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Page 2 of 16 Chen et al. Hepatoma Res 2018;4:72 I http://dx.doi.org/10.20517/2394-5079.2018.103

INTRODUCTION
Hepatocellular carcinoma (HCC) accounts for 80% of all primary liver malignancies. Worldwide, it is the
fifth most common cancer in males, ninth in females, and over half a million of new cases are diagnosed
annually. Asia-Pacific region, East Asia and Sub-Saharan Africa accounts for 82% of all liver cancer cases in
[1]
the world . HCC is the second most common cause of cancer-related deaths in 2012, 1% of all deaths in the
[2]
world can be attributed to HCC every year. The overall survival of HCC was 3%-5% , and mortality to inci-
[3]
dence ratio is 0.95 , suggesting its poor prognosis attributable to the late stage of diagnosis in most of these
cases. An early-stage HCC, on the contrary, is amenable to several curative therapeutic options, and a five-
[4]
year survival of 70%-75% can be achieved . Liver cirrhosis may be due to several risk factors including alco-
hol but chronic hepatitis B or C infections are the most common risk factors of HCC contributing to 70%-
[5,6]
90% of the cases, and nonalcoholic steatohepatitis (NASH) is rapidly gaining prominence .
Several professional societies, including American Association for the Study of Liver Diseases (AASLD), Euro-
pean Association for the Study of the Liver (EASL), Japanese Society of Hepatology and Asian Pacific Associa-
tion for the Study of the Liver, have recommended regular surveillance of HCC in at-risk populations [7-10] . The
goal is to identify HCC at an early stage when it is amenable to curative treatment, therefore reducing mortal-
[6]
ity. Increasing usage of surveillance to detect early HCC is associated with improvement in outcomes . The
[11]
strongest evidence for surveillance is seen in patients with chronic hepatitis B infection . However, whether
surveillance for HCC is truly effective and beneficial is still a topic of debate, owing to the concern of the qual-
ity and paucity of existing evidence. We conducted a systematic review of the literature to better understand the
benefits and disadvantages of HCC surveillance, and the current surveillance modalities.

METHODS
Data sources and searches
A search on the MEDLINE database and Cochrane Database of Systematic Reviews was performed on 19
Jul 2018. Search phrases used were “hepatocellular carcinoma” OR “HCC” OR “Carcinoma, Hepatocellular”
OR “liver cancer” OR “Liver Neoplasms” AND “surveillance” OR “screening” OR “Early Detection of Can-
cer”. We filtered the literature published from January 1 2000 to July 2018 and each literature was manually
screened and selected based on our inclusion and exclusion criteria.

Study selection
All primary studies on HCC surveillance published in English, comprising randomized controlled trials,
cohort studies, case studies and systematic reviews were included. We defined the term “surveillance” as
“repeated use of a test at regular interval over time to detect a previously undiagnosed lesion”. The analysis
was focused on the effect of surveillance on survival and/or mortality of HCC patients, with or without
adjustment for bias. Particular attention was paid to any lead-time bias analysis for survival reporting. Mo-
dalities of HCC surveillance and stages of disease on diagnosis are also included. Exclusion criteria include
studies published in foreign languages, studies on patients with recurrent or metastatic HCC, studies irrelevant
to primary liver cancer, animal or in vitro studies, studies with no mortality/survival data directly comparing
surveillance and non-surveillance group, or cohort studies with a sample size of less than 100 in either group.

Data synthesis and analysis
The data were qualitatively synthesized and summarized on the survival and mortality benefit of HCC sur-
veillance.

RESULTS
The literature search yield 4,557 results in PubMed and 273 in Cochrane Library. We manually screened the
literature from the title and study aims, and full-text articles of all eligible studies were reviewed. All the