Hepatocellular Carcinoma Survival by Etiology: A SEER-Medicare Database Analysis

In the United States, hepatocellular carcinoma (HCC) survival varies with tumor characteristics, patient comorbidities, and treatment. The effect of HCC etiology on survival is less clearly defined. The relationship between HCC etiology and mortality was examined using Surveillance, Epidemiology, and End Results-Medicare data. In a cohort of 11,522 HCC cases diagnosed from 2000 through 2014, etiologies were identified from Medicare data, including metabolic disorders (32.9%), hepatitis C virus (8.2%), alcohol (4.7%), hepatitis B virus (HBV, 2.1%), rare etiologies (0.9%), multiple etiologies (26.7%), and unknown etiology (24.4%). After adjusting for demographics, tumor characteristics, comorbidities and treatment, hazard ratios (HRs) and survival curves by HCC etiology were estimated using Cox proportional hazard models. Compared with HBV-related HCC cases, higher mortality was observed for those with alcohol-related HCC (HR 1.49; 95% confidence interval [95% CI] 1.25-1.77), metabolic disorder-related HCC (HR 1.25; 95% CI 1.07-1.47), and multiple etiology-related HCC (HR 1.25; 95% CI 1.07-1.46), but was not statistically significant for hepatitis C virus-related, rare disorder-related, and HCC of unknown etiology. For all HCC etiologies, there was short median survival ranging from 6.1 months for alcohol to 10.3 months for HBV. More favorable survival was seen with HBV-related HCC. To the extent that HCC screening is more common among persons with HBV infection compared to those with other etiologic risk factors, population-based HCC screening, applied evenly to persons across all HCC etiology categories, could shift HCC diagnosis to earlier stages, when cases with good clinical status are more amenable to curative therapy.