Abstract

Type II diabetes (T2D) may worsen the course of hepatitis C virus infection with a greater risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). In chronic viral infections, the deranged B cell subset signifies uncontrolled disease. The study aimed to verify the relation between B cell subsets’ distribution and liver disease progression in chronic hepatitis C (CHC) patients with T2D. A total of 67 CHC patients were divided into two groups; 33 non-diabetic and 34 with T2D. Each group was subdivided into CHC-without LC or HCC (N-CHC), CHC-with LC (CHC-LC), and CHC-with HCC (CHC-HCC). Twenty-seven healthy individuals also participated as controls. Flow cytometry was used to analyze CD19+ B cell subsets based on the expression of CD24 and CD38. CD19+CD24hiCD38hi Immature/transitional B cells elevated in diabetic than non-diabetic patients. In diabetic patients, while CD19+CD24+CD38− primarily memory B cells were higher in CHC-N and CHC-HCC groups than LC with a good predictive accuracy of LC, the opposite was observed for CD19+CD24−CD38− new memory B cells. Only in diabetic patients, the CD19+CD24intCD38int naïve mature B cells were high in CHC-HCC patients with good prognostic accuracy of HCC. Merely in diabetic patients, several correlations were observed between B cell subsets and liver function. Immature/transitional B cells increase remarkably in diabetic CHCpatients and might have a role in liver disease progression. Memory and Naïve B cells are good potential predictors of LC and HCCin diabetic CHCpatients, respectively. Further studies are needed to investigate the role of the CD19+CD24−CD38− new memory B cells in disease progression in CHC patients.

Highlights

  • Materials and methodsA total of 67 chronic hepatitis C (CHC) patients presented to Al Rajhi Liver Hospital, Assiut, Egypt (tertiary care university hospital) were enrolled in this case–control study

  • Hepatitis C virus (HCV) is the leading cause of chronic liver disease that can eventually lead to liver cirrhosis (LC) and hepatocellular carcinoma (HCC)[1]

  • The ­CD19+ B cells were selected for further analysis of B cell subsets based on the expression of CD24 and CD38. ­CD19+CD24hiCD38hi were considered as immature/transitional B cells, C­ D19+CD24intCD38int are naïve mature B cells, C­ D19+CD24+CD38− are primarily memory B cells, C­ D19+CD24−CD38+ are plasmablasts and ­CD19+CD24−CD38− are new memory B cells

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Summary

Materials and methods

A total of 67 CHC patients presented to Al Rajhi Liver Hospital, Assiut, Egypt (tertiary care university hospital) were enrolled in this case–control study. Ten microliters of each of the monoclonal antibodies (CD19, CD 24, and CD38) were added to the pellet. Appropriate isotype controls were processed in a parallel manner without adding B cell monoclonal antibodies. Cell Quest software (BD, USA) was used for flow cytometric analysis. The ­CD19+ B cells were selected for further analysis of B cell subsets based on the expression of CD24 and CD38. The different B cell subsets were expressed as percentages within the ­CD19+ lymphocytes (Fig. 1). Between groups difference was investigated by the multivariate analysis of covariance (MANCOVA) with age and sex as covariates. Statistical analysis was performed by the SPSS version 20.0 software (IBM, USA)

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