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Liver stiffness and fibrosis-4 alone better predict liver events compared with aspartate aminotransferase to platelet ratio index in a cohort of human immunodeficiency virus and hepatitis C virus co-infected patients from ANRS CO13 HEPAVIH cohort

Chalouni, Mathieua; Sogni, Philippef; Miailhes, Patrickq; Lacombe, Karineg,,h; Poizot-Martin, Isabeller,,s; Chas, Juliei; Vittecoq, Danielj,,k; Neau, Didierb,,c; Aumaitre, Huguest; Alric, Laurentu,,v; Piroth, Lionely,,z; Bouchaud, Olivier*,,†; Katlama, Christinel; Morlat, Philippec,,d; Lascoux-Combe, Carolinem; Gervais, Annen; Naqvi, Alissa; Rosenthal, Eric§; Garipuy, Danielw; Barange, Karlx; Esterle, Laurea; Salmon, Dominiqueo,,p; Wittkop, Lindaa,,e for the ANRS CO13 HEPAVIH study group

European Journal of Gastroenterology & Hepatology: November 2019 - Volume 31 - Issue 11 - p 1387–1396
doi: 10.1097/MEG.0000000000001408
Original Articles: Hepatology

Objectives HIV/hepatitis C virus (HCV) co-infection leads to major complications, and noninvasive markers developed to stage liver fibrosis could be used as prognostic markers. We aimed to compare the performances of liver stiffness (LS), fibrosis-4 (FIB-4), and aspartate aminotransferase to platelet ratio index (APRI) to predict liver-related events in HIV/HCV co-infected patients.

Patients and methods HIV/HCV co-infected patients from the ANRS CO13 HEPAVIH cohort were included if they had LS, FIB-4, and APRI measurements done in a window of 3 months. Primary outcome was the time between inclusion and occurrence of a liver-related event. Univariable and multivariable Fine and Gray models were performed. Predictive performances were compared by the area under the receiver operating characteristic (AUROC) differences after correction of optimistic by bootstrap samples. Best cutoffs to predict liver-related events were estimated by sensitivity and specificity maximization.

Results A total of 998 patients were included. Overall, 70.7% were men. Their median age was 46.8 years. According to LS value, 204 (20.4%) patients had cirrhosis. Overall, 39 patients experienced at least one liver-related event. In univariable analysis, LS AUROC curve was significantly superior to FIB-4 and APRI AUROC curves, being 87.9, 78.2, and 75.0%, respectively. After adjustment on age, CD4 levels, and insulin resistance, no differences were observed. The best cutoffs to identify patients at low or high risk of liver-related events were below 8.5, 1.00, and 0.35 and above 16.5, 4.00, and 1.75 for LS, FIB-4, and APRI, respectively.

Conclusion To predict HCV-related events, APRI had lower performance than LS and FIB-4. FIB-4 is as good as LS to predict HCV-related events, suggesting that it can be used for the management of HIV/HCV co-infected patients and replace LS.

aBordeaux Population Health Research Center, ISPED, Inserm, Team MORPH3EUS, UMR 1219, Bordeaux University

bInfectious and Tropical Disease Unit, Bordeaux, University Hospital Center, Pellegrin Hospital

cUniveBordeaux University

dInternal Medicine Unit, Saint-André Hospital, Bordeaux University Hospital Center

eMedical Information Unit, Public Health Pole, Bordeaux University Hospital Center, Bordeaux

fLiver Unit, Paris Public Hospitals, Cochin Hospital, INSERM U-1223, PasteurInstitute, Paris-Descartes University

gInfectious and Tropical Disease Unit, Paris Public Hospitals, Saint-Antoine Hospital

hUMR S1136, Pierre Louis Epidemiology andPublic Health Institute, Pierre and Marie Curie University

iInfectious and Tropical Disease Unit, Paris Public Hospitals de Paris, Tenon Hospital

jInfectious and Tropical Disease Unit, Paris Public Hospitals, Bicêtre Hospital, University Hospitals Paris Sud

kParis Sud University

lDepartment of Internal Medicine and Clinical Immunology, Paris Public Hospitals, Pitié-Salpétrière Hospital

mInfectious and Tropical Disease Unit, Paris Publics Hospitals, Saint-Louis Hospitals

nInfectious and Tropical Disease Unit, AP-HP, Bichat Claude Bernard Hospital

oInfectious and Tropical Disease Unit, Paris Publics Hospitals, Cochin Hospital

pParis Descartes University, Paris

qInfectious and Tropical Disease Unit, University Hospital Center Lyon, de la Croix Rousse Hospital, Lyon

rINSERM, U912 (SE4S), IRD, UMR-S912- ORS PACA, Regional Health Observatory Provence Alpes Côte d’Azur

sAPHM Sainte-Marguerite, Clinical Immunohematology Unit, Aix Marseille University, Marseille

tInfectious and Tropical Disease Unit, Perpignan Hospital Center, Perpignan

uPurpan Hospital, Internal Medicine, Toulouse University Hospital Center

vToulouse III University

wMedicine Unit, Joseph Ducuing Hospital

xGastroenterology and Hepatology Unit, Purpan Hospital, Toulouse University Hospital Center, Toulouse

yDepartment of Infectiology, Dijon University Hospital Center

zBourgogne University, Dijon

*Infectious and Tropical Disease Unit, Paris Publics Hospitals, Avicenne Hospital

Paris 13 Nord University,Bobigny

Nice University Hospital Center, Infectiology Center, Archet 1 Hospital

§Nice-Sophia Antipolis University, Nice, France

Received 5 October 2018 Accepted 14 January 2019

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Correspondence to Linda Wittkop, MD, PhD, Bordeaux University/School of Public Health (ISPED), Bordeaux Population Health Research Center, Team MORPH3EUS, UMR 1219, CIC-EC 1401, 146 Léo-Saignat Street, 33076 Bordeaux Cedex, France, Tel: + 33 557 574 526; fax: + 33 556 240 081; e-mail:

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