R. Stulpinas1,2, A. Gulla3,4,5,6, A. Grigonyte7, D. Zilenaite-Petrulaitiene1,2, A. Rasmusson1,2, K. Strupas3,5,6, A. Laurinavicius1,2 3Vilnius University, Faculty Of Medicine- Institute Of Medicine, Vilnius, Lithuania 4Memorial Sloan Kettering Cancer Center, Department Of Surgery, New York, NEW YORK, USA 5Vilnius University Hospital Santaros Clinics, Center Of Abdominal Surgery, Vilnius, Lithuania 6Vilnius University, Faculty Of Medicine- Centre For Visceral Medicine And Translational Research, Vilnius, Lithuania 7Vilnius University, Faculty Of Medicine, Vilnius, Lithuania 1Vilnius University, Faculty Of Medicine- Institute Of Biomedical Sciences- Department Of Pathology- Forensic Medicine And Pharmacology, Vilnius, Lithuania 2National Center of Pathology, Affiliate Of Vilnius University Hospital Santaros Clinics, Vilnius, Lithuania
Introduction:
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality worldwide. The main treatment options for early-stage HCC remain partial liver resection (LR) or liver transplantation (LT). This study aims to analyze the impact of CD8+, clinicopathological parameters, and overall survival (OS) of patients who underwent LT or LR for HCC.
Methods:
Patients diagnosed with HCC retrospectively were divided into two groups based on surgical management. All patients who underwent LT met the Milan criteria for transplantation. The other group was considered for LR. Clinical, pathological parameters and scanned CD8+ immunohistochemistry slides of surgically obtained HCC tissue were analyzed. Tumor and CD8+ lymphocyte detection tool was developed using HALO® AI system (Indica Labs, USA). A Hexagonal grid-based computational tool (interface zone immunogradient, Rasmusson et al, Am J Path 2020) was applied to quantify CD8+ cell density profiles across the tumor edges.
Results:
A total of 134 patients who underwent LT (n=28) or LR (n=106) for HCC at Vilnius University Hospital Santaros Klinikos between May 2007 and November 2020 were included. The gender ratio was 3:1 (101 males, mean age 61.3 and 33 females, mean age 58.2). Median follow-up time was 61 and 31 months after LT and LR respectively. During the follow-up, 53% of resected and 25% of transplanted patients deceased. The majority of transplanted patients had a history of HCV infection (n=21, 75%). Univariate analysis revealed younger patient age at the time of LT (<51,5 years, p=0,019) and 3 HCC nodules in recipients' liver (vs. 1-2, p=0,011) to be statistically significant predictors of worse post-transplantation OS. Pre-operative platelet count <70,8×109/l (p=0,013), activated partial thromboplastin time (aPTT) >40,11s (p=0,0096), albumin <32,8g/l (p=0,043), total bilirubin >45µmol/l (p=0,033), and creatinine <63µmol/l (p=0,03) also negatively affected patients' OS after LT. Mean CD8+ lymphocyte density in the regenerative nodules of explanted liver parenchyma around the tumor <4,526 (p=0,027) was also a statistically significant predictor of worse OS post LT.
Conclusion:
Patient age at the time of transplantation, the number of HCC nodules, and pre-operational blood examination along with mean CD8+ lymphocyte density in the tumor-surrounding liver parenchyma could serve as predictors of OS post LT.