Clinical Trials Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Dec 27, 2020; 12(12): 520-533
Published online Dec 27, 2020. doi: 10.4240/wjgs.v12.i12.520
Liver transplant for large hepatocellular carcinoma in Malatya: The role of gamma glutamyl transferase and alpha-fetoprotein, a retrospective cohort study
Volkan Ince, Brian I Carr, Harika Gozukara Bag, Veysel Ersan, Sertac Usta, Cemalettin Koc, Fatih Gonultas, Baris Kemal Sarici, Serdar Karakas, Koray Kutluturk, Adil Baskiran, Sezai Yilmaz
Volkan Ince, Brian I Carr, Veysel Ersan, Sertac Usta, Cemalettin Koc, Fatih Gonultas, Baris Kemal Sarici, Serdar Karakas, Koray Kutluturk, Adil Baskiran, Sezai Yilmaz, Department of General Surgery, Inonu University, Liver Transplantation Institute, Malatya 44280, Turkey
Harika Gozukara Bag, Department of Biostatistics, Inonu University, School of Medicine, Malatya 44280, Turkey
Author contributions: Ince V and Carr BI contributed equally to this work; Ince V, Carr BI, Ersan V, Koc C, Baskiran A and Yilmaz S designed the research study; Ince V, Carr BI, Yilmaz S, Sarici B, Gonultas F, Usta S, Karakas S, and Kutluturk K performed the research; Ince V, Carr BI, Bag HG, Usta S, Karakas S, Kutluturk K and Yilmaz S  contributed new reagents and analytic tools; Ince V, Carr BI, Bag HG, Ersan V, Karakas S, Koc C and Baskiran A analyzed the data and wrote the manuscript; all authors have read and approved the final manuscript.
Institutional review board statement: This study was approved by Inonu University Institutional Review Board (Approval No. 2018/1-9).
Clinical trial registration statement: This study is registered in ClinicalTrials.gov. The registration identification number is NCT04412161.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Data sharing statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.
CONSORT 2010 statement: The authors have read the CONSORT 2010 statement, and the manuscript was prepared and revised according to the CONSORT 2010 statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Volkan Ince, FEBS, MD, Associate Professor, Surgeon, Department of General Surgery, Inonu University, Liver Transplantation Institute, Battalgazi, Malatya 44280, Turkey. volkanince@outlook.com
Received: July 24, 2020
Peer-review started: July 24, 2020
First decision: October 21, 2020
Revised: November 3, 2020
Accepted: November 13, 2020
Article in press: November 13, 2020
Published online: December 27, 2020
Processing time: 149 Days and 21 Hours
Abstract
BACKGROUND

There is increasing interest in transplanting patients with hepatocellular carcinoma (HCC) with tumors greater than 5 cm (Milan criteria). 

AIM

To investigate possible prognostically-useful factors for liver transplantation in HCC patients with large tumors.

METHODS

In this clinical study, 50 patients with HCC who were transplanted at our Liver Transplant Center between April 2006 and August 2019 and had tumors greater than 6 cm maximum diameter were retrospectively analyzed. Their survival and full clinical characteristics were examined, with respect to serum alpha-fetoprotein (AFP) and gamma glutamyl transpeptidase (GGT) levels. Kaplan-Meier survival estimates were used to determine overall survival and disease-free survival in these patients. The inclusion criterion was evidence of HCC. Exclusion criteria were the presence of macroscopic portal vein thrombosis or metastasis and a follow-up period of less than 90 d.

RESULTS

Using receiver operating characteristic curve (ROC) analysis, cutoff values of AFP 200 ng/mL and GGT 104 IU/L were identified and used in this study. Significantly longer overall survival (OS) and disease-free-survival (DFS) were found in patients who had lower values of either parameter, compared with higher values.  Even greater differences in survival were found when the 2 parameters were combined. Two tumor size bands were identified, in searching for the limits of this approach with larger tumors, namely 6-10 cm and > 10 cm. Combination parameters in the 6-10 cm band reflected 5-year OS of 76.2% in patients with low AFP plus low GGT vs 0% for all other groups. Patients with tumors greater than 10 cm, did not have low AFP plus low GGT. The most consistent clinical correlates for longer survival were degree of tumor differentiation and absence of microscopic portal venous invasion.

CONCLUSION

Serum levels of AFP and GGT, both alone and combined, represent a simple prognostic identifier in patients with large HCCs undergoing liver transplant-ation.

Keywords: Hepatic malignancy; Advanced; Gamma glutamyl transpeptidase; Living donor; Beyond; Extended

Core Tip: Excellent long-term survival was found after liver transplantation in patients with hepatocellular carcinoma with a maximum tumor diameter greater than 6 cm and less than 10 cm, in whom serum alpha-fetoprotein was lower than 200 ng/mL and gamma glutamyl transpeptidase was lower than 104 IU/L.