Soroida 2012.

Study characteristics
Patient Sampling	Consecutive HCC patients with cirrhosis caused by hepatitis B virus (HBV) or hepatitis C virus (HCV), who were treated at the Department of Gastroenterology, of the University of Tokyo Hospital, Tokyo, Japan, between January and April 2010, were enrolled (n = 147). Patients with cirrhosis caused by hepatitis B virus (HBV) or hepatitis C virus (HCV), but who did not have HCC (n = 92), were also enrolled. Age range not reported. Males 63%
Patient characteristics and setting
Index tests	Methods for AFP determination were not explained. The cut‐off value was 20 ng/mL.
Target condition and reference standard(s)	Diagnosis of cirrhosis was based on the presence of clinical and laboratory features indicating portal hypertension (the presence of oesophageal varices and/or collateral circulation as observed using an endoscopy, ultrasonography, CT, or MRI). The diagnosis of HCC was made by a dynamic CT or MRI, with hyperattenuation during the arterial phase and washout during the late phase regarded as definite signs of HCC.
Flow and timing	Blood samples were drawn within one month after the diagnosis and prior to the initiation of treatment in HCC patients. In non‐HCC patients, blood samples were obtained within one month since the last surveillance imaging, and the absence of HCC was confirmed at least 6 months after the analysis of blood samples.
Comparative
Notes	No conflicts of interest declared
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Was a case‐control design avoided?	No
Did the study avoid inappropriate exclusions?	Yes
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?			Low concern
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?	Yes
Did all patients receive the same reference standard?	Unclear
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Unclear risk