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DEVELOPMENT AND VALIDATION OF THE ALBI-GAMMA-GLUTAMYL TRANSFERASE SCORE FOR ENHANCED PROGNOSTIC ACCURACY AFTER HEPATOCELLULAR CARCINOMA RESECTION
Miho Akabane¹, Jun Kawashima¹, Abdullah Atlaf¹, Zayed Rashid¹, Shahzaib Zindani¹, Mujtaba Khalil¹, Azza Sarfraz¹, François Cauchy², Federico Aucejo³, Irinel Popescu⁴, Minoru Kitago⁵, Guillaume Martel⁶, Francesca Ratti⁷, Luca Aldrighetti⁷, George A. Poultsides⁸, Yuki Imaoka⁸, Andrea Ruzzenente⁹, Itaru Endo¹⁰, Ana Gleisner¹¹, Hugo P. Marques¹², Vincent Lam¹³, Tom Hugh¹⁴, Feng Shen¹⁵, Timothy M. Pawlik^*1
1Surgery, The Ohio State Wexner Medical Center, Columbus, OH; ²Hopital Beaujon, Clichy, Île-de-France, France; ³Cleveland Clinic, Cleveland, OH; ⁴Institutul Clinic Fundeni Sectia clinica medicina interna, Bucuresti, Romania; ⁵Keio Gijuku Daigaku, Minato-ku, Tokyo, Japan; ⁶University of Ottawa, Ottawa, ON, Canada; ⁷Ospedale San Raffaele Sede di San Raffaele Turro, Milano, Lombardia, Italy; ⁸Stanford University, Stanford, CA; ⁹Universita degli Studi di Verona, Verona, Veneto, Italy; ¹⁰Yokohama Shiritsu Daigaku, Yokohama, Kanagawa, Japan; ¹¹University of Colorado System, Denver, CO; ¹²Hospital Curry Cabral, Lisboa, Lisboa, Portugal; ¹³Westmead Hospital, Westmead, New South Wales, Australia; ¹⁴University of Sydney, Sydney, New South Wales, Australia; ¹⁵Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China

Introduction: Despite being widely used among patients with hepatocellular carcinoma (HCC), the albumin-bilirubin (ALBI) score does not directly indicate liver cell damage or biliary obstruction, which are critical aspects of liver pathology. In contrast, gamma-glutamyl transferase (GGT) reflects hepatic oxidative stress and inflammation—key drivers of cancer progression. We sought to evaluate the combination of ALBI-GGT as a prognostic tool to predict long-term outcomes among patients undergoing resection of HCC.
Methods: Patients who underwent curative-intent hepatectomy for HCC between 2000 and 2023 were identified from an international, multi-institutional database. The cohort was divided into training (65%) and testing (35%) cohorts and multivariable Cox proportional hazards regression analysis was utilized to examine the association of ALBI-GGT on overall survival (OS).
Results: Among 759 patients, median ALBI score was -3.60 [-3.87, -3.26] and median GGT level was 55.0 [31.0–93.0] U/L. On multivariable analysis, 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), as well as 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 independent predictors of OS. There was near linear correlation between increasing ALBI scores and GGT values and higher hazards of death (Figure). A combined ALBI-GGT score demonstrated superior predictive performance in the testing set (AUC 0.68 [0.58–0.72], AIC 1,379) versus ALBI score (AUC 0.62 [0.56–0.69], AIC 1,387) or GGT (AUC 0.65 [0.58–0.72], AIC, 1,378) alone. Time-dependent AUC analysis over the first 5-years following resection consistently demonstrated a better performance by combining ALBI-GGT to predict survival (AUC, 1-year: ALBI-GGT, AUC 0.782; ALBI alone, AUC 0.747; GGT alone, AUC 0.700; 3-year: ALBI-GGT, AUC 0.725; ALBI alone, AUC 0.628; GGT alone, AUC 0.713; 5-year: ALBI-GGT, AUC 0.688; ALBI alone, AUC 0.647; GGT alone, AUC 0.656). ALBI-GGT 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< .001).
Conclusion: ALBI score alone may not be sufficient to prognostically stratify HCC patients. Rather, the combination of ALBI with GGT was a better tool to stratify patients relative to long-term survival following resection of HCC.

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