Table 1. Lablratory Date on Admission cm 53 Kg 74/ 118/76 mmhg PT 27.7 % 18 % T. Bil 18.3 mg/dl 13.7 mg/dlast 2360IU/l ALT 1520 I

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1 FFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFF Vol. 32, pp , 2004 FFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFF T.Bil 18.3mg/dl AST 2360IU/l ALT 1520IU/l 27.7 % methylprednisolone 1500 mg/- 2.6 g/dl prednisolone 3 40 bridging necrosis autoimmune hepatitis AIH 1) AIH

2 Table 1. Lablratory Date on Admission cm 53 Kg 74/ 118/76 mmhg PT 27.7 % 18 % T. Bil 18.3 mg/dl 13.7 mg/dlast 2360IU/l ALT 1520 IU/l 3.5 g/dl ZTT 29U Table 1HBs X CT methylprednisolone MPSL 1500 mg/ Fig. 1 T. Bil 15.6 mg/dl ALT 1160 IU/l PT 20.2 % 5 MPSL 1500 mg mg 750 mg 500 mg 250 mg 2 4 IgG 2483 mg/dl AIH MPSL 250 mg/ prednisolone PSL 40 mg PSL 40

3 AIH Fig. 1. Clinical course of the patient with severe acute-onset of autoimmune hepatitis. alanine aminotransferase (ALT), normal <37IU/l; total bilirubin (T. Bil) normal <1.2mg/dl; prothrombin time (PT), normal >80%; albumin (Alb), normal 4.0g/dl; MPSL, methylpredonisolone; PSL, prednisolone. PT 3 30 % T. Bil mg/dl D/T 0.6 BUN 10 mg/dl 2) 18 CRP 3.3 mg/dl 38 X cefpirom 2 CRP 3.0 g/dl g/dl 8 5 PSL 10 mg 3) z = 2.17 z 0 HLA DR4 AIH 4) Fig Portal-Portal bridging necrosis Portal-Central bridging necrosis piecemeal necrosis 41

4 佐藤 42 明 前山史朗 a ら b Fig. 2. Histological findings in liver biopsy specimens obtained on the 40th hospital day. a. While lobular architecture is essentially preserved, several bridging necroses are seen. (silver impregnation, x4) b. Marked piecemeal necroses, Portal-portal necrosis and portal-central necrosis are seen. (HE stain, x10) c. Note collapse, zonal necrosis, and bile stasis in the centrilobular area, and many focal necroses in the parenchyma. (HE stain, x20) c 胆管には胆汁栓を容れていた 実質域では中心帯を主 るが 8-10) 何より劇症化を阻止する対策が必要である とする虚脱 collapse や帯状壊死が観察され 多数 厚生省ガイドライン 1) では AIH の治療について PT の巣状壊死および肝細胞の好酸性変性 また肝細胞の 50 % 以下の時は PSL 60 mg より開始 肝障害が高度 偽胆管形成も認めた 以上の組織学的諸変化は急激で な例では必要に応じてパルス療法を行う としている かつ激しい実質炎の所見が慢性炎症に加重された像で が高度な肝障害の基準は示されていない 近年 急性 あり 組織学的には慢性肝炎の急性増悪の所見で 自 肝炎重症型という概念が定着してきており われわれ 己免疫性肝炎に合致する組織像と診断された はこれを基準としてパルス療法の適応を検討してい る すなわち急性肝炎重症型とは急性肝炎のうち PT 40 % 以下で肝性昏睡のないものと定義され 11) 脳症 を生じる 劇症肝炎 直前あるいは生じる可能性の高 自己免疫性肝炎の発症様式には潜行発症型と急性発 い状態である 事実 わが国の全国調査 3) では急性肝 症型があることが知られている このうち急性発症型 炎重症型の 30 % が劇症化しており その劇症化阻止 の頻度は欧米では約 25 % とされ 5) わが国では 30 対策が求められている 本症例は初診時 著明な肝細 急性発症型における劇症 胞障害と PT の低下を認めたが 意識清明であったこ 50 % と報告されている 6, 7) は急性型 32 例 とより急性肝炎重症型と診断された HBs 抗原陰性 中 6 例 全例死亡 東條ら 7) は急性型 41 例中 5 例 であったことより HBV の関与の可能性はきわめて低 2 例死亡 と報告し 劇症型の死亡率は高い 劇症 いと考え 飲酒および薬剤服用歴のないこと 中年以 型に対しては最近肝移植による救命例の報告もみられ 後の女性 ZTT の異常高値より AIH を強く疑い パ 型の頻度と予後については 谷合ら 6) 42

5 AIH ZTT ) AIH ) CT 3.6 g/dl g/gl AIH 1).., 2,,, 1997: ) ; 86: ). prospective study : ) Alvarez F, Berg PA, Bianchi FB, Bianchi L, Burroughs AK, Cancado EL, Chapman RW, Cooksley WG, Czaja AJ, Desmet VJ, Donaldson PT, Eddleston AL, Fainboim L, Heathcote J, Homberg JC, Hoofnagle JH, Kakumu S, Krawitt EL, Mackay IR, MacSween RN, Maddrey WC, Manns MP, McFarlane IG, Meyer zum Buschenfelde KH, Vergani D and Zeniya M. International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol. 1999; 31: ) Sherlock S and Dooley J. Disease of the liver and biliary system, 11th ed. Blackwell, Oxford, 2002: ),, ; 41: ), ; 41: ),,,,,,,,, ; 91: ) Kawai K, Michitaka K, Miyauchi S, Sano M, Abe M, Ninomiya T, Matsuura B, Masumoto T, Akbar SM, Horiike N, and Onji M. Acute-onset autoimmune hepatitis treated with living donor-liver transplantation. Intern Med. 2003; 42: ) Herzog D, Rasquin-Weber AM, Debray D, and Alvarez F. Subfulminant hepatic failure in autoimmune hepatitis type 1: an unusual form of presentation. J Hepatol. 1997; 27: ), : ; 88: ),,,,,,,,,,,, ; 34: ),,,, ; 40:

6 Abstract A Case of Severe Acute-Onset Autoimmune Hepatitis Successfully Treated with Methylprednisolone Pulse Therapy Akira Sato 1, Shirou Maeyama 2, Hirohito Kawaguchi 1, Hiroshi Mizuno 1, Hiroshi Suzuki 1 and Fumio Itoh 3 A case of severe acute-onset autoimmune hepatitis (AIH) in a 66-year-old female patient treated with methylprednisolone pulse therapy is reported. She was admitted to our hospital on May 12 in 1998 with marked hepatocellular dysfunction accompanied by severe jaundice. Her percent prothrombin time decreased to 27.7% and CT scan showed a small amount of ascites around the liver, but hepatic encephalopathy was not seen. She was diagnosed as suffering from a severe form of acute hepatitis and methylprednisolone pulse therapy was initiated on the day of admission. After initiation of therapy, transaminase levels rapidly decreased, and she was subsequently treated with oral administration of prednisolone because laboratory findings, such as negative viral serology results, high titers of antinuclear antibodies, and hypergammaglobulinemia, suggested AIH. Although jaundice and serum albumin levels recovered slowly, she experienced remission after 3 months. Liver biopsy performed 40 days after admission revealed severe parenchymal damage characterized by bridging and zonal necrosis in addition to findings of active chronic hepatitis. The histological diagnosis was severe exacerbation of AIH. Immediate high dose prednisolone (methylprednisolone pulse) therapy is recommended for severe forms of acute hepatitis, particularly in cases of AIH, in order to prevent the development of fulminant hepatic failure. 1 Department of Gastroenterology St. Marianna University School of Medicine Yokohama Seibu Hospital, Yasashi-cho, Asahi-ku, Yokohama , Japan 2 Department of Pathology 3 Division of Gastroenterology and hepatology, Department of Internal Medicine St. Marianna University School of Medicine, Sugao, Miyame-ku, Kawasaki , Japan 44

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