Adefovir dipivoxil induced hypophosphatemic osteomalacia in chronic hepatitis B: a comparative study of Chinese and foreign case series

Abstract

BackgroundAdefovir dipivoxil (ADV)-induced renal tubular dysfunction and hypophosphatemic osteomalacia (HO) have been given great consideration in the past few years. However, no standard guidance is available due to a lack of powerful evidence from appropriate long-term prospective case-control studies and variations in the definition of renal adverse events. The aim of this study is to clarify clinical features of ADV-related HO in Chinese chronic hepatitis B patients with long-term ADV treatment in Chinese and non-Chinese comparative case series.MethodsRetrieval of case reports was based on Pubmed, CNKI, Wan Fang and VIP databases using the key words adefovir dipivoxil, hypophosphatemia, osteomalacia and Fanconi syndrome. We divided patients into Chinese (C group) and Foreign (F group) groups according to their nationality. Comparisons involving demographics, clinical manifestations, tests, treatment and prognosis were conducted between the two groups.ResultsOf the patients screened, 120 Chinese patients were identified in the C group, and 32 non-Chinese patients were identified in the F group. The average age of the C group was younger than that of the F group (51.89 years ±10.96 years versus 56.47 years ±11.36 years, t = − 2.084, P = 0.039). No significant difference was found in gender (male to female, 3.29:1 versus 3:1, χ2 = 0.039, P = 0.844). Although there was no significant difference in the duration of ADV therapy before ostalgia onset, the C group tended to develop adverse events earlier, by 2–3 years, while the F group developed adverse events at 4–5 years (Z = − 1.517, P = 0.129). Prognosis was good after adjustment of the ADV dose and supplemental administration of phosphate and calcitriol. Time to resolution of tubular dysfunction was commenced at the first month, and Chinese patients were more prone to recover in the first 3 months than non-Chinese patients (91.3% of patients in the C group versus 56.3% in the F group, Z = − 3.013, P = 0.003).ConclusionsSufficient attention is required for middle-aged males before and during exposure to long-term ADV therapy, regardless of nationality. The clinical picture, laboratory and radiograph alterations are important clues for those patients and are usually characterized by polyarthralgia, renal tubular dysfunction and mineralization defects. Implementation of an early renal tubular injury index is recommended for patients with higher risk, which would prevent further renal injury.

Pathological Femoral Fracture due to Osteoporosis and Hypophosphatemic Osteomalacia Following Adefovir Therapy in a Patient with Chronic Hepatitis B

“…Our case was also a 55 year old male supporting the results of Chen et al (13). We observed right hip fracture and treated the patient conservatively.…”

“…Our case was 55 year-old man receiving ADV therapy for 120 months. Chen et al (13) have studied ADV induced hypophosphatemic osteomalacia in Chinese and non Chinese patients and found out that middle aged men are affected more in both groups and its not associated with nationality.…”

Hypophosphatemic Osteomalacia Associated with Adefovir-induced Fanconi Syndrome Initially Diagnosed as Diabetic Kidney Disease and Vitamin D Deficiency

“…Recently, Chen et al reported that a misdiagnosis of ADV-induced Fanconi syndrome was observed in 27 out of 120 patients. The misdiagnoses included osteoporosis (18.0%), ankylosing spondylitis (16.0%), vertebral disc herniation (12.0%), osteoarthropathy (10.0%), and bone tumors (10.0%) (23).…”

Fanconi syndrome induced by adefovir dipivoxil: a case report and clinical review

“…44 Hypophosphatemia occurs after ADV treatment for 1 year in a time- and dose-dependent manner, and HO appears after 3 to 4 years of treatment. 35 eGFR is considered the best indicator of renal function in patients with chronic renal disease, 45 but some researchers consider eGFR and cystatin C (Cys-C) more sensitive indices of kidney function than serum creatinine in patients with ADV-induced FS. However, other studies describe eGFR as the best index.…”