Plasma IP-10 and IL-6 are linked to Child-Pugh B cirrhosis in patients with advanced HCV-related cirrhosis: a cross-sectional study

Sergio Salgüero,Leire Pérez-Latorre,Salvador Resino,María L Montes,Pilar Garcia-Broncano,José María Bellóno,Luz Maria Medrano,Cristina Diéz,Juan Berenguer,Juan González-García,María Ángeles Jiménez-Sousa,Elba Llop-Herrera

doi:10.1038/s41598-020-67159-3

Abstract

We aimed to evaluate the association of plasma biomarkers linked to inflammation (bacterial translocation, inflammatory response, and endothelial dysfunction), coagulopathy, and angiogenesis with the severity of liver cirrhosis (assessed by the Child-Pugh-Turcotte score, CTP) and Child-Pugh B cirrhosis (CTP 7–9) in patients with advanced hepatitis C virus (HCV)-related cirrhosis. We carried out a cross-sectional study in 97 patients with advanced HCV-related cirrhosis (32 HCV-monoinfected and 65 HIV/HCV-coinfected). Plasma biomarkers were measured by ProcartaPlex multiplex immunoassays. The outcome variable was the CTP score and the Child-Pugh B cirrhosis (CTP 7–9). HIV/HCV-coinfected patients and HCV-monoinfected patients with advanced HCV-related cirrhosis had near-equivalent values of plasma biomarkers. Higher values of plasma biomarkers linked to an inflammatory response (IP-10, IL-8, IL-6, and OPG), endothelial dysfunction (sVCAM-1 and sICAM-1), and coagulopathy (D-dimer) were related to higher CTP values. The most significant biomarkers to detect the presence of Child-Pugh B cirrhosis (CTP 7–9) were IP-10 (p-value= 0.008) and IL-6 (p-value=0.002). The AUC-ROC values of IP-10, IL-6, and both biomarkers combined (IP-10+IL-6) were 0.78, 0.88, and 0.96, respectively. In conclusion, HIV infection does not appear to have a significant impact on the analyzed plasma biomarkers in patients with advanced HCV-related cirrhosis. However, plasma biomarkers linked to inflammation (inflammatory response and endothelial dysfunction) were related to the severity of liver cirrhosis (CTP score), mainly IP-10 and IL-6, which discriminated patients with Child-Pugh B concerning Child-Pugh A.

Highlights

We aimed to evaluate the association of plasma biomarkers linked to inflammation, coagulopathy, and angiogenesis with the severity of liver cirrhosis and Child-Pugh B cirrhosis (CTP 7–9) in patients with advanced hepatitis C virus (HCV)-related cirrhosis
human immunodeficiency virus (HIV)/HCV-coinfected patients had the lowest values of age (p-value
We found a significant association between plasma biomarkers linked to inflammation [inflammatory response (IP-10, IL-8, IL-6, and OPG) and endothelial dysfunction] and CTP score in all patients with advanced HCV-related cirrhosis so that the highest levels of these biomarkers were found in patients with greater severity of cirrhosis, suggesting a more pronounced inflammatory cirrhosis-associated immune dysfunction (CAID) phenotype, which is in line with previously published data in patients with severe cirrhosis[5,6]

Summary

Introduction

We aimed to evaluate the association of plasma biomarkers linked to inflammation (bacterial translocation, inflammatory response, and endothelial dysfunction), coagulopathy, and angiogenesis with the severity of liver cirrhosis (assessed by the Child-Pugh-Turcotte score, CTP) and Child-Pugh B cirrhosis (CTP 7–9) in patients with advanced hepatitis C virus (HCV)-related cirrhosis. HIV/HCV coinfection influences the natural history of chronic hepatitis C, accelerating the progression to cirrhosis and end-stage liver disease in comparison to HCV-monoinfected patients[9,10] This seems to be due to HIV infection that increases immune activation, HCV replication, HCV-induced hepatic inflammation, hepatocyte apoptosis, and microbial translocation[5,11], which, in turn, contribute to the pathogenesis of both acquired immunodeficiency syndrome (AIDS) and non-AIDS related diseases[12,13]. HCV clearance with direct-acting antiviral agents (DAAs) promotes a decrease of liver disease severity and plasma biomarkers linked to bacterial translocation, immune activation, inflammation and coagulopathy in HIV/HCV-coinfected patients[14,15,16,17,18] and HCV-monoinfected patients[16,17,19,20]. HIV/ HCV-coinfected patients must face drug-drug interactions and hurdles with antiviral treatments, which support that patients coinfected with HIV/HCV might still be regarded as a particular population[23]

Methods

Results

Conclusion