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Serum Hyaluronic Acid Correlates with Liver Fibrosis Staging Measured Using Elastometry in HIV/HCV Coinfected Patients but do Not Predict Liver Fibrosis Progression. Norma I. Rallón 1 , José Medrano 1 , Salvador Resino 2 , Clara Restrepo 1 , Vincent Soriano 1 and José M. Benito 1

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  1. Serum Hyaluronic Acid Correlates with Liver Fibrosis Staging Measured Using Elastometry in HIV/HCV Coinfected Patients but do Not Predict Liver Fibrosis Progression Norma I. Rallón1, José Medrano1, Salvador Resino2, Clara Restrepo1, Vincent Soriano1 and José M. Benito1 1Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain and 2Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain

  2. Periportal Portal 1 2 3 4 Septal Cirrhosis Stages of Liver fibrosis

  3. Liver Fibrosis is accelerated in HIV/HCV coinfected patients Lauer and Walker, NEJM 2001 • Establishing liver fibrosis staging is critical, because it determines: • The evolution of liver disease • The indication for therapy • The probability of response

  4. Fibrosis is a complex and multifactorial phenomenon Hyaluronic Acid • The use of non-invasive tools has allowed overcoming the limitations of liver biopsy, especially when periodic assessment is needed. • The value of serum-biomarkers to predict the speed of liver fibrosis progression is unknown.

  5. Hyaluronic Acid and Liver Fibrosis • A biomarker associated with level of liver fibrosis in monoinfected patients Wong et al J Viral Hep 1998 Plevris et al Eur J Gastroenterol Hepatol 2000 McHutchison et al J Gastroenterol Hepatol 2000 • Studies on HCV/HIV coinfected population are scarce Larrouse et al. J of AIDS 2007 Sanvisens et al. J Viral Hep 2009 • No studies so far have analysed the association between HA and liver stiffness measured by transient elastography • No studies have adressed the association of HA with the rate of fibrosis progression in coinfected patients

  6. OBJECTIVES To investigate the potential association between the stage of liver fibrosis at a single timepoint and the levels of Hyaluronic acid in HCV/HIV coinfected patients. To examine the value of Hyaluronic acid to predict the speed of liver fibrosis progression in HCV/HIV coinfected patients

  7. PATIENTS AND METHODS * * The mean follow-up between first and last elastometry was 2.2+1.3years.

  8. PATIENTS AND METHODS Liver fibrosis staging was estimated using FibroScan. Significant liver fibrosis (Metavir >F2) was considered for liver stiffnes values >7.5KPa and cirrhosis (Metavir F4) for >14KPa. Hyaluronic Acid (AH) levels were measured in plasma with an ELISAassay and expressed in ng/ml. AH

  9. STATISTICAL ANALYSIS Objective 1 (cross-sectional study): • Correlation of HA with liver stiffness was assessed using Pearson correlation coefficient. • The diagnostic value of HA for significant (KPa >7.5) and advanced (KPa >14) liver fibrosis was assesed by calculating the area under the receiver operating characteristic (ROC) curves. From these curves, PPV, NPV and LRs were calculated. Objective 2 (longitudinal study): • Liver stiffness progression rate was calculated for each individual as the percentage of increase in KPa over the baseline value per year. • Correlation of HA with liver stiffness progression rate was assessed using Pearson correlation coefficient.

  10. RESULTS

  11. Characteristics of the study population

  12. Plasma HA concentrations were strongly correlated with liver stiffness measurements at baseline (Pearson r=0.77, p<0.0001) Hyaluronic Acid (ng/ml) Baseline Liver Stiffness (KPa)

  13. AUC-ROC for Significant Liver Fibrosis (>7.5 KPa) The best HA level to predict absence of liver fibrosis was 50ng/ml Se 84% Sp 61% NPV 83% LR- 0.27 AUC-ROC: 0.80+0.04 (p<0.0001) 95% CI: [0.732-0.877]

  14. AUC-ROC for Cirrhosis (>14 KPa) The best HA level to predict cirrhosis was 200ng/ml Se 52% Sp 96% PPV 74% LR+ 12.96. AUC-ROC: 0.92+0.03 (p<0.0001) 95% CI: [0.852-0.985]

  15. No association was found between liver stiffness progression rate and baseline HA levels (Pearson r=-0.140, p=0.102)

  16. CONCLUSIONS • Plasma HA levels strongly correlates with liver stiffness values in HIV/HCV-coinfected patients. • The best HA values with clinical significance are <50ng/ml for predicting lack of significant liver fibrosis and >200ng/ml for predicting cirrhosis. • Plasma HA-levels; however, are not associated with liver fibrosis progression, suggesting that greater HA levels are the consequence of liver function impairment and not the cause.

  17. ACKNOWLEDGMENTS To all staff at the Molecular Biology Laboratory and clinicians from the Infectious Disease Department and from Hepatology Unit of the Hospital Carlos III, Madrid, Spain. NEAT European Project (LSHP-CT-2006- 037570)