Efficacy and Tolerability of Combination Therapy with Interferon-Alfa Plus Ribavirin in Patients with Chronic Hepatitis C Virus Infection: A Single-Center Study in Relapsers and Nonresponders to Previous Treatment with High-Dose Interferon-Alfa Monotherapy

Abstract

Background: In chronic hepatitis C virus (HCV) infection, interferon (IFN) monotherapy usually is carried out at doses of 3 to 6 million units (MU) 3 times per week, but treatment efficacy is low.Objective: The aim of our study was to assess the efficacy and tolerability of IFN-alfa 2b in combination with ribavirin in relapsers and nonresponders to high-dose IFN treatment (5 to 6 MU 3 times per week). We measured the biochemical and virologic responses to treatment and the risk for relapse during the 24 weeks following the end of treatment.Methods: Patients with chronic HCV infection (relapsers and nonresponders to a previous treatment with high-dose IFN) received IFN-alfa 2b , 3 MU 3 times per week, and ribavirin, 1000 or 1200 mg/d for 24 or 48 weeks. The patients were then followed up for an additional 24 weeks. Sustained response was defined as normal serum alanine aminotransferase (ALT) level and undetectable HCV RNA 24 weeks after treatment was stopped.Results: Forty-three patients (32 men, 11 women; mean [SD] age, 45 [2] years; 10 relapsers, 33 nonresponders) were included in the study. Four patients were withdrawn from the study at week 4 of treatment because of treatment-related adverse events, and 1 dropped out. At the end of the treatment period, normalization of serum ALT levels and undetectable HCV RNA levels were seen in 58.1% and 30.2% of patients, respectively. No significant difference in virologic response at the end of treatment was found between nonresponders (10/33 [30.3%]) to previous IFN therapy and relapsers (3/10 [30.0%]). At the end of follow-up, 3 (7.0%) treated patients had sustained response (2 nonresponders to the first IFN course and 1 relapser). All of the patients with sustained response were treated for 24 weeks.Accepted for publication December 20, 2002. doi:10.1016/S0011-393X(03)00024-9 Reproduction in whole or part is not permitted.0011-393X/03/$19.00 140Copyright ą 2003 Excerpta Medica, Inc. F. Benini et al. Conclusion:Based on the results of our study, combination therapy with IFN-alfa and ribavirin may be of value in a limited number of patients with chronic HCV infection who do not respond to, or relapse after, a first course of treatment with high-dose IFN monotherapy. (Curr Ther Res Clin Exp. 2003;64:140-150) Copyright Ć 2003 Excerpta Medica, Inc.Key words: chronic hepatitis C virus, high-dose interferon, ribavirin, combination therapy. INTRODUCTIONChronic infection with hepatitis C virus (HCV) is estimated to affect Ͼ5 million people in Europe, almost 4 million in the United States, and 170 million individuals worldwide. 1,2 In ∼15% to 20% of these individuals, infection progresses to chronic hepatitis and cirrhosis. 3,4 Interferon (IFN)-alfa monotherapy has been, for a decade, the only effective treatment for chronic HCV infection, 5-7 but treatment efficacy is low. Sustained response, defined as viral clearance persisting for Ͼ24 weeks after treatment is stopped, occurs in only 30% of treated patients, whereas 15% to 25% of patients relapse during the 24...

Health-related quality of life in thrombocytopenic patients with chronic hepatitis C with or without cirrhosis in the ENABLE-1 and ENABLE-2 studies

“…The pivotal ENABLE trials not only established the efficacy and safety of eltrombopag in patients with HCV-associated thrombocytopenia, but also assessed HRQoL through the Short-Form 36 Health Survey version 2 (SF-36v2) and Chronic Liver Disease Questionnaire–HCV version (CLDQ-HCV) [ 13 – 15 ]. Although effective, therapy with IFN and ribavirin has side effects such as flu-like symptoms, anemia, and emotional changes [ 16 , 17 ] that affect HRQoL [ 5 , 18 ]. Based on published reports documenting the negative effects of IFN-based AVT on HRQoL [ 19 , 20 ], HRQoL in patients in the ENABLE studies was expected to decline during the 24–48 weeks of IFN therapy due to the cumulative nature of the effects of IFN, and to return to baseline levels at the 24-weeks post-treatment follow-up visit [ 19 ].…”