Development and Validation of the ALBI-Gamma-Glutamyl Transferase Score for Enhanced Prognostic Accuracy After Hepatocellular Carcinoma Resection.

Abstract

Background: The albumin-bilirubin(ALBI) score, used for predicting outcomes after hepatocellular carcinoma(HCC) resection, does not directly capture liver cell damage or biliary obstruction. Gamma-glutamyl transferase(GGT), reflecting hepatic oxidative stress and inflammation, may complement the ALBI score. We sought to develop the ALBI-GGT score, a composite prognostic tool, and evaluate its performance in predicting long-term outcomes among patients undergoing HCC resection.

Methods: Patients undergoing curative-intent HCC resection(2000-2023) were identified from an international, multi-institutional database. The cohort was divided into training(65%) and testing(35%) cohorts. Multivariable Cox analysis examined the association of ALBI-GGT score with overall survival(OS).

Results: Among 759 patients, median ALBI score was -2.78[-3.02,-2.48], and median GGT was 55.0[31.0,93.0]U/L. On multivariable analysis, ALBI score(HR:1.473[1.112-1.950];p=0.007) and GGT(HR:1.007[1.004-1.010];p<0.001) were predictors of overall mortality, alongside Tumor Burden Score(HR:1.051[1.015-1.090];p=0.006) and ASA class>2(HR:1.473[1.005-2.161];p=0.047). There was near-linear correlation between increasing ALBI scores and GGT and higher hazards of death. The ALBI-GGT score demonstrated the highest predictive accuracy in the testing set(C-index:0.68[0.58-0.72]), outperforming the ALBI score(0.62[0.56-0.69]) and GGT(0.65[0.58-0.72]). It achieved the lowest Akaike and Bayesian information criterion. Time-dependent AUC analysis showed consistent superiority over 0-60 months. At 1, 3, and 5 years, the ALBI-GGT score had AUCs of 0.782, 0.725, and 0.688, respectively, outperforming ALBI score and GGT. ALBI-GGT score was able to stratify patients into distinct prognostic groups(5-year OS:low ALBI-GGT,85.0% vs. intermediate ALBI-GGT,65.8% vs. high ALBI-GGT,56.8%;p<0.001).

Conclusion: ALBI score alone may be insufficient to prognostically stratify HCC patients. Combining ALBI score with GGT provided a superior tool for stratifying patients relative to long-term survival.