Hyperlipidemia and Nonalcoholic Steatohepatitis Predispose to Hepatocellular Carcinoma Development Without Cirrhosis

Hepatocellular carcinoma (HCC) accounts for 90% of primary hepatic malignancies. With the exception of chronic hepatitis B (CHB), other etiologies of chronic liver disease require progression to cirrhosis before HCC development. Case reports have described HCC in noncirrhotic patients with hepatitis C (HCV) and nonalcoholic fatty liver disease.

The aim of this study was to determine the prevalence of patients without cirrhosis and CHB who developed HCC among a large cohort of HCC patients and to identify independent variables that are associated with no cirrhosis among patients with HCC.

From 2005 to 2015, hepatobiliary cancer patients seen in our liver cancer and liver transplant clinics were evaluated. Patients were included if above18 years old and had histologically confirmed HCC from liver biopsy, resection specimen, or explanted livers. Patients with CHB, non-HCC tumors, or missing paired tumor and nontumor liver histology were excluded. Demographic information, pertinent laboratory values, and comorbid conditions were recorded. Potential predictors were evaluated using both backward stepwise logistic regression model and classification tree model.

Of the 1927 patients screened, 545 HCC patients (411 transplanted, 43 resected, 74 transarterial chemoembolization/radiofrequency ablation, 17 untreated) included, 29 (5.3%) patients had no cirrhosis histologically. Eleven patients had HCV, 3 had alcoholic liver disease, 3 had nonalcoholic fatty liver, and 12 had cryptogenic liver disease. Logistic regression models show that patients with hyperlipidemia and elevated serum alanine aminotransferase are more likely to develop HCC without cirrhosis (odds ratio, 1.73 and 0.40; P<0.05).

This large cohort, histology-confirmed case-controlled study shows that patients with nonalcoholic fatty liver disease and hyperlipidemia with elevated serum alanine aminotransferase (most likely nonalcoholic steatohepatitis) are significantly associated with the development of HCC in the absence of cirrhosis.