Efficacy and safety of peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C virus infection

Abstract

Chronic hepatitis C remains a formidable threat to world health. Progression of chronic hepatitis C is associated with significant morbidity: cirrhosis, hepatic failure and hepatocellular carcinoma. The introduction of combined therapy with pegylated interferons and ribavirin has increased the sustained virologic response (SVR) in the much higher percentage than with previous treatment options, while the level of adverse effects has not changed significantely. The aim of this study was to assess the efficacy and safety of combined therapy (peginterferon alfa-2a + ribavirin) in Serbian population. Patients with genotypes 1 and 4 received a 48-week course of therapy of peginterferon alfa-2a (180 microg/week) and ribavirin (1000-1200 mg/day). Patients with genotypes 2 and 3 received the same doses of both drugs, but during 24 weeks. All patients were scheduled for follow-up visit 24 weeks after the end of treatment. Physicians were instructed to adjust the dose of both drugs if adverse events occurred. Standard PCR tests were used for qualitative and quantitative detection of viral RNA, as well as for determination of patients' genotypes. A total of 95 patients were enrolled in the sutdy. The majority of patients were male (65.26%), aged 40 or under (52.63%), with genotype 1 (63.15%). The average duration of infection was 2.81 + 4.89 years, but still, the majority of patients (51.58%) had HCV infection for less than 2 years. Fibrosis was present in 69.47 % of patients, and cirrhosis in 21.06%. The most common mode of infection was through i.v. drug use (29.48%), but it was unknown in 32.63% of patients. The mean ALT value was 100.44 + 70.26, with the total of 93.68% of patients having elevated ALT level. At the end of treatment (EoT) time point, data were collected from 66 patients (69.47%), while at the end of follow-up (EoFU), data were collected from 68 patients (71.58%). This unusuall drop-out rate of 28.42% was mainly caused by losing contact with patients (14.74%) and premature termination of therapy (13.68%). The primary parameter of efficacy SVR at the EoFU was achieved in 59 out of 68 patients (86.76%), while the secondary efficacy parameter (SVR at the EoT) was achieved in 77.27% of patients. Multiple regression anlysis has established the initial level of ALT, patient's age and fibrosis level as main parameters statistically significantely impacting the outcome of treatment. Although without statistical significance, the trend of better outcomes was associated with early therapy (within 2 years from infection), and while the disease has not progressed (patients with fibrosis achieved SVR at the EoFU in 89.19% vs. 75.00% in patients with cirrhosis). The safety record was good, the most common adverse effects including cytopenia, rash and local reactions at the site of administration. Combination therapy with peginterferon alfa-2a and ribavirin is safe and well tolerated, with SVR achieved in 86.76% of patients.