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Page 2 of 10 Chen et al. Hepatoma Res 2018;4:4 I http://dx.doi.org/10.20517/2394-5079.2017.50

investigated. QBC will be used to develop dynamic prediction model for PLC risk by using its long-term follow-up information
and serial blood samples. This model is expected to improve the efficiency of PLC screening in HBV infection individuals.

Keywords: Prospective cohort, hepatitis B virus, primary liver cancer

HOW WAS THE STUDY INITIATED?
Qidong City, named Qidong County before 1989, is located on the north shore of the Yangtze River and
has a population of approximately 1.1 million. In the Early 1970s, a population-based retrospective survey
on cancer mortality revealed that the mortality rate ascribed to primary liver cancer (PLC) in Qidong was
49.04/10 , placing PLC as the leading cause of cancer mortality in Qidong. This also exceeded the rates of all
5
[1]
other areas in eastern China . Subsequently, a national population-based incidence survey conducted during
1983 to 1987 showed that the PLC incidence rate in Qidong was 85.1/10 in males and 23.3/10 in females,
5
5
respectively , both being in the top rank across mainland China. “Qidong high incidence area of liver
[2]
cancer” became known worldwide subsequently. Two retrospective cohort studies in Qidong indicated that
[3]
[4]
hepatitis B virus (HBV) was a major risk factor contributing to PLC risk with relative risk of 17.4 and 5.93 .
Other etiological factors had also been suggested to explain the endemic of PLC in Qidong, including dietary
aflatoxin contamination , selenium deficiency , and drinking water polluted by blue green algal toxins .
[5]
[7]
[6]
However, the magnitude of the contribution of each etiologic factor to the endemic of PLC and the role of
potential synergistic interactions among these factors were uncertain. In order to extensively investigate the
relationship between HBV infection and PLC endemic, and collect serial bio-samples of cohort members
which were not available from the previous cohorts in Qidong, investigators from Shanghai Cancer Institute
and Qidong Liver Cancer Institute initiated a prospective cohort study named “Qidong Hepatitis B Virus
Infection Cohort (QBC)” in 1991. Later on, a research team from John Hopkins University joined in the
beginning of 1994. The QBC aimed to recruit participants positive with serum hepatitis B surface antigen
(HBsAg) as the exposure group and those who were HBsAg negative as the non-exposure group, and then
to observe prospectively PLC occurrence as the primary outcome. Bio-samples were collected periodically
for analysis of the kinetic changes of viral and host factors during the natural history of HBV infection.
The study protocol and informed consent were approved by the human subjects review committees at the
Qidong Liver Cancer Institute, Shanghai Cancer Institute and John Hopkins University.

WHAT DOES THE STUDY COVER?
The overarching goal of the QBC was to elucidate the causative factors of PLC and to identify effective
measures to prevent this lethal malignancy. Initially, the QBC focused on understanding the proportion
of HBV infection contributing to the endemic of PLC in Qidong. Later, taking advantage of serial plasma
samples, the QBC was expanded to explore the interactions between HBV and aflatoxin exposure as well
as to probe associations of aflatoxin metabolism or metabolizing enzymes with PLC. Additionally, several
molecular epidemiologic studies were carried out to understand the relationship between HBV variations
and PLC occurrence in order to identify new molecular biomarkers for early detection or prediction of PLC
utilizing stored pre-diagnostic plasma samples. Meanwhile, a bio-specimen bank containing longitudinally
collected blood, urine, liver tissues was established successfully.

WHO WAS IN THE STUDY?
Residents living in the Haidong district of Qidong City, which included 7 towns named “Haifu**”, “Jinhai”,
“Xiangyang”, “Juyang”, “Shaozhi”, “Dongyuan”, and “Hefeng*”, were considered as potential participants
[Figure 1]. In the 1980s-1990s, the total number of residents in each of these towns was approximately 15,000,
representing the PLC endemic population of Qidong . From June 1991 to December 1991, local physicians
[8]
carried out door to door visits, asking questions about medical history of viral hepatitis. Residents aged 20-
65 years who claimed to have a history of acute or chronic hepatitis, or who were HBsAg positive in past