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Page 10 of 17 Chen et al. Hepatoma Res 2019;5:12 I http://dx.doi.org/10.20517/2394-5079.2019.03

C [21,114] . In an editorial comment in the BMJ [115] , Law points out that screening of unproved value should not
be advocated, and that before any screening for cancer is introduced, large randomized trials with mortality
end points should be conducted to establish and quantify any benefit. Evaluation of mortality of liver cancer
in a screening population is a point of concern. A recent matched case-control study within the American
Veterans Affairs (VA) health care system found that screening patients with cirrhosis for HCC by US or
AFP alone, or both tests was not associated with decreased HCC-related mortality [116] . Some authors thought
that randomized screening trials are bothersome, but there is no second-best option [103,112] ; others illustrated
[40]
that RCTs of screening for HCC is difficult and ethically questionable , is now not ethically feasible in
clinical practice because screening for liver cancer in cirrhotic patients is routine practice for the majority of
clinicians [117] , even if patients show no interest in such a program [118] . In addition, the AFP use in screening
has long been criticized because of its lower sensitivity and specificity than imaging modalities [60,119] . In
the European clinical practice guidelines for HCC, US was seen as the most appropriate test to perform
surveillance, but the combination with AFP is not recommended [108] . A meta analyses showed that AFP
[69]
provided no additional benefit to US , while others concluded that there is not enough evidence to
support or refute the value of AFP or US screening, or both, of HBsAg positive patients for HCC [120] .
More emphatically, early in this century, it has been stated that “the time has come to bid a fond adieu to
[123]
AFP” [121,122] , or it is “the demise of a brilliant star” , as a test for HCC diagnosis and particularly for HCC
surveillance.
Consensus on liver cancer screening
Despite the large debate over liver cancer screening, there is still much consensus on many of the relevant
aspects of screening. For example, it is emphasized that the cancer screened must have DPP, or the cancer
should be detected early by better sensitive and specific methods; moreover, the appropriate effects of the
screening results can be evaluated, and could prolong the survival and may reduce mortality [20,124,125] . Many
guidelines for the management and monitoring of liver cancer have been issued around the world; for
example, they are available in the United States, Europe, and Asia [105-110] . However, evaluation of current liver
cancer screening has not been carried out in a large scale because there is no consensus on the best strategy
for liver cancer screening. On the other hand, it also believed that there is an urgent need to improve the
strategies of screening and monitoring for liver cancer, in order to detect early stage liver cancer and improve
the survival rate of patients [37,57] . The current problem is that, compared to other cancers, the development of
globally accepted guidelines seems to be less relevant due to the existence of regional differences in etiologies
underlyhing the resultant tumor biology as well as the resources available for management of liver cancer [126] .
However, in recent years, research and practice of targeted liver cancer screening, screening methods and
time intervals have become consistent and reached a point of consensus. For example, screening should be
performed in high-risk populations [19,20,22,43,44,72,87,93,108,127] ; chronic hepatitis B is a high-risk population of liver
cancer [128] . The cost effectiveness of screening will be principally related to the sensitivity and specificity
of the surveillance tools, as well as the efficacy of treatment [123] , and surveillance is deemed cost-effective
if the expected HCC risk exceeds 1.5% per year in patients with hepatitis C and 0.2% per year in patients
with hepatitis B [105] ; The screening methods used included AFP and US, with a recommended interval of
6 months [5,19,20,54,55,59,66,75,76,86,108,129-131] . In a two-stage screening intervention in Taiwan, potential cost-
effectiveness compared with opportunistic screening in the target population of an HCC endemic area is
reported [132] .

PROsPeCTs fOR lIveR CANCeR sCReeNINg
Although there is currently no internationally recognized program for the screening for liver cancer,
except for some aspects of the consensus, in the past decades China has experienced many screening
trials [15,19,20,90,93,97,100,102] , which have fully demonstrated the Chinese characteristics (most patients are
HBV-related liver cancer) and the need for the management and control for the one of its most common
malignancies. Professional societies in Western countries had proposed recommendations and guidelines