Virological responses in chronic hepatitis C patients undergoing prolonged therapy with low-dose Peg-IFNα-2a.

BACKGROUND/AIMS: Standard dose therapy with pegylated interferon α-2a (Peg-IFNα-2a) and ribavirin is not suitable for all patients because of the side effects. This study aims to evaluate the virological responses of low-dose but long-course Peg-IFNα-2a therapy compared with standard therapy. METHODOLOGY: Ninety patients with chronic hepatitis C were divided into three groups according to their tolerance to Peg-IFNα-2a. The courses of treatment were 96 or 48 weeks respectively in patients with HCV genotypes 1b or 2a in the 67.5 µg and 90 µg groups, and were 48 or 24 weeks in the 180 µg groups. Serum HCV RNA was quantified to determine RVR, EVR, SVR and ETR. RESULTS: There were no statistical differences in HCV RNA load, HCV genotype at the baseline of the three groups (p>0.05). The rates of RVR, EVR, SVR and ETR (no significant differences in each group), were 63.04%, 82.61%, 71.74% and 85.87% in all 92 patients. Genotype 1b (95% CI=11.97-82.89; p=0.0075) and RVR (95% CI=0.12-0.53; p<0.001) were important predictors of SVR. CONCLUSIONS: Patients with low-dose but long-course Peg-IFNα-2a therapy had similar virological responses compared to those with standard therapy. HCV genotype and RVR were independent predictors of SVR.

[Dynamic changes in programmed death-1 expression on the surface of T cells in chronic hepatitis C patients undergoing interferon therapy].

OBJECTIVE: To investigate the dynamic changes that occur in T cell subsets, particularly involving the surface expression of programmed death 1 (PD-1), in response to pegylated (Peg)-interferon (IFN) a-2a therapy in patients with chronic hepatitis C virus (HCV) infection. METHODS: Twenty-five patients with HCV genotype 1b chronic infection and 10 healthy controls were enrolled in the study. All the HCV patients received combination antiviral therapy of Peg-IFNa-2a (180 mug/week) plus ribavirin. At treatment weeks 0 (baseline), 4, 12, 24 and 48, the level of PD-1 protein expression on the surface of total peripheral CD8+ and CD4+ T cells was determined by flow cytometry and the level of PD-1 mRNA expression in peripheral blood mononuclear cells (PBMCs) was determined by reverse transcription-polymerase chain reaction. Independent student's t-test were used to compare mean values between the two groups, repeat measure variance analysis was used to compare mean values among multiple groups, and Pearson's correlation coefficient was used to assess correlation significance. RESULTS: Over the course of antiviral therapy, the proportions of CD4+ T cells and CD8+ T cells, as well as the CD4+/CD8+ ratio, increased (F = 81.23, 39.28, and 7.01 respectively; all P less than 0.01). In contrast, the PD-1 protein expression frequency on CD4+ T cells and CD8+ T cells significantly declined (F = 100.11 and 158.40 respectively; all P less than 0.01). The PD-1-mRNA expression level in PBMCs was: 1.40+/-0.26 at baseline, 1.30+/-0.27 at week-4, 1.14+/-0.18 at week-12, 1.06+/-0.26 at week-24, and 0.83+/-0.25 at week-48 (F = 20.09; P less than 0.01). A positive correlation existed between the PD-1 protein expression frequencies on CD4+ T cells and CD8+ T cells and the HCV RNA load detected at baseline (r = 0.82 and 0.75 respectively; all P less than 0.01). CONCLUSION: The ability of Peg-IFN-a-2a-based antiviral therapy to suppress HCV replication may involve reduction of PD-1 protein expression on the surface of CD8+ T cells and CD4+ T cells.

Improved efficacy by individualized combination therapy with Peg IFN-a 2a and ADV in HBeAg positive chronic hepatitis B patients.

BACKGROUND/AIMS: Monotherapy with pegylated interferon alpha (Peg-IFNa) or adefovir dipivoxil (ADV) to HBeAg-positive chronic hepatitis B (CHB) patients has limited effects. This study aims to evaluate therapeutic efficacy and safety of individualized combination therapy with Peg-IFNa and ADV. METHODOLOGY: HBeAg-positive CHB patients (n=160) were enrolled in this multi-center, prospective, randomized, 'real-life' cohort study, of which received Peg IFNa-2a monotherapy or combination therapy with ADV base on the baseline features and treatment response. RESULTS: At week 24, percentages of ALT normalization, HBV DNA undetectable were both higher in individualized treatment group (ITG, 57.50%, 43.75%) than that in standard treatment group (STG, 40.00%, 27.50%; p=0.027, 0.032). The superiority of HBeAg clearance and seroconversion rates in ITG maintained from treatment termination (63.75%, 56.25%) to 48 weeks follow-up (57.50%, 53.75%). At week 96 the combined response rates were 46.25% in ITG compared with 30.00% in STG (p=0.034). Furthermore, there was no statistically significant difference in relapse rates and adverse events between the two groups. CONCLUSIONS: Individualized combination therapy can achieve higher antiviral response rates. In particular, it can accelerate undetectable HBV DNA and elevate HBeAg clearance/seroconversion rates to a greater degree than Peg-IFNa-2a monotherapy.

[The virological response in prolonged therapy of chronic hepatitis C with low-dose peginterferon alpha-2a].

OBJECTIVE: To investigate the virological response in prolonged therapy of chronic hepatitis C (CHC) with low-dose peginterferon alpha-2a. METHODS: The 92 cases of in-patients with chronic hepatitis C in September 2004 to September 2006 were divided to three groups according the endurance of interferon. The dose of peginterferon alpha-2a was 67.5 microg, 90 microg and 180 microg per week in group A, B and C respectively. The treatment duration of peginterferon alpha-2a was 96 or 48 weeks in HCV genotype 1b and 2a in group A and B, and in the group C the duration was 48 or 24 weeks in genotype 1b and 2a patients respectively. Meanwhile, ribavirin for 900-1200 mg per day combined treated with all patients. The quantitation of serum HCV RNA were conducted to determine the rapid virological response (RVR), early virological response (EVR) and sustained virological response (SVR) respectively. RESULTS: There were no significant difference between the three groups in the rate of RVR, EVR and SVR (P > 0.05). There was a higer rate of RVR, EVR and SVR in the genotype 2a group than the genotype 1b group (P < 0.05). HCV genotype was the independent predictor (OR = 12.78, 95%, CI = 11.97-82.89, P = 0.0075) of SVR. CONCLUSION: There was a similar virological response between prolonged therapy of chronic hepatitis C with low-dose peginterferon alpha-2a and the standard dose and duration. The genotype was the independent predictors of SVR in peginterferon alpha-2a antiviral therapy of chronic hepatitis C.