Price threshold analysis of biomarker surveillance for hepatocellular carcinoma in Australia

Abstract

Aim: Novel biomarker panels may have comparable performance to ultrasound with alpha-fetoprotein (US-AFP) in the surveillance of hepatocellular carcinoma (HCC) among individuals with cirrhosis. We performed an economic modeling study to estimate the threshold price at which biomarker-based surveillance would be cost-effective in the Australian healthcare setting.

Methods: We constructed a Markov model to evaluate three strategies: no surveillance, US-AFP surveillance, and biomarker surveillance based on the recently reported GAAD algorithm (gender, age, AFP and des-γ-carboxy prothrombin). The threshold price of biomarker surveillance was estimated relative to US-AFP, using a willingness-to-pay threshold of A$50,000 per quality-adjusted life year (QALY). The base-case analysis assumed an annual HCC incidence of 2% and 70% adherence to surveillance. Sensitivity analyses were performed to evaluate uncertainty in biomarker performance, HCC incidence, and surveillance adherence.

Results: In the base-case scenario, biomarker surveillance yielded a 0.02 QALY gain compared with US-AFP surveillance and a 0.07 QALY gain compared with no surveillance. Relative to US-AFP, biomarker surveillance was cost-effective if priced at ≤ A$454 and dominant if priced at ≤ A$310. Sensitivity analyses showed that the biomarker threshold price ranged from A$165 (with 50% adherence) to A$838 (with an annual HCC incidence of 5%).

Discussion: Biomarker surveillance is a promising intervention for HCC surveillance in people with cirrhosis. Our results suggest that, in the Australian context, it is likely to be cost-effective - and potentially cost-saving - when compared with the existing standard of US-AFP surveillance.

Keywords

Liver neoplasms / biomarkers / mass screening / cost-effectiveness analysis / cirrhosis

References

[1] Sung H,Siegel RL.Global cancer statistics 2020: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J Clin2021;71:209-49

[2] Hong TP,Fink M.Novel population-based study finding higher than reported hepatocellular carcinoma incidence suggests an updated approach is needed.Hepatology2016;63:1205-12

[3] Huang DQ,Tacke F.Global epidemiology of cirrhosis - aetiology, trends and predictions.Nat Rev Gastroenterol Hepatol2023;20:388-98 PMCID:PMC10043867

[4] Association for the Study of the Liver. EASL clinical practice guidelines: management of hepatocellular carcinoma.J Hepatol2018;69:182-236

[5] Marrero JA,Sirlin CB.Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases.Hepatology2018;68:723-50

[6] Omata M,Kokudo N.Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update.Hepatol Int2017;11:317-70 PMCID:PMC5491694

[7] Lubel JS,Strasser SI.Australian recommendations for the management of hepatocellular carcinoma: a consensus statement.Med J Aust2021;214:475-83

[8] Hong TP,Fink M.Surveillance improves survival of patients with hepatocellular carcinoma: a prospective population-based study.Med J Aust2018;209:348-54

[9] Singal AG,Narasimman M.HCC surveillance improves early detection, curative treatment receipt, and survival in patients with cirrhosis: a meta-analysis.J Hepatol2022;77:128-39 PMCID:PMC9232881

[10] Hui S,Le S.Hepatocellular carcinoma surveillance in Australia: current and future perspectives.Med J Aust2023;219:432-8

[11] Parikh ND,Singal AG.Blood-based biomarkers for hepatocellular carcinoma screening: approaching the end of the ultrasound era?.J Hepatol2023;78:207-16 PMCID:PMC10229257

[12] Liebman HA,Tong MJ.Des-gamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma.N Engl J Med1984;310:1427-31

[13] Taketa K,Sekiya C.A collaborative study for the evaluation of lectin-reactive alpha-fetoproteins in early detection of hepatocellular carcinoma.Cancer Res1993;53:5419-23

[14] Li C,Zhang P.Diagnostic accuracy of des-gamma-carboxy prothrombin versus α-fetoprotein for hepatocellular carcinoma: a systematic review.Hepatol Res2014;44:E11-25

[15] Piratvisuth T,Tanwandee T.Development and clinical validation of a novel algorithmic score (GAAD) for detecting HCC in prospective cohort studies.Hepatol Commun2023;7:e0317 PMCID:PMC10635602

[16] Parikh ND,Hutton DW.Cost-effectiveness of hepatocellular carcinoma surveillance: an assessment of benefits and harms.Am J Gastroenterol2020;115:1642-9 PMCID:PMC7541544

[17] Nguyen ALT,Lubel JS.Hepatocellular carcinoma surveillance based on the Australian Consensus Guidelines: a health economic modelling study.BMC Health Serv Res2023;23:378 PMCID:PMC10116722

[18] Nan Y,Lu X.Early-stage hepatocellular carcinoma screening in patients with chronic hepatitis B in China: a cost-effectiveness analysis.J Comp Eff Res2024;13:e230146 PMCID:PMC11044951

[19] Singal AG,Parikh N.Cost-effectiveness of a biomarker-based screening strategy for hepatocellular carcinoma in patients with cirrhosis.Liver Cancer2024;13:643-54 PMCID:PMC11649260

[20] Husereau D, Drummond M, Petrou S, et al; CHEERS Task Force. Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. BMJ. 2013;346:f1049.

[21] Australian Bureau of Statistics. Provisional Mortality Statistics. Available from: https://www.abs.gov.au/statistics/health/causes-death/provisional-mortality-statistics/latest-release. [Last accessed on 5 Sep 2025].

[22] Department of Health and Aged Care Australian Government. MBS Online. Available from: https://www.mbsonline.gov.au/. [Last accessed on 5 Sep 2025].

[23] Department of Health and Aged Care Australian Government. Pharmaceutical Benefits Scheme (PBS). Available from: https://www.pbs.gov.au/pbs/home. [Last accessed on 5 Sep 2025].

[24] Zhao C,Le RH.Poor adherence to hepatocellular carcinoma surveillance: a systematic review and meta-analysis of a complex issue.Liver Int2018;38:503-14

[25] Low ES,Wong D.Hepatocellular carcinoma surveillance and quantile regression for determinants of underutilisation in at-risk Australian patients.World J Gastrointest Oncol2021;13:2149-60 PMCID:PMC8713329

[26] Hui S,Wang A.Hepatocellular carcinoma surveillance in the telehealth era: a single-centre review.J Telemed Telecare2025;31:64-72

[27] Allard N,Wheeler E.The challenge of liver cancer surveillance in general practice: do recall and reminder systems hold the answer?.Aust Fam Physician2017;46:859-64

[28] Coombs PR,Curry GJ.Sonography in a large Australian public ultrasound service: 10 years of change and innovation.Sonography2024;11:169-76

[29] Carter HE,Ramm GA.Cost-effectiveness of a serum biomarker test for risk-stratified liver ultrasound screening for hepatocellular carcinoma.Value Health2021;24:1454-62