Hepatitis-B-associated glomerulonephritis: pathology, pathogenesis, and clinical course.
Hepatitis-B-associated glomerulonephritis (HBGN) is a distinct entity occurring frequently in hepatitis-B-prevalent areas of the world. The disease affects both adults and children who are chronic hepatitis-B-virus (HBV) carriers with or without a history of overt liver disease. The diagnosis is established by serologic evidence of HBV antigens/antibodies, presence of an immune complex glomerulonephritis, immunohistochemical localization of 1 or more HBV antigens, and pertinent clinical history, when available. In this study we present clinicopathologic and follow-up findings in 12 patients (7 children, 5 adults) with hepatitis-B-associated glomerulonephritis. Twelve patients provided 15 renal biopsies and 1 specimen of kidney tissue, obtained at autopsy; these were examined by light microscopy, electron microscopy, and immunohistochemical methods. Membranous glomerulonephritis (MGN) with or without mesangial proliferation was noted in 7 biopsies, mesangiocapillary (membranoproliferative) glomerulonephritis (MCGN) in 5 biopsies, and proliferative glomerulonephritis with or without membranous changes in 2 biopsies. Tubulointerstitial changes were minimal except in 3 adults, in whom they were attributable to arterionephrosclerosis. Ultrastructural findings included the presence of considerable amounts of focal or diffuse granular electron-dense deposits in the glomeruli, in the subepithelial, subendothelial, and mesangial locations, occasionally destroying or replacing the lamina densa of the basement membrane. Variable mesangial proliferation was also observed, with interposition, with focal irregular reduplication of the basement membranes and rare clusters of spherical particles, probably representing viral particles in the deposits. In addition, granular deposits along tubular basement membranes were seen in 1 case. The glomerular deposits stained for 2 or more immunoglobulins, the predominant one being IgG, and variably also for complement components (C3, C4 and C1q). Hepatitis B viral antigens (HBsAg, HBcAg, HBeAg) were demonstrated using acid elution techniques in the deposits in all biopsies where frozen tissue was available, singly or in a variety of combinations and intensities. There were deposits of IgG, C3, C1q, and HBsAg along the tubular basement membranes in 1 case. Follow-up biopsies in 2 cases, 2 and 5 years apart, showed a transformation from a diffuse MGN to MCGN with segmental membranous features. Follow-up biopsy after 3 years in the third patient, who went into clinical remission, revealed partially resolving glomerular lesions. Renal lesions secondary to chronic liver disease, parasitic diseases, certain tropical nephropathies, and lupus nephritis are some of the diseases that may morphologically resemble HBGN. Recognition and differentiation of HBGN from other entities may have significant prognostic and therapeutic implications.(ABSTRACT TRUNCATED AT 400 WORDS)
Venkataseshan
V S
VS
Mount Sinai School of Medicine, New York, NY.
Lieberman
K
K
Kim
D U
DU
Thung
S N
SN
Dikman
S
S
D'Agati
V
V
Susin
M
M
Valderrama
E
E
Gauthier
B
B
Prakash
A
A
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D002648:Child; D005260:Female; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology; D006509:Hepatitis B / Q000150:complications*; D006512:Hepatitis B Core Antigens / Q000032:analysis; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006513:Hepatitis B e Antigens / Q000032:analysis; D006801:Humans; D007105:Immune Complex Diseases / Q000209:etiology; D007678:Kidney Glomerulus / Q000648:ultrastructure*; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged
D000911:Antibodies, Monoclonal; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens