British zyxwvutsrqponm Iournal of Haemutobgy. 1995, 91, 708-713 zyxwvutsr Hepatitis C virus genotypes and severity of chronic liver disease in haemophiliacs GIUSEPPE TAGARIELLO, PATRIZIA PONTISSO,* PIER GIORGIO DAVOLI, MARIA GRAZIA RUVOLETTO,* AGOSTINO TRAm AND ALFREDO ALBERTI* Centre for Blood Diseases, Haemophilia Centre zyxw and Blood Bank Castelfranco Veneto Hospital (TV), Regione Veneto, and *Clinica Medica 11, Department of Internal Medicine, University of Padua, Italy Received 19 April 1995; accepted zyxwvutsrq for publication 6 July 1995 zyxwv ~ Summary. We studied the activity and stage of chronic liver disease in 45 HCV-seropositive/HIV-seronegative patients with severe haemophilia followed for at least 10 years. HCV- RNA was detected in serum in 36 patients (80%) Viraemic cases were further analysed for HCV genotypes: 10 (28%) were infected by type l a , 10 (28%)by type lb, seven (19%) by type 2, four (11%) by type 3, four (11%) had mixed infections (one by l a + lb, one by l a + 2, one by type 2 + 3, and one by la + 2 + 3). ALT levels were within the normal range in 55% of the HCV-RNA negative patients but in only 11% of the viraemic cases. Results show a trend for higher levels of ALT in HCV-RNA-positivepatients compared with those without viraemia (98 f56 v 60 161), and particularly with patients with type 3 HCV infection (148 zyxwv f 44). We suggest that a slow progression of chronic liver disease occurs in haemophilic HCV-positive/HIV- negative patients and conclude that presence of HCV-RNA in serum correlates well with cytolitic damage but, in the time-scale of our follow-up period, commonly used clinical- laboratory parameters cannot predict the chronic evolution of liver infection or identify differences in disease progression in relation to specific HCV subtypes. Keywords: haemophilia, liver disease, HCV, genotypes. Patients with haemophilia were at high risk of post- transfusion hepatitis because of the large use of plasma- derived products before the introduction of virucidical treatment (Kasper & Kipnis, 1972; Hasiba et al, 1977). However, the possibility of other viral infections transmitted by plasma-derived products must be considered in view of the recent reports of an epidemic of type A hepatitis and parvovirus in haemophiliacs (Azzi et al, 1992; Mannucci et al, 1994). Therefore coagulation concentrate replacement therapy must always be considered potentially dangerous, because chronic viral hepatitis and human immunodefi- ciency virus (HV) infection in haemophiliacs may represent a more serious problem than the basic coagulopathy (Darby et al, 1995). Initial studies underestimated the hepatitis C virus (HCV) infection because they were limited to patients with signs of chronic liver disease as determined by abnormal liver function tests. Seroconversion, however, also involves asymptomatic patients (Rumi et al, 1990) and when specific second-generation anti-hepatitis C virus antibodies became Correspondence: Dr G. Tagariello, Centre for Blood Diseases and Haemophilia Centre, Castelfranco Veneto Hospital, 31033 Castel- franc0 Veneto (TV), Italy. available it was clear that nearly 100% of haemophiliac patients treated with plasma-derived clotting factors before the introduction of inactivation methods had in fact become seropositive for HCV (Watson et al, 1992: Laurian et al, 1992). The spectrum of HCV-related infections spans from a completely asymptomatic infection with positive antibody and negative RNA in circulation to different forms of chronic hepatitis, cirrhosis (Makris et al, 1990) and cancer of the liver which has been demonstrated with a higher incidence rate in haemophiliacs (Colombo et al, 1991). Recent data indicate that HCV exists as a family of distinct virus strains and at least six major HCV genotypes have been identified (Simmonds et al, 1993) and there is evidence that these have a variable geographical distribution (Dusheiko et al, 1994; Tisminetzky et al, 1994; Pontisso et al, 1995). It has been also suggested that the activity and prognosis of HCV-related liver disease may be dependent on the genotype of the infecting HCV (Pozzato et al, 1991). Furthermore, several reports agree that the response to interferon-a (INF- a) therapy is also influenced by the HCV genotype (Yoshioka et al, 1992; Chemello et al, 1994). This multiplicity of clinical and therapeutical considerations has prompted us to per- form this study, the aim of which was both to evaluate the 708 zyxwvuts 0 1995 Blackwell Science Ltd