Retrospective Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jun 16, 2018; 6(6): 110-120
Published online Jun 16, 2018. doi: 10.12998/wjcc.v6.i6.110
Prognostic role of alpha-fetoprotein response after hepatocellular carcinoma resection
Narongsak Rungsakulkij, Wikran Suragul, Somkit Mingphruedhi, Pongsatorn Tangtawee, Paramin Muangkaew, Suraida Aeesoa
Narongsak Rungsakulkij, Wikran Suragul, Somkit Mingphruedhi, Pongsatorn Tangtawee, Paramin Muangkaew, Suraida Aeesoa, Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
Author contributions: Rungsakulkij N designed the study, collected and interpreted the data, and wrote the paper; Suragul W collected the data and wrote the paper; Mingphruedhi S collected and analyzed the data; Tangtawee P collected and analyzed the data; Muangkaew P collected the data; Aeesoa S analyzed the data.
Institutional review board statement: This study was reviewed and approved by the Ramathibodi Hospital Institutional Review Board Committee on Human Rights Related to Research Involving Human Subjects (protocol number ID 03-61-25).
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: All authors declare no conflicts-of-interest related to this article.
Data sharing statement: No additional data are available.
Open-Access: This article is an open access article, which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non-Commercial (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://creative commons.org/licenses/by-nc/4.0
Correspondence to: Wikran Suragul, FRCS (Gen Surg), MD, Doctor, Surgeon, Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Praram VI Road, Ratchathewi, Bangkok 10400, Thailand. wikran.sur@mahidol.ac.th
Telephone: +66-2-2011527 Fax: +66-2-2012471
Received: April 26, 2018
Peer-review started: April 27, 2018
First decision: May 9, 2018
Revised: May 11, 2018
Accepted: May 30, 2018
Article in press: May 31, 2018
Published online: June 16, 2018
Processing time: 55 Days and 12.3 Hours
ARTICLE HIGHLIGHTS
Research background

Historically, alpha-fetoprotein (AFP) levels were used to diagnose hepatocellular carcinoma (HCC); however, the current guidelines for the surveillance of high-risk patients include ultrasonography every 3-6 mo without AFP. Although AFP does not currently play a diagnostic role in HCC, it is still a useful marker for estimating the post-surgery follow-up period according to current guidelines.

Research motivation

AFP levels are widely used as a tumor marker for HCC in both pre- and post-treatment cases. Several studies have reported that pre-operative serum AFP levels are a significant prognostic factor for post-treatment survival. However, other studies have reported that AFP was not useful for predicting the poor prognosis group among HCC patients. Finally, a third set of studies reported that changes in serum AFP better predict prognosis; however, we lack a definition of what constitutes a significant change in serum AFP (a response signature) after hepatic resection.

Research objectives

To investigate whether the change in pre-/post-operation AFP levels is a predictive factor for HCC outcomes.

Research methods

We retrospectively analyzed 334 HCC patients who underwent hepatic resection at Ramathibodi hospital, Thailand between January 2006 and December 2016. The patients were classified into three groups according to their change in serum AFP levels: (1) the normal group, pre-operative serum AFP level (pre-AFP) ≤ 20 ng/mL and post-operative serum AFP level (post-AFP) ≤ 20 ng/mL; (2) the response group, pre-AFP > 20 ng/mL and post-AFP decrease of ≥ 50% of pre-AFP; and (3) the non-response group, pre-AFP level > 20 ng/mL and post-AFP decrease of < 50% or higher than pre-AFP level, or any pre-AFP level < 20 ng/mL but post-AFP > 20 ng/mL.

Research results

Univariate and multivariate analyses revealed that multiple tumors [hazard ratio (HR): 1.646, 95%CI: 1.15-2.35, P < 0.05], microvascular invasion (mVI) (HR: 1.573, 95%CI: 1.05-2.35, P < 0.05), and the non-response group (HR: 2.425, 95%CI: 1.42-4.13, P < 0.05) were significant independent risk factors for recurrence-free survival. Similarly, multiple tumors (HR: 1.99, 95%CI: 1.12-3.52, P < 0.05), mVI (HR: 3.24, 95%CI: 1.77-5.90, P < 0.05), and the non-response group (HR: 3.62, 95%CI: 1.59-8.21, P < 0.05) were also significant independent risk factors for overall survival. The non-response group had significantly lower overall survival rates and recurrence-free survival rates than both the normal group and the response group (P < 0.05). Thus, patients with no response regarding post-surgery AFP levels were associated with poor outcomes.

Research conclusions

AFP is a multifaceted serum tumor marker in HCC. Serum AFP responsiveness was found to be a significant prognostic factor for surgical outcomes in the high pre-AFP group, and non-responsive patients were associated with poor outcomes. AFP levels following hepatic resection have important roles in managing HCC patients.

Research perspectives

In the future, the prospective cohort studies in the selected patients group should be conduct to confirmation this hypothesis and the usefulness of the post-operative serum AFP level in the clinical practice.