# Incidental Combined Hepatocellular-Cholangiocarcinoma in Liver Transplant Recipients: A Matched Cohort Study

## TL;DR

This study finds that liver transplant patients with a mixed liver cancer type (HCC-CCA) have worse outcomes than those with pure HCC, highlighting the need for better pre-transplant detection methods.

## Contribution

The study is the first to compare outcomes of HCC-CCA and HCC in liver transplant recipients using matched cohorts based on pre- and post-transplant characteristics.

## Key findings

- HCC-CCA patients had worse overall and recurrence-free survival compared to HCC patients.
- More HCC-CCA patients were outside standard transplant criteria on explant pathology.
- Pre-transplant imaging failed to identify HCC-CCA, necessitating better screening tools.

## Abstract

Mixed hepatocellular carcinoma (HCC) with cholangiocarcinoma (HCC-CCA) is an aggressive primary liver cancer and difficult to distinguish from HCC using non-invasive methods. Outcomes of patients incidentally diagnosed with HCC-CCA after LT relative to pure HCC with similar tumor burden were investigated. Medical records of patients undergoing LT (n = 1,898) for HCC (n = 493) from 6/2008–9/2023 were reviewed. Patients incidentally diagnosed with HCC-CCA were propensity matched to HCC patients undergoing LT. Independent analyses were performed using pre-LT (Match1; identifiable pre-LT) and explant pathology (Match2, more prognostic) characteristics. Incidental HCC-CCA occurred in 19 (3.9%) patients; all assumed to have HCC pre-LT and received HCC-directed neoadjuvant treatment. When matched on pre-LT characteristics (Match1, n = 57), more patients with HCC-CCA were outside Milan or University of California, San Francisco criteria on explant (p = 0.01). More patients with HCC-CCA underwent neoadjuvant microwave ablation (p = 0.02) compared to HCC Match2 (n = 45) but were otherwise similar demographically and clinically. Overall and recurrence-free survival were lower for HCC-CCA in Match1 (p = 0.003 and p < 0.001, respectively) and Match2 (p < 0.001 and p = 0.001, respectively). HCC-CCA has an aggressive phenotype with high recurrence after LT. Better screening tools and biomarkers are needed to distinguish HCC-CCA from HCC to ensure patients receive appropriate treatment and maximize post-LT outcomes.

Flowchart illustrating a matched chorort study on incidental combined hepatocellular-cholangiocarcinoma (HCC-CCA) in liver transplant recipients. It shows that explant pathology after liver transplantation enabled incidental detection of combined HCC-CCA tumors, which were not identidied by pre-transplant radiography. Propensity score matching is used for comparisons. Key results include overall and recurrence-free survival statistics. A side note highlights the need for improved screening tools and distinction between HCC-CCA and HCC before transplant. The study is authored by Sudha Kodali et al., published in Transplant International 2025.