岡本 宏明

We examined the prevalence of hepatitis A virus (HAV) and hepatitis E virus (HEV) infections among 280 Japanese patients infected with human immunodeficiency virus type 1 (HIV) and among 1,000 apparently healthy blood donors as a control. The prevalence of antibody to HAV was significantly higher among the HIV-infected patients than among the healthy donors (25.4% vs. 19.0%, P=0.025). When restricted to subjects aged <50 years, HAV antibody was detected significantly more frequently among the patients than among the donors (15.8% vs. 0.8%, P<0.0001). On the contrary, the prevalence of HEV antibody among the patients was almost equal to that among the donors (12.5% and 10.6%, respectively). HAV and HEV infections among HIV-infected patients deserve further studies.

To investigate the prevalence of hepatitis E virus (HEV) infection among patients on maintenance hemodialysis, serum samples collected in January 2003 from 416 patients who had been undergoing hemodialysis for 7.6 +/- 6.3 (mean +/- standard deviation) (range, 0.3-26.0) years in a dialysis unit in Japan and serum samples that had been collected from these patients at the start of hemodialysis were tested for IgG antibodies to HEV (anti-HEV IgG) by an "in-house" enzyme-linked immunosorbent assay (ELISA). Overall, 39 patients (9.4%) had anti-HEV IgG in January 2003, and included 35 patients (8.4%) who had already been positive for anti-HEV IgG at the start of hemodialysis and 4 patients (1%) who seroconverted after initiation of hemodialysis. Periodic serum samples that had been collected from the four seroconverted patients were tested for HEV antibodies and HEV RNA. The four patients became positive for anti-HEV IgG in 1979, 1980, 1988, or 2003, and continued to be seropositive until the end of the observation period. Although anti-HEV IgM was not detectable in the four patients, three were infected transiently with apparently Japanese indigenous HEV strains of genotype 3. The patient who contracted HEV infection in 1979 had been transfused with 2 U of blood 21 days before the transient viremia: one of the two stored pilot serum samples had detectable HEV RNA with 100% identity to that recovered from the patient. Our study provides evidence of transfusion-transmitted HEV infection in Japan in 1979, and that the prevalence of de novo HEV infection during hemodialysis was low (1.1% or 4/374).

Zoonotic transmission of hepatitis E virus (HEV) from captured wild deer or boars to humans has been suggested. Antibody to HEV was detected in 9% of 35 wild boars and 2% of 117 wild deer tested, and a presumably indigenous HEV of genotype 3 was isolated from a boar in Japan.

Risk factors for acquiring hepatitis E among individuals in industrialized countries including Japan are not fully understood. We investigated whether Japanese blood donors with or without an elevated alanine aminotransferase (ALT) level are likely to have hepatitis E virus (HEV) infection. Serum samples were collected from 5,343 voluntary blood donors including 1,087 donors with elevated ALT of 61-966 IU/L and 4,256 donors with normal ALT ( less than or equal to 60 IU/L) at two Japanese Red Cross Blood Centers, and were tested for the presence of anti-HEV IgG by in-house enzyme-linked immunosorbent assay (ELISA). Overall, 200 donors (3.7%) were positive for anti-HEV IgG, including 32 (2.9%) with elevated ALT and 168 (3.9%) with normal ALT. Serum samples with anti-HEV IgG were further tested for the presence of anti-HEV IgM by in-house ELISA and for HEV RNA by reverse transcription (RT)-polymerase chain reaction (PCR). Three donors with ALT of 966, 62 or 61 IU/L were positive for anti-HEV IgM and HEV RNA. The HEV isolates obtained from the three viremic donors segregated into genotype 3, were 91.5-93.4% similar to each other in the 412 nucleotide sequence of open reading frame 2, and had the highest identity of 91.5-94.9% with the JRA1 isolate which was recovered from a Japanese patient with sporadic acute hepatitis E who had never been abroad, suggesting that these three HEV isolates are indigenous to Japan. This study suggests that a small but significant proportion of blood donors in Japan with or without elevated ALT are viremic and are potentially able to cause transfusion-associated hepatitis E. (C) 2004 Wiley-Liss, Inc.

Background We compared acute hepatitis E (AH-E) and acute hepatitis A (AH-A) to investigate the epidemiology, clinical features, and prognosis of AH-E caused by an indigenous hepatitis E virus (HEV) in Japan. Methods. We enrolled 58 patients diagnosed with AH-A or AH-E (32 men and 26 women; age, 20-72 years) from December 1997 to October 2002. Phylogenetic analysis of the partial 412-nucleotide sequence of open reading frame (ORF) 2 was performed in patients with AH-E. Results. Regarding the geographic distribution of the HEV genotype, genotype III was principally distributed in Honshu Island, and genotype IV in Hokkaido Island (P = 0.0034). The phylogenetic analysis of the ORF2 region revealed that there were significant geographic differences in the distribution of the HEV strains in Japan, with some strains being widespread and some, localized. In comparison with AH-A patients, those with AH-E were older (56.1 +/- 10.6 vs 45.9 +/- 10.8 years; P = 0.0017). The proportion of males among patients with AH-E was significantly higher (P = 0.0001). Pyrexia was often observed in AH-A, and malaise in AH-E. Laboratory data indicate that AH-E induces a weak immunological reaction, whereas jaundice appears earlier in AH-E than in AH-A. One patient with AH-E died of acute hepatic failure, but none of those with AH-A died during the study period. Conclusions. Our results suggest that there are geographical differences between HEV strains in Japan, and that AH-E is more common in males and older patients than AH-A. Laboratory data indicate a weak immunological reaction and early appearance of jaundice in AH-E.

In Indonesia where hepatitis E virus (HEV) is believed to be highly endemic, only three outbreaks of HEV transmission have been documented to date in restricted areas (West Kalimantan and East Java). A total of 1,115 serum samples collected from apparently healthy individuals in Bali, Lombok, and Surabaya in Indonesia in 1996 where epidemic HEV transmissions have never been reported, were tested for IgG class antibodies to HEV (anti-HEV). In Bali, anti-HEV was detected in 20% (54/276) of the tested population, in remarkable contrast with 4% (17/446) in Lombok and 0.5% (2/393) in Surabaya. On the other hand, antibodies to hepatitis A virus were highly prevalent in all three regions (95% in Bali 90% in Lombok, and 89% in Surabaya). Although the majority of the population in Indonesia is Moslem, Balinese people are mostly Hindu and have a habit of consuming pork. Therefore, serum samples were obtained from the 99 farm pigs in Bali and tested for anti-HEV and HEV RNA. The sera from 71 pigs (72%) were positive for anti-HEV and a 2-month-old pig had detectable HEV RNA. The swine HEV isolate recovered from the viremic pig was named SB66-Bali. The SB66-Bali isolate was most closely related to the genotype 4 isolates from China, India, Japan, and Taiwan, but shared only 82.6-90.0% identity in the common 241-412 nucleotides within open reading frame 2 (ORF2). These results indicate that a presumably indigenous HEV strain(s) is circulating in Bali, Indonesia and that HEV infection may occur via zoonosis even in developing countries. (C) 2004 Wiley-Liss, Inc.

Recent studies indicate that hepatitis E virus (HEV) infection occurs not only in developing countries but also in industrialized nations. However, the characteristics of domestic infections of hepatitis E in Japan are not fully understood. We analyzed serum samples from 34 patients who were seen at a city hospital in Sendai, Japan, between January 1997 and December 2002, and who had been given the diagnosis of sporadic acute hepatitis of non-A, non-B, non-C etiology. Among these 34 patients, 3 (9%; all men; aged 54, 59, and 61 years) were positive for both IgG and IgM anti-HEV antibodies and for HEV RNA. The HEV isolates (HE-JASI and HE-JAS3) obtained from case 1 and case 3, respectively, segregated into genotype III; they had the highest nucleotide sequence identity, of 99.5% and 99.0%, with HE-JA7 and HE-JA8, respectively, both of which had been isolated in Iwate, a neighboring prefecture of Sendai. In contrast, the remaining HEV isolate (HE-JAS2), obtained from case 2, segregated into genotype IV; it had the highest nucleotide sequence identity, of 99.8% and 99.3%, with JKK-Sap and HE-JA3, respectively, both of which had been isolated in Hokkaido, Japan, although case 2 had never been to Hokkaido. Our three patients with hepatitis E had not traveled abroad in the preceding 1 year, had had no contact with pigs, and no history of blood transfusion. These results indicate that HEV should be considered as an etiological agent of acute hepatitis of non-A, non-B, non-C etiology in Japan. The risk factor(s) for acquiring domestic HEV infection in Japan needs to be clarified in future studies.

Background. The major transmission route of Helicobacter pylori, oral-oral or fecal-oral, remains to be established. TT virus (TTV), a recently discovered microbe that is prevalent in healthy persons, is believed to be mainly transmitted by nonparenteral routes. The purpose of this study was to test the hypothesis that these two microorganisms have a common mode of transmission. Methods. We investigated the seroprevalence of H. pylori and TTV in a cross-sectional study of 454 healthy Japanese children from birth to age 15 years, living in five different geographic areas. Determination of H. pylori status was based on the presence of specific serum IgG and IgA antibodies, determined using enzyme immunoassays. TTV DNA was detected and the titer was determined using semiquantitative polymerase chain reaction with heminested primers. Results. The overall prevalences of H. pylori and TTV were 12.2% and 21.6%, respectively. An age-related increase of prevalence was shown for H. pylori (P < 0.001), but not for TTV (P = 0.23). Titers of TTV DNA significantly decreased with age (P = 0.02). There were significant geographic differences in TTV prevalence (P < 0.001), but not in H. pylori seroprevalence (P = 0.33). There was no true correlation between the prevalence of these two organisms ( coefficient = -0.02 and P = 0.66). Conclusions. Although Japanese children frequently acquire both H. pylori and TTV, especially in early childhood, their acquisition appears to be independent.