Entecavir maleate versus entecavir in Chinese chronic hepatitis B predominantly genotype B or C: Results at week 144.

Reports on the efficacy and safety of long-term entecavir treatment in chronic hepatitis B (CHB) predominantly genotype B or C are insufficient. This study presents the efficacy and safety of entecavir maleate in Chinese CHB patients. Patients were randomly assigned to receive 48-week treatment with either 0.5 mg/day entecavir (group A) or 0.5 mg/day entecavir maleate (group B), and then all patients received treatment with 0.5 mg/day entecavir maleate from week 49. Two hundred and seventy-five patients with CHB (HBeAg-positive: 218) were analysed, predominantly (98.5%) with genotype B or C. Baseline characteristics were balanced. For the HBeAg-positive CHB patients, the mean HBV DNA level decreased similarly (A: by 6.36 log10 IU/mL vs B: by 6.31 log10 IU/mL) between groups at week 144. The percentages of patients who achieved undetectable HBV DNA were similar (A: 70.59% vs B: 66.67%) between groups. Similar HBeAg loss rates (A: 43.53% vs B: 40.23%; P>.05) and HBeAg seroconversion rates (A: 21.52% vs B: 21.18%) were achieved. For the HBeAg-negative CHB patients, similar reductions in HBV DNA levels from baseline (A: by 6.13 log10 IU/mL vs B: by 5.65 log10 IU/mL) and percentages of patients who achieved undetectable HBV DNA (A: 100% vs B: 100%) were achieved. The overall incidence of adverse events was comparable between groups. In conclusions, 48-week administration of entecavir maleate and entecavir showed similar efficacy and safety in Chinese patients with CHB. Long-term entecavir maleate treatment was effective and safe in CHB patients.

Baseline hepatitis B core antibody predicts treatment response in chronic hepatitis B patients receiving long-term entecavir.

Studies regarding the clinical significance of quantitative hepatitis B core antibody (anti-HBc) in patients with chronic hepatitis B receiving first-line nucleos(t)ide analogues 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 entecavir. This was a retrospective cohort study consisting of 139 Chinese patients enrolled in a multicenter clinical trial treated with entecavir or entecavir maleate for up to 240 weeks. Anti-HBc evaluation was conducted for all the available samples using a newly developed double-sandwich anti-HBc immunoassay. At week 240, 35 (25.2%) patients achieved a serological response (HBeAg seroconversion) and these patients at week 240 had significantly higher levels of anti-HBc (P<.01). We defined 4.65 log10  IU·mL-1 , with a maximum sum of sensitivity and specificity, as the optimal cut-off value of baseline anti-HBc level to predict seroconversion. Patients with baseline anti-HBc ≥4.65 log10  IU·mL-1 had 28.0% (26/93) and 35.5% (33/93) chance of seroconversion at weeks 144 and 240, respectively. The baseline anti-HBc level was the strongest predictor for seroconversion at week 144 (OR: 5.78, 95% confidence interval [CI]: 2.05-16.34, P=.001). The baseline anti-HBc level was a strong predictor for seroconversion at week 240 (OR: 5.36, 95% CI: 2.17-13.25, P<.001). Hence, baseline anti-HBc titre is a useful predictor of long-term entecavir therapy efficacy in HBeAg-positive CHB patients, which could be used to optimize antiviral therapy.

Virological response to antiviral therapy at week 12 indicates a great reduction of intrahepatic hepatitis B virus DNA and cccDNA in HBeAg-positive chronic hepatitis B patients.

Early virological response is considered to be a predictor for the outcome of anti-hepatitis B virus (HBV) therapy. To analyze its correlation to intrahepatic HBV DNA and covalently closed circular DNA (ccc)DNA, 71 hepatitis B virus e antigen (HBeAg)-positive chronic hepatitis B patients were recruited: 34 patients were treated with lamivudine; 13 with interferon-alpha2b; and 24 with sequential therapy of lamivudine-interferon-alpha2b for 48 weeks. Intrahepatic HBV DNA and cccDNA load were measured at the baseline and at Week 48. Fifty-seven patients had virological response at Week 12. Median decreases of serum HBV DNA in patients with or without virological response at Week 12 were 4.0 log(10) (max. 6.2, min. 2.2) and 1.1 log(10) (max. 2.1, min. 0) (Z = -5.766, P = 0.0000), respectively. At Week 48 they were 4.1 log(10) (max. 7.4, min. 1.0) and 2.3 log(10) (max. 7.5, min. 0.3) (Z = -2.760, P = 0.006), respectively. For intrahepatic HBV DNA load they were 1.3 log(10) (max. 4.3, min. -1.2) and 0.6 log(10) (max. 3.5, min. -0.8), respectively, and for HBV cccDNA load they were 1.1 log(10) (max. 4.8, min. -0.5) and 0.5 log(10) (max. 3.0, min. -0.8) (Z = -2.097, P = 0.036), respectively at Week 48. Step-wise logistic regression analysis indicated that the baseline intrahepatic HBV DNA load effected virological response at Week 12 [odds ratio (OR) 0.405; 95% confidence interval (CI) 0.174-0.944; P = 0.036] and HBeAg seroconversion at Week 48 (OR 0.292; 95% CI 0.131-0.649; P = 0.003). In conclusion, virological response at Week 12 indicated a great reduction of intrahepatic DNA and cccDNA load in HBeAg-positive CHB patients. The baseline intrahepatic HBV DNA load affected virological response at Week 12 and HBeAg seroconversion at Week 48.

[Effects of antiviral effects of agents and prognosis of chronic hepatitis B.].

BACKGROUND: To analyze the effects of difference antiviral agents and the effects of the treatments on long-term prognosis. METHODS: Retrospective research method was applied. RESULTS: About 40% of the patients were treated with interferon or lamivudine. After the treatment, in lamivudine group, the negative rate of HBV DNA was the highest. In the interferon group, the sero conversion rates of HBeAg/HBeAb were 22.9%. In the antiviral treatment patients, the disease progression and the occurrence of cirrhosis and liver cancer were much lower than those of the control groups. The mortality of cirrhosis and liver cancer in the HBeAg/HBeAb sero converted group was much lower than that of the group without HBeAg/HBeAb sero conversion groups (P less than 0.05). CONCLUSION: The antiviral effects of interferon and lamivudine were better than those of the other drug groups. The antiviral drugs could relieve the disease progression and reduce the mortality of cirrhosis and liver cancer.

[Cloning and sequence analysis of a gene encoding amastin from Leishmania major].

OBJECTIVE: To clone a gene encoding surface protein from Leishmania major. METHODS: Using T. cruzi amastin DNA sequence as a reference, computer search was done on GenBank and dbEST databases by using BLAST path. A Leishmania major DNA library has been constructed and screened by in situ colony hybridization. RESULTS: A 309nt DNA fragment from Leishmania major was found in dbEST. Leishmania major DNA library was screened using specific primers synthesized according to 309 nt DNA sequence, and a full-length coding sequence for Leishmania major amastin was cloned. The coding sequence consisted of 552 nt, and translated into 183 amino acid residues. The homology is 23.5% at amino acid sequence level between Leishmania major and T. cruzi amastins. CONCLUSION: A full length amastin coding gene for Leishmania major has been cloned.

Inhibition of hepatitis B virus by retroviral vectors expressing antisense RNA.

Two retroviral vectors carrying an antisense gene from the hepatitis B virus (HBV) preS/S or preC/C were constructed and used to infect the human hepatoblastoma cell line 2.2.15, which expresses HBV surface antigen (HBsAg), HBV e antigen (HBeAg) and releases HBV particles. The results showed that the inhibitory effects of antisense gene transfer, mediated by retroviral vectors on the expression of HBV antigens, appeared as early as day 3 after transduction, reached a maximum on day 5 and persisted for at least 11 days. Our data indicate that, on day 5 after introduction, antisense preS/S inhibited HBsAg and HBeAg expression by 71% and 23%, and the antisense preC/C inhibited HBsAg and HBeAg expression by 23% and 59%. HBV DNA production, in the supernatant of the 2.2.15 cells transduced with either antisense preS/S or preC/C, was also reduced on day 5, but the viability of the 2.2.15 cells was not affected. Our results demonstrate that the replication and expression of HBV can be inhibited through antisense gene transfer mediated by retroviral vectors and that the antisense-preC/C or antisense-preS/S may be potentially useful for clinical gene therapy against HBV.

[The effect of interleukin-2, interleukin-4 and tumor necrosis factor on LAK cells activity].

We studied the effect of single or combination of interleukin-2 (IL-2), interleukin-4 (IL-4) and tumor necrosis factor (TNF) on lymphokine-activated killer cells (LAK) activity which killed both of target cells HepG2 and 2 2,1,5 cells induced for seven days. It was shown that LAK activity induced by the combination of triplet of IL-2, IL-4 and TNF was higher than that induced by single or two of IL-2, IL-4 and TNF, and that enhanced LAK activity was associated with the quantity of IL-2 receptor expression and lysosomes of LAK precursors.

[Changes in LAK cell activity in chronic viral hepatitis and treatment with autologous LAK cell transfusion].

We investigated the activity of LAK cells in 10 patients with chronic persistent hepatitis, 20 patients with chronic active hepatitis, 21 patients with post-hepatitic cirrhosis and 21 normal persons. The values were 36.87 +/- 7.44, 30.38 +/- 5.36, 28.84 +/- 4.95 and 44.50 +/- 4.75 respectively (P < 0.05). The LAK cell activity in patients with chronic hepatitis was lower than that of normal persons, especially in those with chronic active hepatitis and post-hepatitic cirrhosis. The causes of lower LAK cell activity in patients with chronic hepatitis were less expression of IL2 receptors on precursors of LAK cells and existing serum LAK cell inhibition factors. We further studied 9 patients with chronic hepatitis B treated with autologous LAK cell transfusions. Factors favoring a more effective result were female sex, ALT elevation after treatment, activity of LAK cells > 10%, and inhibition factor of LAK effector cells existing in serum of patients, with inhibition rate < 50%. These factors might be used as the indications in selecting cases for treatment and predicting the effect of the treatment. As the number of cases observed was rather small, further investigation is needed.