岡本 宏明

A 35-year-old woman who was 14 weeks pregnant visited a gynecology hospital to undergo a surgical abortion. Although she was not jaundiced, and had no signs of hepatitis, liver function was abnormal (ALT, 100 IU/L; AST, 96 IU/L). The serum obtained was negative for markers of hepatitis A, B, and C viruses. However, based on the positive results of non-routine IgM/IgA anti-HEV and HEV RNA assays, the patient was occasionally diagnosed with sporadic acute hepatitis E. The HEV isolate recovered from the patient was phylogenetically close to known genotype 3 HEV strains circulating in Japan, with the highest identity of 93.2%. We believe that testing for hepatitis E should be routine in Japan, in cases of suspected viral hepatitis.

67歳の男性が結婚40年後にC型急性肝炎を発症した．その妻（68歳）がC型慢性肝炎患者であり，C型肝炎ウイルス（HCV）RNAが高力価陽性（>5,000 KIU/ml）であった．両者のHCV遺伝子型はともに1b型で，NS5B領域の1,087塩基長の配列において99.7%の一致率を示した．それに対し，これまでに報告されているHCV/1b株との一致率は最高でも96.7%に過ぎなかった．分子系統樹解析によっても，夫婦の持つHCV株は一つのクラスター（bootstrap値：100%）を形成し，同一株である可能性が強く示唆された．詳細な病歴聴取を行ったが，性交渉（月1, 2回）以外の感染経路はいずれも否定された．高齢夫婦間の感染には加齢に伴う生体側因子が関与していると考えられるが，高齢化社会を迎え，HCV感染者頻度の高い高齢者層でかかるHCV感染が起こる可能性を念頭に置く必要があると考え報告する．

患者は30歳男性．2006年1月から4カ月間中国の雲南省とチベット自治区，ネパール，およびタイの順に旅行し，タイに移動後間もなく褐色尿と黄疸に気づき帰国した．患者血清からはE型肝炎ウイルス（HEV）RNAが検出され，遺伝子型は1型と判定された．取材旅行であったことより日々の飲食を全て記録しており，生ものや生水の摂取は旅行中一切無かったが，ネパールでの水かけ祭「ホーリー」に参加し，泥水を誤飲したことが感染契機になったとみられた．さらに，1型の既知全クローンとの比較から，感染したHEV株は2005年12月にネパールで分離されたHEV株と100%の一致率を示し，ネパールで感染したことがHEVクローンの遺伝子解析から裏付けられた．ネパールでは2006年春においても同種株の流行が続いていたことが推測された．

愛知県内で捕獲された野生イノシシの肉・内臓を摂食し，約1∼2カ月後にE型肝炎を発症した症例を2005年と2006年に2例ずつ合計4例経験した．いずれも中高年男性であり，3例に飲酒歴を認め1例に薬剤服用歴を認めた．4例いずれも著明な肝逸脱酵素の上昇を示し，2例で劇症化が懸念されステロイドパルス治療を施行，うち1例は血漿交換療法を施行した．分離されたHEV株の遺伝子型はいずれも4型であり，互いに98.8∼99.8%の塩基配列一致率を示すと同時に，最近愛知県内の野生イノシシから分離されたHEV株とも99.1∼100%の一致率を示した．一方，これまでに北海道を中心に他県で分離されている4型HEV株との一致率は85.4%∼89.3%に過ぎなかった．以上の結果より，野生イノシシを感染源とする土着HEVの感染が愛知県内で広がりつつあることが危惧され，感染予防の観点から，早急の感染実態の調査・把握が重要である．

輸入感染症の一つで稀な疾患と見なされていたE型肝炎が, 実は人獣共通感染症として国内でも看過できない頻度で発生していることが明らかになった. したがって, E型肝炎は急性肝炎の診断に際し, 常に念頭に置かれるべき疾患の一つであると言える. その特徴として, 1) 中高年の男性に多く, 2) 全国に遍在するが, 北海道で最も多く (全体の約40%), 次いで, 東北・関東地方に多いこと, 3) 大多数は比較的短期間のうちに軽快治癒するが, 劇症肝炎による死亡例や, 黄疸遷延や血液凝固能異常 (プロトロンビン活性 : 40%以下) を示す重症化例が少なからず認められること, などが挙げられる. ブタやイノシシなどの動物の肉や内臓を生, ないし生に近い状態で摂食したあとのE型肝炎発症例が最も多く, 稀ながら輸血感染も確認されているが, 今尚約半数の患者で感染源や感染経路が不明である. 改正感染症法において4類感染症に分類され, 届け出が義務付けられている.

輸入感染症の一つで稀な疾患と見なされていたE型肝炎が, 実は人獣共通感染症として国内でも看過できない頻度で発生していることが明らかになった. したがって, E型肝炎は急性肝炎の診断に際し, 常に念頭に置かれるべき疾患の一つであると言える. その特徴として, 1) 中高年の男性に多く, 2) 全国に遍在するが, 北海道で最も多く (全体の約40%), 次いで, 東北・関東地方に多いこと, 3) 大多数は比較的短期間のうちに軽快治癒するが, 劇症肝炎による死亡例や, 黄疸遷延や血液凝固能異常 (プロトロンビン活性 : 40%以下) を示す重症化例が少なからず認められること, などが挙げられる. ブタやイノシシなどの動物の肉や内臓を生, ないし生に近い状態で摂食したあとのE型肝炎発症例が最も多く, 稀ながら輸血感染も確認されているが, 今尚約半数の患者で感染源や感染経路が不明である. 改正感染症法において4類感染症に分類され, 届け出が義務付けられている.

Serum samples obtained from 289 first-time and 114 repeat donors at the Blood Center of Mongolia (MBC) were tested for serological and molecular markers of hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis delta virus (HDV) infections. Among the 403 blood donors, 33 (8.2%), 21 (5.2%), and 27 (6.7%) tested positive for hepatitis B surface antigen (HBsAg) and/or HBV DNA, HCV RNA, and HDV RNA, respectively. Collectively, 55 donors were viremic for one or more of these viruses, and included 54 first-time donors (18.7%) and 1 repeat donor (0.9%) (P < 0.0001). One discrepant case with HBsAg detectable only at MBC was negative for HBsAg, HBV DNA and anti-HBc in this study. Four donors who were HCV-viremic in this study were negative for anti-HCV by the MBC method. Further efforts to increase the sensitivity and specificity of the currently-used tests are urgently required in Mongolia. Three donors who were positive for anti-HBc and anti-HDV but negative for HBsAg, had both HBV DNA and HDV RNA. This suggests that introduction of a new anti-HDV serological test is useful for not only HDV screening but also HBV screening of anti-HBc-positive, HBsAg negative donors, considering a possibility of viral interference by coexisting HDV.

Two (2.3%) of 87 wild-caught boars in Japan had detectable hepatitis E virus (HEV) RNA. The two boar HEV isolates (wbJTS1 and wbJYG1) obtained in the present study and a previously reported isolate (wbJSGi) whose partial sequence had been determined were sequenced over the entire genome, The wbJSG1, wbJTS1 and wbJYG1 isolates comprised 7225 or 7226 nt, excluding the poly(A) tail, and segregated into genotype 3. They differed by 8.5-11.2 % from each other and by 8.6-18.4 % from 17 reported genotype 3 HEV isolates, including one boar isolate, in the full-length sequence. When compared with 191 reported genotype 3 HEV isolates whose partial sequences were known, these three boar isolates were closer to Japanese isolates than to isolates of non-Japanese origin (89.2 +/- 2.6 vs 85.9 +/- 2.2 %; P < 0.0001). A proportion of wild boars in Japan are infected with markedly heterogeneous HEV strains that are indigenous to Japan and may serve as reservoirs of HEV.

Mongolia is known for its high endemicity for hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis delta virus (HDV) infections among apparently healthy individuals. However, there are little or no data on the prevalence and genotype distribution of HBV, HCV, and HDV among patients with chronic liver disease in Mongolia. Therefore, serum samples obtained in 2004 from 207 patients (age, mean +/- standard deviation, 51.0 +/- 11.9 years) including those with chronic hepatitis (n = 90), liver cirrhosis (n = 41), and hepatocellular carcinoma (n = 76) were tested for serological and molecular markers of HBV, HCV, and HDV infections. Of the 207 patients, 144 (69.6%), 106 (51.2%), and 117 (56.5%) tested positive for hepatitis B surface antigen (HBsAg) and/or HBV DNA, HCV RNA, and HDV RNA, respectively. Collectively, 172 patients (83.1%) were viremic for one or more of these viruses, including dual viremia of HBV/HDV (26.6%) or HBV/HCV (7.7%) and triple HBV/HCV/HDV viremia (30.0%). Of note, triple ongoing infection was significantly more frequent among patients with hepatocellular carcinoma than among those with chronic hepatitis (63.2% vs. 14.4%, P < 0.0001). One hundred sixty patients (77.3%) had a history of blood transfusion and/or surgery. The distribution of HBV genotypes among the 116 HBV-viremic patients was: A (0.9%), B (0.9%), C (6.0%), D (88.8%), and C plus D (3.4%). All 117 HDV isolates were classified into genotype 1. The 106 HCV RNA-positive samples were typed as genotype lb (92.5%), 2a (0.9%), or 1b plus 2a (6.6%); mixed infection of two distinct HCV genotypes was found exclusively in the patients with hepatocellular carcinoma.

Background: There is little data on the evolution of hepatitis C virus (HCV) quasispecies in infants infected by mother-to-infant transmission during long-term follow up. The hypervariable region 1 (HVR1) of the HCV genome was investigated in two mother-infant pairs from birth to 7.6 and 10.2 years, respectively. Methods: Ten cDNA clones of HVR1 generated from HCV-RNA and extracted from serum samples of both pairs were analyzed. The sequences were compared with regard to variability, identity, and hydrophobia profile, and analyzed by phylogenetic studies. Results: The alanine aminotransferase (ALT) level was high with fluctuation in infant A and almost within the normal range in infant B. Sequence diversity was higher in infant A at 7.6 years than in infant B at 9.3 years (sequence identity with the mothers'; 69.3-70.7% vs 85.3-90.7% for nucleotides, and 48% vs 68-72% for amino acids, respectively). Compared to the first samples, amino acid changes greatly increased in infant A (35.2% at 4.9 years and 52% at 7.6 years), but not in infant B (4% at 5.6 years and 27.5% at 9.3 years). Phylogenetic studies revealed that quasispecies in infant A evolved to a greater extent than that in infant B. Hydrophobia profile analyses revealed that dynamic shifts between hydrophilia and hydrophobia occurred in both infants. Conclusions: As in adults, the evolution of HVR1 and variability of quasispecies increased in infants infected through mother-to-infant transmission for 10 years after birth. A large episode of ALT elevation suggested the emergence of escape mutants and the evolution of new quasispecies.

Hepatitis E virus (HEV) is one of the major causative agents of acute hepatitis in many developing countries. Recent intensive examination has revealed the existence of non-imported cases in industrialized countries. The patient was a 25-year-old Japanese female with acute hepatitis. Laboratory test demonstrated positive anti-nuclear antibody (ANA), anti-smooth muscle antibody (ASMA) and high level of serum immunoglobulin G (IgG). The patient was negative for serum markers of hepatitis A, B or C virus infection. She demonstrated a clinical course similar to severe autoimmune hepatitis, including response to prednisolone therapy. After a few years, with the availability of tests for the serum antibodies to HEV, we examined the frozen stocked sera of the patient and found her exact diagnosis was acute hepatitis E. Although we could not detect HEV-RNA, which is positive only in limited period of acute phase, serum IgA and IgG antibodies to HEV were positive and the titer of IgA and IgG antibodies were declined with the time course. In conclusion, we must take into consideration of HEV infection for the diagnosis of acute cryptogenic hepatitis including autoimmune hepatitis. Further studies are feasible to understand the pathogenesis of liver injuries induced by HEV infections. - acute hepatitis; hepatitis E virus; autoimmune hepatitis; viral hepatitis (c) 2005 Tohoku University Medical Press.

Background and Aim: Hepatitis C virus (HCV)-infected patients who responded to interferon (IFN) treatment with clearance of serum HCV RNA may rarely develop hepatocellular carcinoma (HCC). The aim of the present study was to elucidate the risk factors for liver carcinogenesis among such patients. Methods: In total, 126 patients with chronic hepatitis C (CHC) who achieved a sustained virological response (SVR) to IFN monotherapy, which was defined as the absence of detectable HCV RNA in the serum at 6 months after completion of treatment, were enrolled and possible risk factors for HCC were analyzed. Results: During the observation period of 66 +/- 36 months after cessation of IFN treatment, five (4.0%) of the 126 patients developed HCC. The cumulative incidence of HCC at 3, 5 and 10 years was estimated to be 0.9, 4.7 and 7.5%, respectively. The cumulative incidence of HCC was significantly higher among patients with severe fibrosis (F3 or F4) than among patients with no or mild fibrosis (F0 to F2) in the liver before treatment (P = 0.007); among patients with alcohol intake of >= 27 g/day than among patients with that of < 27 g/day (P = 0.015); and among patients who were >= 65 years old than among patients who were < 65 years old at the start of treatment (P = 0.026). Conclusions: Patients with CHC who had severe fibrosis, who had regularly taken moderate amounts of alcohol, or who were >= 65 years at the start of IFN treatment should be carefully followed to detect small and controllable HCC, even after eradication of HCV. (C) 2005 Blackwell Publishing Asia Pty Ltd.

To investigate the prevalence of hepatitis B virus (HBV) genotypes and characteristics of HBV isolates among Japanese patients infected with human immunodeficiency virus type 1 (HIV), serum samples collected between September 1990 and March 2002 from 471 HIV-infected patients (age, 38.8 +/- 11.4 [mean +/- standard deviation] years; male, 90%) were tested for hepatitis B surface antigen (HBsAg) and HBV DNA. Positivity for HBsAg and HBV DNA was seen in 42 patients (8.9%), 41 of whom had contracted HIV infection through sexual activity and 1 had hemophilia. Genotypes of HBV were determined by comparative and phylogenetic analyses of the S gene sequence (396 nucleotides [nt]). The distribution of HBV genotypes among the 42 HBV-viremic patients was: A (50%), B (5%), C (24%), D (5%), E (2%), H (10%), A p I us D (2%), A plus G (2%). The hemophilia patient had HBV genotype D. Genotypes E, G, and H which had not been reported in Japan, were found in one patient each who had traveled to Zambia, the US, and South America, respectively. Genotypes A and D, which are rare in Japan, were found in patients who had no history of traveling abroad. The entire genome of the HB-JI411 (genotype E [3,212 nt]), HB-JI444G (genotype G [3,248 nt]), and HBJI260 (genotype H [3,218 nt]) isolates had the highest identity of 98.3%, 99.9%, and 98.5%, respectively, with reported HBV isolates of the same genotype. Most Japanese patients coinfected with HIV and HBV had HBV genotypes that are found rarely or had not been reported in Japan. (c) 2005 Wiley-Liss, Inc.