Qi 2020.

Study characteristics
Patient Sampling	Patients with HCC treated in Gansu Provincial Hospital from 2016 to 2018 were included. The inclusion criteria for patients with HCC were as follows: (a) 18‐85 years old; (b) patients with pathologically‐confirmed HCC; (c) patients meeting the Chinese guidelines Standardization of Diagnosis and Treatment for Hepatocellular Carcinoma (2017 Edition) The exclusion criteria for patients and controls were as follows: (a) participants with missing laboratory detection data; (b) participant with missing clinical and medical history key data; (c) participant with severe haemolysis, microbial contamination or jaundice; (d) participant that did not meet the requirements for sample collection or treatment; and (e) participant withdrawing from the trial based on the medical consideration by investigators patients with non‐viral liver diseases (including autoimmune liver disease, drug‐induced liver injury, and fatty liver) and hepatitis (mainly hepatitis B and hepatitis C) were included in the chronic disease group Age range: 35‐66. Males 80%
Patient characteristics and setting
Index tests	AFP levels were measured in microparticle chemiluminescence instrument (Abbott). No pre‐definition of a cut‐off value
Target condition and reference standard(s)	HCC: Chinese guidelines 'Standardization of Diagnosis and Treatment for Hepatocellular Carcinoma' (2017 Edition): (a) according to CT, MRI or ultrasound results, typical imaging lesions of HCC are seen, and typical blood flow changes occur in the lesions (b) CT, MRI, or ultrasound suggest suspected small nodules, which are confirmed by positron emission tomography (PET) examination Controls: no definition
Flow and timing	No information on interval between index test and reference standard
Comparative
Notes	"The authors have no conflicts of interest to be declared."
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?	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