Hepatocellular Carcinoma Arising in Non-cirrhotic, Non-alcoholic Steatohepatitis

Abstract

Purpose: Background: Non-alcoholic fatty liver disease is significantly associated with the metabolic syndrome manifested by obesity and insulin resistance. Diabetes (DM) is a known independent risk factor for Hepatocellular carcinoma (HCC). HCC usually occurs in the setting of cirrhosis, with the notable exception of HCC occurring in non-cirrhotic Hepatitis B or with toxin exposure. HCC occurs in cirrhosis related to non-alcoholic steatohepatitis (NASH). There have been case reports in the literature of HCC arising in patients with NASH without cirrhosis. We report 2 additional cases of HCC arising in patients with NASH without cirrhosis. Case 1: A 50 year-old white female with hypertension and anemia presented to our institution for further evaluation of recently diagnosed HCC. She had developed a flu-like illness with abdominal pain, and a computed tomography scan demonstrated 3 liver masses in the left lobe (largest measured 14 cm). There was no history of toxin exposure or alcohol use. She did have a prior history of blood transfusion and oral contraceptive pill use. There was no prior documented diagnosis of DM, but fasting glucose was 121 mg/dL. Physical examination was unremarkable; BMI was 42 kg/m2. The patient underwent left hepatic lobectomy. Histology of the resected liver revealed three discrete nodules measuring 14.5, 6.5, and 2 cm that of well-to-moderately-differentiated hepatocellular carcinoma. The uninvolved liver was non-cirrhotic and showed moderate steatosis consistent with NASH. Case 2: An 84 year-old white female with DM, hypertension, hyperlipidemia, and NASH on a prior liver biopsy presented to an outside institution with nausea. Bidirectional endoscopy noted only a hiatal hernia. Computed tomography of the abdomen revealed a 4.5 cm irregular mass in the dome of the right lobe of the liver. Physical exam was unremarkable; BMI was 25.7 kg/m2. The patient underwent resection of segment 7 of the liver. Histology of the resected liver revealed a 4.2 cm subcapsular, moderately differentiated hepatocellular carcinoma. The adjacent liver demonstrated mild to moderate macrovesicular steatosis consistent with NASH and stage 3 bridging fibrosis without cirrhotic nodularity. Comments: HCC generally occurs in the setting of pre-existing liver damage, namely cirrhosis. We report 2 additional cases of HCC occurring in NASH in the absence of cirrhosis. These cases add to the evidence that HCC can occur in the absence of cirrhosis and suggest that factors contributing to NASH may also predispose to neoplastic development in the absence of cirrhosis. It is concluded that patients with NASH may need screening for HCC.