El Mahdy 2019.

Study characteristics
Patient Sampling	Three groups: Group I (control): 60 apparently healthy individuals Group II (cirrhosis): 75 patients with liver cirrhosis Group III (HCC): 60 patients with HCC Age range and % of males not reported
Patient characteristics and setting
Index tests	The analysis of serum alpha fetoprotein (AFP) (ng/mL) was done by IMMULITE 1000 system supplied by Siemens kit (SIEMENS Medical Solutions Diagnostics, USA). No pre‐definition of cut‐off value
Target condition and reference standard(s)	All HCC patients were diagnosed by characteristic vascular enhancement pattern detected by multislice triphasic spiral CT scan or MRI according to established diagnostic criteria. Cirrhosis‐control US
Flow and timing	No information on interval between index test and reference standard
Comparative
Notes	Authors declared no conflict 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?	Yes
If a threshold was used, was it pre‐specified?	No
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)
Were the index test results interpreted without knowledge of the results of the reference standard?
If a threshold was used, was it pre‐specified?
Could the conduct or interpretation of the index test have introduced bias?
Are there concerns that the index test, its conduct, or interpretation differ from the review question?
DOMAIN 2: Index Test (US)
Were the index test results interpreted without knowledge of the results of the reference standard?
If a threshold was used, was it pre‐specified?
Could the conduct or interpretation of the index test have introduced bias?
Are there concerns that the index test, its conduct, or interpretation differ from the review question?
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