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

Shah, Shailja C.; Ma, Yifei; Scherzer, Rebecca; Huhn, Greg; French, Audrey L.; Plankey, Michael; Peters, Marion G.; Grünfeld, Carl; Tien, Phyllis C.

doi:10.1097/qad.0000000000000654

Cited by 42 publications

(46 citation statements)

References 31 publications

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“…However, CRP, which was almost 50% higher in frail HIV+ men than in non-frail HIV+ men, was essentially identical in frail and nonfrail HIV− men. This discrepancy may be due at least in part to our deliberate inclusion of all HCV-infected HIV− men in the parent biomarker study; this infection can lower CRP levels 33 and was much more common in the HIV− frail men (42%) than in the HIV− nonfrail men (13%). Taken together, the present data suggest that inflammation is associated with frailty in HIV+ men as it is in elderly HIV− populations, but that the mechanisms of this association may differ between HIV− and HIV+ people in the age range studied here.…”

Section: Discussionmentioning

confidence: 98%

Frailty and Circulating Markers of Inflammation in HIV+ and HIV− Men in the Multicenter AIDS Cohort Study

Margolick

Bream

Martı́nez-Maza

et al. 2017

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background Frailty is associated with immune activation and inflammation in the elderly general population, but whether this is true in the younger HIV-infected (HIV+) population is not known. Methods We analyzed 24 serologic biomarkers of monocyte, T cell, or B cell activation in HIV− (n=207) and HIV+ (n=714; 75% virologically suppressed) men who have sex with men in the Multicenter AIDS Cohort Study and were classified as frail or nonfrail according to expression or non-expression of the frailty phenotype at two consecutive study visits. Results After correction for multiple comparisons and adjustment for age, race, study site, and education, frailty in HIV+ men was significantly (p<0.002) associated with higher levels of sCD14, sIL2Rα, sTNF-R2, IL-6, and TNF-α; the association with higher levels of C-reactive protein (CRP) approached significance (p=.003). After further adjustment for BMI, smoking, and co-morbidities, only the association with CRP was significant at p<0.002, with levels approximately 50% higher in frail compared to nonfrail men. These conclusions were not altered by restricting the analysis to HIV+ men who were virologically suppressed. Among HIV− men, none of these markers differed significantly by frailty. Conclusion These data suggest that frailty in virologically suppressed HIV+ men was associated with immune activation beyond that due to treated HIV infection. The inflammatory markers associated with frailty were primarily products of activated monocytes/macrophages. Much, but not all, activation was accounted for by harmful behaviors and comorbidities. However, CRP, which is regulated by IL-6, was elevated in HIV+ frail men independent of these factors.

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Section: Discussionmentioning

confidence: 98%

Frailty and Circulating Markers of Inflammation in HIV+ and HIV− Men in the Multicenter AIDS Cohort Study

Margolick

Bream

Martı́nez-Maza

et al. 2017

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…It is also possible that HCV itself is protective against HS, although the cross‐sectional nature of this study limits our ability to demonstrate this. C‐reactive protein levels are substantially reduced in the setting of chronic HCV, due in part to an attenuated response to interleukin (IL)‐6 in the presence of HCV . Both hepatic and serum levels of IL‐6 are elevated in patients with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, suggesting a role of IL‐6 in the pathogenesis of HS.…”

Section: Discussionmentioning

confidence: 99%

Human immunodeficiency virus–infected and uninfected adults with non–genotype 3 hepatitis C virus have less hepatic steatosis than adults with neither infection

Price

Scherzer

et al. 2017

Hepatology

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Background Hepatic steatosis (HS) is common in persons with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections, but the independent contributions of HCV and HIV to HS is unclear. Methods Magnetic resonance imaging and spectroscopy were used to measure visceral adipose tissue (VAT) and liver fat fraction (LFF) [total lipids/(total lipids+water)] in 356 adults: 57 HCV-monoinfected, 70 HIV/HCV-coinfected, 122 HIV-monoinfected, and 107 HIV/HCV-uninfected. Genotype 3 HCV-infected participants were excluded due to the genotype's reported steatogenic effects. For prevalence estimates, HS was defined as LFF≥0.05. We estimated the association of HIV and HCV status with LFF using multivariable linear regression, adjusting for demographic, lifestyle, and metabolic factors including the homeostasis model assessment estimate of insulin resistance (HOMA-IR) and liver fibrosis defined using the AST-to-platelet ratio index (APRI). Results The prevalence of HS was highest in the uninfected(33%) and HIV-monoinfected(28%), followed by the HCV-monoinfected(19%) and HIV/HCV-coinfected(11%)(p=0.003 across groups). Compared to uninfected participants, after adjusting for demographic, lifestyle, and metabolic factors, HIV monoinfection, HCV monoinfection and HIV/HCV coinfection were associated with 19%(95%CI:-39%,6%), 38%(95%CI:-55%,-12%) and 42%(95%CI:-59%,-18%) lower LFF, respectively. HCV monoinfection and HIV/HCV coinfection remained strongly associated with lower LFF after further adjusting for APRI, and results were unchanged after excluding subjects with suspected cirrhosis. Among the entire cohort, Hispanic ethnicity, male sex, VAT, and HOMA-IR were independently associated with greater LFF. Conclusions Contrary to expectations, HIV/HCV-coinfected and HCV-monoinfected adults had significantly less liver fat than uninfected adults, even after adjusting for demographic, lifestyle, metabolic factors, and hepatic fibrosis. Our findings suggest that non-genotype 3 HCV infection may be protective against HS. The mechanisms by which this occurs and impact of HCV treatment on HS need investigation.

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“…Sixteen studies have evaluated the effect of both HIV mono‐infection and HIV/HCV co‐infection on inflammatory biomarkers. (Table and Table S4) The majority of studies have found that HCV co‐infection further increases the serum levels of IL‐6, IL‐10, and sTNFRI but decreases levels of CRP or hsCRP irrespective of liver function . Shah et al found that CRP levels fell with increasing IL‐6 levels suggesting attenuation of the CRP‐related IL‐6 response .…”

Section: Special Populationsmentioning

confidence: 99%

“…(Table 3 and Table S3) Among CHC patients, elevated levels of BNP, NT-proBNP, 50,51,67,99,[125][126][127][128][129] TnT, and TnI 103,128 have been observed compared to healthy controls. ( Table 4 and Table S4) The majority of studies have found that HCV co-infection further increases the serum levels of IL-6, 133-138 IL-10, 139 and sTNFRI 138 but decreases levels of CRP or hsCRP 133,134,136,[140][141][142] irrespective of liver function. 133 Shah et al found that CRP levels fell with increasing IL-6 levels suggesting attenuation of the CRP-related IL-6 response.…”

Section: Biomarkers Of Cardiac Dysfunctionmentioning

confidence: 99%

Inflammatory and cardiovascular diseases biomarkers in chronic hepatitis C virus infection: A review

Babiker

Hassan

Muhammed

et al. 2019

Clinical Cardiology

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Hepatitis C virus (HCV) infects 180 million people worldwide and over 4 million people in the United States. HCV infection is a major cause of chronic liver disease and is recognized as a risk factor for clinical cardiovascular disease (CVD). Many studies have shown increased prevalence of cardiac and inflammatory biomarkers in patients with chronic HCV infection (CHC), and though these markers may be used to risk stratify people for cardiac disease in the general population their role in the HCV population is unknown. Patients with CHC have elevated cardiac and inflammatory biomarkers compared to noninfected controls which may play a role in CVD risk stratification. We undertook a systematic review of inflammatory and cardiac biomarkers in people with HCV infection with a focus on the effect of CHC on serum levels of these markers and their utility as predictors of CVD in this population. Medline, EMBASE, and Cochrane databases were searched for relevant articles until June 2019. A total of 2430 results were reviewed with 115 studies included. Our review revealed that HCV infection significantly alters serum levels of markers of inflammation, endothelial function, and cardiac dysfunction prior to HCV treatment, and some of which may change in response to HCV therapy. Current risk stratification tools for development of CVD in the general population may not account for the increased inflammatory markers that appear to be elevated among HCV‐infected patients contributing to increased CVD risk.

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

Cited by 42 publications

References 31 publications

Frailty and Circulating Markers of Inflammation in HIV+ and HIV− Men in the Multicenter AIDS Cohort Study

Frailty and Circulating Markers of Inflammation in HIV+ and HIV− Men in the Multicenter AIDS Cohort Study

Human immunodeficiency virus–infected and uninfected adults with non–genotype 3 hepatitis C virus have less hepatic steatosis than adults with neither infection

Inflammatory and cardiovascular diseases biomarkers in chronic hepatitis C virus infection: A review

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