Under current UNOS policy, patients with hepatocellular carcinoma (HCC) and alpha-fetoprotein (AFP) ≥1,000 are required to show a reduction in AFP to <500 ng/mL before liver transplant (LT). However, effects of AFP reduction on post-LT HCC outcomes among HCC patients with moderately elevated AFP between 100 and <1,000 ng/mL are unclear.

Adults in the UNOS registry who underwent LT 1/2005-9/2015 with initial AFP of 100 to 999 ng/mL at listing for MELD exception were included. Primary predictor was AFP at LT, categorized as <100, 100-499, ≥500 ng/mL, and only one pre-LT AFP (AFP 1-value). Survival was compared using the Kaplan-Meier method. Factors associated with post-LT survival and HCC recurrence were assessed in a multivariable Cox regression model. Among 1766 included patients, 50.2% had AFP 1-value, followed by 24.7%, 18.9%, and 6.2% with AFP <100, 100-499, and ≥500 ng/mL, respectively. 5-year post-LT survival rate was lowest in the AFP ≥500 category, at 56.1%, compared to 72.7%, 70.4%, and 65.6% in the AFP <100, 100-499 ng/mL, and AFP 1-value categories, respectively. In multivariable analysis, AFP ≥500 at LT was associated with a greater risk of post-LT death (HR 1.5, 95% CI 1.1-2.1) and HCC recurrence (HR 1.9, 95% CI 1.1-3.1) when compared to AFP <100 ng/mL; other significant variables included donor risk index, age, race/ethnicity, Child’s class, and tumor diameter. Among AFP ≥500 at LT, 40% had AFP ≥1000, but no difference in post-LT survival or recurrence was seen between those with AFP < or ≥1000 ng/mL.

Mandating AFP <500 at LT for all patients, not just for those with initial AFP ≥1000 ng/mL, may improve post-LT outcomes and can be considered in future UNOS policy.