1. Diagnostic Accuracy of Serum Hyaluronic Acid for Advanced Fibrosis/Cirrhosis in Patients Coinfected with HIV and HCV S. Resino,* 1 P. Miralles, 2 D. Micheloud, 1 J. M. Bellón, 2 A. Vargas, 2 P. Catalán, 2 E. Álvarez, 2 J. Cosín, 2 R. Lorente, 2 M. Sánchez-Conde, 2 M. A. Muñoz-Fernández, 2 And J. Berenguer 2 1 Instituto de Salud Carlos III, Majadahonda, Madrid; 2 Hosp.General Universitario Gregorio Marañón, Madrid, Spain Diagnostic Accuracy of Serum Hyaluronic Acid for Advanced Fibrosis/Cirrhosis in Patients Coinfected with HIV and HCV S. Resino,* 1 P. Miralles, 2 D. Micheloud, 1 J. M. Bellón, 2 A. Vargas, 2 P. Catalán, 2 E. Álvarez, 2 J. Cosín, 2 R. Lorente, 2 M. Sánchez-Conde, 2 M. A. Muñoz-Fernández, 2 And J. Berenguer 2 1 Instituto de Salud Carlos III, Majadahonda, Madrid; 2 Hosp.General Universitario Gregorio Marañón, Madrid, Spain OBJETIVE PATIENS AND METHODS RESULTS Hyaluronic acid (HA), an essential component of the extracellular matrix of the liver is produced by hepatic stellate cells and degraded by sinusoidal endothelial cells. HA levels increase with the development of liver fibrosis in patients with HCV. We evaluated serum HA to predict advanced fibrosis (F≥3) and cirrhosis (F4) in HIV+/HCV+ patients. Patients The patients for this study came from the Hospital Gregorio Marañón in Madrid (Spain). They all had documented HIV-HCV coinfection and underwent liver biopsy prior to therapy with interferon and ribavirin. Laboratory data A fasting serum sample was immediately stored and frozen (at a temperature of -70ºC) for further assays, after the patient gave a written consent. Hyaluronic acid (HA) was tested in serum samples mentioned before by a commercially available quantitative ELISA (HA-ELISA; Echelon Biosciences Inc., Salt Lake City, UT, USA). Concentrations were assayed in duplicate. Liver fibrosis was estimated following the criteria established by the METAVIR Cooperative Study Group. Fibrosis was scored as follows: F0, no fibrosis; F1, portal fibrosis; F2 periportal fibrosis or rare portal-portal septa; F3, fibrous septa with architectural distortion; no obvious cirrhosis (bridging fibrosis); and F4, definite cirrhosis. Statistics Results are presented by median and percentiles, and as frequencies and percentages for categorical data. We calculated the diagnostic values of HA, Forn’s, APRI and FIB-4 indexes and assessed their diagnostic accuracy by using the area under the receiver operating characteristic curves (AUROCs). Next, we calculated the sensitivity (Se) and specificity (Sp) of several cut-off points to evaluate the diagnostic accuracy for advanced fibrosis. Thus, we chose the one with the 95% Se (low cut-off) and the one with the 95% Sp (high cut-off). We also calculated the positive predictive value (PPV) and negative predictive value (NPV) for these two cut-off points. Comparison between HA and fibrosis stage were analysed using Mann-Witney U-test. All tests were two-tailed with P values ≤0.05 considered significant. Statistical analysis was performed by SPSS 14.0 software (SPSS INC, Chicago, IL, USA) and STATA 9.1. Our study cohort included 201 patients whose characteristics at the time of liver biopsy are shown in Table 1. Overall, HA increased significantly with the advanced stage of hepatic fibrosis (Figure 1). Moreover, the differences were higher between F0-F1 and F4 in AH levels distribution. For purposes of comparison, we also evaluated three reported simple models consisting of routine parameters to predict liver fibrosis: a) Forn’s index; b) the APRI index; c) FIB-4. The AUROC values of the HA for significant fibrosis (F≥2), advanced fibrosis (F≥3) and cirrhosis (F4) were similar to FIB-4, APRI, and Forn´s indexes (Figure 2). The 95% confidence interval of AUROC of HA for significant fibrosis (0.676; CI95%: 0.603; 0.750) and cirrhosis (0.863; CI95%: 0.795; 0.931) are not overlapped and there is difference statistically significant (p<0.05). Next, we calculated the Se, Sp, PPV and NPV of several cutoff points to evaluate the diagnostic accuracy of HA for significant fibrosis (F≥2), advanced fibrosis (F≥3) and cirrhosis (F4) (Table 2). For significant fibrosis (F≥2) and with the low AH cut-off ( 1800 ng/mL), 36 of 117 (30.8%) patients with significant fibrosis were correctly identified, and only 4 of 84 (4.8%) of the patients without significant fibrosis were misclassified (90% PPV and 49.7% NPV) (Table 2). For advanced fibrosis (F≥3) and with the low AH cut-off ( 2290 ng/mL), 18 of 64 (28.1%) patients with advanced fibrosis were correctly identified, and only 7 of 137 (5.1%) of the patients without advanced fibrosis were misclassified (72% PPV and 73.9% NPV) (Table 2). For cirrhosis (F4) and with the low AH cut-off ( 2400 ng/mL), 11 of 23 (47.8%) patients with cirrhosis (F4) were correctly identified, and only 9 of 178 (5.1%) of the patients without cirrhosis (F4) were misclassified (55% PPV and 93.4% NPV) (Table 2). Paper # H-2320 CONCLUSION HA appears to be and accurate non-invasive method for detection of of advanced fibrosis and cirrhosis in HIV/HCV-coinfected patients. Corresponding author: Salvador Resino, Unidad de Investigación, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda- Pozuelo, Km 2.2; 28220 Majadahonda (Madrid); Telf.: +34 918 223 266; Fax: +34 915 097 946; e-mail: sresino@isciii.es