Biochemical and Serological Characteristics of Children with Membranous Nephropathy Due to Hepatitis B Virus Infection: Correlation with Hepatitis B e Antigen, Hepatitis B DNA and Hepatitis D

Abstract

Fourteen children with biopsy-proven membranous nephropathy associated with hepatitis B virus (HBV-MN) were evaluated biochemically and serologically and compared to 45 children with idiopathic nephrotic syndrome (INS). The mean ages of the two groups were similar (4.9 ± 1.6 vs. 4.6 ± 2.6 years). Serum albumin levels were similar in both groups, but serum cholesterol was significantly reduced in children with HBV-MN compared to INS. Serum C₃ was also significantly depressed in children with HBV-MN compared to INS, but no differences in C₄levels were noted. Serum alanine transaminase as well as aspartate transaminase concentrations were significantly elevated in children with HBV-MN compared to those with INS, suggesting the presence of chronic hepatitis in children with HBV-MN. Hepatitis B surface and e antigens were present in serum of all children with HBV-MN, but only 54% had circulating HBV-DNA particles demonstrable in their serum. Serum C₃ levels were higher in children with HBV-MN and circulating HBV-DNA, compared to those without circulating HBV-DNA. No other serological or biochemical differences occurred between these two groups. Glomerular deposition of IgG and C₃ occurred in 91% of children with HBV-MN; but IgM deposition appeared to occur more frequently and with greater intensity in those children positive for circulating HBV-DNA. Antibody to delta antigen was negative in all children with HBV-MN. We conclude that biochemical and serological differences can be identified between HBV-MN and INS. We also conclude that circulating HB viral DNA does not account for immune complex formation in HBV-MN but may be related to glomerular IgM deposition and that the delta antigen is not important in HBV-MN.

Nephrotic syndrome in South African children: changing perspectives over 20 years

“…The incidence of hepatitis B carriage is extremely low in Indians, and therefore it is not surprising that hepatitis B-associated membranous nephropathy was not detected in these patients. Unlike the patients described here, children with hepatitis B-associated membranous nephropathy seen in Johannesburg, South Africa, have biochemical evidence of liver damage and hypocomplementaemia [25]. None of the patients with hepatitis B-associated disease were treated with steroids, and its use in the idiopathic form of the disease was less than encouraging.…”

Hepatitis B virus-associated nephropathy in black South African children

“…Previous studies showed no differences in clinical presentation except for age; patients with HBVMN presenting at a younger age [29]. However, significant biochemical differences in serum cholesterol, complement (C3), and liver enzyme (serum ALT and AST) levels were noted in a study from South Africa [30]. In our study, substantial biochemical differences between serum triglycerides, complement, and globulin levels were also noted, although the clinical features were similar.…”

“…The lower complement levels in children with HBVMN probably reflect the sequence of active replicating HBV, antibody production, formation of circulating immune complexes, and consequent consumption of complement proteins. Complement activation by circulating HBV-containing immune complexes, with glomerular deposition, has been postulated as the pathogenetic mechanism resulting in accumulation of subepithelial deposits [30]. C3 and C4 levels may be low in patients with HBVMN, and seen in up to 64% of cases in most studies [4,25].…”

“…Underlying chronic hepatitis may be present despite virtually normal liver enzymes [23,30]. In most studies of HBVMN, despite the absence of clinical signs of hepatitis at presentation, liver function tests are usually mildly abnormal, in contrast to IMN, suggesting hepatocyte injury in HBV nephropathy [32][33][34][35].…”

“…Amelioration of nephrotic syndrome is often accompanied by the spontaneous clearance of HBV antigens, especially HBeAg [28,30,32]. In the study from Cape Town, 37 of 71 patients (52.1%) with HBVMN went into remission, associated with HBeAg clearance in 33 (89.2%) after 90 months [7].…”