SAT-585 - Diabetic Hepatosclerosis as A Complication of Longstanding Uncontrolled Type 1 Diabetes Mellitus: An Underrecognized Microvascular Complication?

Background: Diabetic hepatosclerosis is a recently recognized form of liver disease, considered a hepatic manifestation of diabetic microangiopathy. It is seen in longstanding poorly controlled insulin-dependent diabetes, often co-existing with other diabetic microangiopathic complications, like nephropathy and retinopathy.
Clinical

Case: A 29-year-old woman with a history of poorly controlled type 1 diabetes mellitus (with hemoglobin A1c [HbA1c] ranging from 8.9% to >18% over the years), complicated by retinopathy, neuropathy, and nephropathy, was referred to the gastroenterology (GI) clinic for evaluation of abnormal liver function tests. Alkaline phosphatase (ALP) levels were noted to be elevated for four years, while transaminases were normal to slightly elevated. The ALP levels normalized for a year and, subsequently, increased to a peak of 595 U/L (reference range: 9-122). The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels reached a peak of 126 U/L (reference range: 10-35) and 89 U/L (reference range: 10-35) respectively, two months prior to her GI evaluation. Further laboratory testing showed negative viral hepatitis markers. Computed tomography showed a sub-centimeter hepatic hypodensity and dorsal pancreatic agenesis. Magnetic resonance cholangiopancreatography showed a normal biliary tree. Our patient eventually underwent a liver biopsy, which revealed diffuse sinusoidal/perivenular fibrosis with no significant inflammation, steatosis or cirrhosis. The pathology findings were consistent with diabetic hepatosclerosis. Management was focused on glycemic control. ALP levels improved when HbA1c was in target range but started to increase again with suboptimal glucose control.

Discussion: Diabetic hepatosclerosis is a form of hepatic microangiopathy characterized by perisinusoidal fibrosis with basement membrane formation, and no steatosis or cirrhosis. This condition was first described in 2006 based on the review of archived liver biopsies of patients with diabetes. It is typically seen in patients with long-standing diabetes, more commonly in type 1 than in type 2. Similar to our patient, the main biochemical abnormality is the elevation of ALP levels, while aminotransferases are normal or only mildly elevated. The actual prevalence and natural history are not clear, but data from small case series support that this could be an underrecognized condition due to its indolent clinical course.

References:
(1) Hamed AE, et al. Diabetes Association with Liver Diseases: An Overview for Clinicians. Endocr Metab Immune Disord Drug Targets. 2019;19(3):274-280.
(2) Harrison SA, et al. Diabetic hepatosclerosis: diabetic microangiopathy of the liver. Arch Pathol Lab Med. 2006;130(1):27-32.
(3) Vallianou NG, et al. Diabetic hepatosclerosis: True clinical entity or ghost disease? Diabetes Metab Syndr. 2017;11 Suppl 2:S775-S776.

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