The effect of hepatitis C virologic clearance on cardiovascular disease biomarkers in human immunodeficiency virus/hepatitis C virus coinfection

Abstract

Background: Successful hepatitis C virus (HCV) treatment may reduce cardiovascular disease (CVD) risk and improve levels of CVD biomarkers produced outside the liver (nonhepatic biomarkers).

Methods: Stored serum or plasma from before and 24 weeks after end of HCV treatment (EOT) from human immunodeficiency virus (HIV)/HCV-coinfected subjects who received up to 72 weeks of peginterferon/ribavirin, 27 with and 27 without sustained virologic response (SVR) matched by race, ethnicity and sex, were tested for nonhepatic (soluble intercellular adhesion molecule-1 [sICAM-1], soluble P-selectin [sP-selectin], interleukin [IL]-6, d-dimer, and lipoprotein-associated phospholipase A2 [Lp-PLA2]) and hepatic (cholesterol and high-sensitivity C-reactive protein) CVD and macrophage activation markers (soluble CD163 [sCD163] and soluble CD14). Changes in biomarkers and their association with SVR were examined by t tests or Wilcoxon tests and regression models.

Results: Of the 54 subjects, 30 were white, 24 were black, and 44 were male. Pretreatment levels of nonhepatic biomarkers were high: sICAM-1 overall median, 439.2 ng/mL (interquartile range [IQR], 365.6-592.8]; sP-selectin, 146.7 ng/mL (IQR, 94.1-209.9), and IL-6, 2.32 pg/mL (IQR, 1.61-3.49). Thirty-seven of 52 (71%) subjects had Lp-PLA2 >235 ng/mL. Sustained virologic response was associated with decrease in sICAM-1 (P = .033) and sCD163 (P = .042); this result was attenuated after controlling for changes in the alanine aminotransferase level. At 24 weeks after EOT, 17 (63%) SVRs had Lp-PLA2 >235 ng/mL vs 25 (93%) non-SVRs (P = .021).

Conclusions: Hepatitis C virus clearance may reduce hepatic and, subsequently, systemic inflammation and CVD risk in HIV/HCV coinfection.

Keywords: HIV/HCV coinfection; cholesterol; macrophage activation; sustained virologic response; vascular adhesion molecules.

Figure 1.

Effect of SVR on biomarker levels. The length of the box represents the interquartile range (distance between the 25th and 75th percentiles), the horizontal lines within the boxes represent the group median, the diamonds represent the group mean, the whiskers represent the minimum and maximum values within a distance of 1.5 times the IQR below the 25th percentile and above the 75th percentile, and the open circles represent outliers. P values provided are based on ^abetween-group and ^bwithin-group t tests; for sICAM-1 and sCD163, t tests were conducted on log₁₀-transformed values. Abbreviations: EOT, end of HCV treatment; LDL, low-density lipoprotein cholesterol; Lp-PLA₂, lipoprotein-associated phospholipase A₂; sCD163, soluble CD163; sCD14, soluble CD14; sICAM-1, soluble intercellular adhesion molecule-1; SVR, sustained virologic response.

Figure 2.

(A) Regression of change in log₁₀ soluble intercellular adhesion molecule-1 (sICAM-1) after backward variable selection. Variables included in backward variable selection: baseline hepatic fibrosis stage, baseline hepatitis C virus (HCV) RNA level, HCV treatment history (naive or experienced), baseline aspartate aminotransferase (AST), and baseline alanine aminotransferase (ALT) level. (B) Regression of change in log₁₀ sICAM-1 with backward variable selection and adjusting for change in ALT level from baseline to 24 weeks after end of HCV treatment.

Figure 3.

(A) Regression of change in log₁₀ soluble CD163 (sCD163) after backward variable selection. Variables included in backward variable selection: baseline hepatic fibrosis stage, baseline hepatitis C virus (HCV) RNA level, HCV treatment history (naive or experienced), baseline aspartate aminotransferase (AST), and baseline alanine aminotransferase (ALT) level. (B) Regression of change in log₁₀ sCD163 with backward variable selection and adjusting for change in alanine aminotransferase (ALT) level from baseline to 24 weeks after end of HCV treatment. (C) Regression of change in log₁₀ sCD163 with backward variable selection and adjusting for duration of pegylated interferon plus ribavirin (PEG/RBV) therapy.

Figure 4.

Effect of SVR on cardiovascular risk class by Lp-PLA₂ level. The Lp-PLA₂ levels are provided in ng/mL. Abbreviations: EOT, end of hepatitis C virus treatment; Lp-PLA₂, lipoprotein-associated phospholipase A₂; SVR, sustained virologic response.