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
ARTICLE HIGHLIGHTS
Research background

For many years, liver transplantation for hepatocellular carcinoma (HCC) has been performed according to the Milan criteria for patient selection, using a maximum dominant tumor diameter (MTD) of 5 cm and resulting in a 5-year survival of 75%.

Research motivation

It has recently become apparent, that an expansion of the Milan criteria may be possible for patients with a slightly larger MTD than 5 cm to be transplanted and achieve similar good survival. However, the extent by which MTD can be increased has not been clearly identified.

Research objectives

To identify subsets of HCC patients with larger tumors, who also have longer survival after liver transplant, despite having an MTD > 5 cm.

Research methods

We retrospectively evaluated a prospectively accrued database of 50 patients who had HCCs > MTD of 5 cm and were treated by living donor liver transplantation.

Research results

We found that HCC patients with a MTD 6-10 cm could be stratified according to the presence of low or high levels of serum alpha-fetoprotein (AFP) or gamma glutamyl transpeptidase (GGT), or the 2 serum markers in combination. The results showed that patients with a combination of low AFP plus low GGT had excellent long-term survival. Patients who had either low AFP alone or low GGT alone had intermediate survival and patients with both high AFP plus high GGT had the worst survival.

Research conclusions

Measurement of serum AFP and GGT levels permits the identification of HCC patients with tumors greater than the Milan criteria size who can have excellent post-liver transplant survival.

Research perspectives

Future research should be directed towards the identification of new HCC biomarkers that will correlate with tumor biology and will help refine the selection of HCC patients with large tumors who can also benefit from treatment with liver transplantation. This will increase the number of HCC patients who can then benefit from increased survival following liver transplantation.