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Page 2 of 17 Chen et al. Hepatoma Res 2019;5:12 I http://dx.doi.org/10.20517/2394-5079.2019.03

this disease. Based upon the Chinese Cancer Registry Annual Report 2016, the incidence and mortality rates
of liver cancer were 28.17 and 24.70 per 100,000, respectively, thereby contributing to total incident cases of
[2]
394 thousand, and total death cases of 346 thousand a year in mainland China . Liver cancer has long been
a public health challenge in China. While improvements in therapies for this cancer have been developed
[3-6]
widely, and have achieved some progress in the past decades , the overall survival from liver cancer
[5-7]
remains unsatisfactory . This outcome is because the choice of treatment is driven by the cancer stage,
[5]
the resources available, and the level of practitioner expertise . Liver cancer often has no obvious clinical
symptoms and signs in its early stages, and the tumor lumps grow quietly and rapidly. Most patients have
been detected only in an advanced stage, resulting in limited treatment options and a very poor prognosis. A
United States population-based study, for instance, reported that, in 2963 HCC patients diagnosed between
[8]
1992 and 1999, only 13% of the patients received a potentially curative therapy .

Recent survival rate data show that the 5-year survival rates of liver cancer from population-based cancer
[9]
registries in China were around 9.8%-12.1% , and that the 5-year survival rate of liver cancer from a
[7]
hospital-based cancer registry was 11.69% . Furthermore, the 5-year survival rate from clinical series of
data was 4.8% in 1958-1970, 11.2% in 1971-1982, and 45.4% in 1983-1994 for patients who received surgical
[11]
[10]
resection ; and 63.8% for patients who had resection of small liver cancer . The 5-year relative survival
rates for liver cancer during 2002-2012 in Taiwan were 52.0% for stage I, 2.9% for stage IV and 28.9% for
[12]
all stages . A recent Australia report based on cancer registration shows that the 5-year survival was 5%
[13]
during the years 1984-1993, and 16% during 2004-2013 . A current multicenter retrospective investigation
shows that the overall survival is 19.6%, and is derived from 18,275 liver resection patients with HCC in
[14]
China .
[11]
The fact that small or early stage liver cancer had better outcomes for survival has long been recognized ,
and attracted great efforts for the early detection of liver cancer by mass screening in the general population
since the 1970s. In the Qidong area, for instance, population-based mass screening programs were first
applied to field practice [15,16] when alpha-fetoprotein (AFP) was established to be synthesized in cancer of the
liver, and had been proven to be a serological test for this cancer [17,18] .

In the past 4 to 5 decades, the application value of AFP and the screening benefit for early detection has
demonstrated the mixed results [15-23] . So far, there is no internationally recognized program of screening
for the cancer of the liver, nor has a scientific consensus been formed in the academic world. Yet, case
reports and research reports have provided evidence that screening is an effective way to achieve early
detection, early diagnosis and opportunity for early treatment for liver cancer. Screening may have positive
and important significance to improving prognosis and reducing mortality, especially in epidemic areas
of hepatitis B/liver cancer. Here we describe and review the practice of the screening for liver cancer and
discuss the problems arising from this approach.

DIsCOveRy Of AfP AND ITs ClINICAl APPlICATION
After Bergstrandh and Czan discovered alpha-fetoprotein (AFP) in human fetal serum in the 1950s,
former Soviet scholar Abelev discovered that AFP was mainly synthesized from placenta and yolk sac, and
correspondingly AFP could be detected in both human and mammalian embryo serum [17,18] . AFP begins to
be synthesized at 6 weeks of gestation and peaks at 12-15 weeks (AFP in fetal plasma can reach 3 μg/L). After
birth, AFP synthesis is inhibited (content reduced to 50 μg/L); at the end of 12 months, the concentration
[24]
is close to the adult level. Plasma AFP concentration in healthy adults is lower than 20 μg/L . However,
AFP would be re-expressed when hepatocytes become cancerous or have severe injury or other forms of
[26]
diseases [17,25] . Human hepatic stem cells (hHpSCs) are currently considered to express AFP .

[27]
The probable association of AFP with liver diseases and liver cancer was noted in the 1960s. Tatarinov et al.
[28]
and O’Conor et al. found that AFP was detected in the serum of patients with liver cancer; and a human