| Background Adefovir dipivoxil(ADV)induced renal tubular dysfunction,hypophosphatemic osteomalacia(HO),has 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 in chronic hepatitis B infectious areas,variations in definition of renal adverse events leading to results with incompatible conclusions or even contradicted with each other.Further,most of them use limited methods for early diagnosisthat largely underestimate the incidence of HO.The present knowledge in the diagnosis and treatment of ADV-induced HO mainly limited to case report,no available guideline can be implemented in the clinical practice.ObjectiveChina is one of most highly susceptible Asian countries suffering from chronic hepatitis B infection,the incidence of ADV-induced HO significantly increased in the recent ten years since it was approved in the 2005.The aim of this study is to investigate the clinical features of Chinese native patients with ADV-related HO in the demographics,clinical manifestation,tests,diagnosis,treatment and prognosis in long term administration through a Chinese and non-Chinese comparative case series.Methods Retrieval of case reports and relevant renal safety clinical studies was based on PubMed,CNKI,Wan Fang and VIP database using the following key words:adefovir dipivoxil,Fanconi syndrome,hypophosphatemia,osteomalacia and renal insufficiency.We divided patients into Chinese(Native group)and Foreign group(Non-Native group)according to their nationality.Comparison involving demographics,clinical manifestation,tests,treatment and prognosis were conducted between the two groups.Results Of the patients screened,120 Chinese were identified in the Native group,and 32 non-Chinese in the Non-Native group.The Native group was significantly younger than the Non-Native group(51.89years± 10.96 years versus 56.47years ± 11.36 years,t=-2.084,P=0.039).There were no significant differences between the groups in gender(male to female,3.29:1 versus 3:1,?2=0.039,P=0.844).There were over 80%of patients in both groups complicated with cirrhosis.There were no significant differences between the groups in the duration of ADV therapy and duration of ADV therapy before ostalgia onset,with median 60(36,72)months in the Native group versus 57(38,69)months in the Non-Native group(Z=-0.076,P=0.939),36(24,48)months versus 47.5(28,60)months(Z=-1.428,P=0.153).Two to 5 years of ADV therapy accounted for most in both groups(55.7%versus 63.3%,Z=-0.346,P=0.729).Though the differences were not significant,Native group was tend to develop ostalgia earlier,which dominated by 2-3 years,while Non-Native group by 4-5 years(Z=-1.517,P=0.129).Pain usually began from weight-bearing sites of lower limbs.Lab tests were characterized by hypophosphatemia with hyperphosphaturia,hypouricemia,hypercalciuria with normal or subnormal serum calcium,elevated alkaline phosphatase level,glucosuria,proteinuria or even metabolic acidosis.More than 70%of patients in both groups had reduced bone mineral density.Prognosis was well after adjustment of ADV and supplement with phosphate and calcitriol.Time to resolution of renal tubular dysfunction was commenced at the first month,with Chinese were more prone to recover in the first three months(91.3%of patients in the Native group versus 56.3%in the Non-Native group,Z=-3.013,P=0.003)Conclusions 1.Middle-aged males,especially those complicated with cirrhosis need sufficient attention before and during exposure to long-term ADV therapy,regardless of nationality.2.Clinical picture,laboratory and radiograph alterations are important clues for those suspected patients,which is usually characterized by polyarthralgia,renal tubular dysfunction and mineralization defects.3.Implementation of early renal tubular injured index is recommended for patients with higher risk before the onset of ostealgia,which would prevent further renal injury,since most of CHB patients have sufferred from subclinical kidney and bone lesion before ADV exposure. |
PDF Full Text Request