P62 Bacterial translocation in human immunodeficiency virus-infected patients with hepatitis C virus-related cirrhosis: implication in haemodynamic alterations and mortality

Introduction Hepatitis C virus (HCV)-related liver disease follows an accelerated course in patients with human immunodeficiency virus (HIV) co-infection. Liver fibrosis progression to cirrhosis is faster in HIV/HCV coinfected individuals than in HCV-monoinfected subjects. Immunosuppression (lower CD4 cell count), markers of severe liver disease (Child Pugh score) and the absence of HAART are independent predictors of liver-related mortality in patients with end-stage liver disease coinfected with HIV and HCV. However, the intrinsic mechanisms through which HIV infection have an influence in the worse prognosis of these patients remain unknown. Among the possible mechanisms involved in the evolution of both HIV and HCV infection in coinfected patients, we suggest that microbial translocation may contribute to the accelerated course of liver damage in HCV-HIV patients through the activation of immune system. Aim Analysis of the influence of portal hypertension on intestinal permeability in HIV-infected patients with hepatitis C virus (HCV)-related cirrhosis, as well of the prognostic significance of consequent macrophage activation. Method 20 HIV-monoinfected patients, seventy patients with HIV-HVC co-infection, twenty of them with compensated and fifty with decompensated cirrhosis, and twenty healthy controls were evaluated for intestinal permeability and bacterial translocation (lipopolysaccharide-binding protein (LBP)), macrophage activation (soluble CD14 (sCD14), soluble tumour necrosis factor receptor 55 Kd (sTNFRI), and interleukin 6 (IL-6)), and activation of the renin-angiotensin-aldosterone axis. Patients with decompensated cirrhosis were followed during a median period of 429 days. Results LBP concentration was significantly increased in HIV monoinfected patients when compared with healthy controls. Patients with decompensated cirrhosis, but not those with compensated liver disease, show increased LBP levels when compared with HIV monoinfected patients. Patients with increased LBP concentration showed elevated sCD14, sTNFRI and IL-6 levels. 22 patients died, by a liver-related cause, during the follow-up and two more suffered liver transplantation. The mortality at 1 and 2 years was 36 and 56 %. Child-Pugh index, CD4 T cell count, plasma aldosterone and serum IL-6 concentrations independently predicted liver-related mortality. Conclusion The increased intestinal permeability, observed in patients with monoinfection by HIV, is significantly higher in those with concomitant portal hypertension. Parameters indicative of macrophage activation, such as IL-6, in addition of immuno-depression, liver function markers and haemodynamic derangement (plasma aldosterone concentration) influence the survival of HIV-HCV co-infected patients with decompensated cirrhosis.