Two Cases of Hypophosphatemic Osteomalacia After Long-term Low Dose Adefovir Therapy in Chronic Hepatitis B and Literature Review

Overview

Journal J Bone Metab

Date 2014 Apr 8

PMID 24707470

Citations 11

Authors

Hye Jin Jeong

Ji Min Lee

Tae Han Lee

Ji Yeon Lee

Han Byeol Kim

Mi Hwa Heo

Go Choi

Jin Nyeong Chae

Ji-Min Kim

Sang-Hyon Kim

Kun Young Kwon

Affiliations

Soon will be listed here.

Abstract

Adefovir dipivoxil (ADV) is a nucleotide used as long-term therapy of chronic hepatitis B. Many published reports have shown that long-term high-dose therapy with adefovir can be associated with proximal renal tubular dysfunction resulting in significant hypophosphatemia, renal insufficiency and osteomalacia. We have encountered two patients who developed evidence of hypophosphatemic osteomalacia while on long-term low-dose adefovir therapy for chronic hepatitis B. We report on its clinical features and its potential resolution with cessation of the drug and supplementation with phosphate. We also reviewed the other published cases associated with hypophosphatemic osteomalacia after low-dose adefovir therapy. The symptoms and the hypophosphatemia improved after cessation of the drug and supplementation with phosphate in most cases. Patients taking adefovir long-term should receive regular investigation of the phosphate level and renal function.

Citing Articles

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References

Law S, Li K, Ho Y . Acquired Fanconi syndrome associated with prolonged adefovir dipivoxil therapy in a chronic hepatitis B patient. Am J Ther. 2011; 20(6):e713-6. DOI: 10.1097/MJT.0b013e31820c4b20. View

Girgis C, Wong T, Ngu M, Emmett L, Archer K, Chen R . Hypophosphataemic osteomalacia in patients on adefovir dipivoxil. J Clin Gastroenterol. 2010; 45(5):468-73. DOI: 10.1097/MCG.0b013e3181e12ed3. View

Minemura M, Tokimitsu Y, Tajiri K, Nakayama Y, Kawai K, Kudo H . Development of osteomalacia in a post-liver transplant patient receiving adefovir dipivoxil. World J Hepatol. 2010; 2(12):442-6. PMC: 3010514. DOI: 10.4254/wjh.v2.i12.442. View

Lee H, Choi J, Kim T, Eun J . [A case of severe hypophosphatemia related to adefovir dipivoxil treatment in a patient with liver cirrhosis related to hepatitis B virus]. Korean J Hepatol. 2008; 14(3):381-6. DOI: 10.3350/kjhep.2008.14.3.381. View

Sun X, Zhang H, Li X, Xia W, Xing X, Meng X . [A case of adefovir dipivoxil induced hypophosphataemic osteomalacia and literature review]. Zhonghua Nei Ke Za Zhi. 2011; 50(9):754-7. View

Izzedine H, Hulot J, Launay-Vacher V, Marcellini P, Hadziyannis S, Currie G . Renal safety of adefovir dipivoxil in patients with chronic hepatitis B: two double-blind, randomized, placebo-controlled studies. Kidney Int. 2004; 66(3):1153-8. DOI: 10.1111/j.1523-1755.2004.00866.x. View

Tamori A, Enomoto M, Kobayashi S, Iwai S, Morikawa H, Sakaguchi H . Add-on combination therapy with adefovir dipivoxil induces renal impairment in patients with lamivudine-refractory hepatitis B virus. J Viral Hepat. 2009; 17(2):123-9. DOI: 10.1111/j.1365-2893.2009.01160.x. View

Jung Y, Yeon J, Choi J, Kim C, Jung E, Kim J . Fanconi's Syndrome Associated with Prolonged Adefovir Dipivoxil Therapy in a Hepatitis B Virus Patient. Gut Liver. 2010; 4(3):389-93. PMC: 2956354. DOI: 10.5009/gnl.2010.4.3.389. View

Lee K, Kim D . [Management of Chronic Hepatitis B]. Korean J Hepatol. 2008; 13(4):447-88. DOI: 10.3350/kjhep.2007.13.4.447. View

10.

Li L, Dong G, Zhang X, Xie Y . [Adefovir dipivoxil-induced Fanconi syndrome and hypophosphatemic osteomalacia associated with muscular weakness in a patient with chronic hepatitis B]. Nan Fang Yi Ke Da Xue Xue Bao. 2011; 31(11):1956. View

11.

Kwon S, Ahn S, Ko S, Jang Y, Choi Y, Kim B . [A case of osteomalacia related to adefovir in a patient with chronic hepatitis B]. Korean J Gastroenterol. 2010; 56(2):117-20. DOI: 10.4166/kjg.2010.56.2.117. View

12.

Kim D, Sung D, Min Y . Hypophosphatemic osteomalacia induced by low-dose adefovir therapy: focus on manifestations in the skeletal system and literature review. J Bone Miner Metab. 2012; 31(2):240-6. DOI: 10.1007/s00774-012-0384-y. View

13.

Wong T, Girgis C, Ngu M, Chen R, Emmett L, Archer K . Hypophosphatemic osteomalacia after low-dose adefovir dipivoxil therapy for hepatitis B. J Clin Endocrinol Metab. 2010; 95(2):479-80. DOI: 10.1210/jc.2009-2051. View

14.

Fontana R . Side effects of long-term oral antiviral therapy for hepatitis B. Hepatology. 2009; 49(5 Suppl):S185-95. DOI: 10.1002/hep.22885. View

15.

Tanji N, Tanji K, Kambham N, Markowitz G, Bell A, DAgati V . Adefovir nephrotoxicity: possible role of mitochondrial DNA depletion. Hum Pathol. 2001; 32(7):734-40. DOI: 10.1053/hupa.2001.25586. View

16.

Wu C, Zhang H, Qian Y, Wang L, Gu X, Dai Z . Hypophosphatemic osteomalacia and renal Fanconi syndrome induced by low-dose adefovir dipivoxil: a case report and literature review suggesting ethnic predisposition. J Clin Pharm Ther. 2013; 38(4):321-6. DOI: 10.1111/jcpt.12050. View

17.

Shimohata H, Sakai S, Ogawa Y, Hirayama K, Kobayashi M . Osteomalacia due to Fanconi's syndrome and renal failure caused by long-term low-dose adefovir dipivoxil. Clin Exp Nephrol. 2012; 17(1):147-8. DOI: 10.1007/s10157-012-0762-8. View

18.

Gara N, Zhao X, Collins M, Chong W, Kleiner D, Liang T . Renal tubular dysfunction during long-term adefovir or tenofovir therapy in chronic hepatitis B. Aliment Pharmacol Ther. 2012; 35(11):1317-25. PMC: 3443969. DOI: 10.1111/j.1365-2036.2012.05093.x. View

19.

Izzedine H, Launay-Vacher V, Deray G . Antiviral drug-induced nephrotoxicity. Am J Kidney Dis. 2005; 45(5):804-17. DOI: 10.1053/j.ajkd.2005.02.010. View

20.

Wilson D, YORK S, Jaworski Z, YENDT E . STUDIES IN HYPOPHOSPHATEMIC VITAMIN D-REFRACTORY OSTEOMALACIA IN ADULTS. Medicine (Baltimore). 1965; 44:99-134. DOI: 10.1097/00005792-196503000-00001. View