Cui 2003.

Study characteristics
Patient Sampling	Serum PIVKAII and AFP levels and GGTII activity were determined in 90 patients with cirrhosis and 120 patients with HCC. Patients with vitamin K and antibiotic use in the recent 3 months, with a haemoglobin levels under 490 mg dL and free bilirubin concentrations up to 27 mg dLor conjugated bilirubin concentrations up to 22 mg dL were excluded from this study. Age range: 32‐84. Males 70%
Patient characteristics and setting
Index tests	The serum concentration of AFP was determined by electrochemiluminescence immunoassay (Roche, Elecsys 1010/2010 Systems) according to the manufacturer’s instructions. The cut‐off level was fixed at 20 ng/mL.
Target condition and reference standard(s)	In all, 58% (70 out of 120) of HCC patients were diagnosed by fine needle biopsy under the guidance of ultrasonography, and in 16% (19), the diagnosis was confirmed after surgery. Ultrasonography, CT, MRI, and selective celiac angiography diagnosed the remaining patients (26%, 31 out of 120). In patients with cirrhosis, HCC was ruled out on the basis of imaging examinations including sonography and CT)performed on a regular basis. Also, patients with cirrhosis who developed HCC within 1 year from getting serum were excluded.
Flow and timing	No information on interval between index test and reference standard
Comparative
Notes	No information on funding or conflicts of interest
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	No
Did the study avoid inappropriate exclusions?	No
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (AFP)
Were the index test results interpreted without knowledge of the results of the reference standard?	Unclear
If a threshold was used, was it pre‐specified?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Unclear risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 2: Index Test (US+AFP)
DOMAIN 2: Index Test (US)
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Unclear
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Unclear risk