Abstract
BackgroundWe 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.MethodsART-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.ResultsWe 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).ConclusionsIn 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.
Highlights
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
In chronic HBV and HCV infection, sCD14 levels differentiate HBV/HCV-infected subjects with severe liver fibrosis from those with minimal fibrosis, and are associated with the risk of failure to respond to anti-HCV treatment with pegylated-interferon-α/ribavirin, suggesting that the host response to MT might predict the outcome of the disease [5]
In HIV infection, MT has been linked to immune activation (IA) [6] and correlates with the clinical outcome independently of CD4+ counts and HIV RNA levels [7,8]; a common pathogenic role of MT in fuelling viral hepatic illness has been hypothesized
Summary
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. In chronic HBV and HCV infection, sCD14 levels differentiate HBV/HCV-infected subjects with severe liver fibrosis from those with minimal fibrosis, and are associated with the risk of failure to respond to anti-HCV treatment with pegylated-interferon-α/ribavirin, suggesting that the host response to MT might predict the outcome of the disease [5]. In keeping with these findings, MT has been shown to accelerate liver disease progression in cohorts of HIVinfected and HIV uninfected patients [9,10,11], and hamper the response to pegylated-interferon-α/ribavirin treatment in HCV/HIV co-infected patients [12]. In a retrospective case–control study of HIV + and HIV- Ugandan subjects with detectable liver stiffness/ cirrhosis in the absence of HCV infection, Redd et al demonstrated a significant association between monocyte activation and liver disease only in HIV-infected patients, that appeared unrelated to MT [13]
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