Summary of findings 2. 'Summary of findings' table: direct comparison of US, and combination of AFP and US.

Review question: what is the diagnostic accuracy of the combination of alpha‐foetoprotein (AFP) and abdominal ultrasound (US) compared to US for the diagnosis of hepatocellular carcinoma (HCC) in adults with chronic liver disease?
Population: adults with chronic liver disease
Setting: clinical setting (secondary or tertiary care setting) or surveillance programs
Study design: prospective and retrospective cross‐sectional studies
Index tests:abdominal ultrasound; combination of serum alpha‐foetoprotein (AFP) measurement with a cut‐off value of 20 ng/mL and abdominal ultrasound
Target condition: HCC of any size, any stage
Reference standards:the pathology of the explanted liver in case of transplantation;the histology of resected focal liver lesion(s), or the histology of resected or biopsied focal liver lesion(s) with a follow‐up period of at least six months to exclude the presence of focal lesions non detected by the index test and synchronous lesions from the parenchyma surrounding the resected or biopsied area;typical characteristics on cross‐sectional multiphasic contrast CT or MRI, with a follow‐up period of at least six months in order to allow the confirmation of an initial negative result on computer tomography (CT) or on magnetic resonance imaging (MRI).
Limitations in the evidence Risk of bias/ Applicability ‐ Participant selection: high/unclear risk of bias in 2 studies (33%)/ high concern 2 studies (33%) ‐ Index tests: high/unclear risk of bias in 2 studies (33%)/ high concern no study ‐ Reference standard: high/unclear risk of bias in 4 studies (67%)/ high concern 1 study (17%) ‐ Flow and timing: high risk of bias in 6 studies (100%)
Findings
						Implications in a hypothetical cohort of 1000 people
Index test	Number of studies (participants)	Sensitivity (95% CI)	Relative sensitivity (95% CI) P value	Specificity (95% CI)	Relative specificity (95% CI) P value	Assumed prevalence of hepatocellular carcinoma (HCC)a %	True positives will receive appropriately further necessary testing with CT or MRI, or contrast enhanced ultrasound (CEUS) and possibly treatment .	False negatives will be misdiagnosed and not receive appropriate treatment.	True negatives will not appropriately undergo unnecessary further testing with CT, MRI, CEUS, biopsy	False positives will inappropriately undergo further unnecessary testing with CT, MRI, CEUS biopsy.	Certainty of the evidence
US	6 (5044)	76% (56% to 89%)	1.28 (1.03 to 1.539 P = 0.014	93% (80% to 96%)	0.94, (0.87 to 1.01) P = 0.102	5%	38	12	883	67	lowb ⨁⨁◯◯
						30%	228	72	651	49
Combination of AFP (cut‐off 20 ng/mL) and US		96% (88% to 98%)		85% (73% to 82%)		5%	48	2	807	143
						30%	288	12	595	105

^a We chose for exemplification two values of HCC prevalence: 5% for a population at low risk (compensated advanced chronic liver disease and chronic viral hepatitis) Lok 2009 and 30% for a population with high risk, a median of the prevalence in the included cross‐sectional studies conducted in clinical cohorts.

^bDowngraded by two levels: risk of bias, indirectness. Risk of bias downgraded one level because all studies were judged at high risk of bias; indirectness downgraded one level as we considered most studies to have concern regarding applicability mainly in relation to the population (including disease spectrum)

GRADE certainty of the evidence

High: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

The results presented in this table should not be interpreted in isolation from results of the individual included studies contributing to each summary test accuracy measure.