EFFECTS OF LONG-TERM COURSE OF ALPHA-INTERFERON IN PATIENTS WITH CHRONIC HEPATITIS-C ASSOCIATED TO MIXED CRYOGLOBULINEMIA

Objective: To evaluate the efficacy of a long-term course of alpha-int erferon (alpha-IFN) in the treatment of HCV-related mixed cryoglobulin aemia and to determine the impact of cryoglobulinaemia on therapeutic response to IFN in chronic hepatitis C (CHC) patients. Design: Prospec tive controlled study. Setting: University Medical Centre. Participant s: Ninety consecutive CHC patients, 50 with cryoglobulinaemia (25 symp tomatic and 25 asymptomatic; median cryocrit, 8%; chronic persistent h epatitis (CPH) 7, chronic active hepatitis (CAH) 27, cirrhosis 16) and 40 without cryoglobulinaemia (CPH 6, CAH 20, cirrhosis 14). HCV genot ypes in the cryoglobulinaemic and non-cryoglobulinaemic groups were: 1 b 40% and 45%; 2a 40% and 30%; others 20% and 25%, respectively. Inter ventions: Twelve-month course of alpha-IFN 2a, 3 MU, three times weekl y. Main outcome measures: Disappearance of cryoglobulinaemia and relat ed syndrome, clearance of serum HCV RNA and normalization serum transa minase levels at the end of treatment (response) and after 12 months f ollow-up (sustained response). Results: Overall, cryoglobulinaemic pat ients showed a similar response to IFN to those without cryoglobulinae mia (44% vs. 42.5%, respectively). In the cryoglobulinaemic group, sym ptomatic patients showed a lower response rate than asymptomatic patie nts (28% vs. 60%, respectively; P < 0.05). HCV genotype 2a/c, absence of cirrhosis and a low cryocrit (< 9%) were predictive factors of high response rate to IFN. Sustained response in non-cryoglobulinaemic pat ients (22.5%) tended to be higher than in patients with symptomatic cr yoglobulinaemia (4%), as well as among patients carrying genotype 2a/c (67% vs. 10%, respectively; P < 0.02). IFN was effective in controlli ng purpura (80%) but was moderately effective on severe haematuria/pro teinuria, renal insufficiency and neuropathy. Conclusions: A 12-month course of alpha-IFN is effective treatment for HCV-related cryoglobuli naemia. However, patients with CHC associated to symptomatic cryoglobu linaemia have a lower response rate to IFN.