Adefovir dipivoxil-induced development of osteomalacia and Fanconi syndrome during the treatment of hepatitis B virus (HBV)-related cirrhosis
DOI:
https://doi.org/10.7175/cmi.v8i4.969Keywords:
Adefovir dipivoxil, Osteomalacia, Fanconi syndrome, HBV, CirrhosisAbstract
Adefovir dipivoxil is a nucleotide analog reverse transcriptase inhibitor used to treat adult patients affected by HBeAg-positive and HBeAg-negative chronic hepatitis B and with clinical evidence of lamivudine-resistant hepatitis B virus (HBV). Adefovir administered at a dosage of 10 mg/day is generally well tolerated, even if renal toxicity, type Fanconi syndrome, was reported during long-term treatments.
We report a case of osteomalacia with Fanconi syndrome and pathologic fracture of the femur related to long-time (67 months) adefovir treatment (10 mg/day) in a patient with compensated hepatitis B virus (HBV) cirrhosis (Child 5A) and with a previous normal renal function (estimated Glomerular Filtration Rate before adefovir = 78.26 ml/min/1.73 m2; during adefovir treatment = 57.38 ml/min/1.73 m2). The patient was switched to entecavir at a dose of 1 mg/day, with both suppression of viremia and improvement of osteomalacia and Fanconi syndrome; the patient’s follow-up is still ongoing after 22 months.
References
Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981; 30: 239-45; http://dx.doi.org/10.1038/clpt.1981.154
Peters MG, Hann HH, Martin P, et al. Adefovir dipivoxil alone or in combination with lamivudine in patients with lamivudine-resistant chronic hepatitis B. Gastroenterology 2004; 126: 91-101; http://dx.doi.org/10.1053/j.gastro.2003.10.051
Perrillo R, Hann HW, Mutimer D, et al. Adefovir dipivoxil added to ongoing lamivudine in chronic hepatitis B with YMDD mutant hepatitis B virus. Gastroenterology 2004; 126: 81-90; http://dx.doi.org/10.1053/j.gastro.2003.10.050
Marcellin P, Chang TT, Lim SG, et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. N Engl J Med 2003; 348: 808-16; http://dx.doi.org/10.1056/NEJMoa020681
Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepatitis B. N Engl J Med 2003; 348: 800-7; http://dx.doi.org/10.1056/NEJMoa021812
Marcellin P, Chang TT, Lim SGL, et al. Longterm efficacy and safety of adefovir dipivoxil for the treatment of hepatitis Be antigen positive chronic hepatitis B. Hepatology 2008; 48: 750-8; http://dx.doi.org/10.1002/hep.22414
Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, et al. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years. Gastroenterology 2006; 131: 1743-51; http://dx.doi.org/10.1053/j.gastro.2006.09.020
Ha NB, Garcia RT, Trinh HN, et al. Renal dysfunction in chronic hepatitis B patients treated with adefovir dipivoxil. Hepatology 2009; 50: 727-34; http://dx.doi.org/10.1002/hep.23044
Tamori A, Enomoto M, Kobayashi S, et al. Add-on combination therapy with adefovir dipivoxil induces renal impairment in patients with lamivudine-refractory hepatitis B virus. J Viral Hepat 2010; 17: 123-9; http://dx.doi.org/10.1111/j.1365-2893.2009.01160.x
Jung YK, Yeon JE, Choi JH, et al. Fanconi’s syndrome associated with prolonged adefovir dipivoxil therapy in a hepatitis B virus patient. Gut Liver 2010; 4: 389-93; http://dx.doi.org/10.5009/gnl.2010.4.3.389
Wong T, Girgis CM, Ngu MC, et al. Hypophosphatemic osteomalacia after low-dose adefovir dipivoxil therapy for hepatitis B. J Clin Endocrinol Metab 2010; 95: 479-80; http://dx.doi.org/10.1210/jc.2009-2051
Girgis CM, Wong T, Ngu MC, et al. Hypophosphataemic osteomalacia in patients on adefovir dipivoxil. J Clin Gastroenterol 2011; 45: 468-73; http://dx.doi.org/10.1097/MCG.0b013e3181e12ed3
Fabbriciani G, de Socio GV, Massarotti M, et al. Adefovir induced hypophosphatemic osteomalacia. Scand J Infect Dis 2011; 43: 990-2; http://dx.doi.org/10.3109/00365548.2011.581307
Shimohata H, Sakai S, Ogawa Y, et al. Osteomalacia due to Fanconi’s syndrome and renal failure caused by long-term low-dose adefovir dipivoxil. Clin Exp Nephrol 2013; 17: 147-8; http://dx.doi.org/10.1007/s10157-012-0762-8
Wu C, Zhang H, Qian Y, et al. 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: 321-6; http://dx.doi.org/10.1111/jcpt.12050
Kim YJ, Cho HC, Sinn DH, et al. Frequency and risk factors of renal impairment during long-term adefovir dipivoxil treatment in chronic hepatitis B patients. J Gastroenterol Hepatol 2012; 27: 306-12; http://dx.doi.org/10.1111/j.1440-1746.2011.06852.x
Li L, Dong GF, Zhang X, et al. 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: 1956
Tanaka M, Setoguchi T, Ishidou Y, et al. Pathological femoral fractures due to osteomalacia associated with adefovir dipivoxil treatment for hepatitis B: a case report. Diagnostic Pathol 2012; 7: 108; http://dx.doi.org/10.1186/1746-1596-7-108
Mateo L, Holgado S, Mari-oso ML, et al. Hypophosphatemic osteomalacia induced by tenofovir in HIV-infected patients. Clin Rheumatol 2014 May 3 [Epub ahead of print]; http://dx.doi.org/10.1007/s10067-014-2627-x
Saidenberg-Kermanac’h N, Souabni L, Prendki V, et al. Normal plasma FGF23 levels kinetic in tenofovir-related hypophosphatemic osteomalacia in an HIV-infected patient with von Recklinghausen disease. Joint Bone Spine 2011; 78: 306-8; http://dx.doi.org/10.1016/j.jbspin.2010.11.007
De Socio GV, Fabbriciani G, Massarotti M, et al. Hypophosphatemic osteomalacia associated with tenofovir: a multidisciplinary approach is required. Mediterr J Hematol Infect Dis 2012; 4: e2012025; http://dx.doi.org/10.4084/mjhid.2012.025
Clarke BL, Wynne AG, Wilson DM, et al. Osteomalacia associated with adult Fanconi’s syndrome: clinical and diagnostic features. Clin Endocrinol 1995; 43: 479-90; http://dx.doi.org/10.1111/j.1365-2265.1995.tb02621.x
Laing CM, Toye AM, Capasso G, et al. Renal tubular acidosis: developments in our understanding of the molecular basis. Int J Biochem Cell Biol 2005; 37: 1151-61; http://dx.doi.org/10.1016/j.biocel.2005.01.002
De Vuono A, Palleria C, Scicchitano F, et al. Skin rash during treatment with generic itraconazole. J Pharmacol Pharmacother 2014; 5: 158-60; http://dx.doi.org/10.4103/0976-500X.130086
Mumoli L, Gambardella A, Labate A, et al. Rosacea-like facial rash related to metformin administration in a young woman. BMC Pharmacol Toxicol 2014; 15: 3; http://dx.doi.org/10.1186/2050-6511-15-3
Caroleo B, Galasso O, Staltari O, et al. Muscular damage during telbivudine treatment in a chronic hepatitis B patient. Muscles Ligaments Tendons J 2011; 1: 57-60
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