Takikawa 1992.

Study characteristics
Patient Sampling	628 patients who were admitted to Iwate Medical University Hospital or its affiliated hospitals served as the study population. It included 116 patients with HCC (104 with and 12 without liver cirrhosis), 9 with cholangiocellular carcinoma, 18 with metastatic liver cancer, 29 with acute hepatitis, 128 with chronic hepatitis, 253 with liver cirrhosis without HCC, 6 with primary biliary cirrhosis, 2 with focal nodular hyperplasia of the liver, 6 with hepatic haemangioma, 1 with liver abscess, 20 with fatty liver, 22 with extrahepatic malignancies, 13 with disseminated intravascular coagulation syndrome, and 5 asymptomatic carriers of hepatitis B virus. Age range and % males not reported
Patient characteristics and setting
Index tests	AFP: serum levels of AFP were measured by a latex immuno‐agglutination assay kit (LA‐AFP'Eiken', Eiken chemical Co., Tokyo). Cut‐off values were prespecified at 20, 100, 200, and 400 ng/mL. Alpha‐foetoprotein had the highest validity, at the cut‐off value of 100 ng/mL.
Target condition and reference standard(s)	HCC: the diagnosis of HCC was made histologically in 53 patients, and in others by typical findings of imaging methods including ultrasonography, computerized tomography, and angiography. Control group: patients with cirrhosis were followed for at least 6 months from the study in order to exclude coexistent HCC.
Flow and timing	No information on interval between index test and reference standard
Comparative
Notes	No information on 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?	Unclear
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?	No
If a threshold was used, was it pre‐specified?	Yes
Could the conduct or interpretation of the index test have introduced bias?		High 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?	No
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		High risk