うつ病治療中に非アルコール性脂肪肝炎を発症した1例  [in Japanese] Nonalcoholic Steatohepatitis in a Patient Treated for Depression  [in Japanese]

症例は飲酒歴のない32歳,女性.27歳時にうつ病を発症し,初診時に,BMI26.7, HBsAg(-), HCVAb(-),肝酵素は軽度の高値(AST 32IU/l, ALT 32IU/l),血糖値は正常範囲,中性脂肪406mg/dlと高値,腹部エコー検査で脂肪肝を認めた.治療により抑うつ症状は軽快し,肝機能は正常範囲で推移していたが,32歳時に,夫婦関係悪化と姉の脳腫瘍手術というライフイベントが発生した.うつ病の悪化と同時に体重が増加(BMI 30.2)し,肝酵素が上昇した(AST 174IU/l, ALT 183IU/l)ため,肝生検を施行し,非アルコール性脂肪肝炎(NASH)が診断された.75gOGTTは境界型であったがインスリンの過剰分泌を示し,インスリン抵抗性(HOMA指数2.28)を認めた.減量は困難であったが,インスリン抵抗性改善薬ピオグリタゾンが奏効し肝酵素は正常化した.うつとインスリン抵抗性およびNASHの関連が報告されている.本例では,うつ病の悪化が,脂肪肝からNASHに進展する要因になったと推測された.

Insulin resistance is central to the pathogenesis of NASH and is also frequently observed in patients with depression. A 32-year-old woman began treatment for a major depressive disorder when she was 27. She was mildly obese (BMI of 26.7 kg/m^2) and had hypertriglycemia (406 mg/dl) and normal fasting plasma glucose value. Mild elevation of serum levels of transaminases (AST, 32 IU/l; ALT, 32 IU/l) was detected. Both hepatitis B surface antigen and anti-hepatitis C virus antibody were seronegative. Abdominal ultrasonography showed typical fatty liver. She had not been drinking alcohol. Her depression was treated with tricyclic antidepressants, an anti-anxiety drug, levomepromazine and a hypnotic. Her depressive symptoms gradually improved and she was able to begin working after two years. Her serum levels of transaminases has been remained within normal limits. After 5 years, her depression was aggravated by life events (marital conflict and her sister's diagnosis of and surgery for a brain tumor). She also gained weight (BMI of 30.2 kg/m^2) because of stress-related overeating. Her serum levels of transaminases increased (AST, 174 IU/l; ALT, 183 IU/l). She was referred to the Department of Gastroenterology, and a liver biopsy was performed. Liver specimens showed macrovesicular steatosis (>30% hepatocytes), hepatocellular ballooning, pericellular and perivenular fibrosis, and Mallory bodies, and she was diagnosed as having NASH. She was negative for antinuclear antibody. Although a 75 g oral glucose tolerance test showed a normal glucose profile, hyperinsulinemia and insulin resistance (homeostasis model assessment index: 2.28) were found. Treatment with pioglitazone (30 mg daily) resulted in normalization of serum aminotransferase levels. Aggravation of depression, which was induced by stressful life events, might have been a factor in the development of steatohepatitis from fatty liver in this case.