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 clini caltr ials.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.

Hepatocellular carcinoma surveillance in patients with non-alcoholic fatty liver disease

“…Notably, early-stage sensitivity was stable across subgroups, including sensitivities of 85% and 77% in patients with BMI values <30 kg/m 2 and those with BMI ≥30 kg/m 2 , respectively as well as across all examined liver disease etiologies, making mt-HBT a potentially valuable tool for surveillance in patients with NAFLD. A recent network meta-analysis suggested similar efficacy of mt-HBT compared to ultrasound and AFP for early-stage HCC detection [ 69 ], although the authors noted the strength of data differed for the two modalities. In another multicenter validation study HelioLiver Test, another ct-DNA biomarker panel, yielded a sensitivity of 76% (95% CI, 60–87%) for early-stage HCC, significantly higher than AFP and GALAD [ 70 ].…”

Should we undertake surveillance for HCC in patients with MAFLD?

“…Sensitivity of ultrasound for early stage HCC detection was reported to be at 51.6%, and it increased to 74% with the addition of AFP; however, this was offset by decreased specificity (87.9% vs 83.9%, respectively). 57 The quality of liver ultrasound is dependent on the expertise of the performer and is affected by characteristics of the patients. Reviewing the quality of ultrasound exams of 941 patients with cirrhosis, Simmons et al 58 found that in 20% of the cases, the quality was inadequate to exclude HCC.…”

Risk stratification and early detection biomarkers for precision HCC screening

“…Ultrasound is currently the standard screening test used in clinical practice, although its sensitivity is only about 50%. [15] Even combined with AFP, sensitivity is still approximately 70% to detect early-stage HCC. [15] In addition, this performance may be overestimation due to inclusion of Phase 2 biomarker studies in the metaanalysis.…”

“…[15] Even combined with AFP, sensitivity is still approximately 70% to detect early-stage HCC. [15] In addition, this performance may be overestimation due to inclusion of Phase 2 biomarker studies in the metaanalysis. Performance of ultrasound will be further impaired due to the increase of obese patients with NAFLD.…”

“…Furthermore, application of the screening has been more challenging along with the drastic changes in the HCC etiology landscape over the past decade, namely the sharp decline of active HCV infection with the widespread use of new‐generation anti‐HCV drugs and global epidemic of obesity and metabolic disorders 12,13. In addition, sensitivity of the current HCC screening test is suboptimal, and it leads to failures in early HCC diagnosis 14,15. Thus, new tools and strategies are urgently needed to enable more effective HCC screening with improved use and early HCC detection to substantially improve poor HCC mortality.…”