Beyond Morphology: Pretransplant Tumor-to-Liver FDG Uptake Ratio Predicts Hepatocellular Carcinoma Recurrence After Liver Transplantation

Background/Objectives: Tumor size and number do not fully capture the risk of hepatocellular carcinoma (HCC) recurrence after liver transplantation. We examined whether the pretransplant tumor-to-liver maximum standardized uptake value (SUV) ratio on 18F-FDG PET/CT is associated with recurrence, and assessed the previously reported cutoff of 1.43 in an independent cohort. Methods: We retrospectively analyzed 227 adults who underwent liver transplantation for HCC between July 2004 and November 2024 and had pretransplant FDG PET/CT. The primary endpoint was time to recurrence (TTR). The SUV ratio was analyzed as a continuous, log2-transformed variable in Cox models adjusted for age, MELD-Na, alpha-fetoprotein (AFP), and Milan status; the 1.43 cutoff was a secondary analysis. Death without recurrence was treated as a competing event. Results: Over a median follow-up of 80 months, 43 patients developed recurrence and 86 died. Each doubling of the SUV ratio was associated with a higher recurrence rate (adjusted HR 6.68; 95% CI 3.58–12.47) and higher mortality (HR 2.79; 95% CI 1.72–4.53). The 5-year cumulative incidence of recurrence was 44.7% with a ratio >1.43 and 7.5% with a ratio ≤1.43. Only 2 of 51 non-FDG-avid tumors recurred. The ratio added prognostic information to Milan criteria and AFP (likelihood ratio χ2 28.5; p < 0.001) and stratified risk within the Milan criteria (5-year cumulative incidence of recurrence, 26.4% vs. 5.2%). Conclusions: A high pretransplant tumor-to-liver SUV ratio was strongly associated with recurrence independently of Milan status and AFP. External validation with standardized PET protocols is needed before clinical use.