PREDICTIVE FACTORS FOR DEVELOPMENT OF CIRRHOSIS IN PARENTERALLY ACQUIRED CHRONIC HEPATITIS-C - A COMPARISON BETWEEN IMMUNOCOMPETENT AND IMMUNOCOMPROMISED PATIENTS

Background/Aims. The aim of this study was to evaluate the impact of t he host immune status and of virological and environmental parameters on the development of cirrhosis during chronic hepatitis C virus infec tion. Methods: Liver histology (cirrhosis or not, Knodell score) was e valuated according to age, sex, route and age of contamination, alcoho l consumption and immune status in a large series of 553 HBsAg-negativ e patients (whose duration of hepatitis C virus infection could be pre cisely evaluated) divided into three groups: group 1 consisted of 462 immunocompetent subjects (46.1% intravenous drug users, 53.9% transfus ed), infected for a mean of 12.5+/-6.7 years, including 16.6% of alcoh ol abusers (>80 g/day); groups 2a and 2b consisted of 91 immunocomprom ised patients, 52 human immunodeficiency virus-coinfected patients cor responding to group 2a and 39 kidney recipients undergoing immunosuppr essive therapy for group 2b, having been infected by hepatitis C virus for a mean of 12.6+/-5.3 and 11.5+/-5.3 years, respectively. Results: Group I: cirrhosis was present in 11.0% of group 1 patients and in 23 .6% of immunocompetent patients with a duration of hepatitis C virus i nfection of 20 years or more. Forty-three percent of patients with cir rhosis and with hepatitis C virus infection for more than 20 years mer e alcohol abusers. The time taken to develop cirrhosis was 14+/-7 year s in patients infected before the age of 40 years as compared to 8+/-5 years in those infected after 40 years (p<0.001), Groups 2a and 2b: c irrhosis was present in 19.8% of immunocompromised patients, a signifi cantly higher rate than in immunocompetent patients (p<0.01). Alcohol abase did not increase the risk of cirrhosis in this group. All patien ts but one were infected by hepatitis C virus before the age of 40 and the calculated time elapsed until the occurrence of cirrhosis was 12. 4+/-5.5 years. In groups I, 2a and 2b, there was no relation between h istological severity hepatitis C virus genotype and viral load. Four v ariables were independently associated with the occurrence of cirrhosi s in the multivariate analysis: age over 40 at time of contamination ( RR=9.3 in age range 40 to 59 and 91.2 in greater than or equal to 60 y ears); long duration (greater than or equal to 20 years) of hepatitis C virus infection (RR=15.4); alcohol consumption over SO g/d (RR=2.9); and human immunodeficiency virus-coinfection (RR=2.6). Conclusions: O ur study on a large series of well-characterized patients provides an accurate evaluation of the risk of cirrhosis in parenterally-contamina ted immunocompetent hepatitis C virus-infected patients, with an overa ll figure of 11%. It also demonstrates the impact of the host immune s tatus on the risk of severe histological lesions during chronic hepati tis C virus infection. It finally establishes the importance of age at the time of viral infection in the occurrence of cirrhosis, as web as the importance of alcohol consumption, Thus, at least following paren teral infection, both host-related and environmental cofactors play a major role in the severity of the liver lesions associated with hepati tis C virus infection.