A CASE OF HEPATITIS B VIRUS–ASSOCIATED GLOMERULONEPHRITIS WITH PROMINENT ENDOTHELIAL DAMAGE

Hepatitis B virus (HBV)-associated glomerulonephritis (HBV-GN) has become rare in countries with universal HBV vaccination. Cases with presumed long-standing antigenemia are particularly uncommon, especially among individuals living in areas with low HBV prevalence. Although many previous studies reported membranous pattern of HBV-GN, only few referred to endothelial damage.

We report a case of HBV-associated glomerulonephritis with presumed long-standing antigenemia, exhibiting characteristic immune complex deposition and endothelial injury.

Case Presentation:A 38-year-old woman from Vietnam, living in Japan for 10 years, was referred for persistent proteinuria detected during a routine medical check-up. She had no history of hypertension, diabetes, smoking, or medication use. Laboratory data showed proteinuria of 2.36 g/gCr, serum creatinine 0.52 mg/dL, albumin 3.9 g/dL, and normal complements except for mildly increased C4. HBV serology was positive for HBs antigen, HBc antibody, and HBe antigen, however HBV-DNA was undetectable, consistent with the inactive carrier phase. Autoantibodies, HCV, and other infectious markers were negative. Imaging tests excluded malignancy.Pathological Findings:Renal biopsy contained 24 glomeruli, of which one (4.2%) was globally sclerotic. Numerous foam cells were noted in the interstitium, while tubular atrophy, interstitial fibrosis, and arteriosclerosis were minimal. Almost glomeruli showed mild mesangial matrix expansion and segmental basement membrane thickening without endocapillary hypercellularity or crescent formation.Four glomeruli (16.7%) exhibited membranoproliferative glomerulonephritis (MPGN)-like pattern. Periodic acid–methenamine (PAM) and Elastica–Masson stains revealed mesangial matrix expansion and double-contour of the glomerular basement membrane with focal exudative lesions, whereas spike formation was not apparent. Immunofluorescence study demonstrated a nearly full-house pattern with granular deposition of IgG, IgM, C1q, C3c, and C4c predominantly in mesangium, and to a lesser extent, along the capillary walls. . Electron microscopy showed variably sized electron-dense deposits (EDDs) in subepithelial, mesangial and paramesangial areas. Swelling of endothelial cells and subendothelial enlargement indicated endothelial injury. The deposits were homogeneous in composition without organized structures.To investigate the presence of HB antigens , Victoria blue (VB) staining was performed. VB staining demonstrated diffuse blue granules within the mesangial areas, suggesting the presence of HBs antigen. The overall morphology was focal segmental MPGN with endothelial damage.Clinical Course:Given the absence of detectable HBV-DNA, nucleotide analogue therapy was not indicated. The patient was initially treated with an angiotensin-converting enzyme inhibitor, resulting in a marked reduction in proteinuria. As proteinuria gradually exacerbated , an SGLT2 inhibitor was subsequently introduced, leading to stabilization of urinary protein excretion at approximately 1 g/gCr. Seroconversion occurred during the course of therapy, and renal function remained stable without evidence of HBV reactivation throughout follow-up.

This case represents HBV-associated glomerulonephritis likely resulting from prolonged antigen exposure exceeding a decade. Endothelial injury was a prominent feature in this case.No other causes of endothelial damage, such as hypertension, obesity, smoking, medications, or pregnancy, were identified. Thus, chronic immune stimulation with HBV antigens was considered the primary pathogenic factor. This case expands the clinicopathological spectrum of HBV-associated glomerular disease and highlights the importance of considering viral antigenemia as a cause of chronic endothelial injury even in the post-vaccination era.