Assessment and treatment of liver disease in Japanese haemophilia patients.

Abstract

We studied the prevalence of the hepatitis C virus (HCV), human immunodeficiency virus (HIV) and GB virus C or hepatitis G virus (GBV-C/HGV), and characteristics of infections in Japanese haemophilia patients. Haemophilia patients were highly infected with HCV (88.2%) because of frequent use of unheated blood concentrates. Analysis for HCV genotypes revealed characteristics of HCV infection in haemophilia patients. Japanese haemophilia patients were highly infected with rare genotypes in Japan: genotype 1a (26.5%), genotype 3 (14.5%) and genotype 4 (2.4%). HIV infection was observed in 32.3% of haemophilia patients. HCV quasispecies (clones) and direct sequencing were investigated in patients with a single HCV genotype in the hypervariable region 1 of HCV, which resulted in a high degree of diversity. This indicates that even a single genotype of HCV might have multiple origins. GBV-C/HGV infection was noted in 20.9% of Japanese haemophilia patients. Over 40 haemophilia patients with chronic hepatitis C have been treated with interferon alpha for 6 months at total doses of 480-720 million units. About 38% showed clearance of HCV RNA from serum. Six patients with HIV infection were included in the study and they did not show eradication of HCV from the serum. This might derive from that they had high serum HCV RNA titers and genotype 1a or 1b. Histologic assessment was performed in 36 haemophilia patients with HCV. No case showed a histologically normal liver. Hepatic fibrosis in the biopsy specimens was classified into five stages of fibrosis and compared with serum hepatic fibrosis markers. Serum hyaluronic acid mostly correlated with hepatic fibrosis (r = 0.78, P < 0.0001) followed by type IV collagen (r = 0.38, P < 0.05). This suggests that estimation of serum fibrosis markers might be substituted for liver biopsy in haemophilia patients.