Correlates of Elevated Interleukin-6 and C-Reactive Protein in Persons With or at High Risk for HCV and HIV Infections

Abstract

Background HIV and HCV infections may increase interleukin-6 (IL-6) and C-reactive protein (CRP). However, relationships between inflammatory biomarkers, chronic viral infections, clinical factors, and behavioral factors remain poorly understood. Methods Using linear regression, we modeled cross-sectional associations between loge IL-6 or loge CRP levels and HCV, HIV, injection drug use, and comorbidity among 1191 injection drug users. Results Mean age was 47 years, 46.0% reported currently injecting drugs, 59.0% were HCV-monoinfected, and 27% were HCV/HIV-coinfected. In multivariable models, higher loge IL-6 was associated with HCV monoinfection (β=0.191, 95%CI: 0.043 to 0.339) and HCV/HIV coinfection (β=0.394, 95% CI: 0.214 to 0.574). In contrast, HCV monoinfection (β=−0.523, 95%CI: −0.275 to −0.789) and HCV/HIV coinfection (β=−0.554 95%CI: −0.260 to −0.847) were associated with lower CRP. Lower CRP with HCV infection was independent of liver fibrosis severity, synthetic function, or liver injury markers; CRP decreased with higher HCV RNA. Increased injection intensity was associated with higher IL-6 (p=0.003) and CRP (p<0.001); increasing comorbidity (p<0.001) and older age (p=0.028) were associated with higher IL-6; older age was associated with higher CRP among HCV-uninfected participants (p=0.021). Conclusion HIV and HCV infections contribute to chronic inflammation; however, reduced CRP possibly occurs through HCV-virally-mediated mechanisms. Findings highlight potentially modifiable contributors to inflammation.

Association of HIV, hepatitis C virus and liver fibrosis severity with interleukin-6 and C-reactive protein levels

“…Our finding that HIV/HCV-coinfected women had greater IL-6 and lower CRP levels is consistent with a study by Salter et al in HCV-infected (with and without HIV infection) and uninfected adults [9]. That study also examined the association of liver markers (albumin, AST, and ALT) with CRP, but not with IL-6.…”

“…Salter et al also found little association of liver enzymes and markers of liver function with lower CRP [9], as did another small study of HIV/HCV-coinfected adults, but this latter study did not find a correlation of liver stiffness with either IL-6 or CRP [24]. Interestingly, in our study, HCV-infected women without fibrosis appeared to have a 47% lower CRP levels compared to the 28% lower CRP levels in those with fibrosis, suggesting that in the absence of fibrosis, the blunting effect of HCV infection on CRP production are not opposed by the stimulatory effect of IL-6 (observed in the presence of fibrosis).…”

“…[9, 10] Liver fibrosis severity and HCV replication are postulated mechanisms for the attenuated CRP level. The paucity of data describing the effect of liver fibrosis severity on IL-6 and CRP levels likely reflects the difficulties of pursuing liver biopsy in large numbers of patients.…”

Inflammatory, procoagulant markers and HIV residual viremia in patients receiving protease inhibitor monotherapy or triple drug therapy: a cross-sectional study

“…Interestingly, as in prior studies [3,8] hepatitis C coinfection was significantly associated to higher IL-6 level.…”

An Assay: Hepatitis C Doesn磘 Incite Increased C-Reactive Protein Level in Hemodialysis Patients Unless Another Inflammatory Condition is Associated

“…So, a few studies compared acute phase reactants in HCV, and the results are conflicting and not explicitly reported [7] . Another study showed that HIV/ HCV co infection is associated with higher Interleukin-6 but lower CRP levels [8] .…”