Immune activation and microbial translocation in liver disease progression in HIV/hepatitis co-infected patients: results from the Icona Foundation study

BACKGROUND We evaluated whether immune activation (IA) and microbial translocation (MT) might play a role in accelerating liver disease progression in HIV-HBV/HCV co-infected patients. METHODS ART-naïve HIV/viral hepatitis co-infected patients from Icona with a CD4 cell count >200/μl and with a known date of prior HIV neg/pos tests and ≥1 plasma sample stored were included in the study. Plasma MT (LPS, sCD14) and IA (IL-6,TNFα) were measured using ELISA while activated CD8 + CD38 + HLA-DR +  were measured by flow cytometry, with one measurement being performed for all patients and two measurements for a smaller group of subjects. The association between these biomarkers and the time to i) a single ALT >200 IU/l and ii) a Fib-4 >1.45 was also investigated. A standard survival analysis with robust standard errors was used for all evaluations. Follow-up was censored at patients' last clinical follow-up. RESULTS We studied 127 HIV-infected hepatitis viruses co-infected patients (118 HCV, 9 HBV). Overall median (IQR) CD4, VL, age were 596/μl (208-1303), 3.8 log10cp/mL (3-4.3), 34 years (22-56). While heightened TNF-α was associated with a 13-fold increased risk of Fib-4 > 1.45 (RH 13.05, 95% CI 2.43-70; p = 0.003), markers of MT did not show an association with liver illness. Interestingly, higher sCD14 was associated with a decreased risk of Fib-4 > 1.45, independently of other biomarkers considered (RH 0.20, 95% CI 0.04-0,9; p = 0.04). CONCLUSIONS In HIV/hepatitis virus co-infected ART-naive patients, higher TNF-α plasma levels were associated with a 13-fold increase in the risk of progression to a Fib-4 >1.45, suggesting that the pro-inflammatory status in HIV infection might hasten the course of HCV. In view of the fact that sCD14 may hinder the interaction between LPS and the phagocyte membrane CD14, we herewith propose a model which aims to demonstrate that high sCD14 levels might contribute to shelter liver function through the down-regulation of the inflammatory cascade.