Influence of B cells in liver fibrosis associated with hepatitis B virus harboring basal core promoter mutations

Abstract

The development of the liver disease in chronic hepatitis B with common viral variants can be determined through the interaction between the virus and the host immune response. B cells constitute half of the intrahepatic lymphocyte population with an impact on fibrosis. A proliferation-inducing ligand (APRIL) has been shown to have a co-stimulatory activity on B cells. For this study HBV DNA was amplified and then sequenced to show the presence of the basal core promoter (BCP) mutations in the serum from 57 patients with chronic hepatitis B. The range of IgD-positive B cells was detected by immunohistochemistry in liver biopsies; and patients serum was assayed for APRIL levels by enzyme immunoassay. Twenty-seven patients (47.4%) harbored the A1762T-G1764A BCP mutations. Coefficients of logistic regression showed that the effect of increasing IgD-positive B cells in rising odds of the liver disease is the same in the patients with BCP mutation A1762T-G1764A and in the patients without mutation, nevertheless the effect of APRIL is not similar in these two groups of patients. Logistic regression in patients with BCP A1762T-G1764A mutations demonstrated that increasing one score of APRIL decreased the odds of fibrosis stage about 8%. These results suggest that in infection with viral variants of hepatitis B virus, the population of IgD-positive B cells may play a decisive role in later stages of the liver disease which is reduced by APRIL in chronic hepatitis patients with BCP mutations.

Antiviral treatment improves disrupted peripheral B lymphocyte homeostasis in chronic hepatitis B virus-infected patients

“…The percent of CD19 + CD3 − B cells in CHB patients was significantly higher than those in HD, consistent with recent data on chronic HCV infection. 31 B cells play a decisive role in fibrosis and later stages of liver disease, 32 though we did not find a significant difference in liver fibrosis stages.…”

Clinical Feature of Intrahepatic B-Lymphocytes in Chronic Hepatitis B

“…Moreover, it has been shown that the activation of B-cells, in a T-cell independent pathway, produced immunoglobulins and cytokines in the liver that changed fibrotic responses [11, 16]. Our recent study showed the association of IgD positive B-cells with the fibrosis stage in chronic hepatitis B [17]. The intrahepatic lymphocytes are recognized as long-lived recirculating B-cells and are similar to splenic B2 cells that produce cytokines IL-2, IL-4, TNF α , and IL-6 with proinflammatory function and contribute to disease pathogenesis in an antibody-independent fashion, perhaps by modulating T cell responses [16, 18].…”

The Possible Role of TLR2 in Chronic Hepatitis B Patients with Precore Mutation

“…Principally, the stop codon mutation at base 1896 creates the truncated precore peptide that might represents an adaptation to immune pressure [30]. The function of innate immune response as the first line of defense against virus infection as well as its cooperation with adaptive immunity may induce the development of precore mutant variants of HBV [11, 31, 32]. Therefore, the clinical significance of these mutations appears to be linked to the function of host immune system.…”

“…The impact of innate immunity in liver damage also has been identified in several studies [10, 11]. Toll-like receptors (TLRs) describe a group of pattern recognition receptors (PRRs) playing critical roles in the host innate immune response [12].…”