Fumitoki Watanabe

Present status of autoimmune hepatitis in Japan - correlating the characteristics with international criteria in an area with a high rate of HCV infection

BACKGROUND/AIMS A nationwide survey of autoimmune hepatitis (AIH) was carried out in Japan. METHODS Four hundred and ninety-six patients were enrolled by questionnaires sent to 101 hospitals with hepatology specialists. RESULTS The clinical features of Japanese AIH were as follows: most patients were middle-aged women; serum autoantibodies, especially antinuclear antibody, were frequently positive, serum IgG level was high, and HLA-DR4 was the major HLA allotype. Liver-kidney microsomal type 1 antibody was positive in nine of 79 patients tested. Eight of these antibody positive patients were also positive for antinuclear antibody and five for anti-smooth muscle antibody. Ninety-two percent of the patients showed piecemeal necrosis and 60% bridging necrosis; plasma cell infiltration in the portal areas was observed in 50% of the patients. Only 12.3% were diagnosed as having liver cirrhosis. A favorable effect of corticosteroid, normalization of serum transaminases, was observed in 89% of 317 patients, who were treated with an initial dose of over 30 mg/day. Sixty-two patients were positive for hepatitis C virus (HCV) markers. In these patients, however, only one patient was liver-kidney microsomal type 1 antibody positive. Corticosteroid was effective in 30 (81%) of 37 HCV-marker-positive patients treated with this agent. Thus the efficacy of corticosteroid did not differ from that in AIH patients without HCV infection (90%). Similarly, interferon treatment was used in 20 patients, all of whom were positive for HCV-RNA, and resulted in 50% efficacy as determined by normalization of the serum transaminase level 6 months after treatment. The International Diagnostic Scoring System for the diagnosis of AIH worked well in these patients, except for HCV-infected individuals, that is, approximately 10% of the total of AIH patients.

Diagnosing clinical subsets of autoimmune liver diseases based on a multivariable model

BackgroundDiagnosing autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis, and other autoimmune liver diseases remains an imperfect process. We need a more accurate, evidence-based diagnostic system.MethodsWe conducted a national survey and identified 988 cases of liver disease which did not satisfy the inclusion criteria for any liver disease of known etiology. We expected these cases to include autoimmune liver disease (AILD) and its variant forms. We selected 269 prototype cases for which histological re-evaluation of liver biopsy by independent expert hepatopathologists and the original diagnosis coincided. We did a multiple logistic regression analysis to determine explanatory variables that would distinguish cases of AIH and PBC from those of non-AIH and non-PBC, respectively. We constructed a multivariable diagnostic formula that gave AIH and PBC disease probabilities and validated it in a study of an additional 371 cases (validation group).ResultsBased on the results of the statistical analysis, we selected three laboratory tests and four histological features as independent variables correlated to the diagnosis of both AIH and PBC. For the validation group, assuming that the original diagnosis was correct, the sensitivity and specificity for AIH were 86.3% and 92.4%, respectively. For PBC the sensitivity and specificity were 82.5% and 63.7%, respectively. A detailed analysis of inconsistent cases showed that the diagnosis based on the formula had given the correct diagnosis, for either AIH or PBC, except for 5 cases (1.3%) in which disease probability was low for both.ConclusionsA seven-variable formula based on three laboratory tests and four histological features gives significant information for the diagnosis of AILD.

Immunogenetic background of hepatitis B virus infection and autoimmune hepatitis in Japan

SummaryHuman leucocyte antigen (HLA)-typing was studied in 82 hepatitis B carriers and 15 cases of autoimmune hepatitis (AIH) to elucidate the genetic factors which may associated with the etio-pathogenesis of chronic hepatitis in Japan. There were two types of HLA phenotypes: HLA A2 was associated with the progression of the disease induced by HBV infection, and HLA A26 and DR5 were related to the retardation of the disease. A family study confirmed the strong association of these HLA phenotypes with the disease induced by HBV infection. In the analysis of AIH, HLA DR4 is a risk factor related to susceptibility of Japanese AIH which shows different clinical manifestations compared to HLA-DR3-positive AIH, dominantly observed in Western countries. These results suggest that genetic background as expressed by HLA, is an important factor in restricting the development of type B hepatitis and AIH, and can explain racial differences of disease susceptibility.

A case of autoimmune hepatitis diagnosed as liver cirrhosis after 13 yeares following uup without corticosteroid therapy

症例は66歳女性. 1984年に全身倦怠感を主訴に入院. 血液検査および肝生検により自己免疫性肝炎 (Autoimmune hepatitis: AIH) が疑われた. ALT上昇は軽度で安静により自覚症状が改善したため, 患者は副腎皮質ステロイド治療を希望せず, その後医療機関を受診しなかった. 1994年に再受診した際にALTの上昇を認め, ウルソデオキシコール酸 (UDCA) 投与によりALTは持続的に改善したが, 1997年に施行した肝生検で高度な活動性を伴う肝硬変への進展が確認された. 無治療のAIH症例の長期予後を検討し得た報告は極めて稀であり, ALT上昇が軽度で無症状のAIH症例の治療法を考慮するうえで示唆に富む症例と考えられる.