Outside clinical trials liver biopsy is not performed in a large proportion of co-infected patients and repeated liver biopsies would be unacceptable for most patients [6], [7]. In recent years a high number of serum biomarkers and other non-invasive new methods such as fibroscanning, as markers of liver fibrosis, have been evaluated. Most of these studies have assessed associations of these markers with findings from liver biopsy taken at the same time [8]. Although insightful, this line of investigation suffers from two major limitations. Firstly, the cross-sectional design does not allow for studies of temporal changes in biomarker levels. Secondly, these studies do not inform the evaluation of whether the markers are able to predict relevant clinical end points like hepatic decompensation or death.

Mehta et al reported that due to the intrinsic limitations of liver biopsy, the use of this method as a comparator makes it impossible to distinguish a perfectly predictive non-invasive marker from a marker with unacceptable poor predictive potential [9]. Long-term prospective studies of non-invasive methods evaluated against relevant clinical end points are hence required to further advance this research field. One biomarker, hyaluronic acid (HA) is a component of the extra cellular matrix and primarily cleared from the bloodstream by the hepatic sinusoids [10]. Liver disease will therefore reduce the rate of clearance of HA resulting in elevated plasma levels. This biomarker is attractive to evaluate as it is easy, reliable, inexpensive and freely available to measure.

Prior studies, primarily in HCV mono-infected patients, have reported that HA is an accurate individual marker of fibrosis and predictor of hepatic complications [11]�C[18]. In HIV, viral hepatitis is a frequent co-infection, and several HIV-specific factors may affect hepatic metabolism. Therefore, the aim of this study was to further evaluate the predictive potential of HA in a large and well characterized cohort of HIV/viral hepatitis co-infected patients followed over extended periods of time within the EuroSIDA study. Methods Ethics Statement Before any study related activities are performed Local Ethical Committee approval of the study and procedure for obtaining informed consent from participants is obtained according to local and/or national regulations in all countries participating in the study as well as other national regulatory approvals as applicable.

The senior investigator at each clinical site is responsible for obtaining and maintaining this/these approval(s) at all times during the conduct of the study. Patients The EuroSIDA study is a prospective, observational cohort of 18,277 HIV-1�Cinfected patients in 108 centers AV-951 across Europe, Israel, and Argentina. The study has been described in detail previously [19].