Wong 2008.

Study characteristics
Patient Sampling	"All patients referred from different hospitals and clinics to the Joint Hepatoma Clinic of the Chinese University of Hong Kong, which is a tertiary centre for the management of suspected or confirmed liver tumours, between January 2003 and June 2005 were retrospectively studied. Nine hundred and eighty‐two patients visited the Joint Hepatoma Clinic during the study period. Five hundred and seventy‐nine patients were included in the analysis after excluding patients who had non viral hepatitis related disease (n = 168), had missed records (n = 79), had pre‐existing HCC (n = 30), had no USG (n = 119) and no AFP test (n = 7). Patients having chronic liver diseases caused by other aetiologies including alcoholic liver disease, autoimmune liver disease and primary biliary cirrhosis were excluded from the analysis." Age range: 46‐70. Males 83%
Patient characteristics and setting
Index tests	Patients with elevated AFP levels (defined as > 20 ng/mL) and/or with suspicious lesions (any space occupying lesion) on USG were referred to the Joint Hepatoma Clinic for further investigation.
Target condition and reference standard(s)	All patients were assessed with same‐day US and AFP testing in the clinic within 2 weeks of referral. HCC was confirmed by histologic evidence of HCC from liver biopsy, typical appearance of tumour in a triphasic computerised tomography (CT) scan, characteristic lipoidal uptake in CT and/or neovascularisation and arterio‐venous shunting in hepatic arteriography.
Flow and timing	No information on interval between index test and reference standard
Comparative
Notes	Conflict of interest: no conflicts of interest exist.
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?	Yes
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?	Yes
If a threshold was used, was it pre‐specified?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Low 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)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	No
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?		High 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