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Chen et al. Hepatoma Res 2018;4:72 I http://dx.doi.org/10.20517/2394-5079.2018.103 Page 9 of 16

tion, radiofrequency ablation (RFA)/percutaneous ethanol injection, liver transplant]. Among the reported
[18]
studies, up to 53.5% of patients in the surveillance group underwent surgical resection , 53% received liver
[20]
[19]
transplant , 49.1% received RFA . The reported median survival in the surveillance group differs among
[21]
the studies. Singal et al. reported 14.6 months median survival in patients whose HCC was detected from
surveillance imaging [computed tomography (CT)/magnetic resonance imaging (MRI)/contrast-enhanced
[20]
ultrasound/ultrasound (US)] within 6 months of HCC diagnosis; while Oeda et al. reported 56.5 months
of median survival (corrected with lead-time) in the Japanese population, where high-risk cirrhosis patients
were screened every 3-4 months with US and serum biomarkers [AFP/AFP-L3/des-gamma-carboxyprot-
hrombin (DCP)] based on Japanese society of Hepatology practice guidelines. Most of these cohort studies
carry selection bias (specialist centre referrals), lead-time and length-time bias inherent to the study design.
Several studies attempted to correct for the lead-time bias in survival time reporting, based on HCC dou-
bling time (90-120 days) [21,23-26] . Overall, the data from cohort studies demonstrated that HCC surveillance
was associated with early-stage tumor detection and curative treatments. Improved overall survival was
evidenced in the surveillance group as well. Thus, the benefits of surveillance included early diagnosis, more
treatment options, and prolonged survival compared to no surveillance [Table 2].

Several prospective cohort studies were conducted to investigate the benefit of HCC surveillance in at-risk
[26]
populations. Two studies examined surveillance in chronic hepatitis B patients. McMahon et al. con-
ducted a population-based prospective study for 16 years on Alaska natives with chronic hepatitis B patients.
Surveillance modality was 6-monthly AFP. Surveillance detected more early resectable HCC and accorded
[27]
significantly longer survival. A study in Thailand by Ungtrakul et al. recruited 2,293 chronic hepatitis B
patients and surveillance was carried out with 6-monthly AFP and ultrasound. A high 3-year survival of
90% was observed as most patients were able to receive curative treatments. A Taiwanese group evaluated
a community-based HCC surveillance program with abdominal ultrasound. Subjects were selected from a
risk score. Mortality in the surveillance group was reduced compared to the control group and the general
[28]
population . Overall, evidence supports HCC surveillance in at-risk populations because it detects smaller
tumors that are amenable to curative treatment [Table 2].

Harm of surveillance
[16]
The study by Taylor et al. simulated HCC surveillance in cirrhotic patients based on EASL-EORTC recall
policy [Table 1]. It showed more patients experienced unnecessary biopsy or imaging due to false positive
screening results, and the calculated number needed to harm was only 7 compared to a small mortality
benefit. Few cohort studies mentioned the harm of HCC surveillance. One retrospective cohort study by
[29]
Atiq et al. aimed to characterize the correlation of harm and benefits in cirrhosis patients undergoing
HCC surveillance. Surveillance-related harm was defined as additional scans, biopsies, or procedures per-
formed for false-positive or indeterminate results. Around one quarter (27.5%) of the patients experienced
harm, and it was more often related to ultrasound than AFP. This was associated with hepatology subspe-
cialty care, elevated ALT, and portal hypertension with thrombocytopenia. However, psychological harm
and financial harm were not evaluated in this study.

Surveillance modalities
Cancer surveillance tools should be accurate and cost-effective, and able to detect tumor at a stage that cure
is possible. HCC usually develops in populations with defined risk factors. Cirrhosis is the major risk fac-
tor of HCC development, with an annual incidence of 1.5%, which makes HCC a good target for surveil-
lance [30,31] . At present, ultrasound and serum AFP are widely accepted as the primary surveillance tools for
HCC. Here we reviewed the current evidence of HCC surveillance tools.

Imaging
The recommended surveillance modality differs slightly in different parts of the world, but the majority rec-
[32]
ommends ultrasound imaging with or without serum AFP .