83 (95% CI 0.79�C0.88) (Figure 3). A HA cut-off value of 100 ng/mL provided the highest sum of sensitivity (69.03) and specificity (87.0), while the positive predictive value (PPV) and negative predictive selleckchem value (NPV) were 27.6 and 97.5, respectively. Changing the cut-off value to 250 ng/mL increased the PPV to 46.3, but only decreased the NPV to 96.1. There were no differences in these performance estimates when comparing patients with chronic viral hepatitis with those with cleared HCV infection (results not shown). Figure 3 Receiver operating characteristic curve for the ability of plasma hyaluronic acid to predict liver-related events. The multivariate incidence rates ratios (IRR) for any LRE and non-liver-related death are shown in figure 4 and and5,5, respectively.

Age, baseline CD4+ count, HIV viral load and HA level (categorised as ��75, 75�C250 and >250 ng/mL) were significant predictors (p<0.1) of any LRE in the univariate analysis, but HA was by far the strongest predictor. After adjustment only baseline HA level, and CD4+ count were significant predictors of LRE, and HIV-viral load was of marginal significance. Compared to patients with normal HA levels, those with moderately elevated HA levels had a 5-fold increase of any LRE (IRR 5.22; 95% CI 2.86�C9.26, p=0.0007), whilst those with markedly elevated HA level had almost a 30-fold increased incidence of any LRE (IRR 28.22; 95% CI 14.95�C46.00, p<0.0001). Sensitivity analyses using time-updated variables (CD4+ cell count, HIV viral load and time of cART initiation), adjusting for HCV genotype or censoring patients at starting any interferon-based therapy (n=182) did not change the IRRs significantly (results not shown).

Figure 4 Adjusted incidence rate ratios of any liver-related events. Figure 5 Adjusted incidence rate ratios of any non-liver-related events. In a sensitivity analysis, excluding patients with HBV infection, the multivariate IRRs for LRE were similar. With patients with normal HA levels as reference, the IRR (95% CI) was 8.37 (4.09�C17.12; p<0.0001) and 30.63 (15.14�C59.46; p<0.0001) for patients with HA elevated moderately or markedly, respectively. Only eight and seven LRE occurred among HBV+ and patients with resolved HCV infection, respectively, which precluded similar analyses for the two groups.

For non-liver-related death both age, AV-951 CD4, HIV viral load and markedly (but not moderately) elevated HA levels were significant predictors of this outcome, although the risk for those with markedly elevated HA levels was modest (IRR 2.17; 95% CI 1.26�C3.76, p=0.0036) (Figure 5). Conversely, HA levels failed to predict the occurrence of non-fatal or fatal AIDS events all together (results not shown). HA during Follow-up for LRE and Controls 43 (51.2%) patients that developed an LRE during follow-up had HA measured in their last available sample prior to their event (cases). 172 (14.