Prospective Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 14, 2016; 22(34): 7806-7812
Published online Sep 14, 2016. doi: 10.3748/wjg.v22.i34.7806
Hepatocellular carcinoma screening and surveillance in 2293 chronic hepatitis B patients in an endemic area
Teerapat Ungtrakul, Chulabhorn Mahidol, Pattra Chun-on, Charlie Laohapand, Surachate Siripongsakun, Akeanong Worakitsitisatorn, Sirachat Vidhayakorn, Wariya Boonchuay, Jiraporn Dechma, Gaidganok Sornsamdang, Kamonwan Soonklang, Tassanee Sriprayoon, Tawesak Tanwandee, Chirayu U Auewarakul
Teerapat Ungtrakul, Chulabhorn Mahidol, Pattra Chun-on, Charlie Laohapand, Surachate Siripongsakun, Akeanong Worakitsitisatorn, Sirachat Vidhayakorn, Wariya Boonchuay, Jiraporn Dechma, Gaidganok Sornsamdang, Kamonwan Soonklang, Chirayu U Auewarakul, Chulabhorn Hospital, Laksi, Bangkok 10210, Thailand
Chulabhorn Mahidol, Chulabhorn Research Institute, Laksi, Bangkok 10210, Thailand
Chulabhorn Mahidol, Tassanee Sriprayoon, Tawesak Tanwandee, Chirayu U Auewarakul, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkoknoi, Bangkok 10700, Thailand
Author contributions: Ungtrakul T carried out the literature review, study design, statistical analysis, manuscript drafting and revision; Chun-on P, Siripongsakun S, Worakitsitisatorn A and Vidhayakorn S carried out data collection and imaging analyses; Boonchuay W and Dechma J contributed to data collection and patient coordination; Sornsamdang G was responsible for the analysis of serum alpha-fetoprotein and liver function tests; Soonklang K carried out the statistical analysis; Laohapand C and Sriprayoon T contributed to the literature review and study design; Mahidol C, Tanwandee T and Auewarakul CU contributed to proposal development, data analysis and monitoring, and manuscript revision; all authors read and approved the final manuscript.
Supported by Chulabhorn Hospital.
Institutional review board statement: The study was reviewed and approved by the ethical committee of human research of Chulabhorn Research Institute (Certificate no. 18/2553).
Informed consent statement: All study participants provided written consent prior to the study enrollment.
Conflict-of-interest statement: The authors of this manuscript declare that they have no conflicts of interest to disclose.
Data sharing statement: We do not wish to share the data at this stage because the study involving this cohort is still ongoing. Data should be available by July 2023.
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:
Correspondence to: Teerapat Ungtrakul, MD, MSc, Chulabhorn Hospital, 54 Kamphaeng Phet 6, Laksi, Bangkok 10210, Thailand.
Telephone: +662-5766791 Fax: +662-5766791
Received: April 20, 2016
Peer-review started: April 21, 2016
First decision: May 27, 2016
Revised: June 27, 2016
Accepted: August 1, 2016
Article in press: August 1, 2016
Published online: September 14, 2016

To determine the role of screening and surveillance of hepatocellular carcinoma (HCC) in treatment-naïve chronic hepatitis B (CHB) patients.


We recruited 2293 CHB patients (both males and females; aged 20-65 years). All patients were screened and underwent surveillance using abdominal ultrasonography (AUS) and serum alpha-fetoprotein (AFP) assay every 6 mo. The diagnosis, staging and treatment of HCC followed the American Association for the Study of Liver Diseases practice guidelines and the Barcelona Clinic Liver Cancer guidelines. The exclusion criteria included: decompensated cirrhosis; a history of any cancer in the last 5 years; previous antiviral treatment for CHB; concurrent infection with hepatitis C virus or human immunodeficiency virus; a Karnofsky Performance Status score < 60%; or any medical condition preventing eligibility to complete the protocol. The prevalence and incidence rates of HCC were determined; survival rates were calculated at 3-year post HCC diagnosis. The sensitivity and specificity were calculated on a per-patient basis.


Among 2293 treatment-naïve CHB patients, seven cases had HCC at initial screening, giving a prevalence rate of 305 per 100000 persons; 3.3% were diagnosed with liver cirrhosis, all of which were Child-Pugh class A. With a median follow-up time of 42 (range, 3-48) mo, 10 additional cases were diagnosed with HCC, resulting in an incidence rate of 143 per 100000 persons per year. This burden was as high as that reported in other studies from East Asian countries. All HCC patients were aged ≥ 40 years. Most were at an early stage (Stage 0, A or B); 14/17 cases were successfully treated with surgical resection or radiofrequency ablation, with a high 3-year survival rate of 90%. Hemangioma was the most common focal liver lesion in CHB patients detected by AUS; the main causes of AFP elevation at the initial screening were cirrhosis, increased alanine aminotransferase level and HCC. AUS detected 16/17 HCC cases whereas AFP levels ≥ 20 μg/L at diagnosis were observed in only 7/17 patients, most with a tumor size > 5 cm. For HCC screening and surveillance, AUS had a sensitivity and specificity of 94% and 82%, respectively, whereas the sensitivity and specificity of AFP at a cut-off value of ≥ 20 μg/L were 41% and 98%, respectively. Combined use of AUS and AFP assay did not improve effectiveness.


Implementation of active screening and surveillance using AUS to detect early-stage HCC in naïve CHB patients aged ≥ 40 years in an endemic area is of benefit.

Keywords: Liver cancer, Ultrasonography, Alpha-fetoprotein, Early detection, Hepatitis B

Core tip: This large cohort study of 2293 patients revealed a high prevalence rate (305 per 100000 persons) and a high incidence rate (143 per 100000 persons per year) of hepatocellular carcinoma (HCC) in treatment-naïve Thai chronic hepatitis B (CHB) patients through a screening and surveillance semi-annual ultrasonography program. Most patients were at an early stage (Stage 0, A or B) and were successfully treated, with a high 3-year survival rate of 90%. A national screening policy should thus be implemented in CHB patients residing in a developing country with a high incidence rate of HCC such as Thailand, to prevent late-stage HCC development.