Kim 2019a.

Study characteristics
Patient Sampling	The test set for the validation of the biomarker signatures consisted of 82 patients with very early or early HCC and 80 patients with cirrhosis from an independent study evaluating the metagenomics profiling of HCC between April 2017 and October 2018.
Patient characteristics and setting
Index tests	Serum AFP measurement: no specification. No pre‐definition of the cut‐off value
Target condition and reference standard(s)	HCC was mostly diagnosed based on the noninvasive criteria of an international guideline [1,2]. Cirrhosis was diagnosed based on either histological or clinical findings. Age range and % of males not reported
Flow and timing	No data on interval between index test and reference standard.
Comparative
Notes	The authors declare 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?	Yes
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?	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