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. 2019 Jul 26;6(10):ofz347.
doi: 10.1093/ofid/ofz347. eCollection 2019 Oct.

Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as Prognostic Inflammatory Biomarkers in Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), and HIV/HCV Coinfection

Jennifer S Hanberg  1   2 , Matthew S Freiberg  3 , Matthew B Goetz  4   5 , Maria C Rodriguez-Barradas  6   7 , Cynthia Gibert  8 , Kris Ann Oursler  9   10 , Amy C Justice  1   2 , Janet P Tate  1   2 ; VACS Project Team
Affiliations

Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as Prognostic Inflammatory Biomarkers in Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), and HIV/HCV Coinfection

Jennifer S Hanberg et al. Open Forum Infect Dis. .

Abstract

Background: Inflammation in human immunodeficiency virus (HIV)-infected patients is associated with poorer health outcomes. Whether inflammation as measured by the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) adds information to existing prognostic indices is not known.

Methods: We analyzed data from 2000 to 2012 in the Veterans Aging Cohort Study (VACS), overall and stratified by HIV/hepatitis C virus status (n = 89 786). We randomly selected a visit date at which all laboratory values of interest were available within 180 days; participants with HIV received at least 1 year of antiretroviral therapy. We followed patients for (1) mortality and (2) hepatic decompensation (HD) and analyzed associations using Cox regression, adjusted for a validated mortality risk index (VACS Index 2.0). In VACS Biomarker Cohort, we considered correlation with biomarkers of inflammation: interleukin-6, D-dimer, and soluble CD-14.

Results: Neutrophil-to-lymphocyte ratio and PLR demonstrated strong unadjusted associations with mortality (P < .0001) and HD (P < .0001) and were weakly correlated with other inflammatory biomarkers. Although NLR remained statistically independent for mortality, as did PLR for HD, the addition of NLR and PLR to the VACS Index 2.0 did not result in significant improvement in discrimination compared with VACS Index 2.0 alone for mortality (C-statistic 0.767 vs 0.758) or for HD (C-statistic 0.805 vs 0.801).

Conclusions: Neutrophil-to-lymphocyte ratio and PLR were strongly associated with mortality and HD and weakly correlated with inflammatory biomarkers. However, most of their association was explained by VACS Index 2.0. Addition of NLR and PLR to VACS 2.0 did not substantially improve discrimination for either outcome.

Keywords: HCV; NLR; PLR; hepatic decompensation; inflammation.

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Figures

Figure 1.
Figure 1.
Hazard ratios for all-cause mortality associated with neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Levels defined by equal numbers of deaths. Error bars represent 95% confidence intervals. A and C are age-adjusted; B and D are adjusted for Veterans Aging Cohort Study (VACS) 2.0. A and B analyze NLR as an independent variable; C and D analyze PLR as an independent variable. HCV, hepatitis C virus; HIV, human immunodeficiency virus.
Figure 2.
Figure 2.
Hazard ratios for hepatic decompensation (HD) associated with neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Levels defined by equal numbers of HD events. Error bars represent 95% confidence intervals. A and C are age-adjusted; B and D are adjusted for Veterans Aging Cohort Study (VACS) 2.0. A and B analyze NLR as an independent variable; C and D analyze PLR as an independent variable. HCV, hepatitis C virus; HIV, human immunodeficiency virus.
Figure 3.
Figure 3.
Forest plot of C-statistics (death outcome). Center dots represent Harrell’s c; whiskers represent 95% confidence intervals. Left column denotes subgroup; second column indicates covariates in each model. Covariates include categorical neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) and continuous Veterans Aging Cohort Study (VACS) 2.0. Overall cohort includes individuals without documentation of hepatitis C virus (HCV) status. HIV, human immunodeficiency virus.
Figure 4.
Figure 4.
Forest plot of C-statistics (hepatic decompensation outcome). Center dots represent Harrell’s c; whiskers represent 95% confidence intervals. Left column denotes subgroup; second column indicates covariates in each model. Covariates include categorical categorical neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) and continuous Veterans Aging Cohort Study (VACS) 2.0. Overall cohort includes individuals without documentation of HCV status.
See this image and copyright information in PMC

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