Clinical and Experimental Nephrology

, Volume 16, Issue 5, pp 805–810

A case of adefovir-induced membranous nephropathy related to hepatitis B caused by lamivudine-resistant virus after liver transplant due to Byler’s disease

  • Shinich Ebata
  • Seiji Hashimoto
  • Akira Suzuki
  • Masanori Ito
  • Tomochika Maoka
  • Yasunobu Ishikawa
  • Toshio Mochizuki
  • Takao Koike
Case Report

Abstract

We report on how adefovir-induced membranous nephropathy related to hepatitis B was caused by lamivudine-resistant virus after a liver transplant due to Byler’s disease. In 1980, a 2-year-old girl was diagnosed with Byler’s disease (familial progressive familial intrahepatic cholestasis). In 1994 (at the age of 14 years) she underwent a liver transplant with her father as the donor. In 2003, hematuria and proteinuria appeared and shortly afterwards her renal function rapidly decreased. A renal biopsy showed atypical membranous nephropathy, which suggested the possibility of a secondary renal disease. The patient had suffered from chronic hepatitis type B (HBV). In 2001 she was administered lamivudine which is an antiviral drug; it was around this time that hematuria and proteinuria appeared as well as an increase of the virus titer. We believed the HBV-related membranous nephropathy was the cause of the virus titer and the renal histology. We concluded that the patient’s condition had become resistant to lamivudine medication. Therefore, in February 2004 we administered adefovir, a new drug at the time, to treat the HBV. In April 2004, the HB virus titer decreased and the hematuria and proteinuria decreased. The patient’s renal function also showed improvement. HBV-associated nephropathy is caused by HBV antigen deposition in the glomeruli. Generally the first choice of treatment is antivirus therapy. There are many reports demonstrating that administration of interferon and lamivudine are effective; however, there are few reports that show adefovir as an effective treatment for HBV-associated nephropathy.

Keywords

HBV-associated nephropathy Lamivudine Adefovir Byler’s disease 

References

  1. 1.
    Combes B, Shorey J, Barrera A, Stastny P, Eigenbrodt EH, Hull AR, Carter NW. Glomerulonephritis with deposition of Australia antigen–antibody complexes in glomerular basement membrane. Lancet. 1971;2:234–7.PubMedCrossRefGoogle Scholar
  2. 2.
    Takekoshi Y, Tanaka M, Miyakawa Y, Yoshizawa H, Takahashi K, Mayumi M. Free “small” and IgG-associated “large” hepatitis B e antigen in the serum and glomerular capillary walls of two patients with membranous glomerulonephritis. N Engl J Med. 1979;300:814–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Hattori S, Furuse A, Matsuda I. Presence of HBe antibody in glomerular deposits in membranous glomerulonephritis is associated with hepatitis B virus infection. Am J Nephrol. 1988;8:384–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Lai KN, Ho RT, Tam JS, Lai FM. Detection of hepatitis B virus DNA and RNA in kidneys of HBV related glomerulonephritis. Kidney Int. 1996;50:1965–77.PubMedCrossRefGoogle Scholar
  5. 5.
    Imai H, Hamai K, Komatsuda A, Ohtani H, Miura AB. IgG subclasses in patients with membranoproliferative glomerulonephritis, membranous nephropathy, and lupus nephritis. Kidney Int. 1997;51:270–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Kamei K, Nakagawa A, Otsuka Y, Nakayama M, Kobayashi S, Matsuoka K, Iijima K. Chronic glomerulonephritis associated with IgG subclass deficiency. Pediatr Nephrol. 2007;22:1229–34.PubMedCrossRefGoogle Scholar
  7. 7.
    Kuroki A, Iyoda M, Shibata T, Sugisaki T. Th2 cytokines increase and stimulate B cells to produce IgG4 in idiopathic membranous nephropathy. Kidney Int. 2005;68:302–10.PubMedCrossRefGoogle Scholar
  8. 8.
    Takekoshi Y, Tanaka M, Shida N, Satake Y, Saheki Y, Matsumoto S. Strong association between membranous nephropathy and hepatitis-B surface antigenaemia in Japanese children. Lancet. 1978;2:1065–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Takekoshi Y, Tochimaru H, Nagata Y, Itami N. Immunopathogenetic mechanisms of hepatitis B virus-related glomerulopathy. Kidney Int Suppl. 1991;35:S34–9.PubMedGoogle Scholar
  10. 10.
    Zhang JH, Li LS, Zhou H. Is there a hepatitis B virus-associated glomerulonephritis? Identification of HBsAG, HBcAG and HBeAG in kidney with monoclonal antibodies. Chin Med J (Engl). 1989;102:496–504.Google Scholar
  11. 11.
    Wong SN, Yu EC, Lok AS, Chan KW, Lau YL. Interferon treatment for hepatitis B-associated membranous glomerulonephritis in two Chinese children. Pediatr Nephrol. 1992;6:417–20.PubMedCrossRefGoogle Scholar
  12. 12.
    Conjeevaram HS, Hoofnagle JH, Austin HA, Park Y, Fried MW, Di Bisceglie AM. Long-term outcome of hepatitis B virus-related glomerulonephritis after therapy with interferon alfa. Gastroenterology. 1995;109:540–6.PubMedCrossRefGoogle Scholar
  13. 13.
    Conca P, Riccio A, Tarantino G. Successful lamivudine monotherapy in an elderly patient suffering from HBV-related decompensated cirrhosis associated with widespread leukocytoclastic vasculitis. Int J Immunopathol Pharmacol. 2009;22:531–5.PubMedGoogle Scholar
  14. 14.
    Fabrizi F, Dixit V, Martin P. Meta-analysis: anti-viral therapy of hepatitis B virus-associated glomerulonephritis. Aliment Pharmacol Ther. 2006;24:781–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Okuse C, Yotsuyanagi H, Yamada N, Ikeda H, Takahashi H, Suzuki M, Kondo S, Kimura K, Koike J, Itoh F. Successful treatment of hepatitis B virus-associated membranous nephropathy with lamivudine. Clin Nephrol. 2006;65:53–6.PubMedGoogle Scholar
  16. 16.
    Chayama K, Suzuki Y, Kobayashi M, Kobayashi M, Tsubota A, Hashimoto M, Miyano Y, Koike H, Kobayashi M, Koida I, Arase Y, Saitoh S, Murashima N, Ikeda K, Kumada H. Emergence and takeover of YMDD motif mutant hepatitis B virus during long-term lamivudine therapy and re-takeover by wild type after cessation of therapy. Hepatology. 1998;27:1711–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Lok AS, Lai CL, Leung N, Yao GB, Cui ZY, Schiff ER, Dienstag JL, Heathcote EJ, Little NR, Griffiths DA, Gardner SD, Castiglia M. Long-term safety of lamivudine treatment in patients with chronic hepatitis B. Gastroenterology. 2003;125:1714–22.PubMedCrossRefGoogle Scholar
  18. 18.
    Ng YY, Yang WC, Lee ST. Long-term lamivudine therapy in hepatitis B-associated membranous nephropathy? Kidney Int. 2006;69:776.PubMedCrossRefGoogle Scholar
  19. 19.
    Chen EQ, Wang LC, Lei J, Xu L, Tang H. Meta-analysis: adefovir dipivoxil in combination with lamivudine in patients with lamivudine-resistant hepatitis B virus. Virol J. 2009;6:163.PubMedCrossRefGoogle Scholar
  20. 20.
    Schiff ER, Lai CL, Hadziyannis S, Neuhaus P, Terrault N, Colombo M, Tillmann HL, Samuel D, Zeuzem S, Lilly L, Rendina M, Villeneuve JP, Lama N, James C, Wulfsohn MS, Namini H, Westland C, Xiong S, Choy GS, Van Doren S, Fry J, Brosgart CL. Adefovir dipivoxil therapy for lamivudine-resistant hepatitis B in pre- and post-liver transplantation patients. Hepatology. 2003;38:1419–27.PubMedGoogle Scholar
  21. 21.
    Angus P, Vaughan R, Xiong S, Yang H, Delaney W, Gibbs C, Brosgart C, Colledge D, Edwards R, Ayres A, Bartholomeusz A, Locarnini S. Resistance to adefovir dipivoxil therapy associated with the selection of a novel mutation in the HBV polymerase. Gastroenterology. 2003;125:292–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, Marcellin P, Lim SG, Goodman Z, Ma J, Arterburn S, Xiong S, Currie G, Brosgart CL. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B. N Engl J Med. 2005;352:2673–81.PubMedCrossRefGoogle Scholar
  23. 23.
    Chen CH, Lee CM, Tung WC, Wang JH, Hung CH, Hu TH, Wang JC, Lu SN, Changchien CS. Evolution of full-length HBV sequences in chronic hepatitis B patients with sequential lamivudine and adefovir dipivoxil resistance. J Hepatol. 2010;52:478–85.PubMedCrossRefGoogle Scholar
  24. 24.
    Li DF, Jin ZJ, Chen YS, Qiao LM, Zhou J. Adefovir dipivoxil treatment of hepatic cirrhosis complicated with hepatitis B virus associated glomerulonephritis. Zhonghua Gan Zang Bing Za Zhi. 2008;16:349–51.PubMedGoogle Scholar
  25. 25.
    Gara N, Zhao X, Collins MT, Chong WH, Kleiner DE, Jake Liang T, Ghany MG, Hoofnagle JH. Renal tubular dysfunction during long-term adefovir or tenofovir therapy in chronic hepatitis B. Aliment Pharmacol Ther. 2012;35:1317–25.PubMedCrossRefGoogle Scholar
  26. 26.
    Yang YF, Xiong QF, Zhao W, Zhong YD. Complete remission of hepatitis B virus-related membranous nephropathy after entecavir monotherapy. Clin Res Hepatol Gastroenterol. 2012.Google Scholar
  27. 27.
    Zheng XY, Wei RB, Tang L, Li P, Zheng XD. Meta-analysis of combined therapy for adult hepatitis B virus-associated glomerulonephritis. World J Gastroenterol. 2012;18:821–32.PubMedCrossRefGoogle Scholar

Copyright information

© Japanese Society of Nephrology 2012

Authors and Affiliations

  • Shinich Ebata
    • 1
  • Seiji Hashimoto
    • 2
  • Akira Suzuki
    • 3
  • Masanori Ito
    • 1
  • Tomochika Maoka
    • 1
  • Yasunobu Ishikawa
    • 1
  • Toshio Mochizuki
    • 1
  • Takao Koike
    • 1
  1. 1.Department IIHokkaido University Graduate School of MedicineSapporoJapan
  2. 2.Department of NephrologyNTT East Japan Sapporo HospitalSapporoJapan
  3. 3.Department of PathologyKKR Sapporo Medical CenterSapporoJapan

Personalised recommendations