基本情報
- 所属
- 自治医科大学 医学部感染・免疫学講座ウイルス学部門 客員教授 (名誉教授)
- 学位
- 医学博士(自治医科大学(JMU))
- J-GLOBAL ID
- 200901036866152058
- researchmap会員ID
- 1000063749
- 外部リンク
研究キーワード
22経歴
6-
2020年4月 - 現在
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2020年4月 - 現在
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2003年4月 - 2020年3月
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1998年 - 2003年
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1987年 - 1998年
学歴
1-
1973年4月 - 1979年3月
受賞
4-
2008年
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1997年
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1992年
論文
599-
Clinical journal of gastroenterology 17(5) 1001-1002 2024年10月
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Virus research 348 199438-199438 2024年7月19日Previous studies have emphasized the necessity of surveillance and control measures for hepatitis E virus (HEV) infection in wild boars, an important reservoir of HEV. To assess the current situation of HEV infection in wild boars in Japan, this study investigated the prevalence and genetic diversity of HEV among wild boars captured in 16 prefectures of Japan during 2018-2023. Serum samples from 968 wild boars were examined for anti-HEV IgG antibodies and HEV RNA. The prevalence of anti-HEV IgG varied geographically from 0 % to 35.0 %. HEV RNA was detected in 3.6 % of boars, with prevalence varying by prefecture from 0 % to 22.2 %. Genotype 3 was the most prevalent genotype (91.9 %), followed by genotype 4 (5.4 %), with one strain closely related to genotype 6. The prevalence of HEV infection among wild boars decreased from 2018/2019 to 2022/2023 with significant declines in levels of anti-HEV IgG antibodies (14.5 % vs. 6.2 %, P < 0.0001) and HEV RNA (7.6 % vs. 1.5 %, P < 0.0001). Regional analysis showed varying trends, with no HEV RNA-positive boars found in several regions in recent years. A plausible factor contributing to the decline in HEV infection is the application of countermeasures, including installing fences to prevent intrusion into pig farms, implemented in response to the emergence of classical swine fever virus (CSFV) infection in wild boars and domestic pigs, with incidents reported annually since 2018. Further investigation is warranted to explore the association between countermeasures to CSFV infection and the decrease in HEV infection among wild boars.
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Clinical journal of gastroenterology 2024年5月15日Spontaneous reactivation of the Hepatitis B virus (HBV) is rare in individuals with previously resolved infections. This report presents the case of a 71 year-old Japanese woman who experienced HBV reactivation without any prior immunosuppressive therapy or chemotherapy. Before the onset of liver injury, the patient was negative for hepatitis B surface antigen (HBsAg) but positive for hepatitis B surface antibody. She subsequently developed liver injury, with the reappearance of HBsAg and HBV DNA. The patient was successfully treated with tenofovir alafenamide, and prednisolone. Full-genome sequencing of HBV revealed subgenotype B1 without hepatitis B e-negative mutations in the precore and core promoter regions and 12 amino acid alterations in the pre-S1/S, P, and X genes. Notably, the S gene mutations D144A and K160N, which alter the antigenicity of HBsAg and potentially contribute to its reactivation, were identified. This case emphasizes the importance of vigilance for spontaneous reactivation of resolved HBV, highlighting the need for comprehensive genomic analysis to understand the associated virological intricacies.
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Medicine International 4(3) 2024年3月7日 査読有り
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Reports 6(4) 55-55 2023年11月17日Hepatitis E virus (HEV) genotypes 3 and 4 are zoonotic strains that are primarily transmitted through the consumption of undercooked pork or game meat. They also cause asymptomatic infections, acute hepatitis, acute-on-chronic liver failure, chronic hepatitis, and extrahepatic manifestations. Here, we report a man in his 80s who had chronic hepatitis B, took entecavir for it, and presented with higher levels of alanine aminotransferase (ALT) and jaundice. An abdominal computed tomography scan revealed choledocholithiasis with cholecystolithiasis. Although endoscopic papillary balloon dilatation was performed for the removal of a common bile duct stone, the abnormal liver function tests, including jaundice, were prolonged. After other viral hepatitis and other causes of the liver injury were ruled out, as his serum was positive for immunoglobulin A anti-HEV and HEV genotype 3b RNA, we diagnosed him as having acute hepatitis E. In this case, with chronic hepatitis B and a common bile duct stone, the prolonged abnormal results for the liver function tests seemed to be caused by HEV infection. In conclusion, in cases with high ALT levels after removing choledocholithiasis, other factors, including HEV infection, should be considered to determine the cause of abnormal liver function test results. The further examination of hepatitis D virus infection and high ALT levels may be needed in HBV-infected individuals.
MISC
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JOURNAL OF GENERAL VIROLOGY 84(9) 2351-2357 2003年9月Among ten patients who contracted sporadic acute or fulminant hepatitis E between 2001 and 2002 in Hokkaido, Japan, nine (90 %) had a history of consuming grilled or undercooked pig liver 2-8 weeks before the disease onset. We tested packages of raw pig liver sold in grocery stores as food in Hokkaido for the presence of hepatitis E virus (HEV) RNA by RT-PCR. Pig liver specimens from seven (1(.)9%) of 363 packages had detectable HEV RNA. Partial sequence analyses revealed that the seven swine HEV isolates belonged to genotype III or IV. One swine HEV isolate (swJL145) from a packaged pig liver had 100 % identity with the HE-JA18 isolate recovered from an 86-year-old patient in Hokkaido. Two swine HEV isolates (swJL234 and swJL325) had 98(.)5-100% identity with the HE-JA4 isolate. obtained from a 44-year-old patient in Hokkaido. These results indicate that inadequately cooked pig liver may transmit HEV to humans.
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HEPATOLOGY RESEARCH 26(3) 237-242 2003年7月We encountered a patient with sporadic acute hepatitis E who had not traveled to areas endemic for hepatitis E virus (HEV) infection and may have been infected in Japan. The patient was a 47-year-old male who had no history of blood transfusion or contact with travelers to hepatitis E-endemic regions or unspecified individuals. The disease presented with general malaise, fever, and brown urine as chief complaints in April 2002. Various hepatitis virus markers were negative, but IgM class antibodies to hepatitis E virus (anti-HEV) and HEV RNA were positive, and the patient was diagnosed with acute hepatitis E. The entire nucleotide sequence (7240 bases) of HEV (HE-JK4) isolated from this patient was determined and compared with known HEV strains. HE-JK4 belonged to genotype IV and exhibited higher similarities to genotype IV HEV strains previously isolated in Japan than to those isolated in China, Taiwan, and Vietnam. The patient's family members living with him were negative for anti-HEV IgG and IgM, but their pet cat was anti-HEV IgG-positive. This finding suggests a potential route of infection of sporadic cases of hepatitis E in Japan. Since the presence of HEV indigenous to Japan is predicted, HEV infection should be considered in the diagnosis of acute hepatitis of unknown cause, even for patients who have not traveled abroad. (C) 2003 Elsevier B.V. All rights reserved.
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HEPATOLOGY RESEARCH 26(2) 91-97 2003年6月Interstitial pneumonia (IP) is a serious adverse event of interferon alpha (IFNalpha) treatment for chronic hepatitis C (CH-C). Among 558 CH-C patients who received IFNalpha treatment with or without ribavirin between January 1992 and June 2002, six patients (1.1%) developed IP, including one patient who developed IP in 1993 and again in 2002. Among the seven cases who contracted IP, at the onset of IP, seven (100%), five (71%), and two cases (29%) had elevated serum levels of KL-6, surfactant protein A (SP-A), and surfactant protein D (SP-D), respectively. Prior to starting IFN treatment (baseline), the serum SP-A and SP-D levels were within the normal range in all seven cases, but the serum KL-6 level was elevated in five of the seven cases, contrasting with that in three of 48 age-adjusted CH-C patients who did not develop IP during IFN treatment (71 vs. 6%; P = 0.0003). Furthermore, the circulating KL-6 level at baseline was significantly higher among the seven cases than among the controls (543+/-105 vs. 304+/-98 U/ml, P = 0.0001). These results indicate that measurement of the circulating KL-6 level in CH-C patients before IFN treatment may be useful for predicting the occurrence of IP during IFN treatment. (C) 2003 Elsevier Science B.V. All rights reserved.
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日本消化器病学会雑誌 100(4) 454-458 2003年4月5日 査読有り
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JOURNAL OF GENERAL VIROLOGY 84(4) 851-862 2003年4月Japanese patients with sporadic acute hepatitis E are infected with polyphyletic strains of hepatitis E virus (HEV). Hepatitis E is considered a zoonotic disease. Thus far in Japan, only three strains of swine HEV have been identified and an antibody study for HEV antibodies has not been done on Japanese pigs. To determine the prevalence of swine HEV infection in Japan and the extent of genetic variation among Japanese swine HEV strains, we tested serum samples obtained from 2500 pigs from 2 to 6 months of age at 25 commercial swine farms in Japan for the presence of IgG antibodies to HEV and swine HEV RNA. Anti-HEV antibodies were detected in 1448 pigs (58%). One-hundred-and-thirteen (115%)of the 750 3-month-old pigs and 24 (13%) of the 180 4-month-old pigs were positive for swine HEV RNA. The nucleotide sequence of a 412 bp region within open reading frame 2 of the 137 swine HEV isolates was determined. Sequence analyses revealed that the 137 isolates shared 76(.)6-100% nucleotide sequence identities and were classifiable into genotype III (93%) or IV (7%) and that the isolates from the same farm were greater than or equal to 97(.)1% similar to each other. Phylogenetic analysis showed that the Japanese swine and human HEV isolates segregated into four clusters, with the highest nucleotide identity being 94(.)4-100% between swine and human isolates in each cluster. These results indicate that swine HEV is widespread in the Japanese swine population and further support the hypothesis that swine serve as reservoirs for HEV infection.
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JOURNAL OF CLINICAL MICROBIOLOGY 41(3) 1342-1343 2003年3月
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JOURNAL OF GENERAL VIROLOGY 84(2) 421-427 2003年2月Serum samples collected periodically from a 40-year-old Japanese woman who had not travelled abroad and who had contracted sporadic acute hepatitis E in 1993 were semi-quantitatively tested by enzyme immunoassay for IgM, IgA and IgG antibodies to hepatitis E virus (HEV). Anti-HEV IgM and IgA antibody levels were the highest (11 : 2400 dilution and 1 : 3400 dilution, respectively) on day 9 after the onset of hepatitis and then decreased rapidly in a parallel manner. Anti-HEV IgG antibody levels were the highest (11 :17000 dilution) on day 145 and then decreased gradually but remained at high titres (1 : 2200 dilution) even 8.7 years after the onset of hepatitis. An HEV isolate, HE-JA10, recovered from the patient's serum at admission was closely related to a genotype III strain isolated in the United States (US1), with 92.2% identity over the full-length genome, and was most closely related to the JMY-Haw isolate of Japanese origin (95.4% identity).
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JOURNAL OF MEDICAL VIROLOGY 69(2) 207-214 2003年2月One hundred fifty-four consecutive patients with sporadic acute hepatitis, who were seen at a city hospital in the Kathmandu valley of Nepal in 1997, were studied. IgM antibodies to hepatitis A virus were detected in four patients (3%), IgM antibodies to hepatitis B core in four patients (3%), hepatitis B surface antigen in 20 (13%), and hepatitis C virus RNA in four patients (3%). IgM antibodies to hepatitis E virus (HEV) (anti-HEV IgM) and HEV RNA were detected in 77 (50%) and 48 (31%), respectively. Consequently, 86 patients (56%) including nine HEV-viremic patients it out anti-HEV IgM, were diagnosed with hepatitis E. The cause of hepatitis was not known in 53 patients (34%). All 48 HEV RNA-positive samples were genotyped as 1, and subtyped further as la in 17 (35%), 1c in 29 (60%), and mixed infection of la and 1c in 2 (4%). A seasonal difference in the prevalence of HEV subtypes was recognized. Before the rainy season (January to July), both la and 1c isolates were found: the intrasubtypic difference was up to 9.0% and 1.7%, respectively, in the 412-nucleotide sequence of open reading frame 2. During the rainy season (August), only 1c isolates (n = 17) with 99.5-100% identity were found; 13 of 17 isolates had the same sequence, being identical to the 3 isolates that emerged at the end of July. These results suggest that a particular HEV 1c strain spread widely during the rainy season and was implicated in a small epidemic in the Kathmandu valley in August 1997.
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Perspectives in Medical Virology 10 241-254 2003年TTV is a unique, unenveloped human virus with a genome of circular, single (minus)-stranded DNA of a total length of 3.6-3.9 kb, and it has a characteristic genomic organization and transcription profile that are not observed in known members of the Circoviridae family. It has been proposed by the ICTV Circoviridae Study Group that TTV is to be named as Torque Teno virus classifiable into a novel genus Anellovirus, unassigned to any family. At least 39 genotypes of TTV have been identified, and they are classified into five distantly-related groups (1-5). The natural history and pathogenic potential of TTV are currently under intensive investigation. Although the precise relationship between TTV infection and viral hepatitis remains to be established, it is likely that certain genotypes of TTV or some strains of TTV cause hepatitis in some clinical and epidemiological settings. As TTV replicates not only in the liver but also in other tissues such as the bone marrow and lung tissue, TTV infection may also be associated with extrahepatic disorders as suggested in several recent studies [91-97]. Therefore, detailed cross-sectional and longitudinal studies are required to address the exact role of TTV in children and adults with cryptogenic liver disease or other diseases that are currently of unknown etiology, with regard to the genotypes and viral load of TTV. © 2003 Elsevier Inc. All rights reserved.
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Internal Medicine 42(11) 1065-1071 2003年Hepatitis E virus (HEV) is a major cause of acute hepatitis in many developing countries. HEV is transmitted principally by the fecal-oral route, and water-borne epidemics are characteristic of hepatitis E. Recently, there is growing consensus that HEV-associated hepatitis also occurs among individuals in industrialized nations who had no history of travel to endemic areas. Zoonotic spread of HEV has been suggested as human and swine HEV strains are closely related genetically and experimental cross-species infection of swine HEV to a chimpanzee and that of human HEV to swine have been demonstrated. This review describes the clinical, epidemiological and virological characteristics of domestic HEV infection in Japan, the genetic relatedness of Japanese human and swine HEV strains, and possible modes of HEV transmission, emphasizing that HEV should be considered in the diagnosis of acute or fulminant hepatitis of non-A, non-B, non-C etiology, even in patients who have not traveled abroad.
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Transplantation 76(9) 1369-1375 2003年
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J Gen Virol 84(5) 1245-1251 2003年
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JOURNAL OF INFECTIOUS DISEASES 186(10) 1535-1536 2002年11月
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肝臓 43(7) 332-335 2002年7月25日国内で発症したE型肝炎の報告は極めて少ない. 特に国内で感染し発症したと思われる散発性E型急性肝炎の報告は1994年に安藤らが報告した1例のみである. 今回我々は海外渡航歴のない国内感染と思われるE型急性肝炎の1例を経験した. 症例は45歳の男性. 海外渡航歴, 輸血歴及び不特定な人との性的接触を認めない. 全身倦怠感, 皮膚の黄染を主訴に発症. 各種肝炎のマーカー陰性かつ, IgM anti-HEV抗体が陽性に引き続きIgG anti-HEV抗体の上昇が確認された. 以上より本症例はE型急性肝炎と診断した. 本症例の感染経路は明らかではないが, 原因不明の急性肝炎の診断には, たとえ海外渡航歴がなくともHEV感染を考慮すべきであると考えられた.
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Hepatology Research 24(2) 91-94 2002年
書籍等出版物
5-
Elsevier/Academic Press 2005年 (ISBN: 0122499514)
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Elsevier 2004年 (ISBN: 0444514872)
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Viral Hepatitis and Liver Diseases 1994年
共同研究・競争的資金等の研究課題
16-
国立研究開発法人日本医療研究開発機構 肝炎等克服実用化研究事業・肝炎等克服緊急対策研究事業 2023年4月 - 2026年3月
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日本学術振興会 科学研究費助成事業 2013年4月 - 2015年3月
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日本学術振興会 科学研究費助成事業 2011年 - 2012年
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日本学術振興会 科学研究費助成事業 2010年 - 2012年
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日本学術振興会 科学研究費助成事業 2007年 - 2008年