Involvement of CD95 and ligand in CD4+ T-cell and CD8+ T-cell depletion and hepatic cytolysis in patients with chronic viral hepatitis B.

Franklin S Azebaze Agueguia,Marie C Okomo Assoumou,Emilia Lyonga,Graeme B Jacobs,George Mondinde Ikomey,Cedric H Mbakam,Martha Tongo Mesembe,Paul Talla,Elise Guiedem

doi:10.4102/ajlm.v10i1.1224

Franklin S Azebaze Agueguia, Marie C Okomo Assoumou + Show 7 more

Open Access

https://doi.org/10.4102/ajlm.v10i1.1224

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Abstract

BackgroundChronic viral hepatitis B (HBV) is characterised by progressive hepatocyte destruction and T-cell depletion. The mechanisms of the CD95-CD95 ligand (CD95L) signalling pathway during this chronic disease and the cirrhotic process remains unclear.ObjectiveWe evaluated the involvement of the CD95-CD95L receptor-ligand system in T-cell depletion and hepatic cytolysis in patients with chronic HBV.MethodsThis was a cross-sectional study conducted from September to December 2018 at the Yaoundé General Hospital, Cameroon. Four mL of whole blood was collected and analysed. The CD95 and CD95L levels, as well as the CD4+ T-cell and CD8+ T-cell counts, were performed by enzyme-linked immunosorbent assay and flow cytometry.ResultsOf the 130 HBV-positive patients, 36 (27.7%) were cirrhotic and 94 (72.3%) were non-cirrhotic. The cirrhotic patients had significantly elevated CD95 (p < 0.001) and CD95L (p = 0.001) plasma levels, compared with non-cirrhotic patients. The CD4/CD8 ratios were lower in cirrhotic patients, compared to non-cirrhotic patients (p < 0.001). There were statistically significant correlations between CD95 level and CD4+ T-cell counts, between CD95 level and CD8+ T-cell counts, between CD95 level and the CD4/CD8 ratio, between CD95 level and fibrosis score, and between CD95L level and fibrosis score.ConclusionCD95 and CD95L could be involved in T-cell depletion and hepatic cytolysis during the pathogenesis of chronic HBV and could potentially be used as biomarkers for immunological and hepatic monitoring in patients with chronic HBV.

Highlights

The hepatitis B virus (HBV) is the leading cause of chronic liver disease and remains a major global health burden.[1]
These results corroborate those of Peter et al.: they observed low constitutive expression of CD95 in non-cirrhotic patients with chronic HBV, compared to patients with cirrhosis related to HBV.[8]
The expression of CD95 increases in response to a primary stimulus and this makes hepatocytes more susceptible to stimulation by CD95 ligand (CD95L). This hypothesis is supported by the observation that induction of CD95 expression occurs following chronic lymphatic histiocytic inflammation in different epithelial cells.[6]. These results suggest that liver damage in HBV-infected patients may primarily involve the destruction of hepatocytes by T-cells using the CD95-CD95L receptor-ligand system

Summary

Introduction

The hepatitis B virus (HBV) is the leading cause of chronic liver disease and remains a major global health burden.[1]. The severity of liver lesions caused by infection varies according to the immune status of the patient.[2] An appropriate immune response leads to the necrosis of infected hepatocytes and the elimination of the virus.[1] An excessive immune response induces massive hepatocyte destruction, while immunotolerance is marked by abundant but asymptomatic viral multiplication without destruction of hepatocytes.[3] In chronic carriers of HBV, this immune response exists, but it is insufficient to eliminate the virus.[3]. Chronic viral hepatitis B (HBV) is characterised by progressive hepatocyte destruction and T-cell depletion. The mechanisms of the CD95-CD95 ligand (CD95L) signalling pathway during this chronic disease and the cirrhotic process remains unclear

Results

Discussion

Conclusion