Hitoshi Nakano

Hepatitis C Virus Seroconversion Rate in a Hyperendemic Area of HCV in Japan: A Prospective Study

We have studied the prevalence, seroconversion rate of anti-hepatitis C virus (HCV), and the transmission of HCV in a cohort of individuals living in a hyperendemic area of HCV in Japan. We investigated 509 subjects, of which 375 could be studied again after 5 years. A remarkable high prevalence of anti-HCV (23.4-24.0%) was observed. Of 287 subjects negative at the first examination in 1990, 4 became positive until the second in 1995 (seroconversion rate: 0.28% per year). Furthermore, we investigated the route of transmission in HCV seroconverted subjects through a detailed interview. All of the HCV seroconverted subjects had past histories of medical treatment. Seroconversion rates of HCV in a hyperendemic area of HCV, were extremely high. Medical treatment was considered to be a causative route of HCV transmission.

SERO-EPIDEMIOLOGIC STUDY OF HEPATITIS C VIRUS INFECTION IN FUKUOKA, JAPAN

Abstract: We conducted an epidemiological study of 509 residents of H town, Fukuoka, Japan, to investigate the high mortality rate from liver disease. Antibodies to hepatitis C virus (HCV) (anti-HCV) were detected in 120 residents (23.6%); HCV RNA in 91 (17.9%), and hepatitis B surface antigen (HBsAg) in 13 (2.6%). Multivariate logistic regression analyses showed that presence of anti-HCV, male gender, and history of liver disease were associated with the presence of liver dysfunction, and that age of more than 40 years and a particular district were associated with the presence of anti-HCV. HCV RNA was more frequently detected in anti-HCV-positive men than women (41, or 85.4% versus 50, or 69.4%) (P < 0.05). The incidence of liver dysfunction was significantly higher in HCV RNA-positive men than women (32, or 66.7% versus 22, or 30.6%) (P < 0.05). These findings suggest that: (1) HCV was correlated with the high mortality rate from liver diseases, (2) there were district-related differences in the incidence of HCV, and (3) the lower frequency of elimination of HCV from men may explain why they showed a high mortality from liver disease.

Antibody response to inactivated hepatitis A vaccine

Abstract We examined the seroconversion rate and level of hepatitis A virus antibodies induced by inactivated hepatitis A vaccine. Inactivated hepatitis A vaccine was administered intramuscularly to 127 healthy antibody negative subjects at doses of either 0.5 and 1.0 μ g two or three times. Convalescent sera from 21 adults with acute hepatitis A were also assayed. Serum antibody titers were measured by enzyme-linked immunosorbent assay. Seroconversion occurred in all 127 subjects (43 children, 84 adults). Acquired antibody levels in children in the early stage were higher than those in adults. Protective titers appeared 6 weeks after initial inoculation in 126 of 127 subjects and were maintained for at least 3 years in a 11 subjects. Mean maximum titer in subjects inoculated twice and three times after the initial vaccination were 393 mIU ml −1 at 6 weeks and 2745 mIU ml −1 at 7 months, respectively. Titers at 6 and 12 months after the initial vaccination were significantly higher in subjects with the 1.0 μ g inoculation than with 0.5 μ g. Titers in females were significantly higher than in males. The mean titer after inoculation was 1.1% of the convalescent titer in patients with acute hepatitis A. Neither adverse clinical events nor abnormal laboratory tests were observed after vaccination. Hepatitis A virus antibodies appeared reliably after inoculation with inactivated vaccine, persisting for at least 3 years. Although seroconversion rate was not age- or sex-dependent, the acquired titer was higher in children and females than in elderly males.

Analysis of serum hepatitis A virus antibody response in different courses of hepatitis A virus infection

Changes in the serum hepatitis A virus anti-body (anti-HAV) response in patients with different clinical courses of HAV infection were examined using immune adherence hemagglutination (IAHA). Anti-HAV was detected 2–6 weeks after the onset of clinical symptoms in patients with the typical course of acute hepatitis A and 1–4 weeks after the onset in those with fulminant hepatitis A. Maximal anti-HAV titers were observed 8–20 weeks after the onset of clinical symptoms, and changes in anti-HAV were similar in the typical and the prolonged course of acute hepatitis A, but maximal antibody titers were higher in the prolonged course. Maximal anti-HAV titers in patients with subclinical HAV infection were significantly lower than titers in patients with the typical and prolonged courses of acute hepatitis A, and in those with fulminant hepatitis A. High titers of anti-HAV remained positive for at least 6 years after infection in patients with clinical infection and for at least 4 years in patients with subclinical infection on follow-up. These findings suggest that the maximum anti-HAV titer correlates with the clinical severity of HAV infection; knowledge of the antibody response should be useful for analyzing the pathogenesis of HAV infection.

Incidence of anti-HTLV-1 antibody in liver disease

SummaryPositivity for serum anti-HTLV-1 antibody (anti-HTLV-1) in 171 patients with various chronic liver diseases and 22 asymptomatic hepatitis B virus (HBV) carriers was compared with that of 200 healthy controls in the Chikugo district of Japan. The rate of anti-HTLV-1 positivity in patients with liver disease was 8.1% (14/171) and was higher than that (3.5%: 7/200) in healthy controls, but the difference was not significant. However, in patients with liver disease with a history of blood transfusion, the positive rate was 18.4% (7/38) which was significantly higher than that for healthy subject (P< 0.001). On the other hand, in 133 liver disease patients without blood transfusion, anti-HTLV-1 positivity was significantly higher (P< 0.05) in patients with hepatitis B surface antigen (11.3%: 6/53) than in those without it (1.3%: 1/80). These data suggest that the high incidence of anti-HTLV-1 in our patients with liver disease was due to the transmission of HTLV-1 by the same routes (maternal transmission and blood transfusion) and probably at the same time as the hepatitis viruses (HBV and hepatitis C virus).

A pilot study of natural interferon γ therapy for chronic hepatitis C

Abstract Background: To assess the effectiveness and side effects of interferon (IFN)γ therapy for chronic hepatitis C. Materials and methods: A single dose of 1 × 10 6 IU of natural IFNγ was administered intramuscularly daily for 4 weeks to five patients with chronic active hepatitis C. Alanine aminotransferase levels, 2′-5′ oligoadenylate synthetase activity, β 2 microglobulin levels, IFNγ activity and HCV RNA levels were measured in sera. Results: ALT level, 2′-5′ oligoadenylate synthetase (2-5AS) activity, β 2 microglobulin (BMG) level, and IFNγ activity increased from 1–2 weeks after the start of IFNγ. However, HCV RNA levels did not decrease during IFNγ administration. There were no serious adverse reactions. Conclusions: IFNγ, which has attracted attention for its immunoenhancement, is worthy to be investigated as a therapy for chronic hepatitis C. However, the use of IFNγ in combination with IFNα, β or other antiviral agents may be more rewarding because of the possibly weak antiviral action of IFNγ.

The relationship between LeY antigen and the therapeutic efficacy of interferon in chronic hepatitis C

The expression of LeY antigen (Fuc alpha 1-->2Gal beta 1-->4 [Fuc alpha-->3] GlcNAc beta 1-->R), recognized by the monoclonal antibody BM-1, was studied in peripheral blood T-lymphocyte subpopulations in patients with viral hepatitis, and in liver tissue of patients with acute viral hepatitis. The relationship between the expression of LeY antigen on peripheral blood T-lymphocytes and the effects of interferon (IFN) therapy for chronic hepatitis type C were also evaluated. LeY antigen is not markedly expressed in B or T-lymphocytes of healthy individuals. However, it was strongly expressed in CD8 and CD4 T-lymphocytes in patients with viral hepatitis. In the acute phase of acute viral hepatitis, the expression of LeY antigen was more markedly expressed on peripheral CD8 T-lymphocytes than on CD4 T-lymphocytes. In chronic hepatitis type B and type C, it was significantly expressed more often on CD4 T-lymphocytes. In the liver tissues of patients with acute viral hepatitis, LeY antigen was expressed on hepatocytes and infiltrating lymphocytes. IFN therapy for chronic active hepatitis type C proved most effective when LeY antigen was more markedly expressed on the patients CD4 and CD8 peripheral blood T-lymphocytes before treatment. Further studies are needed to clarify the relationship between the mechanisms of hepatic cell injury and LeY antigen.

Kupffer cell function and endotoxin.

The aim of this paper is to show the relationship between Kupffer cell function and endotoxin in the experimental liver injury and clinical liver disease.We all have a bacterial flora in our intestine as a source of endotoxin, and once liver injury was occured, in association with the failure of Kupffer cell function of the liver, these endogenous endotoxin will appear in the peripheral circulation.The results of our clinical study on hepatitis A and alcoholic liver disease, suggest the reticuloendotherial system of the liver markedly damaged and systemic endotoxemia is thought to be responsible for the various clinical manifestations and the excerbation of the course of these disease, and that endotoxin plays an important role in the pathogenesis of liver injury in hepatitis A and alcoholic liver disease.

Abstracts of Selected Papers Presented at the 76th General Meeting of the Japanese Society of Gastroenterology

S OF SELECTED PAPERS PRESENTED AT THE 76TH GENERAL MEETING OF THE JAPANESE SOCIETY OF GASTROENTEROLOGY March 29-31, 1990, Tokyo, Japan Chairman: Haruo KAMEDA, M.D.