Peginterferon plus ribavirin over two years may be successful in patients with chronic hepatitis C and a very slow virologic response

To THE EDITOR: Standard treatment of chronic hepatitis C genotype 1 consists of a 48-week course of peginterferon in combination with ribavirin. It has been shown that the best predictor of treatment outcome is virologic response during the early phase of therapy: The sooner HVC-RNA becomes negative in the serum, the higher the chance of achieving a sustained virologic response (SVR) and the shorter the necessary treatment duration [1]. Thus, in patients with a rapid virologic response (PCR negative at week 4), the termination of treatment after 24 weeks can be considered [2]. In contrast, for patients with a partial early virologic response (PCR positive at week 12, but ]2 log10 decline as compared to baseline) prolongation of therapy until week 72 is recommended [3]. As retrospective analyses of phase III trials have shown that the probability of achieving a SVR is only 0.8 2% if HCV-RNA is detectable in the serum at week 24, current guidelines recommend that treatment should be stopped in these patients [1,4]. However, in phase III studies, combination therapy with peginterferon and ribavirin was administered for only 48 weeks and at present there are no data on whether patients with a positive PCR at week 24 could be cured by a longer course of treatment. To the best of our knowledge, this is the first report on a patient who became HCV-RNA-negative later than week 24, relapsed after 72 weeks of therapy and finally had a SVR after a second treatment of 2 years. In June 2002, a 40-year-old male patient with a history of intravenous drug abuse from 1980 until 1992 presented at the outpatient clinic of our department with chronic hepatitis C genotype 1b. Since 1992, the patient took part in a substitution programme with morphine. Liver biopsy revealed fibrosis stage F4 (Metavir score) and baseline viral load was 6.2 10 IU/ml (COBAS AMPLICOR HCV MONITOR† test, v.2.0; Roche, Basel, Switzerland). In August 2002, the patient was included in a randomized trial and received peginterferon a2a 180 mg/week (Pegasys†; Roche) plus ribavirin 1200 mg/day (Copegus†; Roche) plus amantadine 100 mg twice daily (PK-Merz†; Merz, Frankfurt, Germany) [5]. Qualitative PCR (COBAS AMPLICOR HCV test; v.2.0, Roche) was positive at week 12 and week 24, so the patient was withdrawn from the study, but as qualitative PCR was negative at week 28, treatment with peginterferon a-2a and ribavirin was continued until week 72. Qualitative PCR remained negative throughout the remaining treatment period, but shortly after the end of therapy the patient suffered a relapse. Because of his young age and the advanced fibrosis, a second course of treatment with peginterferon a-2a plus ribavirin 1200 mg/day was started in October 2005, in accordance with the wishes of the patient. Baseline viral load was 1.6 10 IU/ml. At week 12, the viral load had decreased to 6.8 10 IU/ ml. The first negative qualitative PCR was obtained at week 28. Treatment was continued until week 110. At follow-up visits 1, 3, 6 and 12 months after the end of therapy, the patient was still PCR negative. Despite a history of depression and seizures, antiviral therapy over a period of more than 2 years was tolerated without major side effects and without dose reduction. In conclusion, our findings reinforce the hypothesis that a longer suppression of viraemia is necessary for achieving SVR in patients with a late response to therapy [3]. Furthermore, this case provides evidence to show that a subgroup of genotype 1 patients