Development of osteomalacia in a post-liver transplant patient receiving adefovir dipivoxil

Abstract

We report the case of a patient treated with living do norrelated liver transplantation who suffered from osteomalacia during adefovir dipivoxil (ADV)containing antiviral therapy for lamivudineresistant hepatitis B virus infection. The patient had generalized bone pain, with severe hypophosphatemia after 20 mo of ADV therapy. Radiographic studies demonstrated the presence of osteomalacia. The peak plasma ADV level was 38 ng/mL after administration of ADV at 10mg/day. It was also found that ADV affected the metabolism of tacrolimus, a calcineurininhibitor, and caused an increase in the plasma levels of tacrolimus. The disability was reversed with the withdrawal of ADV and with mineral supplementation. ADV can cause an elevation of plasma tacrolimus levels, which may be associated with renal dysfunction. High levels of ADV and tacrolimus can cause nephrotoxicity and osteomalacia. This case highlights the importance of considering a diagnosis of osteomalacia in liver transplantation recipients treated with both ADV and tacrolimus.

Hypophosphatemic osteomalacia and renal Fanconi syndrome induced by low-dose adefovir dipivoxil: a case report and literature review suggesting ethnic predisposition

“…Literature review revealed only 12 other cases of hypophosphatemic osteomalacia induced by low‐dose (10 mg daily) ADV (see Table ). The age of these patients varied from 22 to 74 years, with a median of 51·6 years.…”

“…Male: female ratio was 10:3. Most cases (11/13) involved subjects of East‐Asian ethnicity, including Korean, Cambodian, Chinese and Japanese . The other two cases did not specify ethnicity .…”

Adefovir-induced Fanconi syndrome: diagnostic pearls and perils of late or missed diagnosis

“…Nephrotoxicity associated with high-dose ADV typically has a late onset ([6 months) [15]. The time to onset of low-dose ADV-induced FS, based on case reports, ranges from a few months to [5 years [4][5][6][7][8][9][10][11][12]. In our patient, it took more than 2 years before the tubulopathy became apparent.…”

“…From the series of case reports so far, the time to resolution after cessation of ADV ranged from a few weeks to months [4][5][6][7][8][9][10][11][12]. A previous trial with high-dose ADV treatment showed a median time to resolution of renal dysfunction of 15 weeks, with the nephrotoxicity failing to resolve completely at 41 weeks after onset in 16 % of the patients [15].…”

“…The first report of ADV-associated hypophosphatemic osteomalacia was published in 2008 [4], with a number of reported cases of ADV-induced FS [5][6][7][8][9][10][11][12] since then. Most of the cases published were in East Asian subjects, which may either suggest a racial predilection, or an indication of the increased prevalence of hepatitis B infection requiring ADV treatment in East Asia.…”