Mutations in a hydrophilic part of the core gene of hepatitis C virus in patients with hepatocellular carcinoma in China.

We investigated the association between hepatocellular carcinoma (HCC) and the genomic characteristics of the hepatitis C virus (HCV) isolated from residents of the inshore region of the Yangtze River, an area that has one of the highest incidence of HCC in China. We determined the genomic heterogeneity of HCV, and the sequence divergence of the HCV core gene in individuals with chronic hepatitis and HCC. HCV genotype II was predominant among these isolates, which were homologous to other Chinese and Japanese HCV isolates. The rate of nucleotide substitutions in the core gene was significantly greater for isolates from HCC patients than for those from individuals with chronic hepatitis. The nucleotide substitutions were unevenly scattered along the core gene; a cluster of missense mutations was apparent in the region encoding the second hydrophilic domain of the core protein. The rate of occurrence of missense mutations per nucleotide substitution was significantly greater in this clustering variable region (CVR) of the core gene than in the remaining core gene sequence. These observations suggest that mutations in the CVR may be involved in the pathogenesis of chronic HCV infection during hepatocellular carcinogenesis.

Prevention of posttransfusion hepatitis by screening with second-generation anti-HCV antibody and clinical features of HCV infection.

After adaptation of the second-generation anti-hepatitis C virus (HCV) test, the incidence of post-transfusion hepatitis (PTH) resulted in 5.2% (11/208), which was significantly lower than that 10.5% (22/209) demonstrated by screening donor blood for C100-3 antibody. The 11 cases of PTH, three were classified as definite PTH and the other were as suspected one. Of two cases with definite PTH and two cases with suspected PTH, their blood samples after transfusion became positive for HCV-RNA, and three cases of those showed a second peak of alanine aminotransferase (ALT) more than 4 weeks after operation. On the other hand, of seven cases containing one definite PTH, their blood samples after transfusion became negative for HCV-RNA, and five cases of those showed ALT peaks within 4 weeks after operation, and returned to normal levels of ALT thereafter. Moreover, in cases of definite PTH, the periods of surgery and anesthesia were longer and the volume of bleeding was much more during operation than in cases of suspected PTH, although the differences were not statistically significant. These findings suggested that cases of PTH include those of transient liver disease attributable to surgery as well as those of HCV infection. In 11 cases of PTH, we consider that 2 cases is true PTH, because these are HCV-RNA positive and have second peak more than 4 weeks after operation and 5 cases is questionable by clinical date. Thus new diagnostic criteria should have established.

Prevalence of HCV-antibodies and HCV-RNA in donor blood in Tokushima Prefecture.

The incidence of C100-3 among the blood specimens qualified for transfusion according to the conventional criteria was 1.1%. The incidence of C100-3 in donor blood in Tokushima Prefecture is not significantly different from that reported for all Japan. Of the donors positive for the conventional screening test and C100-3, 73.6% showed high ALT levels. For all antibodies, the incidence of HCV-RNA was very low in the donors positive for a single antibody, but was high in those positive for multiple antibodies. All of the donors showing the 3 antibodies were positive for HCV-RNA. While a test for multiple antibodies is thought to be effective for the screening of HCV, more blood needs to be discarded, having a serious cost-performance problem. The O.D. value for C100-3 and the 2nd antibody seem to be useful reference value for antibody titers.

Incidence of hepatitis C virus (HCV) antibodies and HCV-RNA in blood donors and patients with liver diseases in the inshore area of the Yangtze River.

The Nantong area is a high risk region for primary hepatocellular carcinoma (PHC) in the inshore area of the Yangtze River. However, no detailed data are available about hepatitis C virus (HCV) infection in this area. We examined the incidences of anti-HCV and HCV-RNA in blood donors with hepatitis B surface antigen (HBsAg)- and hepatitis B core antibody (HBcAb)-negative and patients with chronic liver diseases in the Nantong area at Nantong Medical College, Jiangsu Province, the People's Republic of China. The incidences of HBV markers (HBsAg and/or HBcAb), anti-HCV (C100-3), second generation anti-HCV, HCV-RNA and any marker of HCV in the Nantong area were found to be: 0.0, 0.7, 0.4, 0.2 and 0.7% in donor bloods; 16.9, 0.0, 3.4, 15.7 and 16.9% in patients with acute hepatitis; 82.8, 2.7, 4.8, 7.5 and 10.2% in those with chronic hepatitis; 86.4, 4.5, 9.1, 4.5 and 11.4% in those with liver cirrhosis; 87.5, 6.3, 0.0, 0.0 and 6.3% in those with PHC; and 21.8, 1.3, 1.3, 0.0 and 1.3% in patients without liver diseases, respectively. Although the Nantong area is a high risk region for PHC, these data suggest that HCV infection is not an important aetiological factor for PHC in this area.

HCV infection and its clinical features in recipients of blood screened for HCV (C100-3) antibody.

After adoption of the anti-hepatitis C virus (C100-3) test, the incidences of definite and suspected cases of post-transfusional hepatitis (PTH) were 3.3% (7/209) and 7.2% (15/209), respectively. Four patients with definite PTH and seven patients with suspected PTH became positive for hepatitis C virus (HCV)-related antibodies or HCV-RNA after transfusion. These cases that became positive for anti-HCV or HCV-RNA showed a peak of alanine aminotransferase (ALT) more than 4 weeks after operation. Only rare cases that showed ALT peaks within 4 weeks after operation became positive for HCV-related antibodies or HCV-RNA. The peak ALT levels in cases showing positive conversion tended to be higher than those in cases showing no conversion. Judging from these results, cases of suspected PTH include those of transient liver disease attributable to surgery as well as clear cases of HCV infection. Thus new diagnostic criteria are required including data on HCV antibodies or HCV-RNA.