1 Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN.
2 Division of Digestive and Liver Diseases, Department of Internal Medicine, Cedars-Sinai Medical Center, Los Angeles, CA.
3 Comprehensive Transplant Center, Cedars Sinai Medical Center, Los Angeles, CA.
4 Samuel Oschin Comprehensive Cancer Institute, Cedars Sinai Medical Center, Los Angeles, CA.
5 Department of Health Science Research, Mayo Clinic College of Medicine and Science, Rochester, MN.
6 Division of Gastroenterology and Hepatology, Geisinger Medical Center, Danville, PA.
Diabetes increases the risk of liver disease progression and cirrhosis development in patients with non-alcoholic steatohepatitis (NASH). The association between diabetes and the risk of hepatocellular carcinoma (HCC) in NASH cirrhosis patients is not well quantified. All patients with the diagnosis of NASH cirrhosis seen at Mayo Clinic Rochester between January 2006 and December 2015 were identified. All adult liver transplant registrants with NASH between 2004 and 2017 were identified using the UNOS/OPTN registry for external validation. Cox proportional hazard analysis was performed to investigate the association between diabetes and HCC risk. Among 354 Mayo Clinic patients with NASH cirrhosis, 253 (71%) had diabetes and 145 (41%) were male. Mean age at cirrhosis evaluation was 62. During a median follow up of 47 months, 30 patients developed HCC. Diabetes was associated with an increased risk of developing HCC in univariate (hazard ratio [HR] = 3.6, 95% confidence interval [CI] =1.1-11.9, P=0.04) and multivariable analysis (HR = 4.2, 95% CI =1.2-14.2, P=0.02). In addition, age (per decade: HR = 1.8, 95% CI =1.2-2.6, P<0.01) and low serum albumin (HR = 2.1, 95% CI =1.5-2.9, P<0.01) were significantly associated with an increased risk of developing HCC in multivariable analysis. Other metabolic risk factors including BMI, hyperlipidemia and hypertension were not associated with HCC risk. Among UNOS NASH registrants (N=6,630), 58% had diabetes. Diabetes was associated with an increased risk of developing HCC in univariate (HR = 1.4, 95% CI =1.1-1.8, P<0.01) and multivariable (HR = 1.3, 95% CI =1.0-1.7, P=0.03) analysis. In conclusion, diabetes is associated with an increased risk of HCC in patients with NASHcirrhosis.