aMAP risk score predicts hepatocellular carcinoma development in patients with chronic hepatitis

Abstract

Background & aims: Hepatocellular carcinoma (HCC) is the leading cause of death in patients with chronic hepatitis. In this international collaboration, we sought to develop a global universal HCC risk score to predict the HCC development for patients with chronic hepatitis.

Methods: A total of 17,374 patients, comprising 10,578 treated Asian patients with chronic hepatitis B (CHB), 2,510 treated Caucasian patients with CHB, 3,566 treated patients with hepatitis C virus (including 2,489 patients with cirrhosis achieving a sustained virological response) and 720 patients with non-viral hepatitis (NVH) from 11 international prospective observational cohorts or randomised controlled trials, were divided into a training cohort (3,688 Asian patients with CHB) and 9 validation cohorts with different aetiologies and ethnicities (n = 13,686).

Results: We developed an HCC risk score, called the aMAP score (ranging from 0 to 100), that involves only age, male, albumin-bilirubin and platelets. This metric performed excellently in assessing HCC risk not only in patients with hepatitis of different aetiologies, but also in those with different ethnicities (C-index: 0.82-0.87). Cut-off values of 50 and 60 were best for discriminating HCC risk. The 3- or 5-year cumulative incidences of HCC were 0-0.8%, 1.5-4.8%, and 8.1-19.9% in the low- (n = 7,413, 43.6%), medium- (n = 6,529, 38.4%), and high-risk (n = 3,044, 17.9%) groups, respectively. The cut-off value of 50 was associated with a sensitivity of 85.7-100% and a negative predictive value of 99.3-100%. The cut-off value of 60 resulted in a specificity of 56.6-95.8% and a positive predictive value of 6.6-15.7%.

Conclusions: This objective, simple, reliable risk score based on 5 common parameters accurately predicted HCC development, regardless of aetiology and ethnicity, which could help to establish a risk score-guided HCC surveillance strategy worldwide.

Lay summary: In this international collaboration, we developed and externally validated a simple, objective and accurate prognostic tool (called the aMAP score), that involves only age, male, albumin-bilirubin and platelets. The aMAP score (ranged from 0 to 100) satisfactorily predicted the risk of hepatocellular carcinoma (HCC) development among over 17,000 patients with viral and non-viral hepatitis from 11 global prospective studies. Our findings show that the aMAP score had excellent discrimination and calibration in assessing the 5-year HCC risk among all the cohorts irrespective of aetiology and ethnicity.

Keywords: HCC; Hepatitis B virus; Hepatitis C virus; Non-alcoholic fatty liver disease; Risk score.

Conflict of interest statement

Conflicts of interest GP has served as advisor/lecturer for Abbvie, Dicerna, Gilead, GlaxoSmithKline, Ipsen, Janssen, Merck Sharp & Dohme, Roche and Spring Bank, and has received research grants from Abbvie and Gilead. VS has served as an advisor or lecturer for Abbvie and Gilead, and has received research grants from Abbvie and Gilead. GD has served as an advisor/lecturer for Genkyotex, Ipsen, Pfizer and Novartis, and has received research grants from Abbvie and Gilead. TB has served as advisor/consultant/lecturer for Abbvie, Alexion, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Janssen, Merck Sharp & Dohme/Merck, Novartis, Roche, and Vertex, and has received research support from Abbvie, Bristol-Myers Squibb, Gilead, Janssen, Merck Sharp & Dohme/Merck, Novartis and Roche. MB has served as an advisor/lecturer for Abbvie, Dicerna, Gilead, GlaxoSmithKline, Janssen, Merck Sharp & Dohme, Roche and Spring Bank, and has received research grants from Abbvie and Gilead. JLC has served as a consultant and/or speaker for Abbvie, Gilead, Ipsen, and Merck Sharp & Dohme. HLAJ has served as a consultant for Arbutus, Arena, Enyo, Gilead Sciences, GlaxoSmithKline, Janssen, Medimmune, Merck, Roche, Vir Biotechnology Inc., and Viroclinics, and has received grants from AbbVie, Arbutus, Bristol Myers Squibb, Gilead Sciences, Janssen, Medimmune, Merck and Roche. PH has spoken to, or been on, advisory boards for AbbVie, BMS, Eisai Ltd, Falk, Ferring, Gilead, Gore, Janssen, Lundbeck, MSD, Norgine, Novartis, ONO Pharmaceuticals, Pfizer and Roche. WLI has received speaker and consultancy fees from Roche, Janssen Cilag, Gilead Sciences and Novartis, educational grants from Boehringer Ingelheim, Merck Sharp & Dohme, and Gilead Sciences, and research grant support from GlaxoSmithKline, Pfizer, Gilead Sciences, Janssen Cilag, Abbvie and Bristol-Myers Squibb. PL has served as advisor for Abbvie, Eiger, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck/Merck Sharp & Dohme, MYR Pharma and Roche. JH has received consulting fee from AbbVie, Arbutus, Bristol Myers Squibb, Gilead Sciences, Johnson &Johnson, and Roche and received grants from Bristol Myers Squibb and Johnson & Johnson. SM, VS, JFF, LL and AG are employees of, and own stock in, Gilead Sciences. CZ and LS are employees of Hangzhou YITU Healthcare Technology Co. Ltd. The other authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details.

Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.