Liver transplant for combined hepatocellular-cholangiocarcinoma: United States outcomes and influence of the MMaT-3 policy

INTRODUCTION: There is absence of updated population-level data for liver transplantation (LT) for combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and on the impact of current allocation practices, including the Median MELD at Transplant minus 3 (MMaT-3) policy era. METHODS: Using the UNOS registry, we compared adult LT candidates and recipients with cHCC-CCA, hepatocellular carcinoma (HCC), and cholangiocarcinoma (CCA). Outcomes included waitlist mortality (WM), waitlist dropout (WD), graft survival (GS), and patient survival (PS), analyzed using Kaplan-Meier, multivariable Cox regression, and Fine-Gray competing risk models stratified by policy era. RESULTS: 309 candidates had cHCC-CCA. At 3 years, cHCC-CCA had the lowest WM (4.6%) and WD (29.0%) compared with CCA (27.7%, 64.9%) and HCC (15.6%, 39.8%) (P < 0.001). After adjustment, cHCC-CCA was associated with reduced WD (HR 0.56, P = 0.008) and WM (HR 0.33, P = 0.028). Conversely, 15-year GS (25.5%) and PS (27.3%) were lowest for cHCC-CCA (both P < 0.001), with higher adjusted risk of graft loss (HR 1.79) and mortality (HR 1.67). Notably, cHCC-CCA post-LT survival improved from the pre-MMaT-3 to the post-MMaT-3 era. CONCLUSION: cHCC-CCA exhibits favorable waitlist, yet lower long-term post-LT survival compared with HCC and CCA. The improved outcomes observed in the MMaT-3 era suggest that refined selection may have optimized post-LT survival in cHCC-CCA.