Bacterial translocation is associated with more severe liver fibrosis in HIV/hepatitis C-co-infected people
People with more advanced fibrosis and faster progression of liver disease have higher levels of intestinal bacteria in their blood than those without these markers of liver disease.
The presence of intestinal bacteria in blood (bacterial translocation) is associated with more severe liver disease in people who are co-infected with HIV and hepatitis C virus, Spanish investigators report in the online edition of the Journal of Acquired Immune Deficiency Syndromes.
Large numbers of HIV-positive people are co-infected with hepatitis C virus. Liver disease caused by hepatitis C is an important cause of serious illness and death in these patients.
The pace of liver disease is faster in co-infected people than in those who are hepatitis C-monoinfected. However, the reasons for this are unclear.
Bacterial translocation is the mechanism by which some enteric conditions cause liver disease. Infection with HIV has also been associated with bacterial translocation. This may cause the chronic immune activation that contributes to the accelerated course of liver disease seen in co-infected people.
Investigators in Madrid wanted to establish a clearer understanding of bacterial translocation in co-infected people and the association between the severity of bacterial translocation and the extent and pace of liver disease.
They therefore designed a study involving 255 co-infected people who had undergone a liver biopsy between 2000 and 2007. In addition,100 HIV/hepatitis C-uninfected people who had been blood donors were included as controls. All participants had tests to see if they had the DNA of intestinal bacteria in their blood. The stage and pace of liver fibrosis was assessed in those with HIV and hepatitis C.
The co-infected participants had a median age of 40, three-quarters were men, and their median CD4 cell count was 483 cells/mm3. Most (85%) were taking antiretroviral therapy and 71% had an undetectable viral load.
Baseline hepatitis C viral load was above 500,000 IU/ml in 73% of co-infected participants.
Significant fibrosis was present in 53% of patients and 27% had advanced fibrosis.
Intestinal bacteria were detectable in the blood of 96% of co-infected participants compared to 7% of controls (p < 0.001).
Moreover, co-infected participants with a CD4 cell count below 350 cells/mm3 had significantly higher levels of bacteria in their blood than those with CD4 cell counts above this level (157 vs 112 copies/ml, p = 0.03).
“HIV/hepatitis C virus-co-infected patients had higher plasma levels of bacterial DNA than healthy controls,” write the investigators. “Patients with CD4 cell counts < 350 cells/mm3 had higher plasma bacterial DNA than those with CD4 cell counts above 350 cells/mm3.”
People with more advanced fibrosis and faster progression of liver disease had higher levels of intestinal bacteria in their blood than those without these markers of liver disease (p < 0.05).
Each 100 copy/ml increase in bacterial load increased by 20% the chance of having a higher fibrosis score (OR = 1.20; 95% CI, 1.00-1.44, p = 0.045). Participants with a bacterial load above 175 copies/ml had the highest risk of having more advanced liver fibrosis (OR = 3.04; 95% CI, 1.37-6.75, p = 0.006) and faster progression of liver disease (OR = 2.97; 95% CI 1.24-7.09, p = 0.014).
“Our data show that bacterial translocation was associated with severe liver disease among HIV infected patients with chronic hepatitis C,” conclude the authors. “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-co-infected patients.”
By Michael Carter
Garcia-Alvarez M et al. Bacterial DNA translocation and liver disease severity among HIV infected patients with chronic hepatitis C. J Acquir Immune Defic Syndr, online edition. DOI: 10.1097/QAD.0b013e31826ea109, 2012.