Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 28, 2015; 21(16): 4933-4945
Published online Apr 28, 2015. doi: 10.3748/wjg.v21.i16.4933
Prognostic roles of preoperative α-fetoprotein and des-γ-carboxy prothrombin in hepatocellular carcinoma patients
Makoto Meguro, Toru Mizuguchi, Toshihiko Nishidate, Kenji Okita, Masayuki Ishii, Shigenori Ota, Tomomi Ueki, Emi Akizuki, Koichi Hirata
Makoto Meguro, Toru Mizuguchi, Toshihiko Nishidate, Kenji Okita, Masayuki Ishii, Shigenori Ota, Tomomi Ueki, Emi Akizuki, Koichi Hirata, Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Hokkaido 060-8543, Japan
Author contributions: Meguro M and Mizuguchi T contributed equally to this work; Meguro M and Mizuguchi T design this study, analyzed, interpreted and drafted the manuscript; Meguro M and Mizuguchi T, Nishidate T, Okita K, Ishii M, Ota S, Ueki T and Akizuki E acquire the data; Mizuguchi T and Hirata K contributed to statistical advice.
Supported by Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan, [Grant No. 24791437 and No. 26461920 (to Meguro M), No. 13377023 (to Hirata K), and No. 23591993 (to Mizuguchi T)]; A grant from the Yuasa Memorial Foundation was awarded to Mizuguchi T.
Ethics approval: The study was reviewed and approved by the institutional review boards of the Sapporo Medical University.
Informed consent: The study design conformed to the ethical guidelines of the Declaration of Helsinki, and all study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest: There are no conflict-of-interests for all co-authors.
Data sharing: 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://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Makoto Meguro, MD, PhD, Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, Hokkaido 060-8543, Japan. meguro@sapmed.ac.jp
Telephone: +81-11-6112111 Fax: +81-11-6131678
Received: September 30, 2014
Peer-review started: September 30, 2014
First decision: October 29, 2014
Revised: November 11, 2014
Accepted: December 14, 2014
Article in press: December 16, 2014
Published online: April 28, 2015
Abstract

AIM: To clarify the utility of using des-γ-carboxy prothrombin (DCP) and α-fetoprotein (AFP) levels to predict the prognosis of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) and the hepatitis C virus (HCV) infections.

METHODS: A total of 205 patients with HCC (105 patients with HBV infection 100 patients with HCV infection) who underwent primary hepatectomy between January 2004 and May 2012 were enrolled retrospectively. Preoperative AFP and DCP levels were used to create interactive dot diagrams to predict recurrence within 2 years after hepatectomy, and cutoff levels were calculated. Patients in the HBV and HCV groups were classified into three groups: a group with low AFP and DCP levels (LL group), a group in which one of the two parameters was high and the other was low (HL group), and a group with high AFP and DCP levels (HH group). Liver function parameters, the postoperative recurrence-free survival rate, and postoperative overall survival were compared between groups. The survival curves were compared by log-rank test using the Kaplan-Meier method. Multivariate analysis using a Cox forward stepwise logistic regression model was conducted for a prognosis.

RESULTS: The preoperative AFP cutoff levels for recurrence within 2 years after hepatectomy in the HBV and HCV groups were 529.8 ng/mL and 60 mAU/mL, respectively; for preoperative DCP levels, the cutoff levels were 21.0 ng/mL in the HBV group and 67 mAU/mL in the HCV group. The HBV group was significantly different from the other groups in terms of vascular invasion, major hepatectomy, volume of intraoperative blood loss, and surgical duration. Significant differences were found between the LL group, the HL group, and the HH group in terms of both mean disease-free survival time (MDFST) and mean overall survival time (MOST): 64.81 ± 7.47 vs 36.63 ± 7.62 vs 18.98 ± 6.17 mo (P = 0.001) and 85.30 ± 6.55 vs 59.44 ± 7.87 vs 46.57 ± 11.20 mo (P = 0.018). In contrast, the HCV group exhibited a significant difference in tumor size, vascular invasion, volume of intraoperative blood loss, and surgical duration; however, no significant difference was observed between the three groups in liver function parameters except for albumin levels. In the LL group, the HL group, and the HH group, the MDFST was 50.09 ± 5.90, 31.01 ± 7.21, and 14.81 ± 3.08 mo (log-rank test, P < 0.001), respectively, and the MOST was 79.45 ± 8.30, 58.82 ± 7.56, and 32.87 ± 6.31 mo (log-rank test, P < 0.001), respectively.

CONCLUSION: In the HBV group, the prognosis was poor when either AFP or DCP levels were high. In the HCV group, the prognosis was good when either or both levels were low; however, the prognosis was poor when both levels were high. High levels of both AFP and DCP were an independent risk factor associated with tumor recurrence in the HBV and HCV groups. The relationship between tumor marker levels and prognosis was characteristic to the type of viral hepatitis.

Keywords: Hepatocellular carcinoma, Hepatitis B, Hepatitis C, Des-γ-carboxy prothrombin, α-fetoprotein

Core tip: There is no consensus regarding using cutoff levels of tumor markers to predict survival and recurrence after hepatectomy for hepatocellular carcinoma. Furthermore, the prognostic characteristics of these tumor markers according to hepatitis type remain unclear. The α-fetoprotein (AFP) cutoff level for recurrence within 2 years after surgery was 21.0 ng/mL in the hepatitis C virus (HCV) group compared with 529.8 ng/mL in the hepatitis B virus (HBV) group. Furthermore, patients in the HBV group with high levels of either AFP or des-γ-carboxy prothrombin (DCP) had poor prognoses, as did those patients with high levels of both tumor markers. In contrast, only those patients in the HCV group who had high levels of both AFP and DCP had poor prognoses. We believe that to predict prognosis, preoperative levels of tumor markers should be distinguished and assessed according to the type of viral hepatitis.