HBV associated nephrotic syndrome: resolution with oral lamivudine

Abstract

A 6 year old boy presenting with a five month history of fever, lethargy, and anorexia, was found to have hepatitis B associated membranous glomerulonephropathy and nephrotic syndrome. After two months treatment with oral lamivudine, his proteinuria cleared and serum albumin and aminotransferases normalised, associated with disappearance of hepatitis B e antigen (HBeAg) and appearance of anti-HBeAg antibodies. After 12 months, without side effects, lamivudine was discontinued. He remains well 11 months off treatment. W orldwide, hepatitis B (HBV) infection is an important cause of nephrotic syndrome. The typical renal lesion is membranous glomerulonephropathy (HBVMN). Previous studies showed improvement with alfa interferon (IFN) therapy. [1][2][3][4][5][6][7][8] Lamivudine is a nucleoside analogue inhibitor of HBV DNA polymerase, which has advantages over IFN for HBV treatment, having less frequent side effects and oral route of administration. To our knowledge, this is the first reported case of HBV associated nephrotic syndrome treated with lamivudine therapy. CASE REPORTThe patient, a child of mixed race (mother white, father white/Filipino), migrated to Australia from South Africa at 2 1 ⁄2 years of age. Before leaving South Africa, he had received childhood vaccinations at a community clinic and sutures for a minor laceration at a local hospital. He presented at 6 years, 3 months of age with a five month history of recurrent fever, lethargy, and anorexia. There was no other significant past medical or family history. He looked well, with weight 19.5 kg (25th percentile) and height 110 cm (3-10th percentile). There was mild digital clubbing, leuconychia, and palmar erythema, but no other peripheral stigmata of chronic liver disease. He was normotensive. The abdomen was soft and non-tender. Borderline hepatomegaly was present (liver span 9 cm), but there was no splenomegaly, renal mass, ascites, or peripheral oedema. Physical examination was otherwise unremarkable.Persistent heavy proteinuria (urinary albumin/creatinine ratio 390 mg/mmol (normal <5)) and intermittent microscopic haematuria were noted. Serum albumin was persistently decreased at 24-26 g/l. Urea and creatinine were normal. Complements were reduced: C3 0.63 g/l (normal range 0.89-1.73) and CH50 25% (normal range 56-174). Renal and abdominal ultrasound was normal. Mild elevations of serum aminotransferases were noted: alanine aminotransferase (ALT) 77 U/l (normal range 17-63), aspartate aminotransferase (AST) 61 U/l (normal range 15-45). Bilirubin, γ glutamyl transferase, alkaline phosphatase, and coagulation were normal. Autoantibodies (antinuclear, antineutrophil cytoplasmic, and antiglomerular basement membrane) were negative and he was seronegative for Epstein-Barr and cytomegalovirus. HBV infection was confirmed with positive HBV surface antigen (HBsAg), HBV e antigen (HBeAg), and HBV core antibody. Antibodies to HBeAg and HBsAg were negative. His mother and four siblings were HBV seronegative.Renal biopsy (fig 1) showed stage 2 membranous ...

Effect of HBV polymerase inhibitors on renal function in patients with chronic hepatitis B

“…In contrast, in our observational cohort with relatively young patients without arterial hypertension or Diabetes mellitus the initiation of HBV-polymerase therapy seems to contribute to a milder decrease in renal function. This observation may be explained by an improvement of renal impairment by HBV-associated membranous nephropathy as reported from small patient series or individual cases [24][25][26][27]. However, in our multivariate linear mixed effects model HBV-DNA did not show a significant association with change in eGFR.…”

Virological features of hepatitis B virus‐associated nephropathy in Japan

“…Although deposition of HBeAg in renal tissues by immunostainings could not be confirmed, excess HBeAg originated from patients with high HBV-DNA level might influence the development of HBV-associated nephropathy. As reported previously, antiviral treatments such as IFN [Garcia et al, 1985;Mizushima et al, 1987;de Man et al, 1989;Lisker-Melman et al, 1989;Wong et al, 1992;Conjeevaram et al, 1995;Lin, 1995;Bhimma et al, 2002a,b] or lamivudine [Connor et al, 2003;Filler et al, 2003;Okuse et al, 2006] were effective for the HBVassociated nephropathy in this study.…”

Treatment of hepatitis B virus-associated glomerulonephritis: A meta-analysis

“…Antiviral therapy has been recommended in many studies for HBV-GN since it can effectively inhibit HBV replication and attenuate proteinuria [9,[25][26][27][28][29][30][31][32][33] . Our results demonstrated that antiviral therapy could significantly improve the remission rate of proteinuria, the clearance rate of HBeAg, and renal progression.…”