# The role of the comprehensive complication index in the prediction of tumor-related death in transplanted patients with hepatocellular carcinoma

## TL;DR

This study shows that a high Comprehensive Complication Index after liver transplant increases the risk of cancer-related death in patients with liver cancer.

## Contribution

The study identifies the Comprehensive Complication Index as a novel independent predictor of HCC-related mortality after liver transplantation.

## Key findings

- A CCI score of ≥42 was associated with a 3.35-fold increased odds of HCC-related death.
- High CCI was also linked to higher risks of overall death, recurrence, and early recurrence.
- Including CCI in predictive models may improve accuracy in forecasting adverse outcomes after liver transplantation.

## Abstract

Liver transplantation (LT) is the primary treatment for selected patients with hepatocellular carcinoma (HCC). However, HCC-related mortality post-LT remains a significant concern, with up to 10% of cases reported in international series. Identifying risk factors for adverse clinical outcomes is essential. We hypothesized that post-LT HCC-related mortality rates are higher in patients with a high (≥ 42) Comprehensive Complication Index (CCI) calculated at discharge. This study aims to compare post-LT HCC-related mortality rates between two groups of patients with high versus low CCI following LT for HCC. This study included data from seven collaborative European centers. A cohort of 1121 HCC patients transplanted between 2005 and 2019, surviving more than six months post-LT, was analyzed retrospectively. Patients were divided into two groups based on the CCI at discharge: Low-CCI Group (n = 942, 84.0%) and High-CCI Group (n = 179, 16.0%). An inverse probability of treatment weighting (IPTW) approach was applied for analysis. In the post-IPTW cohort, four multivariable logistic regression models with mixed effects identified independent risk factors for HCC-related death, overall death, recurrence, and early recurrence. A CCI score of ≥ 42 emerged as an independent risk factor across all models. Specifically, CCI ≥ 42 was associated with increased odds of HCC-related death (OR = 3.35; P < 0.0001), overall death (OR = 2.63; P < 0.0001), overall recurrence (OR = 2.09; P = 0.001), and early recurrence (OR = 1.88; P = 0.02). A CCI score at discharge should be considered a critical factor for recurrence and HCC-related mortality risk. Incorporating CCI into standard post-LT predictive models may enhance prognostic accuracy for adverse HCC outcomes.

The online version contains supplementary material available at 10.1007/s13304-025-02101-8.