Abstract

BackgroundPrevious studies have revealed that hepatitis B virus (HBV) infection may be related to rheumatoid arthritis (RA), but there are no studies on the presence of HBV antigens or nucleic acid in synovium from patients with RA with HBV infection. In the present study, we investigated the presence of HBV in the synovium and its clinical significance in RA.MethodsFifty-seven consecutive patients with active RA (Disease Activity Score 28-joint assessment based on C-reactive protein ≥ 2.6) and available synovial tissue who had completed 1 year of follow-up were recruited from a prospective cohort. The patients were divided into chronic HBV infection (CHB, n = 11) and non-CHB groups according to baseline HBV infection status. Clinical data were collected at baseline and at 1-, 3-, 6-, and 12-month follow-up. Radiographic changes of hand/wrist at baseline and month 12 were assessed with the Sharp/van der Heijde-modified Sharp score (mTSS). HBV in synovium was determined by immunohistochemical staining for hepatitis B virus surface antigen and hepatitis B virus core antigen (HBcAg) and by nested PCR for the HBV S gene.ResultsHBcAg was found in the synovium of patients with RA with CHB (7 of 11, 64%), which was confirmed by PCR for the HBV S gene. Compared with the non-CHB group, more CD68-positive macrophages, CD20-positive B cells, and CD15-positive neutrophils infiltrated the synovium in the CHB group (all p < 0.05). There were smaller improvements from baseline in most disease activity indicators mainly at month 12, and a significantly higher percentage of CHB patients experienced 1-year radiographic progression (ΔmTSS ≥ 0.5 unit/yr, 64% vs. 26%, p = 0.024). Multivariate logistic regression analysis showed that CHB status (OR 14.230, 95% CI 2.213–95.388; p = 0.006) and the density of synovial CD68-positive macrophages (OR 1.002, 95% CI 1.001–1.003; p = 0.003) were independently associated with 1-year radiographic progression.ConclusionsThe presence of HBV in RA synovium may be involved in the pathogenesis of local lesions and exacerbate disease progression in RA.

Highlights

  • Previous studies have revealed that hepatitis B virus (HBV) infection may be related to rheumatoid arthritis (RA), but there are no studies on the presence of HBV antigens or nucleic acid in synovium from patients with RA with HBV infection

  • Joint damage, including joint erosion (JE) and joint space narrowing (JSN), was assessed with the Sharp/van der Heijde modified Sharp score by two experienced observers (JDM from the Department of Rheumatology and XZ from the Department of Radiology) who were blinded to clinical data as we described previously [15]

  • The results showed that Chronic hepatitis B virus infection (CHB) status, female sex, smoking status, and treatment-naïve status as well as higher baseline Modified total Sharp score (mTSS) were significantly associated with 1-year radiographic progression (Table 3)

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Summary

Introduction

Previous studies have revealed that hepatitis B virus (HBV) infection may be related to rheumatoid arthritis (RA), but there are no studies on the presence of HBV antigens or nucleic acid in synovium from patients with RA with HBV infection. Hepatitis B virus (HBV) infection is a major cause of chronic liver diseases, such as liver cirrhosis and hepatocellular carcinoma. The genome of this DNA virus encompasses four partially overlapping open reading frames, of which the pre-S/S region encodes the viral surface antigen (HBsAg) and the pre-core/core gene encodes the e antigen (HBeAg) and the core antigen (HBcAg) [4].

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