AASLD: Diabetes and HCV May Portend Liver Cancer in Patients with Fibrosis

BOSTON, Oct. 30 -- The presence of diabetes may triple the risk of hepatocellular carcinoma in patients with advanced fibrosis or cirrhosis from hepatitis C infection, researchers reported here.

The five-year risk of developing hepatocellular carcinoma in the presence of diabetes was 18.6%, compared with 5.3% for those without diabetes, Bart J. Veldt, M.D., of Erasmus MC University Medical Center in Rotterdam, and colleagues, reported at the American Association for the Study of Liver Diseases meeting here.

Previous studies had shown that the presence of diabetes was associated with an increased risk for hepatocellular carcinoma, but the magnitude was unclear. Diabetes increases the risk of non-alcoholic steatohepatitis (NASH), and hepatocellular carcinoma can, in turn, be a late complication of NASH, the authors noted.

"Diabetes mellitus is more prevalent among patients with chronic hepatitis C than in the general population," they wrote in a poster presentation. "Liver disease contributes to insulin resistance, as it leads to a progressive impairment of insulin secretion and it induces hepatic insulin resistance."

The chronic inflammation, fibrosis, and cirrhosis associated with HCV infection may also contribute to hepatocellular carcinoma risk, they noted.

"Therefore, among patients with both chronic hepatitis C and diabetes, there are two potential ways in which hepatocellular carcinoma may develop: by the metabolic pathway and by the carcinogenic effect of the hepatitis C virus," they wrote.

The investigators conducted a study to quantify the risk of hepatocellular carcinoma among 541 consecutive patients with chronic HCV and biopsy proven advanced fibrosis or cirrhosis (Ishak score of 4 to 6); 85 of the 541 patients (16%) also had diabetes.

All of the patients were treated with pegylated interferon with or without Rebetol (ribavirin) at one of five large hepatology centers in Germany, The Netherlands, Switzerland, and Canada.

The mean patient age at inclusion was 49. There were no significant differences in body mass index between the diabetic and non-diabetes patients.

The prevalence of diabetes was 10.5% among patients with an Ishak fibrosis score of 4, 12.5% for Ishak 5 and 19.1% for Ishak 6.

In multiple regression analysis only fibrosis stage was significantly associated with an increase risk for diabetes. The odds ratio for Ishak 5 fibrosis compared with Ishak 4 was 1.77 (95% confidence interval, 0.61-5.17), and for Ishak 6 vs. Ishak 4 was 2.92 (95% CI, 1.24-6.88, P=0.04)

During a mean follow-up of 3.3 years, 11 patients (13%) with diabetes developed hepatocellular carcinoma, compared with 27 patients (5.9%) who did not have diabetes. The five-year occurrence of hepatocellular carcinoma was 18.6% (95% CI, 6.8%-30.4%) for patients with diabetes, and 5.3% (95% CI, 2.3%-8.3%) for patients without diabetes (P=0.026).

In multivariate Cox regression analysis of patients with Ishak 6 cirrhosis, the authors found that diabetes was independently associated with the development of hepatocellular carcinoma.

"Fibrosis itself turned out to be the major risk factor for determining diabetes mellitus," they wrote. "Although diabetes mellitus and hepatocellular carcinoma may thus both result from advanced liver disease, diabetes mellitus is still an independent predictor of hepatocellular carcinoma if we correct for fibrosis stage and other markers of advanced liver disease such as platelet counts, bilirubin, albumin, and portal tracts. An explanation for these observations may be that hyperinsulinemia itself enhances the proliferation of cancer cells."