To investigate the effect of hepatitis delta virus (HDV) superinfection on the long-term outcome of Japanese subjects with chronic hepatitis B virus (HBV) infection, we examined the presence of antibodies to hepatitis delta antigen (anti-HD) in serial serum samples collected from 1127 subjects with chronic HBV infection. The subjects were followed for at least 36 months (mean: 121.3 months) between 1973 and 1991. Among 69 cases where anti-HD was detected, eight (12%) developed liver cirrhosis (LC) and six (9%) developed hepatocellular carcinoma (HCC). However, among 1058 cases without anti-HD, there were 43 patients (4%) who developed LC and 29 (3%) who developed HCC. The prevalence of LC and HCC was significantly higher among the cases with anti-HD than those without anti-HD. The proportion of LC and HCC per 1000 person years was 10.46 and 7.84, respectively among cases with anti-HD, and 4.05 and 2.73 among those without anti-HD, respectively. The overall relative risk of LC and HCC was 2.58 and 2.87, respectively; 95% confidence interval (CI): LC, 1.14-5.13; HCC, 1.03-6.23. These results indicate that in the Kure district in Japan, where HDV infection of persons infected with HBV is about 6%, such superinfection increases the risk of LC and HCC.

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To clarify the relationship between hepatitis C virus (HCV) genotypes and liver disease, we typed HCV genomes in the sera of 151 blood donors, 180 patients with type C chronic liver disease (CLD), and 30 haemophiliacs residing in Hiroshima, Japan. All of the subjects were positive for anti-HCV and HCV-RNA, and were examined for seroreactivity to HCV-specific antigens. The HCV genotypes were determined by polymerase chain reaction (PCR) with type-specific primers deduced from the putative core region of the HCV genome. Significantly more (P < 0.001) type III HCV was found in the samples from the CLD patients (80%) than in those from the blood donors (55%). Significantly more (P < 0.001) type III HCV was found in the samples from the blood donors (29.1%) than in those from the CLD patients (11.7%). There was no significant difference in the distribution of the HCV types among the patients with chronic active hepatitis, liver cirrhosis, and hepatocellular carcinoma. A four-antigen recombinant immunoblot assay (RIBA-2) assay was used to compare the serum samples for their reactivity to a range of structural and nonstructural peptides specific for HCV (5-1-1, C100-3, C33c, and C22-3). The frequency of seropositivity to 5-1-1 and C100-3 was significantly higher (P < 0.001) in type II HCV-infected blood donors than in type III HCV-infected donors (68.2% and 65.9% vs. 4.5% and 22.7%, respectively). Among the type III HCV-infected individuals, the CLD patients had a significantly higher (P < 0.01) frequency of seropositivity to 5-1-1 than the blood donors (33.3% vs. 4.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

The chromosomal location of human papillomavirus (HPV) 16 DNA sequences integrated in a cell line derived from argyrophil small cell carcinoma of the uterine cervix was determined by means of fluorescence in situ hybridization (FISH). The HPV 16 DNA sequences were integrated near a fragile site and the location of the c‐myc oncogene at 8q24.1. Amplification of the integrated viral sequences resulted in an abnormally banded region. The amplified HPV 16 DNA sequences were also detected in every interphase nucleus by FISH.

A new cell line, designated TC-YIK, was established from YIK-1 tumor cells, derived from argyrophil small cell carcinoma (ASCC) of the uterine cervix, and serially heterotransplanted into nude mice, integrating human papillomavirus type 16 (HPV16) DNA. The population doubling time of TC-YIK was approximately 21.6 hours at the 119th subculture. Subcutaneous injection of 1 x 10(8) TC-YIK cells into nude mice yielded a solid tumor. The cytologic appearance of TC-YIK was similar to that of YIK-1. The TC-YIK cells contained argyrophil granules and neurosecretory granules in the cytoplasm and showed positive immunohistochemical staining for neuron-specific enolase, serotonin, and chromogranin. Thus, TC-YIK retained the histochemical characteristics of ASCC. The TC-YIK cells contained HPV16 DNA in a multiple-copy integrated form and actively transcribed the integrated HPV16 genome. Amplification of the c-myc oncogene was observed in the TC-YIK cells. These data suggest that TC-YIK is a useful in vitro experimental model of ASCC and that HPV16 and c-myc may play some role in the genesis of this malignant tumor and/or maintenance of the transformed TC-YIK phenotype.