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Page 6 of 10 Yilmaz et al. Hepatoma Res 2018;4:46 I http://dx.doi.org/10.20517/2394-5079.2018.49

Table 2. Recommendations for non-cirrhotic adults
Continent Time interval
Guidelines Target population Modality
(months)
North America AASLD-2017 No recommendation for surveillance of non-cirrhotics at this time
AASLD-2010 HBV carriers: US 6
- Asian female > 50 years
- Asian male > 40 years
- Family history of HCC
- African/North American Blacks
CASL-2014 Same as AASLD-2010 US 6
Asia APASL-2017 Non-cirrhotic (HBsAg positive): US and AFP 6
- Asian females > 50 years
- Asian males > 40 years
- Africans aged > 20 years
- History of HCC in the family
CHINESE-2017 Chronic liver diseases of any etiology US and AFP 6
JSH-2015 and JSH- High risk patients (chronic hepatitis B or C) US and three tumor 6
LCSG-2014 markers AFP/PIVKA-
II/AFP-L3
Europe EASL-2018 Non-cirrhotic HBV patients at intermediate or high risk of US 6
HCC*
Non-cirrhotic F3 patients regardless of etiology**
SPANISH-2016 (AEEH, No recommendation for surveillance of non-cirrhotics at this time
SEOM, SERAM, SERVEI
and SETH)
SEOM-2015 High-risk HBV chronic hepatitis patients (higher viral load, US 6
viral genotype or Asian or African ancestry)
Non-cirrhotic patients with chronic hepatitis C and
advanced fibrosis (F3)
ESMO-ESDO-2012 Non-cirrhotic HBV carriers with high viral load (> 10,000 US 6
copy/mL)
Non-cirrhotic patients with chronic hepatitis C and
advanced fibrosis (F3)
*According to PAGE-B classes for Caucasian subjects, intermediate or high risk of HCC (10-17 and ≥ 18 score points, respectively;
**considered for surveillance based on an individual risk assessment. HCC: hepatocellular carcinoma; F3: bridging fibrosis; HBV: hepatitis
B virus; AFP: alpha-fetoprotein; US: ultrasound

REMARKS FROM GUIDELINES & COMMENTS
All three continents propose a 6-month screening interval using ultrasonography with or without AFP, re-
gardless of cirrhosis, except Japan. Japanese guidelines suggest a shorter interval (3-4 months) for extremely
high-risk cirrhotic patients, the three tumour markers (AFP/PIVKA-II, /AFP-L3) along with ultrasound and
EOB-MRI with 6-12 months interval, or dynamic CT.

Based on the tumour doubling time (range 29 to 398 days), the 6-month interval represents a reasonable
[43]
[42]
choice , since shorter interval detects more small lesions, but does not improve detection of small HCC .
The incidence of HCC in the target population and available facilities may affect the screening interval.
However, there is still a question about optimal interval for screening ranging from 4 to 8 months [2,26,30] .

Sensitivity of ultra-sonogram is ranging from 58% to 89% with specificity greater than 90% when used as a
screening test before they presented clinically, other than that it seems to be less effective for detecting early-
stage HCC (sensitivity of only 63%) [2,26,44,45] .

AFP is not recommended along with ultrasound in North America and Europe because the present studies
were not directed to determine an improvement in survival. AFP is usually elevated in cirrhosis intermit-
tently, but markedly elevation in small tumour is rare [2,16,26,30] . Therefore, APASL suggests cut-off value (set at
200 ng/mL) of AFP for screening programs when used in combination with US. Combined with US, AFP
provides additional detection in 6%-8% of cases not previously identified by US, confirmed more recently [2,46] .

Serological tests that are under investigation for early diagnosis of HCC include (PIVKA II) AFP-L3, alpha-
fucosidase, and glypican. These markers have been tested mostly for diagnosis and prognosis, but need to be