Via practica 10/2006

HIGH VIROLOGIC SUSTAINED RESPONSE TO FORMER YOUNG INTRAVENOUS DRUG ABUSERS WITH CHRONIC HEPATITIS C TREATED BY PEGYlATED INTERFERON – ALFA PLUS RIBAVIRIN (PRELIMINARY REPORT)

Chronic HCV infection is responsible for substantial liver-related morbidity and mortality, related to chronic hepatitis, cirrhosis and hepatocellular carcinoma. The most risk group with high rate of hepatitis C virus (HCV) infection in Slovakia represent the former drug abusers (prevalence 25 – 40 %). The current standard treatment for chronic hepatitis C (CHC) represent combination therapy with pegylated interferon alfa (PEG-IfN-α) and ribavirin (R). Objectives: The objectives of the clinical study were to assess virological response at 12. week, at the end of treatment (ETR), the sustained virological (SVR) and biochemical response in the group of former drug abusers with chronic hepatitis C (CHC) treated by PEGIfN- α and R. Patients and methods: Seventy five former drug abusers (naive patients) (17 f, 58 M) with average age of 27 years (aged from 18 to 41 years) were preliminary evaluated in the clinical study. Prior to therapy abstinence to drug abuse 6 and more months has been required. The CHC has been based by positive viral tests (Innotest HCV Ab IV, Innogenetics, Belgium, RT-PCR, Cobas Amplicor, HCV test v. 2.0, Roche,Germany, Versant HCV genotype Assay (liPa) Bayer HealthCare, USA, or linear Array HCV genotyping test Roche, Germany), increased levels of aminotranferases (AlT) and histology of liver biopsy. Grade of fibrosis 0 was assessed in 15 pts (23 %), fibrosis 1 in 35 pts (54 %), fibrosis 2 in 14 pts (21 %) and fibrosis 3 in 1 pt (2 %), respectively. In 10 subjects the liver biopsy was not done. PEG-IfN-α (Pegasys inj á 180 μg, PegIntron inj á 80 – 150 μg s.c; 1,5 μg/kg/week) was administered once weekly by s.c. route and R in daily dose 800 – 1 200 mg (Copegus tbl á 200 mg, Rebetol tbl á 200 mg). The doses of both preparations were calculated by patient´s weight. Duration of treatment was 24 weeks in patients with genotype 3 and 48 weeks with genotype 1, respectively. SVR was considered if qualitative test HCV RNA was negative 24 weeks after the completion of the treatment. Results: Genotype 3 of HCV was assessed in 48/64 % (10 f, 38 M) of subjects and genotype 1 in 27/36 % (7 f, 20 M), respectively. End-oftreatment response was 70/93 %. Overall SVR rate was 96 %, 72 subjects had negative HCV RNA and only 3 patients (males) with genotype 1 had no response (86 % SRV with genotype 1). The levels of AlT decreased significantly after 12 weeks treatment (AlT 1.61 μkat/l vs. 0.64 μkat/l, P < 0.001) and were in reference levels in the rest of the follow-up. The most frequent treatment related side-effects were flulike syndrom, anorexia, weight loss, neurologic symptoms (depression, irritability) and leukopenia with neutropenia and trombocytopenia, respectively. Conclusion: Young age, short duration of HCV infection, high prevalence of genotype 3 and low grade of liver fibrosis in majority of pts and good adherence of patients to treatment were crucial predictive factors resulting in high SVR. The active searching of pts by intensive cooperation with the psychologists, psychiatrics and other specialists shorten duration of infection resulting in early enrolment into the treatment.

Keywords: chronic hepatitis C, pegylated interferon-α, ribavirin, former young intravenous drug abusers.