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Page 8 of 16 Chen et al. Hepatoma Res 2018;4:72 I http://dx.doi.org/10.20517/2394-5079.2018.103

Trevisani et al. [25] , Retro- US + AFP 1988-1998 370 vs. Europe Cirrhosis: 6 months vs. NA Median Curative 41
2002 spec- every 6-12 451 (Italy) all 12 months vs. survival vs. 27
tive months 6 months NS: (months, (P < 0.001)
vs. 12 Non-advanced: lead-time
months vs. 68.7 vs. 60.4 corrected):
NS vs. 31 30 vs. 14
HBV: 13.6 Advanced: 31.3
vs. 20.4 vs. vs. 39.6 vs. 69 3-year: 48
20.5 vs. 23
HCV: 66.6
vs. 62.5 vs.
55.9
Alcohol: 8.5
vs. 7.2 vs.
13.8
Chen et al. [76] , Retro- Clinical mar- 1991- 1998 4385 vs. Asia (Tai- Cirrhosis: 7 NA HR: 0.76 NA NA
f
2002 spec- kers + US 458 wan) vs. un- (0.38-1.52)
tive known
HBV: 65.9
vs. 67.0
HCV: 18.2
vs. 14.9
Yuen et al. [60] , Retro- AFP +/- US 1995-1997 142 vs. Asia (HK) Cirrhosis: Tumor < 3 cm: NA Median Curative
2000 spec- 164 85.2 vs. 40.1 vs. 4.9 survival resection:
tive 68.9 Tumor < 5 cm: (months): 26.8 vs. 7.9
(P = 61.3 vs. 11.6 22 vs. 5 (P < 0.001)
0.0013) Multifocal: TACE: 45.1
32.4 vs. 50 vs. 32.3
PV invasion: (P = 0.03)
9.2 vs. 38.4
(P < 0.001)
a
Tumor stages per Liver cancer study group of Japan guidelines, based on: (1) tumor diameter ≤ 20 mm; (2) single tumor; (3) no vascular
b
invasion; tumors that met three, two, one or none of the conditions were classified as stage I, II, III, or IV respectively; Hazard ratio in
c
routine surveillance (≥ 1 US surveillance annually) vs. inconsistent surveillance compared to no surveillance; comparison groups: routine
d
surveillance vs. inconsistent surveillance vs. no surveillance; comparison groups: surveillance 1-6 months vs. 7-12 months vs. 13-24
e
months vs. 25-36 months vs. never screened; comparison groups: HCC diagnosed from surveillance 6-12 months vs. incidental diagnosis
f
vs. symptomatic diagnosis; 6 markers: (1) positive hepatitis B surface antigen (HbsAg); (2) positive antibody for hepatitis C (anti-HCV);
(3) alpha-fetoprotein (AFP) ≥ 20 ng/mL; (4) aspartate transaminase (AST) ≥ 40 IU/L; (5) alanine transaminase (ALT) ≥ 45 IU/L; and (6)
family history of HCC. Adj HR: adjusted hazard ratio; BCLC: Barcelona Clinic Liver Cancer staging; CEUS: contrast-enhanced ultrasound;
CT: computed tomography; DCP: des-gamma-carboxyprothrombin; dx: diagnosis; HBV: hepatitis B virus; HCC: hepatocellular carcinoma;
HCV: hepatitic C virus; HK: Hong Kong; HR: hazard ratio; NA: not available; LTx: liver transplant; OR: odds ratio; RFA: radiofrequency
ablation; PEI: percutaneous ethanol injection; S: surveillance group; NS: no surveillance group; TACE: transarterial chemoembolization;
TNM: tumor, node, metastasis staging system of the American Joint Committee on Cancer; Tx: treatment; Unadj: unadjusted; US:
ultrasound
[16]
ficulty of conducting RCTs on HCC surveillance among cirrhotic patients. Hence, Taylor et al. used the
Markov model to simulate a HCC surveillance program on cirrhotic patients, and to study the benefit and
harm of surveillance. A small absolute mortality benefit was found in the HCC surveillance group, with a
number needed to screen of 77. After a focal lesion was identified, further investigations were carried out
based on EASL-EORTC (European Association for the Study of the Liver and the European Organization
[17]
for Research and Treatment of Cancer) recall policy . However, many more patients experienced additional
unnecessary imaging or biopsy due to false positive results, with a number needed to harm of 7 only [Table 1].

Cohort studies
There are a large number of cohort studies on the efficacy of HCC surveillance in our literature search over
the past 20 years. We included twenty-four retrospective cohort studies that compared survival and/or mor-
tality of surveillance-detected HCC to incidentally diagnosed HCC [Table 2]. In general, the patients in the
surveillance group have chronic viral hepatitis [hepatitis B virus (HBV) and hepatitis C virus (HCV)] infec-
tion or cirrhosis of any etiology [Table 2].

Patients in the surveillance group had earlier stages of HCC at diagnosis: 22.8%-80.3% of surveillance group
patients had Barcelona Clinic Liver Cancer staging (BCLC) stage 0/A disease. Not surprisingly, more patients
in the surveillance compared to non-surveillance group underwent curative HCC treatment [surgical resec-