Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009

Zobair M Younossi, Munkhzul Otgonsuren, Linda Henry, Chapy Venkatesan, Alita Mishra, Madeline Erario, Sharon Hunt

HCC is increasingly reported in patients with NAFLD. Our aim was to assess the prevalence and mortality of patients with NAFLD-HCC. We examined SEER registries (2004-2009) with Medicare-linkage files for HCC which was identified by the ICD-O-3 codes using topography and morphology codes 8170-8175. Medicare-linked data was used to identify NAFLD, hepatitis C (HCV), hepatitis B (HBV), alcoholic liver disease (ALD), and other liver disease using ICD-9-CM codes. NAFLD was also defined by clinical diagnosis (cryptogenic cirrhosis, obese-diabetics with cryptogenic liver disease). Logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of HCC. In addition, adjusted hazard ratios (HRs) for one-year mortality were estimated by Cox proportional hazard regression. 4929 HCC cases and 14.937 controls without HCC were included. Of the HCC cases, 54.9% were related to HCV, 16.4% to ALD, 14.1% to NAFLD and 9.5% to HBV. Across the six-year period (2004 to 2009), number of NAFLD-HCC showed 9% annual increase. NAFLD-HCC were older, had shorter survival time, more heart disease and were more likely to die from their primary liver cancer (all p<.0001). Of those who received a transplant after HCC (n=488); only 5% was related to NAFLD-HCC. In multivariate analysis, NAFLD increased the risk of 1-year mortality (OR: 95% CI =1.21 (1.01-1.45). Additionally, older age, lower income, un-staged HCC increased risk of 1-year mortality while receiving liver transplant and having localized tumor stage were protective (all p<0.05). NAFLD is becoming a major cause of HCC in the U.S. NAFLD HCC is associated with shorter survival time, more advanced tumor stage and lower possibility of receiving liver transplant. This article is protected by copyright. All rights reserved.