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Noninvasive Diagnosis of Hepatic Fibrosis in HIV/HCV-Coinfected Patients

Larrousse, María MD*; Laguno, Montserrat MD*; Segarra, Marta PhD; De Lazzari, Elisa; Martínez, Esteban MD*; Blanco, José Luis MD*; León, Agathe MD*; Deulofeu, Ramón PhD§; Miquel, Rosa MD; Milinkovic, Ana MD*; Lonca, Montserrat MD*; Miró, José María MD*; Biglia, Alejandra MD*; Murillas, Javier MD*; Gatell, José María MD*; Mallolas, Josep MD*

JAIDS Journal of Acquired Immune Deficiency Syndromes: November 1st, 2007 - Volume 46 - Issue 3 - p 304-311
doi: 10.1097/QAI.0b013e3181520502
Clinical Science

Background: Several serum markers reflecting extracellular matrix status have been correlated with liver fibrosis in non-HIV-infected patients with chronic hepatitis C infection. These indexes have been less examined in HIV/HCV-coinfected individuals.

Objective: We aimed to evaluate the predictive value of serum markers for liver fibrosis in HIV-infected patients with chronic hepatitis C virus (HVC).

Methods: Serum levels of metalloproteinases 1 and 2 (MMP-1 and -2), tissue inhibitors of matrix metalloproteinases (TIMP-1), procollagen type III N-terminal peptide (PIIINP), and hyaluronic acid (HA) were measured in HIV-infected patients with chronic hepatitis C at the time of obtaining a liver biopsy and before the consideration of anti-hepatitis C therapy.

Results: One hundred and nineteen consecutive HIV-HVC coinfected patients were included. TIMP-1 (r = 0.6; P < 0.001), TIMP-1/MMP-1 ratio (r = 0.5; P < 0.001), TIMP-1/MMP-2 ratio (r = 0.3; P < 0.001), MMP-2 (r = 0.2; P = 0.044), PIIINP (r = 0.4; P < 0.001), and HA (r = 0.5; P < 0.001) were positively and significantly correlated with the fibrosis stage. In the multivariate analysis, TIMP-1 (odds ratio [OR] = 1.004, 95% confidence interval [CI]: 1.002 to 1.006, P = 0.001) and HA >95 μg/dL (OR = 6.041, 95% CI: 1.184 to 30.816, P = 0.031) were independently associated with liver fibrosis. The area under the curve of score to discriminate mild (F0-F1) from significant (F2-F4) fibrosis in the received-operating analysis using the variables TIMP-1 and HA was 0.84, with a sensitivity of 72.9% and a specificity of 83.1%.

Conclusion: TIMP-1 and HA were quite sensitive and specific for predicting the degree of liver fibrosis in HIV-infected patients with chronic hepatitis C. These parameters may become a noninvasive alternative to liver biopsy when the degree of liver fibrosis needs to be estimated.

From the *Infectious Diseases Unit, †Biochemistry, ‡Biostatistics and Epidemiology, §Biochemical Service, and ∥Pathology Service, Hospital Clínic Universitari de Barcelona-IDIBAPS, University of Barcelona, Barcelona, Spain.

Received for publication January 23, 2007; accepted July 13, 2007.

Dr. Larrousse was supported in part by the Spanish Ministry of Health (FIS 2006).

Presented at Interscience Conference on Antimicrobial Agents and Chemotherapy (ICCAC), December 2005.

Correspondence to: María Larrousse, MD, Infectious Diseases Unit, Hospital Clinic, Villarroel 170, 08036 Barcelona, Spain (e-mail:,

© 2007 Lippincott Williams & Wilkins, Inc.