Prediction of Hepatic Fibrosis in Patients Coinfected With HIV and Hepatitis C Virus Based on Genetic Markers

Fernández-Rodríguez, Amanda PhD*; Berenguer, Juan MD†,‡; Jiménez-Sousa, María A. PhD*; Guzmán-Fulgencio, María PhD*; Micheloud, Dariela MD§; Miralles, Pilar MD†,‡; López, Juan Carlos MD†,‡; Bellón, José María PhD; Aldamiz-Echevarria, Teresa MD†,‡; García–Broncano, Pilar BSc*; Carrero, Ana MD†,‡; Álvarez, Emilio MD; Resino, Salvador PhD*

JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0b013e3182a06eb6
Basic and Translational Science
Abstract

Objective: To assess the ability of the cirrhosis risk score (CRS) to predict liver fibrosis progression in HIV/hepatitis C virus (HCV)-coinfected patients.

Design: Retrospective follow-up study.

Methods: Based on a minimum follow-up time of 10 years with HCV infection, 190 HIV/HCV-coinfected patients were classified according to their METAVIR score: (1) 25 nonprogressor patients who did not develop fibrosis (F0) and (2) 165 progressor patients who developed fibrosis (F ≥ 1). Seven polymorphisms of CRS signature and IL28B genotype were performed using the GoldenGate assay. The CRS signature was calculated by naive Bayes formula as previously described.

Results: Nonprogressors had CRS values significantly lower than progressors (0.61 versus 0.67; P = 0.043). Among the progressors, we observed similar CRS values through all the fibrosis stages (F1/F2/F3/F4). The percentage of patients with CRS > 0.70 (high risk of developing fibrosis) was higher in progressors than in nonprogressors; but the percentages with values between 0.50 and 0.70 (intermediate risk) and <0.50 (low risk) were quite similar for each of the fibrosis stages (P = 0.047). The area under the receiver-operating characteristic curve of CRS for discriminating nonprogressor versus progressor was 0.625 (P = 0.043). When clinical variables were considered (age at HCV infection, intravenous drug use, gender, IL28B, and HCV genotype), the area under the receiver-operating characteristic curve of CRS improved up to 0.739 (P < 0.001).

Conclusions: CRS itself seems not to be a good marker for identifying HIV/HCV-coinfected patients who are at high risk of developing liver fibrosis. However, CRS score coupled with clinical factors might help to distinguish between nonprogressors and progressors patients.

Author Information

*Viral Infection and Immunity Unit, National Centre of Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain;

Infectious Diseases and HIV Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain;

Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; and

Departments of §Internal Medicine;

Pathology, Hospital General Universitario, Gregorio Marañón, Madrid, Spain.

Correspondence to: Salvador Resino, PhD, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda-Pozuelo, Km 2.2, 28220 Majadahonda, Madrid, Spain (e-mail: sresino@isciii.es).

Supported by Fondo de Investigacion de Sanidad en España (FIS) (Spanish Health Founds for Research) Grants PI08/0738, PI11/00,245; PI08/0928, and PI11/01,556; Red Española de Investigación en SIDA (RIS) (AIDS Research Network) Grants RD12/0017/0024 and RD12/0017/0004; and “Fundación para la Investigación y la Prevención del Sida en España” (FIPSE) Grant 361020/10]. A. F. R., M. G. F., P. G. B., and M. A. J. S. are supported by “Instituto de Salud Carlos III” Grants UIPY-1377/08, CM09/00,031, FI12/00,036, and CM10/00,105, respectively.

Presented in part at the 20th Conference on Retroviruses and Opportunistic Infections (CROI): The cirrhosis risk score (CRS) implication in fibrosis prediction among human immunodeficiency virus/hepatitis C virus coinfected patients, 20th Conference on Retroviruses and Opportunistic Infections (CROI 2013), March 3–6, 2013, Atlanta, GA.

The authors have no conflicts of interest to disclose.

Received February 07, 2013

Accepted June 13, 2013

© 2013 by Lippincott Williams & Wilkins