American Journal of Gastroenterology ISSN 0002-9270 C  2007 by Am. Coll. of Gastroenterology doi: 10.1111/j.1572-0241.2007.01223.x Published by Blackwell Publishing Are Chronic Hepatitis C Viral Infections More Benign in Patients With Hemophilia? Nimer Assy, M.D., 1,3,8 Norman Pettigrew, M.D., 4,5 Sam S. Lee, M.D., 3,6 Rabindra K. Chaudhary, Ph.D., 7 J. Johnston, M.D., 2,3,5 and Gerry Y. Minuk, M.D. 1,3,5 1 Liver Disease Unit, 2 Hemophilia Clinic, Departments of 3 Medicine and 4 Pathology, 5 University of Manitoba, Winnipeg, Manitoba, Canada; 6 University of Calgary, Calgary, Alberta, Canada; 7 The Laboratory Centre for Disease Control, Ottawa, Ontario, Canada; and 8 Liver Unit, Ziv Medical Center, Technion Institute, Haifa, Israel BACKGROUND Cirrhosis is associated with thromboses of the intrahepatic vasculature. This raises the possibility AND AIMS: that HCV infections in hemophiliacs may differ from those in nonhemophiliacs METHODS: Liver biopsy findings from 12 hemophiliacs and 20 age- and gender-matched, nonhemophiliac controls with chronic hepatitis C viral (HCV) infections were compared for inflammatory activity and fibrosis. RESULTS: The mean ages of hemophiliacs and controls were 35.0 ± 3.0 yr and 39.6 ± 5.6 yr, respectively (P = 0.2). Serum aspartate aminotransferase (AST) levels were lower (44 ± 13 vs 70 ± 43 U/L) and the duration of the partial thromboplastin (PTT) time longer (49.2 ± 16.9 vs 31.2 ± 1.2 s.) in hemophiliacs than in controls (P < 0.02 and <0.001, respectively). Six of the seven hemophiliac patients (86%) and 8/17 controls (46%) were infected with genotypes 1a or 1b with the remainder being infected with 2b, 3a, or 3b. Histological activity and fibrosis scores were significantly lower in hemophiliacs than in controls (1.9 ± 0.6 vs 3.6 ± 2.7 and 0.3 ± 0.2 vs 1.5 ± 1.5, P < 0.05 and P < 0.01, respectively). None of the hemophiliacs had histological evidence of advanced disease (bridging fibrosis and/or cirrhosis) as compared to 7/20 (30%) controls (P < 0.05). CONCLUSION: HCV infections in hemophiliacs may be less severe than in HCV infected patients without hemophilia. (Am J Gastroenterol 2007;102:1–5) INTRODUCTION Most hemophilia patients, who in the past have been treated with large-pool plasma-derived clotting factor concentrates, are persistently infected with the hepatitis C virus (1). The natural history of chronic hepatitis C viral (HCV) infections of the liver has yet to be clearly defined. This is especially true amongst hemophiliacs where HCV infections are com- mon but limitations in obtaining histological specimens for analysis have hampered attempts to document the histologi- cal severity of the disease. The more widespread use of trans- jugular liver biopsies (2) should enable such studies to now be performed. HCV mono-infection has a very slow progression in hemophilia patients, but patients with hemophilia who are co-infected with HCV and HIV can exhibit a comparatively rapid progression of liver disease (3). Potential adverse outcomes of chronic HCV infection in- clude cirrhosis, hepatic failure, hepatic or portal vein throm- bosis, and hepatocellular carcinoma. Previous data from Wanless et al. indicating that cirrhosis is associated with and may result from extensive thromboses of the intrahep- atic vasculature raises the possibility that the natural history of HCV infections in hemophiliacs may differ from that in the nonhemophiliac population (4, 5). Supporting this hy- pothesis also are data from ourselves and others indicating that aspirin and enoxaparin attenuate fibrosis progression in rat models of hepatic fibrosis (6). To further test this hypoth- esis, we documented the histological severity of liver disease in 12 chronic HCV infected hemophiliacs and compared the results to those obtained from 20 age- and gender-matched control patients without hemophilia. The results of the study support the hypothesis that HCV infection in hemophiliacs has a more benign course than in the nonhemophilia popula- tion. MATERIALS AND METHODS The liver biopsies reviewed for this study were identified from chart reviews of patients attending viral hepatitis outpatient clinics at the Health Sciences Centre, Winnipeg, Manitoba, and the Foothills Hospital, Calgary, Alberta, Canada from 1990 to 1995. Both centers have the facilities and personnel 1