Diabetic Hepatosclerosis: Diabetic Microangiopathy of the Liver

Abstract

Abstract Context.—Liver disease associated with diabetes mellitus is common and usually takes the form of simple steatosis or nonalcoholic steatohepatitis. After observing a noncirrhotic form of hepatic sinusoidal fibrosis in patients with long-standing diabetes mellitus who underwent liver biopsy, we set about to characterize this novel entity. Design and Setting.—Cases with the hallmark histologic findings were gathered at Saint Louis University School of Medicine and the Armed Forces Institute of Pathology. Patients.—The clinical records were examined in a systematic fashion. Results of light microscopy and prepared immunohistochemical stains were reviewed. Main Outcome Measures.—Clinical findings of patients with the histologic, detailed light microscopic, and immunohistochemical findings on biopsies. Results.—Twelve patients were identified from biopsy findings; all had a history of long-standing diabetes mellitus and a noncirrhotic form of hepatic sinusoidal fibrosis not associated with nonalcoholic steatohepatitis. Most of these patients had a body mass index less than 25 kg/m2 and had substantial evidence of microvascular complications, including retinopathy, nephropathy, and peripheral and autonomic neuropathy. Alkaline phosphatase elevation was common. Liver biopsy specimens showed extensive dense perisinusoidal fibrosis, and immunostaining revealed basement membrane components in a perisinusoidal distribution. Features of nonalcoholic steatohepatitis were not present in the biopsy specimens. Conclusions.—We propose the term diabetic hepatosclerosis for this entity and suggest that it represents a form of diabetic microangiopathy affecting the liver. Further studies are needed to precisely characterize diabetic hepatosclerosis and to understand mechanisms of pathogenesis and the clinical significance.