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Page 2 of 8 Chen et al. Hepatoma Res 2019;5:25 I http://dx.doi.org/10.20517/2394-5079.2019.12

diagnosis of HCC improved the survival of high-risk HBsAg carriers. To ensure cost-effectiveness, we suggest
using different screening strategies according to the individual risk of hepatocarcinogenesis.

Keywords: Hepatitis B surface antigen, retrospective cohort, hepatocellular carcinoma, surveillance

INTRODUCTION
Chronic persistent hepatitis B virus (HBV) infection is a global disease, and its prevalence is highest in Africa and
East Asia . The chronic relapsing inflammation caused by HBV leads to chronic hepatitis, liver cirrhosis, and
[1-4]
hepatocellular carcinoma (HCC) . Patients with HBV are generally asymptomatic and unaware of their illness
[4]
until they reach the advanced stage. Early diagnosis of HCC through periodic surveillance has become one of
the strategies for management of chronic hepatitis B surface antigen (HBsAg) carriers . Diagnosis of HCC
[5-7]
in the early, treatable stages leads to improved survival . This is especially important for areas with endemic
[7,8]
HBV infection [1-3,9] . The methods for early detection of HCC mainly rely on alpha-fetoprotein (AFP), AFP-lectin
3 fraction (AFP-L3), des-γ-carboxy prothrombin, and liver ultrasound (US) [5-8,10,11] . Many new biomarkers are
under investigation [12-14] , but they appear to be more expensive and were not found to be significantly superior
to AFP and US in a large population survey .
[15]
In addition to detection tools, a number of other variables, including duration of surveillance, individual
risk, and patient attitude, may also contribute to the effectiveness of surveillance. We have been performing
surveillance for early detection of HCC in a hepatitis B carrier clinic for more than 30 years . This analysis
[5,6]
was conducted to assess our results and to improve our surveillance strategy.

METHODS
The HBsAg-Carrier Clinics of Chang Gung Memorial Hospital in Taipei and Linkou Medical Centers have
been in operation since 1980, and they provide an easily accessible service for chronic HBsAg carriers in
Taiwan. Most patients who visit the HBsAg-Carrier Clinics are asymptomatic upon entry. They visit the
clinics because the presence of HBsAg has been incidentally detected upon blood donation, in a general
check-up, or in a work-up for a non-liver-related disease, or they are referred from our outpatient department
as stable HBsAg carriers with normal alanine aminotransferase (ALT).

A total of 15,235 HBsAg carriers with persistent HBsAg for more than six months had been registered in the
HBsAg-Carrier Clinics by 2012. Patients with dual infections were excluded. The subjects underwent 275,324
visits and had a mean follow-up duration of 10.0 ± 7.65 years. Upon registration with the clinic, the subjects
underwent liver biochemical tests and testing for serologic markers of hepatitis viruses, AFP, and real-time
liver US. After this initial visit, the subjects were followed-up every 3-12 months, with ALT, AFP, and US as
the basic measures.

This HBsAg-Carrier Clinics has three full-time clinic staffs and a private line telephone to arrange registration
and visits. The clinic staffs recorded basic information, delivered patient education, collected data from each
visit, and entered these data into the hospital’s main computer. One of the main aims of this clinic is to
detect HCC at the early stage. For patients unable to keep up with the follow-up schedule, reminder letters
are sent.

In this study, we examined data from the HBsAg-Carrier Clinic from 1980-2012. This long-term follow-up
analysis of chronic HBsAg carriers was approved by the human research committee of Chang Gung Memorial
Hospital (IRB No: 201600523B0).