Bacterial DNA Translocation and Liver Disease Severity Among HIV-Infected Patients With Chronic Hepatitis C

Abstract

We carried out a cross-sectional study to explore whether bacterial 16S ribosomal DNA (bactDNA) shows association with severity of liver disease among human immunodeficiency virus/hepatitis C virus coinfected patients. Patients with advanced fibrosis (F3/F4), moderate activity grade (A2/A3), and high fibrosis progression rate (FPR > 0.15) had higher values of plasma bactDNA levels than did patients without these markers of liver disease (P < 0.05). The chance of having a fibrosis stage or activity grade increased was 1.20 [95% confidence interval (CI) = 1.0 to 1.44, P = 0.045] and 1.22 (95% CI = 1.1 to 1.45, P = 0.029) times greater for every 100 copies per microliter of plasma bactDNA. Likewise, the odds of having values of FPR > 0.15 was 1.18 (95% CI = 0.98 to 1.42, P = 0.089). In addition, patients with high bactDNA levels (≥175 copies per microliter) had the highest odds of having high values of Metavir score and FPR (P < 0.05). Our data show that bacterial translocation is associated with severe liver disease among human immunodeficiency virus-infected patients with chronic hepatitis C.

Liver Stiffness Is Associated With Monocyte Activation in HIV-Infected Ugandans Without Viral Hepatitis

“…4 These findings differ from studies examining liver disease in HIV/HCV-coinfected individuals. 9,10 It should be noted that elevated transient elastography measurements may not predict morbidity and mortality in the same way they do in the presence of HCV coinfection. In addition, two markers of overall immune activation, CRP and D-dimer, were not found to be associated with liver stiffness in this population.…”

“…4,7,8 Immune activation and intestinal microbial translocation (MT) have been implicated as causes of numerous types of liver disease in humans and in animal models. 4,9,10 Moreover, immune activation appears to drive HIV progression. 11 Based on these previous studies, we hypothesized that liver stiffness in HIV-infected Ugandans was associated with innate immune activation.…”

“…12 However, others have found evidence of MT in HIV-HCV coinfection, but only in the presence of cirrhosis or advanced fibrosis. 9,10 We performed a retrospective case-control study of subjects with detectable liver stiffness and cirrhosis from Rakai, Uganda, to examine the contribution of immune activation and MT to liver disease within this cohort. 3 …”

Optimal vitamin D plasma levels are associated with lower bacterial DNA translocation in HIV/hepatitis c virus coinfected patients

“…Furthermore, hepatic macrophages or Kupffer cells are responsible for clearing bacterial translocation products; but these cells may be infected by HIV and it might result in their impaired ability to clear these bacterial translocation products [23]. Moreover, bacterial translocation is a mechanism that contributes to liver diseases [15,24]. There is some evidence that bacterial translocation promotes hepatic fibrogenesis [25] and the presence of bactDNA in patients with cirrhosis is associated with hemodynamic consequences [26].…”

“…Basic fibroblast growth factor (bFGF) was measured via enzyme-linked immunosorbent assay of Invitrogen Corporation (Camarillo, California, USA). to amplify the DNA sequence encoding the well conserved 16S rRNA subunit (16S rDNA) and the conditions for the amplification reaction were as previously described [15]. Several statistical cutoffs were selected for 16S rDNA plasma levels: low [<46 copies/ml (25th percentile, p25th)], moderate [46 copies/ml (p25th) to 78 copies/ml (p50th)], high [78 copies/ml (p50th) to 159 copies/ml (p75th)], and very high [>159 copies/ml (p75th)].…”