Publications

BACKGROUND

Hepatitis C virus (HCV) infection is associated with chronic inflammation; yet studies show greater interleukin (IL)-6, but lower C-reactive protein (CRP) levels. We determined whether liver fibrosis severity and HCV replication affect the ability of IL-6 to stimulate the production of CRP from the liver.

METHODS

We used multivariable generalized linear regression to examine the association of HIV, HCV and transient elastography-measured liver stiffness with IL-6 and CRP in participants (164 HIV-monoinfected; 10 HCV-monoinfected; 73 HIV/HCV-coinfected; 59 neither infection) of the Women's Interagency HIV Study. Significant fibrosis was defined as liver stiffness greater than 7.1 kPa.

RESULTS

IL-6 was positively correlated with CRP levels in all women, but CRP levels were lower in HCV-infected women (with and without HIV infection) at all levels of IL-6. HCV-infected women with fibrosis had nearly 2.7-fold higher IL-6 levels compared to controls [95% confidence interval (CI 146%, 447%]; HCV-infected women without fibrosis had IL-6 levels that were similar to controls. By contrast, CRP was 28% lower in HCV-infected women with fibrosis (95% CI -55%, 15%) and 47% lower in HCV-infected women without fibrosis (95% CI -68%, -12%). Among the HCV-infected women, higher HCV-RNA levels were associated with 9% lower CRP levels per doubling (95% CI -18%, 0%).

CONCLUSION

Liver fibrosis severity is associated with greater IL-6 levels, but the stimulatory effect of IL-6 on CRP appears to be blunted by HCV replication rather than by liver fibrosis severity. Investigation of the potential CRP rebound after HCV-RNA eradication and persistent liver fibrosis on organ injury is needed.

Tuberculosis (TB) remains an important cause of hospitalization and mortality in the United States. Prevention of TB transmission in acute care facilities relies on prompt identification and implementation of airborne isolation, rapid diagnosis, and treatment of presumptive pulmonary TB patients. In areas with low TB burden, this strategy may result in inefficient utilization of airborne infection isolation rooms (AIIRs). We reviewed TB epidemiology and diagnostic approaches to inform optimal TB detection in low-burden settings. Published clinical prediction rules for individual studies have a sensitivity ranging from 81% to 100% and specificity ranging from 14% to 63% for detection of culture-positive pulmonary TB patients admitted to acute care facilities. Nucleic acid amplification tests (NAATs) have a specificity of >98%, and the sensitivity of NAATs varies by acid-fast bacilli sputum smear status (positive smear, ≥95%; negative smear, 50%-70%). We propose an infection prevention strategy using a clinical prediction rule to identify patients who warrant diagnostic evaluation for TB in an AIIR with an NAAT. Future studies are needed to evaluate whether use of clinical prediction rules and NAATs results in optimized utilization of AIIRs and improved detection and treatment of presumptive pulmonary TB patients.