Re-treatment with peginterferon-ribavirin and direct antiviral agents of patients with chronic hepatitis C after failure of intensified treatment / 中华实验和临床病毒学杂志

Objective@#To explore the persistent viral response rate (SVR) in patients with refractory chronic hepatitis C after interferon (IFN) (peginterferon 360 μg qw) and ribavirin (PR) therapy failure. The SVR of patients with refractory chronic hepatitis C was improved by PR combined with direct antiviral agents (DAA) and proper extension of the course of therapy was applied.@*Methods@#Seventeen cases of refractory chronic hepatitis C after IFN(peginterferon 360 μg qw) and ribavirin therapy failure were given PR combined with DAA treatment. The side effects were observed and corresponding adjustments were made on drug dosage, and SVR was recorded.@*Results@#The 17 cases completed the whole course of treatment with PR combined with DAA for 24 weeks. All the 17 patients obtained rapid viralogical response (RVR) and SVR. After treatment, the SVR rate was 100% in patients including those with virologic relapse, retreated or previously non-responsive patients with refractory chronic hepatitis C. The adverse reaction of PR combined with DAA 24 weeks was generally mild.@*Conclusions@#The use of PR combined with DAA re-treatment in patients with refractory chronic hepatitis C can achieve SVR and shorten the treatment time. PR combined with DAA re-therapy is one of effective treatments to improve the rate of sustained viral response in patients with refractory chronic hepatitis C.

Study on effect of intensive treatment for refractory chronic hepatitis C patients / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore the effect of intensive treatment for refractory chronic hepatitis C, and to improve the sustained viral response (SVR) rate of treatment with interferon plus ribavirin by optimizing therapeutic dose and course.</p><p><b>METHODS</b>Patients who did not acquire response or partial response by standard therapy (PEG-IFN alpha subcutaneous injection weekly plus Ribavirin 10.5 mg/kg) every day were enrolled and retreated with intensive treatment of 10 MU interferon every other day or 360 microg pegylated interferon alpha-2a weekly according to patients' wishes, and ribavirin 15 mg/kg every day. Serum HCV RNA was detected at baseline,treatment week 4, 12 and every 12 weeks succedent and 24 weeks after treatment end. Course of treatment was 72 to 96 weeks according to viral response. SVR was the mark of therapeutic effect.</p><p><b>RESULTS</b>18 patients completed whole range therapy and follow-up, in which 12 patients acquired SVR, 5 patients treatment failure and 1 relapse. 3 patients acquired rapid viral response (RVR), and they all got complete Early Viral Response (cEVR) and SVR. RVR Patients' viral loads were significantly lower than that of patients who did not acquire RVR (t = 4. 687, P < 0.001). In 15 patients who did not acquire RVR, 8 patients acquired cEVR, and 9 acquired SVR. SVR rate of patients who were administered PEG-IFN alpha-2a was 4/5, 11 patients who acquired cEVR all acquired SVR, while in 7 patients who did not acquire cEVR, only 1 patient acquired SVR.</p><p><b>CONCLUSIONS</b>High percent patients, who did not acquire response or partial response by previous standard antiviral therapy, could gain SVR by intensive dose interferon plus Ribavirin. In intensive treatment procedure, adjusting and prolonging course according to viral response after HCV RNA turned negative were important measures to improve refractory Chronic Hepatitis C SVR rate.</p>

Lamivudine-interferon alpha 2b sequential therapy versus lamivudine monotherapy in HBeAg-positive chronic hepatitis B patients / 中华传染病杂志

Objective To compare the efficacy and safety of Iamivudine-interferon sequential therapy and lamivudine monotherapy in HBeAg-positive chronic hepatitis B (CHB) patients.MethodsA total of 172 patients with HBeAg-positive CHB were randomized to sequential group (n=83) or lamivudine group (n=89).Sequential group were administrated with lamivudine 100 mg/d and 5 million units interferon alpha 2b subcutaneous injection every other day for 24 weeks were added since week 25 of treatment.Lamivudine group were administrated with lamivudine 100 mg/d for 48 weeks.All subjects were followed up for 24 weeks after drug withdrawal.Measurement data with homogeneity of variance were analyzed by using t test and data with heterogeneity of variance were analyzed by using rank sum test.The comparison of rates was done by chi square test or Fisher exact test.ResultsThe baseline hepatitis B virus (HBV) DNA levels of patients in sequential group and lamivudine group were (7.8±1.0) and (7.9±1.1) lg copy/mL,respectively (P＞0.05),and the baseline alanine aminotransferase (ALT) levels were (210.5 ± 150.1 ) and (211.9 ± 160.9) U/L,respectively (P＞0.05).At the end of treatment,higher ALT levels [(78.4±146.1) vs (36.1±32.4) U/L,P＜0.05)] and HBV DNA levels [(4.5±1.5) vs (3.8±1.3) lg copy/mL,P＜0.05)] levels,lower response rates (65.8％ vs 83.5％,P＜0.05),and similar HBeAg loss rates (31.6％ vs 22.2％,P＞0.05) and HBeAg seroconversion rates (27.6％ vs 16.0％,P＞0.05) were found in sequential group compared with lamivudine group.At the end of follow-up,higher ALT levels [(126.0±143.1) vs (82.7±83.0) U/L,P＜0.05)],similar HBV DNA levels [(5.3±1.5) vs (5.0±1.5) lg copy/mL,P＞0.05)],similar HBeAg loss rates (25.0％ vs 32.3％,P＞0.05) and HBeAg seroconversion rates (25.0 ％ vs 26.2 ％,P＞0.05) were found in sequential group compared with lamivudine group.YMDD motif mutation rate in sequential group was lower than lamivudine group at week 48 of treatment (10.5％ vs 26.9％,P＜0.05).ConclusionsLamivudine-interferon sequential therapy and lamivudine monotherapy are both effective in HBeAg-positive CHB patients,while HBV mutations are reduced in patients with sequential therapy.

Hyperthermal lipiodol embolization and thermocoagulation for the treatment of primary hepatocellular carcinoma / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore the efficacy of hyperthermal lipiodol embolization and thermocoagulation for the treatment of primary hepatocellular carcinoma.</p><p><b>METHODS</b>One hundred and thirty-one cases were randomized into two groups: the hyperthermal dilute lipiodol embolization group (63 cases) and the chemoembolization group (68 cases). With Seldinger's method, We first placed the catheter to the targeting vessel superselectively and then put the hyperthermal dilute lipiodol (110 degrees C) 10~30ml to the tumor vessels to IV degree for the former group; gave the lipiodol-epirubicin emulsion by the same way to the latter group.</p><p><b>RESULTS</b>The rate of tumor minification and AFP normalization in the hyperthermal lipiodol embolization group was higher than that in the lipiodol-epirubicin embolization group. The side effects and the liver damage were mild in the former group. The survival time of the patients in the former group was longer than that in the latter group.</p><p><b>CONCLUSIONS</b>Embolization of the tumor vessels with hyperthermal dilute lipiodol is more thorough due to its better fluidity. The thermocoagulation of the hyperthermal dilute lipiodol becomes stronger for its higher specific heat. It is therefore a good technique for the treatment of primary hepatocellular carcinoma.</p>

Expression and functional analysis of fusion protein for the human anti-HBsAg scFv antibody fragment-consensus interferon / 中国免疫学杂志

Objective:Express a human anti-HBsAg single chain antibody fragment(scFv)-consensus interferon (cIFN) fusion protein by bacterial expression system and analyse the function of the fusion protein.Methods:Human anti-HBsAg single chain monoclonal antibody cDNA encoding the variable regions of immunoglobulin from PBMC of Hepatitis B patient. Consensus interferon gene was produced by overlap PCR.A plasmid for production of cIFN-scFV fusion protein was constructed, then the expression vector pRA cIFN-scFV transformed with the E.coli strain BL21(DE3). The gene product was analysed SDS-PAGE and Western blotting, then was solubilized by guanidine hydyochloride, refolded by conventional dilution method, and purified using metal-chelating chromatography. The immune and functional analysis of the resulting fusion protein have been studied by ELISA,FACS(Flow cytometry),MTS assay and hemaglutination inhibition test.Results:The authors isolated and characterized the human anti-HBsAg single chain antibody fragment(scFv)-consensus interferon (cIFN) fusion protein. The resulting human anti-HBsAg scFv-cIFN fusion protein was bound to react with HBsAg and cIFN, this react show that highly specific and bioactivity.Conclusion:A human anti-HBsAg single chain antibody fragment(scFv)-consensus interferon (cIFN) fusion protein was produced by bacterial expression system in this study. This genetically engineered human anti-HBsAg scFv-cIFN fusion protein promises to be an important reagent for hepatitis B immunotherapy.

Randomized,Open-label and active controlled study of PEG-IFN?-2a in the treatment of chronic hepatitis C in China / 中华传染病杂志

Objective To investigate the efficacy, tolerability and safety profiles of PEG IFN alpha 2a(PEG IFN? 2a) in the treatment of chronic hepatitis C in China. Methods 208 patients with chronic hepatitis C were included, and divided into two groups randomly, PEG IFN? 2a group and IFN? 2a Group respectively. There was no significant difference between two groups in pretreatment HCV RNA, HCV genotype and other clinical data. The main parameters to valuate the efficacy were virological response and biochemical response. The side effects were intensively observed. Results Sustained virological response rate in PEG IFN? 2a group was significantly higher than that in IFN? 2a group (41.51% and 16.67% respectively, P