Subacute liver failure in obese women

OBJECTIVES: Steatosis or steatohepatitis, common conditions associated with obesity, are usually considered to be stable or only slowly progressive. We have encountered a small number of patients with a history of obesity and a subacute course of liver failure over a period of 4-16 wk from the onset of symptoms. The patients had findings suggestive of an acute exacerbation of previously unrecognized nonalcoholic steatohepatitis (NASH). METHODS: The patients were ascertained from our liver disease registry, which, at the time of the study, contained 2380 patients: 167 had NASH and 215 had cryptogenic cirrhosis. Five of these patients were identified with a subacute course of their illness. RESULTS: The patients were female, aged 41-65 yr, and obese (BMI >30, mean 41 +/- 9, range 32-52). One patient had type 2 diabetes treated by diet alone and one had a history of glucose intolerance. None had known prior liver disease and two had no prior medical problems. All five presented with fatigue and lethargy. Over 4-16 wk, the patients developed frank encephalopathy, ascites, jaundice, and multiorgan failure. An extensive evaluation revealed no clear etiology of their disease, although initial imaging studies consistently showed evidence of previously unrecognized cirrhosis. Four patients died from complications of liver failure and the fifth patient underwent OLT. Histology revealed cirrhosis with variable numbers of balloon cells in all five patients, frank steatohepatitis in three, necrosis in two, and microvesicular (with macrovesicular) steatosis in one. CONCLUSIONS: These patients, all obese and middle-aged women with no history of liver disease, had previously unrecognized cirrhosis and sudden deterioration of uncertain cause. We speculate, based on the clinical and histological findings, that these patients had undiagnosed NASH with silent progression to cirrhosis followed by subacute liver failure. We propose that obesity-related liver disease may infrequently present as severe, subacute illness.