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Bacterial Translocation Linked to Severe Liver Disease among HIV/HCV Coinfected People

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HIV positive people with hepatitis C coinfection who had evidence of intestinal bacteria in their blood -- known as bacterial translocation -- had more advanced liver fibrosis and faster fibrosis progression, researchers reported in the August 28, 2012, advance edition of the Journal of Acquired Immune Deficiency Syndromes.

HIV can cause damage to the intestinal lining that allows bacterial in the gut to leak out into the bloodstream. The presence of bacteria and its toxins outside the gut can trigger a persistent inflammatory response that may contribute to problems throughout the body.

Mónica García-Álvarez from Instituto de Salud Carlos III in Madrid and colleagues performed a cross-sectional study to explore whether the presence of bacterial ribosomal DNA in the blood was associated with liver disease severity among HIV/HCV coinfected patients. On average, coinfected people tend to experience faster liver disease progression than individuals with hepatitis C alone.

The analysis included 255 coinfected participants who underwent liver biopsies between 2000 and 2007. A majority (about 75%) were men and the median age was 40 years. Most (about 85%) were on combination antiretroviral therapy, about 70% had undetectable HIV viral load, and the median CD4 T-cell count was 483 cells/mm3. At baseline, 53% had significant fibrosis (Metavir stage F2 or higher) and 27% had advanced fibrosis (stage F3 or higher).

The researchers measured bacterial DNA levels and compared them against those of 100 health blood donors without HIV or HCV infection. Liver fibrosis stage, fibrosis progression rate, and necro-inflammatory activity grade were assessed for the coinfected patients.

Results

  • Almost all coinfected participants (96%) had detectable plasma bacterial DNA, compared with only 7% of uninfected control subjects.
  • Coinfected patients with CD4 counts < 350 cells/mm3 had significantly higher levels of bacterial DNA in their blood.
  • Participants with advanced fibrosis or cirrhosis (stage F3-F4), moderate to advanced necro-inflammatory activity (grade A2-A3), and rapid fibrosis progression rates (> 0.15) had significantly higher bacterial DNA levels than people with milder liver disease.
  • The chance of having an increased fibrosis stage was 1.2 times, or 20%, higher for every additional 100 copies/mL of plasma bacterial DNA.
  • Similarly, the chance of having an increased necro-inflammatory activity grade was 1.22 times, or 22%, higher for every additional 100 copies/mL of bacterial DNA.
  • The odds of having a fibrosis progression rates > 0.15 was 1.18 times, or 18%, higher in people with more bacterial DNA.
  • Participants with high bacterial DNA levels > 175 copies/mL had the greatest likelihood of having higher fibrosis scores (odds ratio [OR] 3.04, or 3 times higher risk).
  • This group also was more likely to have more rapid fibrosis progression rates (OR 2.97, or nearly 3-fold higher risk).

Based on these findings, the study authors concluded, "Our data show that bacterial translocation is associated with severe liver disease among HIV infected patients with chronic hepatitis C."

"Future studies are needed to validate these results and to evaluate whether plasma levels of bacterial DNA are a predictive and/or surrogate marker of liver disease in HIV/hepatitis C coinfected patients," they added.

10/16/12

Reference

M García-Álvarez, J Berenguer, M Guzman-Fulgencio, et al. Bacterial DNA translocation and liver disease severity among HIV infected patients with chronic hepatitis C. Journal of Acquired Immune Deficiency Syndromes. August 28, 2012 (Epub ahead of print).