Dysfunctional B-cell Activation in Cirrhosis Resulting from Hepatitis C Infection Associated with Disappearance of CD27-positive B-cell Population
Overview
Authors
Affiliations
Unlabelled: Chronic hepatitis C virus (HCV) infection is a leading cause of cirrhosis and hepatocellular carcinoma (HCC). Both advanced solid tumors and HCV have previously been associated with memory B-cell dysfunction. In this study, we sought to dissect the effect of viral infection, cirrhosis, and liver cancer on memory B-cell frequency and function in the spectrum of HCV disease. Peripheral blood from healthy donors, HCV-infected patients with F1-F2 liver fibrosis, HCV-infected patients with cirrhosis, patients with HCV-related HCC, and non-HCV-infected cirrhotics were assessed for B-cell phenotype by flow cytometry. Isolated B cells were stimulated with anti-cluster of differentiation (CD)40 antibodies and Toll-like receptor (TLR)9 agonist for assessment of costimulation marker expression, cytokine production, immunoglobulin (Ig) production, and CD4(+) T-cell allostimulatory capacity. CD27(+) memory B cells and, more specifically, CD27(+) IgM(+) B cells were markedly less frequent in cirrhotic patients independent of HCV infection. Circulating B cells in cirrhotics were hyporesponsive to CD40/TLR9 activation, as characterized by CD70 up-regulation, tumor necrosis factor beta secretion, IgG production, and T-cell allostimulation. Last, blockade of TLR4 and TLR9 signaling abrogated the activation of healthy donor B cells by cirrhotic plasma, suggesting a role for bacterial translocation in driving B-cell changes in cirrhosis.
Conclusion: Profound abnormalities in B-cell phenotype and function occur in cirrhosis independent of HCV infection. These B-cell defects may explain, in part, the vaccine hyporesponsiveness and susceptibility to bacterial infection in this population.
Jordens M, Oswald H, Heinrichs L, Gassmann N, Wittig L, Luedde T World J Surg Oncol. 2025; 23(1):9.
PMID: 39762956 PMC: 11705658. DOI: 10.1186/s12957-024-03651-8.
Infections in decompensated cirrhosis: Pathophysiology, management, and research agenda.
Ferguson Toll J, Sola E, Perez M, Piano S, Cheng A, Subramanian A Hepatol Commun. 2024; 8(10).
PMID: 39365139 PMC: 11458171. DOI: 10.1097/HC9.0000000000000539.
Liver Cirrhosis: The Immunocompromised State.
Rodriguez-Negrete E, Galvez-Martinez M, Sanchez-Reyes K, Fajardo-Felix C, Perez-Resendiz K, Madrigal-Santillan E J Clin Med. 2024; 13(18).
PMID: 39337069 PMC: 11432654. DOI: 10.3390/jcm13185582.
Li Y, Quan X, Tai Y, Wu Y, Wei B, Wu H World J Hepatol. 2024; 16(8):1156-1166.
PMID: 39221101 PMC: 11362904. DOI: 10.4254/wjh.v16.i8.1156.
A Comprehensive Review of Hepatitis B Vaccine Nonresponse and Associated Risk Factors.
Tahir A, Shinkafi S, Alshrari A, Yunusa A, Umar M, Hudu S Vaccines (Basel). 2024; 12(7).
PMID: 39066348 PMC: 11281605. DOI: 10.3390/vaccines12070710.