Prospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2015; 21(18): 5654-5662
Published online May 14, 2015. doi: 10.3748/wjg.v21.i18.5654
Ascites and alpha-fetoprotein improve prognostic performance of Barcelona Clinic Liver Cancer staging
Asmaa I Gomaa, Alzhraa Al-Khatib, Wael Abdel-Razek, Mohammed Saad Hashim, Imam Waked
Asmaa I Gomaa, Wael Abdel-Razek, Mohammed Saad Hashim, Imam Waked, Hepatology Department, National Liver Institute, Menoufiya University, Shebeen El-Kom 35111, Egypt
Alzhraa Al-Khatib, Oncology Department, National Liver Institute, Menoufiya University, Shebeen El-Kom 35111, Egypt
Author contributions: Gomaa AI and Waked I conceived and designed the study; Gomaa AI, Hashim MS and Al-Khatib A collected the data; Gomaa AI, Abdel-Razek W, Hashim MS and Waked I analyzed and interpreted the data, and revised the manuscript; Gomaa AI and Waked I wrote the manuscript; Waked I revised and approved the final version of the manuscript.
Supported by Science and Technology Development Fund (STDF), Egypt, Project No. 1519.
Ethics approval: The study was reviewed and approved by the National Liver Institute Review Board (IRB00003413).
Informed consent: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest: None related to this work, Waked I is a speaker for Hoffman La Roche, MSD, BMS, and Gilead; advisory boards for Janssen, Hoffman La Roche, and MSD; investigator in clinical trials for Hoffman La Roche, BMS, Bayer, Janssen, AbbVie, and Minapharm.
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: Asmaa I Gomaa, MD, Hepatology Department, National Liver Institute, Menoufiya University, Shebeen El-Kom 35111, Egypt. aibrahim@liver-eg.org
Telephone: +20-100-6157160 Fax: +20-48-2234586
Received: November 15, 2014
Peer-review started: November 17, 2014
First decision: December 11, 2014
Revised: December 31, 2014
Accepted: January 16, 2015
Article in press: January 16, 2015
Published online: May 14, 2015
Processing time: 183 Days and 18.2 Hours
Abstract

AIM: To assess how ascites and alpha-fetoprotein (AFP) added to the Barcelona Clinic Liver Cancer (BCLC) staging predict hepatocellular carcinoma survival.

METHODS: The presence of underlying cirrhosis, ascites and encephalopathy, Child-Turcotte-Pugh (CTP) score, the number of nodules, and the maximum diameter of the largest nodule were determined at diagnosis for 1060 patients with hepatocellular carcinoma at a tertiary referral center for liver disease in Egypt. Demographic information, etiology of liver disease, and biochemical data (including serum bilirubin, albumin, international normalized ratio, alanine and aspartate aminotransferases, and AFP) were evaluated. Staging of the tumor was determined at the time of diagnosis using the BCLC staging system; 496 patients were stage A and 564 patients were stage B. Patients with mild ascites on initial ultrasound, computed tomography, or clinical examination, and who had a CTP score ≤ 9 were included in this analysis. All patients received therapy according to the recommended treatment based on the BCLC stage, and were monitored from the time of diagnosis to the date of death or date of data collection. The effect of the presence of ascites and AFP level on survival was analyzed.

RESULTS: At the time the data were censored, 123/496 (24.8%) and 218/564 (38.6%) patients with BCLC stages A and B, respectively, had died. Overall mean survival of the BCLC A and B patients during a three-year follow-up period was 31 mo [95% confidence interval (95%CI): 29.7-32.3] and 22.7 mo (95%CI: 20.7-24.8), respectively. The presence of ascites, multiple focal lesions, large tumor size, AFP level and CTP score were independent predictors of survival for the included patients on multivariate analysis (P < 0.001). Among stage A patients, 18% had ascites, 33% had AFP ≥ 200 ng/mL, and 8% had both. Their median survival in the presence of ascites was shorter if AFP was ≥ 200 ng/mL (19 mo vs 24 mo), and in the absence of ascites, patients with AFP ≥ 200 ng/mL had a shorter survival (28 mo vs 39 mo). For stage B patients, survival for the corresponding groups was 12, 18, 19 and 22 mo. The one-, two-, and three-year survival rates for stage A patients without ascites and AFP < 200 ng/mL were 94%, 77%, and 71%, respectively, and for patients with ascites and AFP ≥ 200 ng/mL were 83%, 24%, and 22%, respectively (P < 0.001). Adding ascites and AFP ≥ 200 ng/mL improved the discriminatory ability for predicting prognosis (area under the curve, 0.618 vs 0.579 for BCLC, P < 0.001).

CONCLUSION: Adding AFP and ascites to the BCLC staging classification can improve prognosis prediction for early and intermediate stages of hepatocellular carcinoma.

Keywords: Alpha-fetoprotein; Ascites; Barcelona Clinic Liver Cancer; Hepatocellular carcinoma; Survival

Core tip: Although the Barcelona Clinic Liver Cancer (BCLC) system contains Child-Turcotte-Pugh classification as a main variable, a patient within BCLC stage A or B may have ascites, which can interfere with the recommended treatment. An elevated alpha-fetoprotein level, which is an integral part of other staging systems, may also impact prognosis and influence treatment decision. In this study, we evaluated the utility of adding ascites and the alpha-fetoprotein level to the BCLC system for predicting prognosis and survival in a large cohort of early and intermediate hepatocellular carcinoma patients at a tertiary referral center for liver disease in Egypt.