Research and Development, Veterans Affairs Puget Sound Health Care System, Seattle Washington.
We aimed to determine whether combining serum AFP level with HCC tumor burden allows better stratification of post-transplantation survival in patients with HCC undergoing liver transplantation. We calculated the risk of post-transplantation mortality associated with serum AFP level or HCC tumor burden, adjusting for donor and recipient characteristics, among all adult, first-time liver transplantations performed in the US between 2002-2011 (n=45,267). Serum AFP level, rather than tumor burden, was the tumor characteristic most strongly associated with post-transplantation survival. While recipients with HCC and serum AFP ≤ 15 ng/mL at the time of transplantation had no excess post-transplantation mortality (adjusted hazard ratio [AHR] 1.02, 95% CI 0.93-1.12), those with serum AFP 16-65 (AHR 1.38, 95% CI 1.23-1.54), 66-320 (AHR 1.65, 95% CI 1.45-1.88), and >320 ng/ml (AHR 2.37, 95% CI 2.06-2.73) had progressively worse post-transplantation mortality, compared to recipients without HCC. Patients with tumor burden exceeding the Milan criteria, who are usually excluded from transplantation, had excellent post-transplantation survival if their serum AFP was 0-15 ng/mL (AHR 0.97, 95% CI 0.66-1.43). In contrast, patients within the Milan criteria, who are routinely considered to be transplant candidates, had poor survival if their serum AFP was substantially elevated (AHR 1.92, 95% CI 1.71-2.14, for serum AFP ≥66 ng/mL). Changes in serum AFP level while on the waiting list corresponded closely to changes in post-transplantation mortality. In conclusion, absolute serum AFP level and changes in serum AFP level strongly predict post-transplantation survival independently of tumor burden. We hope that these data may be used, in combination with other factors, to inform future studies and ongoing discussions aiming to improve eligibility criteria for liver transplantation in patients with HCC.