Phase 3 Validation of PAaM for Hepatocellular Carcinoma Risk Stratification in Cirrhosis

Authors

Naoto Fujiwara
Camden Lopez
Tracey L Marsh
Indu Raman
Cesia A Marquez
Subhojit Paul
Sumit K Mishra
Naoto Kubota
Courtney Katz
Hiroaki Kanzaki
Michael Gonzalez
Lisa Quirk
Sneha Deodhar
Pratibha Selvakumar
Prithvi Raj
Neehar D Parikh
Lewis R Roberts
Myron E Schwartz
Mindie H Nguyen
Alex S Befeler
Stephanie Page-Lester
Sudhir Srivastava
Ziding Feng
K Rajender Reddy
Saira Khaderi
Sumeet K Asrani
Fasiha Kanwal
Hashem B El-Serag
Jorge A Marrero
Amit G Singal
Yujin Hoshida

Language

English

Publication Date

3-1-2025

Journal

Gastroenterology

DOI

10.1053/j.gastro.2024.10.035

PMID

39521255

PMCID

PMC7617545

PubMedCentral® Posted Date

9-1-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Background & aims: Hepatocellular carcinoma (HCC) risk stratification is an urgent unmet need for cost-effective HCC screening and early detection in patients with cirrhosis to improve poor HCC prognosis.

Methods: Molecular (prognostic liver secretome signature with α-fetoprotein) and clinical (aMAP [age, male sex, albumin-bilirubin, and platelets] score) variable-based scores were integrated into PAaM (prognostic liver secretome signature with α-fetoprotein plus age, male sex, albumin-bilirubin, and platelets), which was subsequently validated in 2 phase 3 biomarker validation studies: the statewide Texas HCC Consortium and nationwide HCC Early Detection Strategy prospective cohorts, following the prospective specimen collection, retrospective blinded evaluation design. The associations between baseline PAaM and incident HCC were assessed using Fine-Gray regression, with overall death and liver transplantation as competing events.

Results: Of 2156 patients with cirrhosis in the Texas HCC Consortium, PAaM identified 404 (19%) high-risk, 903 (42%) intermediate-risk, and 849 (39%) low-risk patients with annual HCC incidence rates of 5.3%, 2.7%, and 0.6%, respectively. Compared with low-risk patients, high- and intermediate-risk groups had sub-distribution hazard ratios for incident HCC of 7.51 (95% CI, 4.42-12.8) and 4.20 (95% CI, 2.52-7.01), respectively. Of 1328 patients with cirrhosis in the HCC early detection strategy, PAaM identified 201 high-risk (15%), 540 intermediate-risk (41%), and 587 low-risk (44%) patients, with annual HCC incidence rates of 6.2%, 1.8%, and 0.8%, respectively. High- and intermediate-risk groups were associated with sub-distribution hazard ratios for incident HCC of 6.54 (95% CI, 3.85-11.1) and 1.77 (95% CI, 1.02-3.08), respectively. Subgroup analysis showed robust risk stratification across HCC etiologies, including metabolic dysfunction-associated steatotic liver disease and cured hepatitis C infection.

Conclusions: PAaM enables accurate HCC risk stratification in patients with cirrhosis from contemporary etiologies.

Keywords

Humans, Carcinoma, Hepatocellular, Liver Neoplasms, Male, Female, Liver Cirrhosis, Middle Aged, Risk Assessment, Aged, Biomarkers, Tumor, Early Detection of Cancer, alpha-Fetoproteins, Risk Factors, Incidence, Texas, Prospective Studies, Retrospective Studies, Bilirubin, Prognosis, Predictive Value of Tests, Platelet Count, Reproducibility of Results, Serum Albumin, Hepatocellular Carcinoma, Cirrhosis, Biomarker, Risk Stratification

Published Open-Access

yes

Recommended Citation

Fujiwara, Naoto; Lopez, Camden; Marsh, Tracey L; et al., "Phase 3 Validation of PAaM for Hepatocellular Carcinoma Risk Stratification in Cirrhosis" (2025). Faculty and Staff Publications. 4438.
https://digitalcommons.library.tmc.edu/baylor_docs/4438