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Chen et al. Hepatoma Res 2018;4:4 I http://dx.doi.org/10.20517/2394-5079.2017.50 Page 3 of 10

Figure 1. Location of the participants in the Qidong hepatitis B virus infection cohort

screenings during physical examination were regarded as potential candidates. A total of 1157 potential
candidates were identified and invited for HBsAg testing by the ELISA kit from Shanghai Kehua Bio-
engineering Co., Ltd (KHB) within the following 6 months to confirm their HBsAg carrier status. Only those
who were confirmed to be HBsAg positive in the second-round test and who signed the informed consent
were enrolled into the study as participants in the HBV exposed sub-cohort. Meanwhile, local residents who
claimed no history of hepatitis and who tested negative for HBsAg with a similar distribution of age, gender,
living habits (type of drinking water and staple food), and living places were invited to participate in the
HBV unexposed sub-cohort upon receiving their signed consent. Exclusion criteria were the same for both
sub-cohorts, including those who had been diagnosed with cancer of any site, or who subsequently died
within the first 12 months after enrollment into the cohort [Figure 2]. The final number of the participants in
HBsAg positive and HBsAg negative sub-cohorts in May 1992 were 852 and 786, respectively. The mean age
of HBsAg-positive participants was 37.06 ± 11.24 years (251 in below 30 years group (group I), 301 in between
30-40 years group (group II), 300 in above 40 years group (group III); while the mean age of HBsAg-negative
participants was 41.20 ± 12.12 years (158 in group I, 237 in group II, 391 in group III). The male to female
ratios in HBsAg-positive group was 5.45:1, and in HBsAg-negative group was 6.08:1.

HOW OFTEN WAS THE FOLLOW-UP?
All participants were followed up at least once every year. From 2009 to 2017, those who were HBsAg
positive and had one of the following conditions: α-fetoprotein (AFP, tested by KHB ELISA Kit) and
alanine aminotransferase (ALT) (tested by dinitrophenylhydrazine method using KHB reagent) higher
than normal value, or abnormal liver ultrasound (GE Healthcare) findings such as liver nodule and liver
cirrhosis, were followed every 6 months. The annual active follow-ups were usually conducted in April and
October, while non-respondents were tracked during the traditional Chinese Lunar New Year to guarantee
a high response rate. Subjects who presented symptoms such as indigestion, jaundice, or discomfort in
hepatic zones were immediately arranged to receive upper abdomen ultrasonic screening and recheck of
serum AFP levels. Each participant continues to have free access to clinics affiliated with the Qidong Liver
Cancer Institute to receive a free physical examination if he/she felt any discomfort or experienced any
indisposed symptoms.

The occurrence of PLC was found not only by the routine active follow-up, but also by annual data linkage
with the Qidong Cancer Registry, a well-maintained population-based cancer registry . For deceased
[9]
individuals, death certificates were requested from the Qidong Death Registry, another population-based
registry in Qidong. Non-responders were regularly contacted by both staff members of the QBC and local
physicians until participants were confirmed to have withdrawn. With such active and passive follow-up,
loss to follow-up only occurred when participants migrated out of Qidong and failed to respond. Since the