Etsuko Hashimoto

症例は26歳女性．2008年（21歳時）健康診断で肝機能障害を指摘され当科紹介受診となった．各種ウイルスおよび自己抗体は陰性で，BMI 25.1（152 cm/58 kg）と軽度肥満と，美容のためにビタミン剤などのサプリメント摂取歴を認めたことから食事運動療法および摂取サプリメントを中止し経過観察となったが，生活習慣の指導，肝庇護療法を開始した後もトランスアミナーゼは高値のまま推移した．2010年，2012年に施行した肝生検では確定診断には至らず，その後それまで限局性だった高エコー領域が肝全体に多発し，腫瘍マーカーの著明な上昇を認めたため，悪性腫瘍鑑別のため2013年3回目の肝生検施行となった．生検の結果，悪性疾患の合併はないものの急激な線維化進展を認め，直接胆道造影の結果から原発性硬化性胆管炎（PSC）の確定診断となった．本症例は5年間の経過中，急速な線維化の進行に伴い，特異なエコー画像所見と病理所見が観察された貴重な症例と考え報告した．

Aim: The aim of this study was to elucidate the clinical and histological features, response to corticosteroid therapy and long‐term outcome of primary biliary cirrhosis (PBC) with features of autoimmune hepatitis (AIH).Methods: Among 280 PBC patients under ursodeoxycholic acid administration, we identified 28 patients with AIH features fulfilling the following criteria: sustained high levels of serum aminotransferases and high immunoglobulin G levels with positivity for antinuclear antibodies or anti‐smooth muscle antibodies (ASMA) and/or histological features of moderate to severe interface hepatitis or moderate to severe lobular hepatitis. We analyzed PBC patients with AIH features, focusing mainly on therapeutic responses to corticosteroids.Results: Patients with PBC with AIH features included 26 women (93%). Their median age was 55 years, and the median follow‐up period was 7.5 years. Eight of these 28 patients were not actually treated with corticosteroids due to medical conditions. Among the 20 patients receiving corticosteroid therapy, 15 were responders and five were non‐responders. A high alkaline phosphatase (ALP) level, negativity for ASMA and positivity for gp210 were identified as risk factors for lack of a response to corticosteroid therapy. Among 28 PBC patients with AIH features, the responders to corticosteroids had an excellent prognosis, while those who could not be treated with corticosteroids and non‐responders to corticosteroids had a poor outcome.Conclusion: Patients with PBC with AIH features benefit from corticosteroid therapy. Features of PBC such as high ALP level, negativity for ASMA and positivity for gp210 appear to predict a poor response to corticosteroids.

Aim:  To elucidate gender differences and the influence of obesity and/or metabolic syndrome‐related fatty liver on alcoholic liver disease (ALD), we analyzed characteristic features of ALD.Methods:  We investigated 266 ALD patients (224 males and 42 females) without hepatocellular carcinoma stratified by gender and the presence of cirrhosis. Male and female patients matched for age and total ethanol intake were also analyzed. A diagnosis of ALD was based on alcohol intake (>70 g daily for more than 5 years), clinical features, and exclusion of other liver diseases. The prevalence of obesity, lifestyle‐related diseases, and psychological disorders were assessed.Results:  The prevalence of psychological disorders showed a significant gender difference among all ALD patients (12% in males versus 43% in females, P < 0.001), as well as in patients matched for age and total ethanol intake. There were 156 cirrhotic patients. Absence of dyslipidemia, presence of diabetes, and high total ethanol intake were selected as independent predictors of cirrhosis in males by multivariate analysis after excluding laboratory data of liver function tests. The prevalence of obesity was significantly lower in cirrhotic male patients than in non‐cirrhotic male patients (34% vs. 20%, P = 0.023). Among females, there were no significant predictors of cirrhosis on multivariate analysis after eliminating liver function tests. The prevalence of obesity and diabetes was similar in non‐cirrhotic and cirrhotic female patients. The prevalence of psychological disorders was 47% in cirrhotic females with ALD.Conclusions:  Obesity was not common in cirrhotic ALD. Psychological disorders seem to be important for female ALD.

Background: Chronic colitis-harboring TCRα^{− / −} × AIM^{− / −} mice showed PBC-like bile duct damage in the liver. Bacterial infection is one of the candidates for the pathogenesis of PBC. We demonstrated that the bacterial cell wall component lipotheicoic acid (LTA) was detected at sites of inflammation around damaged bile ducts in PBC patients. The aim of this study was to investigate the pathophysiology of the liver and other organs in TCRα^{− / −} × AIM^{− / −} mice. Methods: Thirteen female TCRα^{− / −} × AIM^{− / −} mice were sacrificed at 24 weeks of age. The liver, stomach, small intestine, colon, pancreas, kidney and spleen were studied for pathological examination. Using anti-LTA antibody as the primary antibody, an immunohistochemical study was carried out. Results: In the liver, LTA was mainly detected in the portal area with inflammation, and some of the cytoplasm of hepatocytes. Inflammations were also observed in the stomach, intestine, pancreas and kidney. Throughout the gastrointestinal tract, from the stomach to the colon, LTA was detected in the epithelium at sites of inflammation. Furthermore, LTA was detected around both pancreatic ducts with inflammation and distal renal tubules with inflammation. Conclusions: The development of inflammations in the liver as well as extensive organs, strongly suggests a close relationship between bile duct damage and systemic multifocal epithelial inflammations, perhaps involving bacterial LTA, in TCRα^{− / −} × AIM^{− / −} mice.