A Viral Conundrum: Hepatitis D and Immune-Complex Glomerulonephritis

Introduction: Viral-associated glomerulonephritis (GN) is a well-recognized phenomenon, notably seen with hepatitis B (HBV), hepatitis C and HIV. These viral infections can lead to diverse histologic glomerular lesions, including immune-complex GN. There is little literature on Hepatitis D (HDV) associated GN. It is considered a hybrid virus as it uses HBV's surface antigen (HBsAg) as its envelope protein for replication. We present a case of nephrotic syndrome, with biopsy-proven immune-complex GN with active HDV infection. Case Description: 42-year-old South Asian woman G8P7 at 14w gestation with past medical history of chronic HBV, HDV, and latent TB presented with acute kidney injury (creatinine 1.3 mg/dL, baseline 0.92 mg/dL) and new nephrotic syndrome with urine protein-to-creatinine ratio 3.5 g/g and albumin 2.8 g/dL. Initial kidney biopsy deferred due to pregnancy. Course was complicated by severe pre-eclampsia requiring emergent C-section, and postpartum kidney biopsy with evidence of immune-complex GN with segmental sclerosis. HDV viral load was elevated to 270k, HBV viral load negative, and autoimmune serologies were negative. Glomerular disease was determined to be due to chronic Hepatitis B and coinfection with active Hepatitis D. Discussion: There are few reports establishing a correlation between hepatitis D and immune-complex GN. In this patient with chronic HBV and HDV co-infection, there was high suspicion of the hepatitis D being the causative pathogen given the elevated viral load. Immunosuppressive therapy was deferred for the patient’s GN, and HDV treatment was initiated with an experimental regimen (Bulevirtide and Tenofovir), with improvement of the viral load and proteinuria from peak 5.7 g/g to 1.2 g/g. This case demonstrates a potential novel association between hepatitis D and immune-complex GN, responsive to Hep D targeted anti-viral therapy.