Obesity and diabetes as a risk factor for hepatocellular carcinoma

Ten percent of patients who undergo resection for hepatocellular carcinoma (HCC) associated with chronic liver disease have no detectable cause for this underlying liver disease. Recent studies have shown that patients with cryptogenic chronic liver disease frequently have risk factors for nonalcoholic fatty liver disease (NAFLD). This study examines the incidence of risk factors for NAFLD in patients with chronic liver disease who underwent resection for HCC. Among 210 patients with chronic liver disease who underwent resection for HCC, 18 (8.6%) had no identifiable cause for the underlying liver disease. These patients were assessed for obesity, diabetes mellitus, and histological features of the tumor and the adjacent liver parenchyma. Comparisons were made with matched patients with alcohol- and chronic-viral-hepatitis-related HCC. The prevalence of obesity (50% vs. 17% vs. 14%), diabetes (56% vs. 17% vs. 11%), aspartate aminotransferase/alanine aminotransferase ratio<1 (50% vs. 19% vs. 17%), and steatosis>20% (61% vs. 17% vs. 19%) was significantly higher in patients with cryptogenic liver disease than in patients with alcohol abuse and chronic viral hepatitis (P<0.0001 for each). Well-differentiated tumors were significantly more common in patients with cryptogenic liver disease (89% vs. 64% in patients with alcohol-related HCC vs. 55% in patients with chronic viral hepatitis-related HCC, P<0.0001). In conclusion, the hypothesis that obesity and diabetes mellitus may be important risk factors for cryptogenic chronic liver disease in patients with HCC is supported by the analysis of surgically treated patients. Whether HCC is primarily related to obesity and diabetes mellitus or secondarily to a NAFLD-like parenchymal lesions remains to be clarified.