HBeAg seroconversion achieved by sequential peginterferon alfa-2a therapy in chronic hepatitis B patients with unsatisfactory end point following entecavir treatment / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and safety of peginterferon alfa-2a (Peg-IFNa-2a) therapy for treating chronic hepatitis B (CHB) in patients who failed to achieve a satisfactory end point with entecavir (ETV) treatment.</p><p><b>METHODS</b>Fifty-seven CHB patients with positivity for hepatitis B e antigen (HBeAg) who had completed a standard ETV monotherapy course, of at least 96 weeks, and who had achieved a virological response (defined as HBV DNA less than 500 copies/ml) but without HBeAg seroconversion (defined as 0.227 PEI U/ml less than HBeAg less than or equal to 50 PEI U/ml) were enrolled in the study. The patients were randomly assigned to receive a 48-week treatment with Peg -IFNa-2a (experimental group, n = 27) or continued ETV therapy (control group, n = 30). Serum samples were collected from all patients for assessment of biochemical, virological and serological responses to treatment. Inter-group differences were statistically evaluated by t-test or Chi-squared test.</p><p><b>RESULTS</b>The baseline levels of alanine aminotransferase, hepatitis B surface antigen (HBsAg), and HBeAg were similar between the patients comprising the experimental and controls groups. At treatment week 48, the experimental group showed significantly higher rates of HBeAg clearance (Peg-IFNa-2a: 40.7% vs. ETV: 16.7%, x2 = 4.079, P less than 0.05) and seroconversion (37.0% vs. 13.3%, x2 = 5.110, P less than 0.05). The experimental group also showed higher rates of HBsAg clearance (7.4% vs. 0%) and HBV DNA relapse (11.1% vs. 0%), but the differences did not reach statistical significance (x2 = 2.307 and 3.519, both P more than 0.05). However, the level of HBsAg was significantly lower in the experimental group (2866.0+2580.4 vs. 4335.8+2650.0 IU/ml, t = 5.11, P less than 0.05).</p><p><b>CONCLUSION</b>HBeAg-positive CHB patients with unsatisfactory response to initial ETV monotherapy achieved HBeAg seroconversion and clearance following sequential Peg-IFN a-2a treatment.</p>

Efficacy of lamivudine and adefovir de novo combination therapy or after mono-therapy in chronic hepatitis B patients / 中华肝脏病杂志

To investigate the efficacy of 104 weeks of lamivudine (LAM) and adefovir (ADV) de novo combination therapy, as compared to optimized combination therapy administered after 48 weeks of treatment with lamivudine or adefovir mono-therapy, in chronic hepatitis B (CHB) patients. A total of 174 patients with CHB were equally divided among three treatment groups: LAM mono-therapy; ADV mono-therapy; and LAM + ADV combination therapy. The patients in the LAM + ADV group were treated with LAM plus ADV for 104 consecutive weeks. The patients in the LAM or the ADV groups were first treated for 48 weeks with LAM or ADV, respectively, after which the patient's virological response was assessed. According to the results, the patient was continued on mono-therapy or switched to combination therapy for the subsequent 56 weeks. Virological and biochemical examinations were carried out at weeks 48 and 104. The rates of undetectable HBV DNA in the LAM mono-therapy, ADV mono-therapy, and LAM-ADV combination therapy groups at week 48 were 68%, 50%, and 84%, and at week 104 were 80%, 72%, and 95%, respectively. For the same groups, the virus breakthrough rates at week 48 were 15%, 0%, and 0%, and at week 104 were 18%, 2%, and 0%, respectively. Statistical analysis showed significant differences for the rate of undetectable HBV DNA between LAM + ADV group and LAM group at week 48 (x2 = 4.473, P= 0.034) and at week 104 (x2 = 5.795, P = 0.016), LAM + ADV group and ADM group at week 48 (x2 = 14.802, P less than 0.001) and week 104 (x2 = 5.547, P = 0.001). The hepatitis B e antigen (HBeAg) seroconversion rates at week 48 were 15% (x2 = 4.543, P = 0.033), 13% (x2 = 4.035, P = 0.045) and 38%, and at week 104 were 21% (x2 = 4.438, P = 0.035), 17% (x2 = 4.223, P = 0.04) and 44%, respectively, among patients positive for HBeAg. Statistical analysis showed that the differences among the three groups for each of these parameters were statistically significant (all, P less than 0.05). When compared with LAM or ADV mono-therapy followed by LAM+ADV at week 48, the LAM plus ADV de novo combination therapy for 104 weeks provided CHB patients with better virological and serological responses and a lower drug resistance rate.

Prevalence and clinical characteristics of thyroid disease induced by chronic hepatitis B treated with polyethylene glycol (peg) interferon-alpha / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To study the prevalence and clinical characteristics of thyroid disease induced by chronic hepatitis B treated with polyethylene glycol (peg) interferon-alpha.</p><p><b>METHODS</b>Totally 210 patients with chronic hepatitis B were monitored for thyroid function and thyroid antibodies before application of polyethylene glycol (peg) interferon-alpha therapy and every 3 months during and after the treatment.</p><p><b>RESULTS</b>After treatment with polyethylene glycol (peg) interferon-alpha, 6.7% (14/210) of patients had thyroid disease, in which 5.2% (11/210) had hyperthyroidism and 1.4% (3/210) had hypothyroidism. The proportion of the hyperthyroidism and hypothyroidism in women were 11.8% (6/51) and 3.9% (2/51), higher than 3.1% (5/159) and 0.6% (1/159) in male (P < 0.05). In women subjects, higher proportion of those who developed thyroid disease were positive for antibody against thyroid peroxidase (TPOAb) before treatment and positive for antibody against thyroid globulin (TgAb) during the treatment as compared with those who did not develop thyroid disease (P < 0.05).</p><p><b>CONCLUSION</b>Patients with chronic hepatitis B treated with polyethylene glycol (peg) interferon-alpha therapy are prone to develop thyroid disease. Women positive for TPOAb and TgAb may be at increased risk for developing thyroid disease.</p>

Study on the efficacy and HBeAg seroconversion related factors of telbivudine and entecavir therapy in HBeAg positive chronic hepatitis B patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the efficacy of Telbivudine and Entecavir for therapy of HBeAg positive chronic hepatitis B for 52 weeks.</p><p><b>METHODS</b>In this random and control study, the efficacy of Telbivudine and Entecavir treatments were compared in 180 patients with HBeAg positive chronic hepatitis B.The patients were randomly assigned to a daily 600 mg Telbivudine treatment group or daily 0.5 mg Entecavir group for 52 weeks.</p><p><b>RESULTS</b>At week 52, HBV DNA undetectable rate was better in the Entecavir-treated group than in the Telbivudine-treated group, but didn't reach statistical significance. The viral breakthrough rates were significantly lower in the Entecavir-treated group than in the Telbivudine-treated group (x2 = 4.09, P <0.05). The clearance and seroconversion of HBeAg and the mean reductions of HBeAg from baseline at week 52 were significantly greater in the telbivudine-treated group than in the entecavir-treated group (x(2) clearance = 4.63, x(2) seroconversion = 4.80, (t-mean) reductions = 2.02; P < 0.05). The HBeAg seroconversion rates were not associated with both baseline ALT and baseline HBV DNA in both groups (P more than 0.05). In Telbivudine-treated group, the HBeAg decline is more than 2 log at week 24, HBeAg decline is more than 1 log at week 12 and the HBeAg baseline were independent factors correlated to HBeAg seroconversion rates at week 52 by Binary Logistic analysis, and also in entecavir-treated group the HBeAg decline is more than 2 log at week 24, HBeAg decline is more than 2 log at week 36 and the HBeAg decline is more than 2 log at week 12 were independent factors correlated to HBeAg seroconversion rates at week 52.</p><p><b>CONCLUSION</b>Significant difference of HBeAg seroconversion rates at week 52 existed between Telbivudine-treated group and Entecavir-treated group. Entecavir is significantly superior to Telbivudine with less resistance to nucleosides. HBeAg decline is more than 2 log at week 24 is the best predicting factor for HBeAg seroconversion at week 52.</p>

Individualized respond guidance treatment of chronic hepatitis C with combination of peginterferon α-2a and ribavirin / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study individualized treatment of chronic hepatitis C (CHC) genotype 1 patients using respond guided therapy (RGT) of peginterferon α-2a in combination with ribavirin.</p><p><b>METHODS</b>140 patients with CHC genotype 1 received peginterferon α-2a 180 microg injection once a week in combination with ribavirin 800-1200 mg/d. Patients achieved RVR after 4 weeks treatment (group A) were randomized into 2 subgroups and proceeded with 24 and 48 weeks treatments (subgroups A1 and A2) respectively. Patients who had not received RVR but achieved cEVR at week 12 (group B) were further divided into 2 subgroups randomly and treated for 48 and 72 weeks (subgroups B1 and B2), respectively. Patients with PVR at week 24 were treated for 72 weeks (group C1), while patients without PVR at week 24 discontinued treatment (group C2). All Patients were followed-up for 24 weeks after the end of treatment.</p><p><b>RESULTS</b>For patients treated for 24 weeks, the ETR rate was 100%, the SVR rate was 65.9%, and the relapse rate was 34.1%. For those treated for 48 weeks, the ETR, SVR and relapse rate were 95.3% , 82.8% and 12.5% respectively. For those treated for 72 weeks, the above rates were 82.1%, 67.9% and 14.3% respectively. SVR rates of subgroup A1 and A2 were 65.9% and 84.4% respectively and the difference was statistically significant (P<0.00). The HCV RNA loads were less than 1x10(6) copy/ml in group A and the SVR were 72.7% and 100% respectively with 24 and 48 weeks treatment, and the difference was insignificant statistically (P>0.05). SVR in subgroup B1 and B2 were 78.9% and 73.7% respectively and the difference was statistically insignificant (P>0.05). The SVR in group C1 was raised to 55. 6%.</p><p><b>CONCLUSIONS</b>RVR and cEVR were respond guided prediction factors for CHC treatment. SVR among patients with RVR was higher in 48-week treatment than those with 24 weeks treatment. For patients with baseline virus load less than 1x10(6) copy/ml and achieved RVR, treatment duration can be shortened to 24 weeks. Treatment extension to 72 weeks can not result in SVR increase among patients without RVR but with cEVR. However, treatment extension to 72 weeks can increase SVR among those patients with PVR.</p>

Comparison of the reliability of two ELISA kits for detecting IgM antibody against hepatitis E virus / 中华预防医学杂志

<p><b>OBJECTIVE</b>To study the reliability of two ELISA kits for detecting IgM antibody against hepatitis E virus (HEV).</p><p><b>METHODS</b>Serum samples from 92 healthy subjects, 71 cases suspected of hepatitis E, 55 patients with confirmed diagnosis of acute hepatitis E, 50 individuals with rheumatoid factor (RF) positive and 54 persons with anti-HAV IgM positive were detected with three hepatitis E diagnostic kits. MP-IgM (MP, Singapore), Wantai-IgM and anti-HEV IgG (Wantai, China). HEV RNA was analyzed with RT-PCR in 52 of 71 cases suspected of hepatitis E.</p><p><b>RESULTS</b>In healthy subjects,cases suspected of hepatitis E and confirmed acute hepatitis E, the concordance between the two anti-HEV IgM reagents was 73.39% (160/218) and the significant differences in the positive rates of two assays were not observed [46.79% (102/218) vs 44.04% (96/218), chi2 = 0.62, P > 0.05]. Of 71 patients suspected of hepatitis E, the sensitivity for diagnosing acute hepatitis E of Wantai-IgM and MP-IgM were 83.08% (54/65) and 78.46% (51/65) (chi2 = 0.16, P > 0.05), respectively. Among those suspected of hepatitis E with HEV RNA positive, the sensitivity of Wantai-IgM was obviously higher than that of MP-IgM [(97.14%, 34/35) vs (74.29%, 26/35), chi2 = 4.9, P < 0.05]. 48 of 55 patients (87.27%) with confirmed diagnosis of hepatitis E were Wantai-IgM positive while 37 (67.27%) was MP-IgM positive (chi2 = 4.0, P < 0.05). The specificity of Wantai-IgM was higher than MP-IgM [100.00% (202/202) vs 89. 11% (180/202), chi2 = 20.05, P < 0.005]. RF and anti-HAV IgM might cause MP-IgM false positive without interference on Wantai-IgM.</p><p><b>CONCLUSION</b>Wantai-IgM should be a good ELISA kit for the diagnosis of acute hepatitis E.</p>

Correlations between preS1-antigen, HBV-DNA and HBV serum markers in patients with chronic hepatitis B / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the correlations between preS1 antigen, HBV-DNA and hepatitis B virus (HBV) serum markers in patients with chronic hepatitis B.</p><p><b>METHODS</b>The HBV markers, preS1 antigen and HBV-DNA were determined using enzyme- linked immunosorbent assay and quantitative PCR in 1158 patients with chronic hepatitis B.</p><p><b>RESULTS</b>In these patients, the HBV-DNA positivity rate was 68.9%, significantly higher than preS1 antigen positivity (54.8%, chi2=53.24, P<0.005). The positivity rates of both HBV-DNA and PreS1-antigen were significantly higher in HBeAg-positive patients than in HBeAg-negative patients (P<0.005). The coincident rates of preS1-antigen and HBeAg with HBV-DNA were 56.9% and 63.3%, respectively. PreS1 antigen had higher sensitivity but lower specificity than HBeAg. The detection rates of preS1 antigen and HBeAg increased with the level of HBV-DNA, and preS1 antigen positivity was higher than that of HBeAg in patients with low HBV-DNA levels.</p><p><b>CONCLUSION</b>Detection of HBV serum markers along with preS1 antigen and HBV-DNA may help assess the status of viral replication and therapeutic efficacy in patients with chronic hepatitis B. PreS1 antigen may serve as an auxiliary indicator in HBeAg-negative cases or when HBV-DNA detection is impossible.</p>