A phase II, single-arm, open-label, multicenter clinical study to evaluate the efficacy and safety of sofosbuvir combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection / 中华肝脏病杂志

Objective@#To evaluate the efficacy and safety of sofosbuvir (Nanjing Zhengda Tianqing Pharmaceutical Co., Ltd.) combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection.@*Methods@#Treatment-naïve or treatment experienced genotype 2 chronic hepatitis C patients from sixteen research centers of China were screened. All subjects received once-daily dose of sofosbuvir (400 mg) combined with ribavirin (body weight < 75 kg, 1 000 mg/day, 400 mg in the morning and 600 mg in the evening; body weight > 75 kg, 1 200 mg/d, 600 mg in the morning and 600 mg in the evening) for 12 weeks. Patients were followed-up for a period of 12 weeks after discontinuation of treatment. Continuous variables were expressed as mean ± standard deviation. The proportion of subjects with virologic response at different follow-up time points and 95% confidence intervals were estimated by maximum likelihood ratio and Clopper-Pearson interval.@*Results@#132 cases with genotype 2 chronic hepatitis C virus infection from sixteen research centers of China were included, 12 cases of whom were associated with cirrhosis, and the remaining 120 cases were not associated with cirrhosis. One hundred and thirty-one cases completed the study, and one patient lost to follow-up at week 4 after the end of treatment. The sustained virological response rate was 96.2% (95% confidence interval: 92.37% - 99.16%) after 12 weeks of drug withdrawal. Virological relapse occurred in four cases. Of the 132 subjects enrolled in the study, 119 (90.2%) reported 617 adverse events during treatment, of which 359 (76.5%) were TEAE related to sofosbuvir and/or ribavirin. There were nine TEAEs of grade 3 and above, and six cases (4.5%) of them had six severe adverse events. Only one serious adverse event was associated with sofosbuvir and ribavirin (unstable angina pectoris). There were no adverse events leading to drug discontinuation or death.@*Conclusion@#Sofosbuvir combined with ribavirin has a high SVR rate in the treatment of genotype 2 chronic hepatitis C virus infection, and most of the adverse events occurred were mild with acceptable safety profile.

Clinical effect and safety of 144-week treatment with entecavir capsules in treatment-naïve HBeAg-positive patients with chronic hepatitis B / 中华肝脏病杂志

Objective@#To investigate the clinical effect and safety of entecavir capsules in the treatment of treatment-naïve HBeAg-positive patients with chronic hepatitis B (CHB).@*Methods@#A total of 158 HBeAg-positive CHB patients were given oral entecavir capsules at a dose of 0.5 mg/time once a day for 144 weeks. Clinical outcome and safety were evaluated at baseline and at 24, 48, 72, 96, 120, and 144 weeks of treatment respectively. The Fisher’s exact test was used for the analysis of categorical data.@*Results@#After 144 weeks of treatment, 90.91% of all patients achieved virologic response (< 69 IU/ml), the normalization rate of alanine aminotransferase was 88.18%, the clearance rate of HBeAg was 33.33%, and the seroconversion rate of HBeAg was 24.07%. Of all patients, 2 dropped out due to adverse events and 5 experienced serious adverse reactions.@*Conclusion@#Entecavir capsules can inhibit viral replication and have good safety in treatment-naïve HBeAg-positive CHB patients.

Long term treatment of lamivudine in chronic hepatitis B patients with severe liver fibrosis——ten-year follow-up outcomes of NUCB 4006 trial / 中华传染病杂志

Objective To evaluate the clinical and histological outcomes in a cohort of chronic hepatitis B (CHB) patients who had histologically confirmed severe liver fibrosis and received lamivudine (LAM) therapy for up to 10 years. Methods Thirty-nine CHB patients with severe liver fibrosis (Ishak fibrosis score≥4) were treated with LAM for up to 10 years. Disease progression liver histological improvement, virological and biochemical responses were evaluated during follow-up. Data were analyzed using paired t test, Fisher exact test and Willcoxon test. Results Twenty-eight patients completed the 10-year follow-up. There were 5 (17.9% ) patients with disease progression.At the end of follow up, 16 patients received a second liver biopsy, which showed significant improvement of histological activity index (1.1 ± 1.4 vs 7. 1 ± 3.2, t =- 0.82, P＜0.01 ) and Ishak fibrosis score (3.6±2.2 vs 5.3±0.7, t= -2.89, P＜0.05) compared to baseline. There were 3 cases with Ishak fibrosis score improved from F5 to F0. Among 27 patients, 3(11% ) cases achieved hepatitis B surface antigen (HBsAg) loss and 2 (7 % ) achieved HBsAg seroconversion. At the end of follow-up, 19 out of 23 (83% ) hepatitis B e antigen (HBeAg) positive patients obtained HBeAg loss and 9 (39 % ) obtained HBeAg seroconversion. During LAM treatment, 11 patients experienced virological breakthrough or detected documented LAM-related resistance mutation. The viral loads of all patients were below 1 ×103 copy/mL at the end of follow-up after rescued by add-on or switch to another nucleotide analog.Conclusions Long-term LAM therapy can delay the disease progression in CHB patients with severe liver fibrosis, increase HBsAg and HBeAg loss rates, sustain suppression of HBV replication at a low level and even totally reverse the liver fibrosis in some patients. The effect of LAM resistance mutation on disease outcomes would be reduced by rescue therapy.

Lamivudine and thymosin α1 combination therapy for patients with chronic hepatitis B / 中华临床感染病杂志

Objective To evaluate the efficacy and safety of lamivudine combined with thymosin α1 therapy for patients with chronic hepatitis B.Methods Sixty-eight eligible patients with chronic hepatitis B were enrolled in this multi-center randomized controlled rlinical trial.Patients were randomized into the trial group and the control group(n=34 for each).Patients in trial group received thymosin α1 for 6 months and lamivudine for 12 menths:patients in control group received lamivudine for 12 months only.The rates of serum HBV DNA clearance.HBeAg loss,HBeAg seroconversion,ALT normalization and the safety of thymosin α1 were observed at 3rd.6th,12th and 18th month during and after the treatment.Results At 12th month of the treatment,there were significant differences in the rates of serum HBV DNA clearance,HBeAg loss and ALT normalization between two groups(χ2=31.17,7.17 and 5.92,P＜0.05);at 6th month after the treatment.there were significant differences in the rates of sernm HBV DNA clearance and HBeAg loss between two groups(χ2=4.53 and 7.17,P＜0.05).HBV DNA was not detected in 2 patients during 6-month follow-up study and no sever side effect was observed throughout the study.Conclusion The conlbination of lamivudine and thymosin α1 is safe and has better effect than the monotherapy of lamivudine in patients with chronic hepatitis B.

The clinical epidemiologic characteristics of patients infected with hepatitis C virus post blood transfusion in Shanghai area / 中华传染病杂志

Objective To investigate the clinical epidemiologic characteristics of patients with hepatitis C virus(HCV)infection post blood transfusion.Methods The polymerase chain reaction (PCR)and enzyme linked immunosorbent assay(ELlSA)were used to detect HCV RNA and antiHCV,respectively.Analysis was performed for patients' age distribution,cause of primary diseases,exposure years,ingredient and amount of transfusion,incubation period and liver function damage.The statistical processing were performed with chi-square test,t-test and correlation analysis.Results HCV RNA levels were higher than 3.0 log10 copy/mL in 85.3%infected patients with a median of 5.99log10 copy/mL,among which 19.7%patients showed viral load 3.0 to 4.0 log10 copy/mL and 69.9%showed 5.0 to 6.0 log10 copy/mL.Eighty-one point six percent(40/49)of infected persons were confirmed as HCV RNA positive by HCV RNA qualitative analysis,while 99.7%(383/384)patientswere detected as anti-HCV positive by serological test.The sensitivity of serological test was higher than both HCV RNA quantitative and qualitative assays(F=57.138,P=0.000;F=63.149,P=0.000,respectively).HCV infection post blood transfusion was more common in people of 30 to 60years old.Most cases(84.4%)got the first time exposure during 1990 to 1994.More than 10%cases had primary disease as obstetrics, orthopedics or gastrointestinal tract hemorrhage. Eighty percent received whole blood product transfusion.The mean interval between transfusion and clinical diagnosis was (86.0±54.6 ) months. Eighty nine percent of infected patients had liver function damage, while most of them showed elevated alanine aminotransferase (ALT) with no more than 5 upper limits of normal (ULN). Conclusions Post transfusion HCV infection mainly happened in adulthood. Infected patients usually have liver function damage with elevated ALT with no more than 5 ULN and medium HCV RNA levels.

To screen and evaluate the efficacy of antiviral drugs in duck animal model / 中华传染病杂志

0bjective To study the potency of Entecavir Maleate(ETVM),Entecavir(ETV) and Adefovir(ADV) on suppressing duck hepatitis B virus (DHBV) replication.Methods DHBV DNA positive ducks were used as experimental animal model.Ail these ducks were randomized to different arms and respectively given high,medium and low dosage of ETVM,ETV and ADV.ETVM and ETV were given orally daily respectively for six weeks and ADV orally 3 times every week for six weeks.The serum DHBV DNA levels were tested every 2 weeks at day 0 and,after that,at week 2,4.6 and 8 respectively by real-time fluorescent quantitative polymerase chain reaction(PCR).The results were analyzed by paired-samples t test.Results The treatment resulted in the reduction of viral load among all ETVM.ETV or ADV treated groups.The viral load of DHBV DNA at pretreatment and week 6 in the ETVM high dosage group were(7.34±1.33)and(2.12±2.50)lg copy/mL,respectively(P<O.01) and in the ETV high dosage group,the load of DHBV DNA were(8.02±0.56)and(4.36±1.64)lg copy/mL at pretreatment and week 6,respectively (P<0.01).DHBV DNA rebounds were observed after treatment cessation in these groups.The results showed that ETVM and ETV had superior antiviral activity compared tO ADV by rapidly and intensively inhibiting DHBV DNA replication in hepatitis B infected ducks.while the potency of ETVM was even better than ETV.Conclusions Both ETVM and ETV'S antiviral activities are much better than that of ADV while ETVM has the best antiviral efficacy.DHBV animal model is a good model tO screen and evaluate antiviral activity of different drugs and compounds.

Three-year treatment of HAART regimen in 43 hemophilia patients co-infected with HIV and HCV / 中华传染病杂志

Objective To observe the efficacy and safety profile of three-year treatment of HAART in 43 Hemophilia patients co-infected with HIV and HCV. Methods 43 hemophilia patients co-infected HIV and HCV were treated with HAART for 3 years. CD4、 CD3、 CD8 and NK cell counts of the patients were detected by FCM, and the viral load in the plasma was detected with FDA recommended bDNA method. Results The average CD4 count of the 43 patients increased to 257/mm3 (P