Peginterferon {alpha}-2b and ribavirin therapy in chronic hepatitis C genotype 4: impact of treatment duration and viral kinetics on sustained virological response

Abstract

Background: The response rates and duration of peginterferon alpha (PEG-IFN-alpha) and ribavirin combination therapy in chronic hepatitis C genotype 4, the prevalent genotype in the Middle East and Africa, are poorly documented.

Aims: To compare the efficacy and safety of 24, 36, or 48 weeks of PEG-IFN-alpha-2b and ribavirin therapy in chronic hepatitis C genotype 4.

Methods: In this prospective, randomised, double blind study, 287 patients with chronic hepatitis C genotype 4 were randomly assigned to PEG-IFN-alpha-2b (1.5 mug/kg) once weekly plus daily ribavirin (1000-1200 mg) for 24 weeks (group A, n = 95), 36 weeks (group B, n = 96), or 48 weeks (group C, n = 96) and followed for 48 weeks after completion of treatment. Early viral kinetics and histopathological evaluation of pre- and post treatment liver biopsies were performed. The primary end point was viral clearance 48 weeks after completion of treatment.

Results: Sustained virological response was achieved in 29%, 66%, and 69% of patients treated with PEG-IFN-alpha-2b and ribavirin for 24, 36, and 48 weeks, respectively, by intention to treat analysis. No statistically significant difference in sustained virological response rates was detected between 36 and 48 weeks of therapy (p = 0.3). Subjects with sustained virological response showed greater antiviral efficacy (epsilon) and rapid viral load decline from baseline to treatment week 4 compared with non-responders and improvement in liver histology. The incidence of adverse events was higher in the group treated for 48 weeks.

Conclusion: PEG-IFN-alpha-2b and ribavirin for 36 or 48 weeks was more effective in the treatment of chronic hepatitis C genotype 4 than treatment for 24 weeks. Thirty six week therapy was well tolerated and produced sustained virological and histological response rates similar to the 48 week regimen.

Figures

Figure 1

Study design and study flow chart. All patients with chronic hepatitis C (HCV) genotype 4 were screened prior to enrolment. A total of 287 subjects fulfilled the inclusion criteria and were randomly assigned to the three treatment schedules and received at least one dose of the study medication (see patients and methods). Eight patients were excluded after receiving one or two doses because they refused to continue therapy or did not come for treatment. PEG-IFN-α-2b, peginterferon alpha-2b.

Figure 2

Early virological response (EVR) at weeks 12, end of treatment virological responses (ETR: weeks 24, 36, and 48 after therapy in groups A, B, and C, respectively), and sustained virological response (SVR: 48 weeks after completion of therapy). (A) Comparison of outcome of treatment in the three patient groups: group A, peginterferon alpha-2b (PEG-IFN-α-2b) plus ribavirin (n = 95) for 24 weeks; group B, PEG-IFN-α-2b plus ribavirin for 36 weeks (n = 96), and PEG-IFN-α-2b plus ribavirin for 48 weeks (n = 96). (B) Percentage of patients achieving early virological response at week 12 and sustained virological response to the different treatment regimen in genotype 4.

Figure 3

Hepatitis C virus (HCV) RNA kinetics in chronic hepatitis C genotype 4 patients treated with peginterferon α-2b plus ribavirin. Graphs show triphasic or biphasic HCV kinetic patterns in four representative patients: slow responders (A, B) and fast responders (C, D).

Figure 4

Rates of histological response in the three groups who received peginterferon alpha-2b plus ribavirin for 24, 36, or 48 weeks. Histological response was defined as ⩾2 point improvement in necroinflammatory score (grading). Histological response in shown for sustained virological responders (SVR), relapsers, non-responders (NR), and all patients. Bars represent change from baseline median total grading score.