Background:  HIV infection increases hepatitis C virus (HCV) persistence, the plasma abundance of HCV RNA, and cirrhosis incidence, but the mechanisms are unknown. HIV-related systemic immune activation has been linked with microbial translocation, as represented by plasma lipopolysaccharide (LPS), LPS binding protein, soluble CD14 (sCD14), Aleuria aurantia lectin, a lectin-reactive IgG that recognizes a-Gal epitopes, and endotoxin-core antibodies, which bind and neutralize LPS.

Methods:  To test the hypothesis that immune activation is associated with progression of HCV-related liver disease, we studied 23 subjects with cirrhosis and 104 controls with 2 biopsies >3 years apart with minimal fibrosis. Serum contemporaneous with disease was tested as was serum collected as early as 10 years previously on a subset. By using Spearman correlation coefficients, we correlated clinical data with levels of LPS, LPS binding protein, sCD14, A. aurantia lectin, and endotoxin-core antibodies  

Results:  Subjects with cirrhosis had elevated LPS (p <0.0001), sCD14 (p = 0.04), A. aurantia lectin (p = 0.01), as well as lower levels of endotoxin-core antibodies (p = 0.03). Likewise, 29 HIV-infected subjects had increased LPS (p = 0.01), LPS binding protein (p = 0.002), sCD14 (p = 0.01), and lower levels of endotoxin-core antibodies (p = 0.007) compared with 59 HIV-uninfected subjects. In these subjects and in a subset of HIV seroconverters, significant differences in microbial translocation were not detected until CD4 counts <350/mm³. Elevations in LPS antedated cirrhosis and, in a multivariate logistic regression model containing each inflammatory molecule and HIV infection, all associations with cirrhosis were sustained. Interestingly, after accounting for these factors, the strength of the association of HIV and cirrhosis was diminished.

Conclusions:  Markers of microbial translocation are strongly associated with both HCV-related cirrhosis and HIV infection suggesting immune activation may be a common pathogenic mechanism.