Background: Interferon alfa is used widely for patients with chronic hepatitis C virus (HCV) infection. Little is known, however, of the relationship between patients' sex and the effectiveness of interferon alfa treatment in these patients.

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JUN HAYASHI, YASUHIRO KISHIHARA, KOUZABURO YAMAJI, NORIHIRO FURUSYO, TETSURO YAMAMOTO, YOUNGDUK PAE, YOSHITAKA ETOH, HIDEYUKI IKEMATSU, AND SEIZABURO KASHIWAGI gesting that HCV injures the liver indirectly through the To clarify the virological differences in patients with immune system. chronic hepatitis C virus (HCV) infection with and with-We have studied individuals from a rural area of Japan out liver damage, we assessed HCV markers in 306 pawhere HCV infection is common and where serial testing for tients from a rural area of Japan. Genotypes of HCV aminotransferases has been done routinely for the past 10 RNA were determined by polymerase chain reaction, years. 8 To clarify virological differences between asymptomand levels of RNA were determined by branched DNA atic HCV carriers and patients with chronic hepatitis C, we signal-amplification assay. All patients had undergone determined HCV RNA genotype, HCV RNA levels, and seannual tests for alanine aminotransferase (ALT) levels quences of the putative core region of the HCV genome in a from 1986 to 1995. Patients were categorized into three cohort of patients in this area. three groups. We selected 10 patients from group A with Liver biochemical tests, including measurements of alaninEaminonormal ALT levels and 10 from group C with abnormal transferase (ALT), aspartate aminotransferase, and g-glutamyllevels for sequence analysis of the HCV core region (nt transpeptidase levels, have been performed in these residents once 169-378) of five clones from each patient. More mutations a year since 1986. Since 1993, we have surveyed 2,046 of the resiwere found in the 50 clones from the 10 patients from dents of the village for HCV and hepatitis B virus markers, and 334 group C than in the 10 patients from group A. In group patients with chronic HCV infection were identified. 8 An abnormal A, all mutations were synonymous so that the deduced biochemical liver test result was defined as an ALT level ú36 IU/ L. Patients with chronic HCV infection who were also positive for amino acid sequences were identical among clones from hepatitis B surface antigen were excluded from this analysis. All each patient, whereas in group C 16 of 57 mutations were patients were tested for HCV RNA at least twice, at an interval of nonsynonymous so that the deduced amino acid se-6 months or longer, before being classified as having chronic HCV quences showed differences in the five clones of eight of infection. Of the 334 HCV-infected patients, 306 (162 men, 144 10 patients. In conclusion, the HCV core region was women) were selected for the present study based on having had highly conserved in patients with normal liver biochem-annual examinations for 10 years (retrospectively from 1986 to 1992, ical test results but not in those with abnormal results. prospectively from 1993 to 1995). Our results suggest that abnormal liver biochemical testMethods. All serum samples were separated and stored at 020ЊC results in patients with chronic HCV infection may be until they were tested for ...

Abstract. To determine the natural course of hepatitis B surface antigen (HBsAg) disappearance in chronic hepatitis B virus (HBV) infection and the factors related to its disappearance, 946 HBsAg carriers in Okinawa, Japan were prospectively followed for up to 19 years (mean ϭ 9.2 years). The disappearance of HBsAg, as determined by radioimmunoassay (RIA), was observed in 62 (6.6%) and the overall annual disappearance rate was 0.79%/year. Its disappearance was more frequent in 60 (7.4%) of 815 serum samples negative for hepatitis B e antigen (HBeAg) by RIA at entry compared with only two (1.5%) of 131 serum samples that were HBeAg positive by RIA at entry (P Ͻ 0.05). Stepwise logistic regression analysis showed that age and HBsAg subtype were significantly associated with HBsAg disappearance (both P Ͻ 0.05), and that carriers with subtype adr (odds ratio ϭ 2.87) had an increased probability of clearing HBsAg compared with carriers with subtype adw. Conversely, HBeAg disappearance was earlier in those with the adw subtype than in those with adr. Hepatitis B virus DNA was not detected by the polymerase chain reaction after HBsAg disappearance in any of the 62 from whom it had disappeared. The HBsAg titer, as measured by reverse passive hemagglutination, was related to the time to its disappearance; the higher the titer, the longer the time to disappearance. These findings suggest that HBeAg negativity, a more advanced age, and low titers of HBsAg are favorable factors for HBsAg disappearance in the natural course of chronic HBV infection. Moreover, HBsAg subtype adr was a predictive factor for HBsAg disappearance, whereas subtype adw was predictive of early HBeAg disappearance.It has been conservatively estimated that there are 350 million chronic hepatitis B virus (HBV) carriers throughout the world.1 This virus is a serious problem in many countries since it causes chronic liver disease and hepatocellular carcinoma. [2][3][4] Diagnosis is made by the detection of hepatitis B surface antigen (HBsAg) in serum. The disappearance of HBsAg and the appearance of antibody to HBsAg (anti-HBs) in sera have been reported to indicate the clearance of HBV particles and the cessation of hepatocyte injury. [5][6][7] Our laboratory previously reported that the Yaeyama District of Okinawa, Japan was highly endemic for HBV infection, 8 and that the number of newly infected residents has decreased there, as estimated in our long-term study. 9 In another Okinawa study, we found that the rate and age of seroconversion from hepatitis B e antigen (HBeAg) to antibody to HBeAg (anti-HBe) were higher and younger in cases with the HBsAg subtype adw than in those with subytpe adr, suggesting that the HBsAg subtype may be closely associated with the HBeAg/anti-HBe status.

To explore the effect of human T lymphotropic virus type 1 (HTLV-1) infection on hepatitis C virus (HCV) infection, a survey for these viral infections was conducted that involved 2280 residents in an area in which HTLV-1 and HCV are endemic. The response of patients with HCV and HTLV-1 to interferon (IFN)-alpha treatment was also assessed. Antibody to HCV was detected in 13.8% of the residents tested, and antibody to HTLV-1 was detected in 15.4%. The prevalence of HCV RNA was significantly higher among residents who had antibodies to both HCV and HTLV-1 than in those who had antibodies to HCV only (P<.05). Sustained elimination of HCV RNA by IFN was significantly more frequent among patients with HCV alone than among those with HCV and HTLV-1. By logistic regression analysis, HTLV-1 infection was associated with nonresponse to IFN treatment. Thus, HTLV-1 infection affects the clearance, both natural and in association with IFN treatment, of HCV.