External validation of the PAGE-B score for HCC risk prediction in people living with HIV/HBV coinfection.
HIV infection
Hepatitis B virus
hepatocellular carcinoma
liver cirrhosis
liver neoplasms
model validation
risk assessment
risk prediction models
tenofovir
Journal
Journal of hepatology
ISSN: 1600-0641
Titre abrégé: J Hepatol
Pays: Netherlands
ID NLM: 8503886
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
received:
06
10
2022
revised:
21
12
2022
accepted:
23
12
2022
medline:
18
4
2023
pubmed:
24
1
2023
entrez:
23
1
2023
Statut:
ppublish
Résumé
HBV coinfection is common among people living with HIV (PLWH) and is the most important cause of hepatocellular carcinoma (HCC). While risk prediction tools for HCC have been validated in patients with HBV monoinfection, they have not been evaluated in PLWH. Thus, we performed an external validation of PAGE-B in people with HIV/HBV coinfection. We included data on PLWH from four European cohorts who were positive for HBsAg and did not have HCC before starting tenofovir. We estimated the predictive performance of PAGE-B for HCC occurrence over 15 years in patients receiving tenofovir-containing antiretroviral therapy. Model discrimination was assessed after multiple imputation using Cox regression with the prognostic index as a covariate, and by calculating Harrell's c-index. Calibration was assessed by comparing our cumulative incidence with the PAGE-B derivation study using Kaplan-Meier curves. In total, 2,963 individuals with HIV/HBV coinfection on tenofovir-containing antiretroviral therapy were included. PAGE-B was <10 in 26.5%, 10-17 in 57.7%, and ≥18 in 15.7% of patients. Within a median follow-up of 9.6 years, HCC occurred in 68 individuals (2.58/1,000 patient-years, 95% CI 2.03-3.27). The regression slope of the prognostic index for developing HCC within 15 years was 0.93 (95% CI 0.61-1.25), and the pooled c-index was 0.77 (range 0.73-0.80), both indicating good model discrimination. The cumulative incidence of HCC was lower in our study compared to the derivation study. A PAGE-B cut-off of <10 had a negative predictive value of 99.4% for the development of HCC within 5 years. Restricting efforts to individuals with a PAGE-B of ≥10 would spare unnecessary HCC screening in 27% of individuals. For individuals with HIV/HBV coinfection, PAGE-B is a valid tool to determine the need for HCC screening. Chronic HBV infection is the most important cause of hepatocellular carcinoma (HCC) among people living with HIV. Valid risk prediction may enable better targeting of HCC screening efforts to high-risk individuals. We aimed to validate PAGE-B, a risk prediction tool that is based on age, sex, and platelets, in 2,963 individuals with HIV/HBV coinfection who received tenofovir-containing antiretroviral therapy. In the present study, PAGE-B showed good discrimination, adequate calibration, and a cut-off of <10 had a negative predictive value of 99.4% for the development of HCC within 5 years. These results indicate that PAGE-B is a simple and valid risk prediction tool to determine the need for HCC screening among people living with HIV and HBV.
Sections du résumé
BACKGROUND & AIMS
HBV coinfection is common among people living with HIV (PLWH) and is the most important cause of hepatocellular carcinoma (HCC). While risk prediction tools for HCC have been validated in patients with HBV monoinfection, they have not been evaluated in PLWH. Thus, we performed an external validation of PAGE-B in people with HIV/HBV coinfection.
METHODS
We included data on PLWH from four European cohorts who were positive for HBsAg and did not have HCC before starting tenofovir. We estimated the predictive performance of PAGE-B for HCC occurrence over 15 years in patients receiving tenofovir-containing antiretroviral therapy. Model discrimination was assessed after multiple imputation using Cox regression with the prognostic index as a covariate, and by calculating Harrell's c-index. Calibration was assessed by comparing our cumulative incidence with the PAGE-B derivation study using Kaplan-Meier curves.
RESULTS
In total, 2,963 individuals with HIV/HBV coinfection on tenofovir-containing antiretroviral therapy were included. PAGE-B was <10 in 26.5%, 10-17 in 57.7%, and ≥18 in 15.7% of patients. Within a median follow-up of 9.6 years, HCC occurred in 68 individuals (2.58/1,000 patient-years, 95% CI 2.03-3.27). The regression slope of the prognostic index for developing HCC within 15 years was 0.93 (95% CI 0.61-1.25), and the pooled c-index was 0.77 (range 0.73-0.80), both indicating good model discrimination. The cumulative incidence of HCC was lower in our study compared to the derivation study. A PAGE-B cut-off of <10 had a negative predictive value of 99.4% for the development of HCC within 5 years. Restricting efforts to individuals with a PAGE-B of ≥10 would spare unnecessary HCC screening in 27% of individuals.
CONCLUSIONS
For individuals with HIV/HBV coinfection, PAGE-B is a valid tool to determine the need for HCC screening.
IMPACT AND IMPLICATIONS
Chronic HBV infection is the most important cause of hepatocellular carcinoma (HCC) among people living with HIV. Valid risk prediction may enable better targeting of HCC screening efforts to high-risk individuals. We aimed to validate PAGE-B, a risk prediction tool that is based on age, sex, and platelets, in 2,963 individuals with HIV/HBV coinfection who received tenofovir-containing antiretroviral therapy. In the present study, PAGE-B showed good discrimination, adequate calibration, and a cut-off of <10 had a negative predictive value of 99.4% for the development of HCC within 5 years. These results indicate that PAGE-B is a simple and valid risk prediction tool to determine the need for HCC screening among people living with HIV and HBV.
Identifiants
pubmed: 36690280
pii: S0168-8278(23)00011-9
doi: 10.1016/j.jhep.2022.12.029
pii:
doi:
Substances chimiques
Antiviral Agents
0
Tenofovir
99YXE507IL
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
947-957Investigateurs
I Abela
(I)
K Aebi-Popp
(K)
A Anagnostopoulos
(A)
M Battegay
(M)
E Bernasconi
(E)
D L Braun
(DL)
H C Bucher
(HC)
A Calmy
(A)
M Cavassini
(M)
A Ciuffi
(A)
G Dollenmaier
(G)
M Egger
(M)
L Elzi
(L)
J Fehr
(J)
J Fellay
(J)
H Furrer
(H)
C A Fux
(CA)
H F Günthard
(HF)
A Hachfeld
(A)
D Haerry
(D)
B Hasse
(B)
H H Hirsch
(HH)
M Hoffmann
(M)
I Hösli
(I)
M Huber
(M)
D Jackson-Perry
(D)
C R Kahlert
(CR)
L Kaiser
(L)
O Keiser
(O)
T Klimkait
(T)
R D Kouyos
(RD)
H Kovari
(H)
K Kusejko
(K)
N Labhardt
(N)
K Leuzinger
(K)
Martinez de Tejada B
(M)
C Marzolini
(C)
K J Metzner
(KJ)
N Müller
(N)
J Nemeth
(J)
D Nicca
(D)
J Notter
(J)
P Paioni
(P)
G Pantaleo
(G)
M Perreau
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A Rauch
(A)
L Salazar-Vizcaya
(L)
P Schmid
(P)
R Speck
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M Stöckle
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(P)
A Trkola
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G Wandeler
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M Weisser
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S Yerly
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Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.