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

Abstract

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.

FIGURE 1

Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) schematic flow diagram. HCC, hepatocellular carcinoma; SLR‐MA, systematic literature review and meta‐analysis.

FIGURE 2

Pooled estimates of sensitivity at 90% fixed‐target specificity for each modality and comparisons to mt‐HBT in any stage HCC and early stage HCC surveillance. Data show 95% CrI in black and 95% predictive intervals in red. AFP, alpha‐fetoprotein; CrI, credible interval; HCC, hepatocellular carcinoma; mt‐HBT, multitarget hepatocellular carcinoma blood test; Post PR, posterior probability; SUCRA, surface under cumulative ranking curve; US, ultrasound; US+AFP, ultrasound plus alpha‐fetoprotein.

FIGURE 3

Pareto frontier (sensitivity vs. specificity) for pooled observed operation of each modality in any and early stage HCC. AFP, alpha‐fetoprotein; HCC, hepatocellular carcinoma; mt‐HBT, multitarget hepatocellular carcinoma blood test; US, ultrasound; US+AFP, ultrasound plus alpha‐fetoprotein.