[Efficacy of combination therapy with pegylated-interferon alfa-2a plus ribavirin in autoantibody-positive chronic hepatitis C patients].

To evaluate the therapeutic efficacy of antiviral combination therapy with pegylated-interferon alpha-2a plus ribavirin (RBV) in patients with autoantibody-positive chronic hepatitis C (CHC) and to investigate the impact of the presence of autoantibodies on the treatment outcome. Eighty-six consecutive CHC patients who underwent a 48-week treatment regimen composed of Peg-IFNa-2a (135 or 180 mug/wk) plus weight-based RBV ( less than or equal to 65 kg, 800 mg/d; 65 to 75 kg, 1000 mg/d; more than or equal to75 kg, 1200 mg/d ). Prior to treatment (baseline) and at end of treatment (EOT; week 48), levels of antinuclear antibody (ANA), anti-smooth muscle antibody (SMA), anti liver/kidney microsomal antibody type 1 (LKM1), anti-La (SSB), and anti liver cytosolic-1 (LC-1) were detected by indirect immunofluorescence. At baseline, during treatment (weeks 4, 12, 24, and 36), EOT, and 24 weeks after EOT, levels of HCV RNA were assessed by real-time quantitative PCR. Rapid virological response (RVR) was defined as HCV RNA less than 10(3) copy/ml at week 4. Sustained virologic response (SVR) was defined as HCV RNA load below the lower limit of detection at 24 weeks after EOT. Correlation between autoantibodies and treatment-induced reduced HCV RNA load was assessed by univariate analysis of variance or chi-squared tests. Autoantibodies were detected in 24 patients, which included 14 ANA-positive patients, five SMA-positive patients, three LKM1-positive patients, one patient with double-positivity for ANA and SSB, and one patient with double-positivity for ANA and LC-1. The autoantibody-positive patients and autoantibody-negative patients showed similar rates of RVR (70.8% vs. 72.5%, P more than 0.05) and SVR (81.4% vs. 82.2%, P more than 0.05). Antiviral therapy with Peg-IFNa-2a RBV can effectively reduce the HCV RNA load in autoantibody-positive CHC patients; however, the presence of autoantibodies may not be an independent predictor of therapy outcome.

[Association of interleukin 28B polymorphisms with response to pegylatedinterferon plus ribavirin therapy for chronic hepatitis C].

OBJECTIVE: To investigate the characteristics of gene polymorphisms at rs12979860 of interleukin 28B (IL28B) and explore the relationships between the genetic polymorphisms and the antiviral therapy efficiency for chronic hepatitis C patients in the Sichuan region of China. METHODS: Data from 56 patients treated for 48 weeks with PEG-IFN alpha-2a plus weight-based Ribavirin (RBV), which were followed for 24 weeks after the end of treatment, were analyzed. And the IL28B rs12979860 genotype was detected by polymerase chain reaction-restriction techniques (PCR) and sequencing analysis. RESULTS: Two genotypes, CC (76.8%) and CT (23.2%), were identified in the study. There are no significant correlation in sex, age, body weight, routes of infection, baseline ALT value, baseline viral load and hepatitis C viral (HCV) genotype between the patients with CC genotype and CT genotype (P>0.05). PEG-IFN alpha-2a plus RBV showed a conspicuous therapeutic effect in patients of the Sichuan region of China, and the rate of sustained virological response (SVR) was 82.1% (46/56). The higher rates of SVR were observed in patients with IL28B genotype CC than genotype CT (90.7% versus 53.8%, P=0.009). Statistically higher proportion of SVR wasn't observed in patients with lower baseline viral load (< or =6 x 10(5) IU/mL) [88.2% versus 79.5% in patients with higher baseline viral load (> or = 6 x 10(5) IU/mL), P=0.684] and statistically lower proportion of SVR wasn't observed in patients infected with HCV genotype 1 (76.9% versus 92.9% in patients infected with HCV genotype non-1, P = 0.363). The higher rates of SVR were observed in patients with IL28B genotype CC than patients with genotype CT in the group of higher baseline viral load (> or = 6 x 10(5) IU/mL) (87.5% versus 42.9%, P=0.033) and in HCV genotype 1 infected patients (89.7% versus 50.0%, P=0.025). CONCLUSION: CC genotype was accounted for the majority at rs12979860 in patients of the Sichuan region of China. The higher rates of SVR were observed in IL28B genotype CC than genotype CT. Compared to HCV viral genotype and baseline viral load, IL28B genotype may predict the treatment effect of greater value.

[Association between the influential factors and the effectiveness of pegylated interferon alpha-2a plus ribavirin as a combination treatment for chronic hepatitis C patients].

To evaluate the efficacy and to investigate the association between the length of the treatment period and the cumulative dose of pegylated interferon alpha-2a (PegIFN alpha-2a) plus ribavirin (RBV) and the effectiveness of antiviral therapy. We analyzed data from 117 patients treated for 48 weeks with PEG-IFN alpha-2a (135mug or 180mug/week) plus weight-based RBV (800 mg/d for patients is less than or equal to 65 kg, 1000 mg/d for patients 65-75 kg and 1200 mg/d for patients is more than or equal to 75 kg) under care at West China Hospital. HCV RNA was assessed at baseline, Week 4, 12 and 24, the end of treatment (EOT) and after 24 weeks follow-up (sustained virological response; SVR) with a test range of 1.0*10(3) to 5.0*10(7) IU/ml. Patients were stratified by age, gender, weight, route of transmission, duration of infection, baseline HCV RNA level and PegIFN alpha-2a or RBV dosage. HCV genotype was assessed in 29 patients (genotype 1b, 21; genotype 2a, 7; genotype 1b/2a, 1). Rapid virological response (RVR; HCV RNA negative at week 4), complete early virological response (cEVR; HCV RNA negative at week 12), EOT response, and SVR were achieved in 88 (75.2%), 110 (94%), 114 (97.4%) and 96 (82.1%) patients, respectively. Younger age, lower weight and shorter speculated infection years were associated with higher SVR rates (91.4% vs 72.9%, x2=6.796, P value is less than 0.05; 85% vs 50%, x2=5.433, P value is less than 0.05; 96.7% vs 77%, x2=5.852, P value is less than 0.05). SVR significantly increased with treatment length (38.5%, 66.7%, and 88.8% for is less than or equal to 29 weeks, 29-38 weeks, and is more than or equal to 38 weeks, respectively). SVR significantly increased with total cumulative treatment doses (38.5%, 66.7% and 88.8% for is less than or equal to 60%, 60%-80% and is more than or equal to 80% of PegIFN dose respectively; 33.3%, 85.3% and 96.8% for is less than or equal to 60%, 60%-80% and is more than or equal to 80% in RBV dose respectively) in all patients. Less than 80% of standard dose of RBV was not sufficient even if given enough PegIFN (is more than or equal to 80% cumulative treatment dose) in patients who achieved RVR. Chinese patients treated with peginterferon alpha-2a plus ribavirin have high rates of SVR. It is important to complete the target length of treatment and to continue the target dosage to achieve SVR.