Journal zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA of Hepatology 1996; 25: 591-598 Printed in Denmark All rightsreserved M unks@ zard. Copenhagen Copyright 0 European Association for the Studv of the Liver 1996 Journal of Hepatology ISSN0168.8278 Ribavirin treatment for patients with chronic hepatitis C: results of a placebo-controlled study Geoffrey Dusheiko’, Janice Main2, Howard Thomas2, Olle Reichard3, Christine Lee”, Amar Dhillon’, Suhra Rassam’, Aril Fryden4, Henk Reesink’, Margaret Bassendine6, Gunnar Norkrans7, Theo Cuypers*, Nice Lelie’, Paul Telfer”, Jon Watson’, Christine Weegink’, Peter Sillikens”and Ola Weiland’ Departments of Medicine and Pathology ‘Royal Free Hospital, and ‘St. Mary’s HospitalLondon, 6Freeman Hospital, Newcastle; “Haemophilia Center Royal Free Hospital, United Kingdom; ‘Division of Infectious Diseases, Danderyd Hospital, ‘Huddinge Hospital, and Karolinska Institute, “University Hospital, Linkoping, ‘Ostra Hospital, Goteborg, Sweden; ‘Vereenigen Voor Ziekenverpleging, ‘CLB, Amsterdam, “Organon Teknika Laboratories, The Netherlands Background/Aims: Small, uncontrolled studies of ribavirin for patients with chronic hepatitis C have reported efficacy in chronic hepatitis C. We have evaluated the efficacy and safety of a 24- week course of oral ribavirin in patients with chronic hepatitis C, compared to placebo. Methods: A total of 114 patients were randomised to ribavirin or placebo. Ribavirin was adminis- tered in doses of 1000 or 1200 mg/day for 24 weeks. Efficacy was determined in the intention- to-treat population: 76 received ribavirin and 38 placebo. Results: Ribavirin was significantly more effective than placebo in reducing and normalising serum ALT levels: 42/76 (55%) of ribavirin-treated patients vs 2/38 (5 %) placebo recipients had either normalisation of the ALT levels or a reduction from baseline of at least 50% (~~0.001). ALT lev- els were normal in 22/76 (29%) of ribavirin- treated patients vs O/38 placebo recipients (pcO.001). Twenty-four weeks after stopping riba- virin, the majority of patients had abnormal ALT levels. There was no difference between the treat- ment groups in reduction or disappearance of HCV-RNA levels. HCV RNA disappeared during zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHG P ATIENTS with hepatitis C infection frequently de- velop chronic hepatitis (l-3). This may progress to cirrhosis, although this progression is usually in- Received 25 August 1995; revised and accepted 9 January 1996 Correspondence: Prof. G. Dusheiko, Viral Hepatitis Study Group, Royal Free Hospital, Pond Street, London NW3 2QG, UK. Tel:+44 171 830 2993. Fax. +44 1714314581. treatment in 3% of ribavirin-treated patients and 3% of placebo recipients. More ribavirin than pla- cebo patients showed improvement in total Knodell score (45% vs 31%), but these differences were not statistically significant. Analysis of each component of a histology activity index revealed no statistically significant differences between treatment groups. Ribavirin patients had fewer lymphoid aggregates than did placebo recipients at the post-treatment assessment (p=O.O5). Ribavi- rin was associated with reversible haemolytic anaemia: a fall in haemoglobin occurred in 3% of placebo- and 32% (25/78) of ribavirin-treated patients, respectively (pcO.001). Conclusions: These data indicate that ribavirin was no more effective than placebo in reducing or eliminating HCV-RNA levels, and was not signifi- cantly more effective than placebo in improving hepatic histology after 6 months of treatment. The role of a 6-month treatment of chronic hepatitis C with ribavirin alone, without a significant effect on HCV RNA, is therefore limited. Key words: Antivirals; Chronic hepatitis; Hepati- tis C antiviral therapy; Ribavirin. sidious. Interferon-a treatment results in sustained biochemical responses (normal serum aminotrans- ferases) in 15%-20% of those treated for 6 months (4,5). As side effects are not uncommon in treated pa- tients, other therapies are therefore being sought to improve the treatment of chronic hepatitis C. Ribavirin (1 -Beta-D-ribofuranosyl- 1 H- 1,2,4-tria- zole-3-carboxamide) is a water-soluble nucleoside 591