Li 2016a.

Study characteristics
Patient Sampling	In this retrospective study, 95 patients with chronic hepatitis B who were diagnosed with a small HCC (≤ 2 cm) or a cirrhotic nodule between July 2014 and September 2015 were involved. The patient inclusion criteria were as follows: (1) ElastPQ measurements were performed on lesion and background liver, (2) lesion nature was confirmed by pathology or at least 2 of the three contrast‐enhanced imaging modalities (CEUS, CECT, or CEMRI), and (3) the cirrhotic nodule had follow‐up for more than 6 months with no malignancy changes observed in physical examinations. Age range: 38‐61. Males 87%
Patient characteristics and setting
Index tests	AFP: threshold pre‐specified: cut‐off ≤ 20 ng/mL
Target condition and reference standard(s)	In the small HCC group, 53 patients were included, with 26 patients confirmed by pathology and 27 patients confirmed by at least 2 of the 3 contrast enhanced imaging modalities (CEUS, CECT, CEMRI). Case‐control study
Flow and timing	Reference standard: pathology, contrast‐enhanced ultrasound, contrast‐enhanced CT, contrast‐enhanced MRI No data on interval between index test and reference standard
Comparative
Notes	The authors declared no 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?	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?	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