Statistics from Altmetric.com
Connor and colleagues1 (see 446) report rapid resolution of a hepatitis B associated membranous glomerulopathy and nephrotic syndrome after two months of oral lamivudine. We would like to add our experience with lamivudine in a similar case.
A 5 year old female of Vietnamese origin presented with a two week history of periorbital swelling and weight gain. She had 3 plus protein, 10–20 dysmorphic red blood cells, and red blood cell casts in her urine. Serum albumin was low at 19 g/l, cholesterol was 9.8 mmol/l, and serum complement C3 and C4 were reduced (0.61 g/l and <0.1 g/l, respectively). She was hepatitis B surface antigen positive and hepatitis B surface antibody negative. The physician caring for her at that time placed her on prednisone 60 mg/m2/day in three divided doses, and referred her to our service six weeks later, as the nephrotic syndrome was unresponsive to steroids. Her viral load initially was 1090 pg/ml of hepatitis B DNA in peripheral blood, and rose to >2000 pg/ml after four weeks of steroids, when ALT peaked at 72 U/l. A renal biopsy revealed stage II membranous glomerulonephritis. A liver biopsy showed focal lobular and portal inflammation and changes consistent with a mild chronic hepatitis.
She was started on lamivudine at a dose of 50 mg once daily (2.5 mg/kg), with steroids being weaned off over four weeks. Two weeks later the hepatitis B DNA dropped to 1686 pg/ml, decreased to to 7 pg/ml two months later, and was undetectable at three months. She continued to be hepatitis e antigen positive without detectable e antibodies. The patient’s proteinuria was cleared after three months of treatment, and serum albumin remained normal thereafter. She continued to take lamivudine for 13 months without rebound proteinuria. Six months after discontinuing lamivudine she remained clinically well, her urinalysis showed 0.04 g of protein per 24 hours, and there was microscopic haematuria. Hepatitis B DNA rose to >2000 pg/ml, indicating continued active viral replication. A repeat renal biopsy showed multiple electron dense deposits which had been incorporated into the lamina densa with fragmentation of the latter, consistent with a membranous glomerulonephritis stage II/III. She has evidence of hyperfiltration with a glomerular filtration rate of 163 ml/min/1.73 m2 as determined by 99Tc DTPA clearance.
The ideal treatment for hepatitis B associated membranous nephropathy in children is yet to be determined. There is one retrospective analysis of six studies comprising a total of 82 children that showed 60% complete remission 12 months after the diagnosis, 7.3% renal failure, 2.4% end stage renal failure, and 30% persistent disease.2 Steroid therapy should not be used as it does not appear to be beneficial, and the steroids may enhance viral replication in mononuclear cells.3 The average duration of proteinuria is 30 months.4 We believe that treatment with lamivudine in this case likely suppressed the virus and resulted in early remission of clinical nephrotic syndrome; however, the subsequent rebound in viral load and renal biopsy results probably indicates loss of viral supression, leading to the subclinical relapse. It is unknown at this time if the strain of hepatitis B has developed resistance to lamivudine. Effective viricidal agents may be needed to prevent relapses of hepatitis B induced membranous glomerulonephritis. Finally, further work is needed to investigate the efficacy of this treatment in a larger cohort and to establish guidelines about the duration of such therapy.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.