Risk Profile of Hepatocellular Carcinoma Reveals Dichotomy among US Veterans

Abstract

Hepatocellular carcinoma (HCC) is traditionally associated with chronic liver injury resulting from hepatitis B virus (HBV) and hepatitis C virus (HCV) infection or excessive consumption of alcohol. In addition, recent evidence links HCC to diabetes. Since these risk factors are prevalent among US veterans, we analyzedcontribution of various etiologies toHCC incidence in this population. Clinicopathological correlates of 150 male US veterans diagnosed with HCC between 2001 and 2010 were analyzed and compared to frequency-matched (2:1) non-cancer controls in a single center. HCC was associated with cirrhosis (odds ratio [OR], 250.84; 95 % confidence interval [CI], 86.92-723.88; p < 0.0001), chronic hepatitis B (OR, 34.30 95 % CI, 1.97-598.47; p = 0.015), chronic hepatitis C (OR, 6.84; 95 % CI, 3.89-12.04; p < 0.0001), alcohol use (OR, 6.76; 95 % CI, 4.35-10.52; p < 0.0001), and smoking (OR, 1.83; 95 % CI, 1.23-2.89; p = 0.009), but surprisingly not with diabetes. Only in a subgroup of HCC patients with no "traditional" risk factors did diabetes become a strong independent predictor of HCC when compared to HCC patients with at least one such risk factor (OR, 10.69; 95 % CI, 1.88-60.63, p = 0.007). This subgroup was further distinguished by older age, increased prevalence of hypertension, nonsmoking, and a trend to develop noncirrhotic HCC. While HCC in US veterans is overwhelmingly linked to cirrhosis due to "traditional" risk factors, it also occurs with a separate clinical profile characterized by diabetes and no evidence of cirrhosis, suggesting distinct mechanisms of hepatocarcinogenesis and needs for surveillance.