Comparison of a multitarget blood test to ultrasound and alpha‐fetoprotein for hepatocellular carcinoma surveillance: Results of a network meta‐analysis

Ultrasound‐based surveillance has suboptimal sensitivity for early detection of hepatocellular carcinoma (HCC) in patients with cirrhosis. There are several emerging alternatives, including a novel multitarget HCC blood test (Mt‐HBT). We compared performance of mt‐HBT against ultrasound with or without alpha‐fetoprotein (AFP) for early HCC detection in patients with cirrhosis. Per the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) guidelines, two reviewers searched PubMed, Cochrane, Embase, and clinicaltrials.gov databases from January 1990 through December 2020 to identify studies reporting sensitivity and/or specificity of ultrasound and AFP for overall and early stage HCC detection in patients with cirrhosis. Mt‐HBT diagnostic performance was derived from a clinical validation study. A network meta‐analysis model was built for comparative assessment, and pooled estimates of sensitivity at a fixed specificity were estimated based on Bayesian binormal receiver operating characteristic models for each modality. Forty‐one studies (comprising 62,517 patients with cirrhosis) met inclusion criteria. Ultrasound‐alone sensitivity was 51.6% (95% credible interval [CrI], 43.3%–60.5%) for early stage HCC detection, which increased with the addition of AFP to 74.1% (95% CrI, 62.6%–82.4%); however, this was offset by decreased specificity (87.9% vs. 83.9%, respectively). With specificity fixed at 90%, mt‐HBT sensitivity for early stage HCC detection was higher than ultrasound alone (18.2%; 95% CrI, 0.2%–37.7%) and similar to ultrasound with AFP (−3.3%; 95% CrI, −22.3%–17.4%). Pairwise posterior probabilities suggested a preference for mt‐HBT over ultrasound alone in 97.4% of cases but only 36.3% of cases versus ultrasound with AFP. Conclusion: A blood‐based mt‐HBT has higher sensitivity than ultrasound alone for early stage HCC detection but similar sensitivity compared to ultrasound and AFP. Mt‐HBT could be a comparable alternative to existing methods for HCC surveillance in patients who are at risk.