The Relationship between Diabetes Mellitus, Cirrhosis, and Hepatocellular Carcinoma in Patients with Fatty Liver Disease

Diabetes mellitus is an independent predictor of cirrhosis and hepatocellular carcinoma (HCC) among patients with fatty liver disease, according to study results presented by lead author Evan Raff, MD, of the department of Internal Medicine, University of Alabama at Birmingham, during a poster session at the 2013 American College of Gastroenterology in San Diego, CA.

Diabetes mellitus is among the risk factors for chronic liver disease, along with infection with hepatitis B or C virus, heavy alcohol consumption, and nonalcoholic fatty liver disease.

In this retrospective study, to explore the relationship between diabetes and the progression of steatohepatitis, also known as fatty liver disease, researchers looked at medical charts from 2007 to 2011 of patients whose steatohepatitis-related disease was managed at a single tertiary center. The data review included demographics; comorbidities including diabetes mellitus, cirrhosis and complications, and hepatocellular carcinoma; and laboratory, imaging and histology. Other causes of liver disease and excess history of alcohol use were excluded in diagnosis.

Patients with and without diabetes mellitus were compared using chi-square and t-tests for categorical and continuous variables, respectively. Independent association of diabetes mellitus with cirrhosis and hepatocellular carcinoma were examined using a logistic regression model and data were reported as an odds ratio with a 95 percent confidence interval.

Among the 503 patients with steatohepatitis, 276 had nonalcoholic steatohepatitis. Patients with diabetes compared to those without were more often female, obese, consumed less than one alcoholic drink a day, and had hypertension and a history of cholecystectomy and non-alcoholic steatohepatitis. In addition, these patients had higher percentages of cirrhosis and more often developed hepatic encephalopathy, with a trend for higher stage 3 or 4 fibrosis in 95 cases that were biopsied.

Researchers found that diabetes mellitus independently predicted the presence of cirrhosis in those with diabetes, in spite of lower model variable for end-stage disease score. Model variables also included gender, platelet count, obesity, AST/ALT ratio, and nonalcoholic steatohepatitis as diagnosis. The hepatocellular carcinoma model controlled for cirrhosis. Out of 31 patients who received a liver transplant, 19 had diabetes mellitus and all had similar post-transplant survival rates over a median follow-up time of 12 months and 16 months, respectively, for patients with diabetes and those without the disease.

Researchers concluded that diabetes mellitus is independently associated with the development of cirrhosis and hepatocellular carcinoma among patients who have fatty liver disease. Compared with nondiabetics, patients with diabetes and steatohepatitis-related liver disease were more likely to develop hepatocellular carcinoma and cirrhosis and at faster rates. They suggested future studies in patients with fatty liver disease to examine the role of diabetes control and anti-diabetic drugs in the development of cirrhosis and its complications in patients, as well as the impact of diabetes in cirrhotics in relation to overall survival, transplantation, and post-transplant outcomes. The study authors also suggested adopting more aggressive screening guidelines for hepatocellular carcinoma among this disease population.