RR 1.71, 95% CI 1.29, 2.28, P = 0.0002; RR 1.86, 95% CI 1.36, 2.54, P < 0.0001; and RR 1.87, 95% CI 1.21, 2.90, P = 0.005). The rate of drug-resistance was higher in the LDT group than in the ETV group (RR 3.76, 95% CI 1.28, 11.01, P = 0.02). In addition, no severe adverse drug reactions were observed in the two groups. And the rate of increased creatine kinase in the LDT group was higher than in the ETV group (RR 5.58, 95% CI 2.22, 13.98, P = 0.0002). CONCLUSION:LDT and ETV have similar virological and biomedical responses, and both are safe and well tolerated. However, LDT has better serological response and higher drug-resistance.

What MELD score mandates use of entecavir for ACLF-HBV HBeAg-negative patients?

AIM: To investigate optimal timing for therapeutic efficacy of entecavir for acute-on-chronic hepatitis B liver failure (ACLF-HBV) in hepatitis B e antigen (HBeAg)negative patients. METHODS: A total of 109 inpatients with ACLF-HBV were recruited from the Department of Infectious Diseases of the Third Affiliated Hospital, Sun Yat-sen University from October 2007 to October 2010. Entecavir 0.5 mg/d was added to each patient's comprehensive therapeutic regimen. Patients were divided into threegroups according to model for end-stage liver disease (MELD) score: high (≥ 30, 20 males and 4 females, mean age 47.8 ± 13.5 years); intermediate (22-30, 49 males and 5 females, 45.9 ± 12.4 years); and low (≤ 22, 28 males and 3 females, 43.4 ± 9.4 years). Statistical analysis were performed using SPSS 11.0 software. Data with normal distribution were expressed as mean ± SD and comparisons were made with Student's t tests. A value of P < 0.05 was considered statistically significant. Viral loads were related exponentially and logarithmic data were used for analysis. RESULTS: For 24 patients with MELD score ≥ 30, treatment lasted 17.2 ± 16.5 d. Scores before and after treatment were significantly different (35.97 ± 4.87 and 40.48 ± 8.17, respectively, t = -2.762, P = 0.011); HBV DNA load was reduced (4.882 ± 1.847 copies log10/mL to 3.685 ± 1.436 copies log10/mL); and mortality rate was 95.83% (23/24). Of 54 patients with scores of 22-30, treatment lasted for 54.0 ± 43.2 d; scores before and after treatment were 25.87 ± 2.33 and 25.82 ± 13.92, respectively (t = -0.030, P = 0.976); HBV DNA load decreased from 6.308 ± 1.607 to 3.473 ± 2.097 copies log10/mL; and mortality was 51.85% (28/54). Of 31 patients with scores ≤ 22, treatment lasted for 66.1 ± 41.9 d; scores before and after treatment were 18.88 ± 2.44 and 12.39 ± 7.80, respectively, (t = 4.860, P = 0.000); HBV DNA load decreased from 5.841 ± 1.734 to 2.657 ± 1.154 copies log10/mL; and mortality was 3.23% (1/31). CONCLUSION: For HBeAg-negative patients with ACLF-HBV, when entecavir was added to comprehensive therapy, a MELD score ≥ 30 predicted very poor prognosis due to fatal liver failure.

Predictors for Efficacy of Combination Therapy with a Nucleos(t)ide Analogue and Interferon for Chronic Hepatitis B

This study aims to explore the efficacy of interferon-α（IFN-α） combined with either entecavir（ETV） or adefovir（ADV） therapy versus IFN-α mono-therapy for chronic hepatitis B（CHB） patients, and to identify the factors associated with treatment outcomes. Totally, 159 CHB patients receiving interferon-based treatment for 48 weeks were enrolled in this retrospective study, including IFN-α mono-therapy group（group A, n=44）, IFN-α plus ADV group（group B, n=53） and IFN-α plus ETV group（group C, n=62）. The primary measures of efficacy assessments were the changes in HBs Ag. Cox regression analysis was used to identify the predictors of treatment outcomes. The predictive values of the factors were assessed by ROC analysis. For patients with baseline hepatitis B surface antigen（HBs Ag） level 〈1000 IU/m L, the reductions in mean HBs Ag levels at week 48 were greater in group C than that in group A（P〈0.05）. Higher rate of HBeAg seroconversion was achieved in the combined therapy group than in IFN-α mono-therapy group at week 48（P〈0.05）. Two factors were independently associated with HBeAg seroconversion： baseline HBeAg level 〈2.215 log10 index/m L and △HBeAg（decline in HBeAg from baseline） 〉0.175 log10 at week 12. In conclusion, interferon-α plus ETV therapy can accelerate HBs Ag decline as compared with interferon-α mono-therapy in CHB patients with lower baseline HBs Ag levels, and the combination therapy was superior to IFN-α mono-therapy in increasing the rate of HBeAg seroconversion. Baseline HBeAg and △HBeAg at week 12 can independently predict HBeAg seroconversion in patients subject to interferon-based therapy for 48 weeks.