Fukui H

Risk factors for the development of hepatocellular carcinoma among patients with chronic hepatitis C who achieved a sustained virological response to interferon therapy

Background and Aim:  Hepatitis C virus (HCV)‐infected patients who responded to interferon (IFN) treatment with clearance of serum HCV RNA may rarely develop hepatocellular carcinoma (HCC). The aim of the present study was to elucidate the risk factors for liver carcinogenesis among such patients.

Genotypes and multiple infections with hepatitis C virus in patients with haemophilia A in Japan

SUMMARY. Hepatitis C virus (HCV) RNA was tested for, and HCV genotypes determined, in 96 patients with haemophilia A in Japan. Of 88 patients aged ≥ 10 years, 74 (84%) were positive for HCV RNA at a frequency higher than that in patients aged less than 10 years (one of eight, 13%P<0.001). Genotype I/1a was detected in 30 (40%), II/1b in 12 (16%), III/2a in eight (11%), IV/2b in five (7%) and V/3a in 12 (16%); mixed infection with HCV of two different genotypes was identified in the remaining nine (12%). This distribution was markedly different from that in 767 Japanese HCV carriers without haemophilia, in whom II/1b accounted for the majority (68.7%), I/1a was rare (0.5%), V/3a was absent, and mixed infection was observed rarely (1.3%). Mixed infection was transient in all of the seven haemophilic patients who were followed for 1 to 7 years. One of them was infected with genotype II/ 1b and an unclassifiable genotype, which showed nucleotide sequence similarity to genotype 4c from Zaire (82% homology in the El gene) and to 4a from Egypt (91% homology in a part of the NS5b region). In this patient, HCV of genotype II/1b disappeared while that of group 4 survived during a 4‐year observation period. These results indicate different epidemiology of HCV genotypes in Japanese haemophiliacs, attributable to HCV contaminating factor VIII imported in the past, and an increased opportunity in haemophiliacs for mixed infection with HCV of different genotypes.

Circulating KL-6 level at baseline is a predictive indicator for the occurrence of interstitial pneumonia during interferon treatment for chronic hepatitis C.

Interstitial pneumonia (IP) is a serious adverse event of interferon alpha (IFNalpha) treatment for chronic hepatitis C (CH-C). Among 558 CH-C patients who received IFNalpha treatment with or without ribavirin between January 1992 and June 2002, six patients (1.1%) developed IP, including one patient who developed IP in 1993 and again in 2002. Among the seven cases who contracted IP, at the onset of IP, seven (100%), five (71%), and two cases (29%) had elevated serum levels of KL-6, surfactant protein A (SP-A), and surfactant protein D (SP-D), respectively. Prior to starting IFN treatment (baseline), the serum SP-A and SP-D levels were within the normal range in all seven cases, but the serum KL-6 level was elevated in five of the seven cases, contrasting with that in three of 48 age-adjusted CH-C patients who did not develop IP during IFN treatment (71 vs. 6%; P=0.0003). Furthermore, the circulating KL-6 level at baseline was significantly higher among the seven cases than among the controls (543+/-105 vs. 304+/-98 U/ml, P=0.0001). These results indicate that measurement of the circulating KL-6 level in CH-C patients before IFN treatment may be useful for predicting the occurrence of IP during IFN treatment.