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Differences in Posttransplant Hepatocellular Carcinoma Recurrence by Etiology of Liver Disease

The 5‐year incidence of posttransplant hepatocellular carcinoma (HCC) recurrence is 8%‐20%. Several studies have evaluated pretransplant risk factors for HCC recurrence, but nearly all data have treated HCC as a homogeneous condition across all etiologies of liver disease despite differences in tumor biology and baseline incidence of HCC. We sought to evaluate the impact of etiology of liver disease, maximum pretransplant alpha‐fetoprotein (AFP), and the interaction of the 2 factors on the risk of HCC recurrence. We performed a retrospective cohort study of HCC transplant recipients using United Network for Organ Sharing (UNOS) data from 2002 to 2016. A competing risks regression was performed to identify variables associated with HCC recurrence and an interaction term between etiology and maximum AFP category. Among 18,406 recipients, 1484 patients experienced HCC recurrence over 3.1 years of median follow‐up time. There was a significant interaction between AFP category and etiology of liver disease (P < 0.001). Among patients with a maximum AFP <100 ng/mL, those with alcoholic liver disease had the lowest risk of recurrence. In contrast, in patients with a maximum AFP of 100‐499, 500‐1000, or >1000 ng/mL, those with alcoholic liver disease had the highest risk of HCC recurrence among all etiologies. In conclusion, risk of HCC recurrence differs by etiology of liver disease, and the significance of elevated pretransplant AFP varies by etiology. Patients with alcoholic liver disease and elevated maximum AFP are at a uniquely high risk of HCC recurrence. These findings have potential UNOS policy implications because the transplant selection process may ultimately benefit from etiology‐specific criteria.