Follow-Up of Adefovir Dipivoxil Induced Osteomalacia: Clinical Characteristics and Genetic Predictors.
Follow-Up of Adefovir Dipivoxil Induced Osteomalacia: Clinical Characteristics and Genetic Predictors.
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阿德福韦酯诱发骨软化症的随访：临床特征和遗传预测因素
DOI：
10.3389/fphar.2021.636352
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发表时间：
2021
影响因子：
5.6
通讯作者：
Zhang ZL
中科院分区：
文献类型：
--
作者：
Zhao J;Feng WG;Wei Z;Zhou J;Chen XY;Zhang ZL
阿德福韦酯在中国临床上被广泛用于慢性乙型肝炎的治疗。探讨阿霉素(ADV)所致骨软化的临床特点和预后，分析51个药物转运蛋白基因变异与骨软化的关系。收集接受ADV治疗的患者的临床和随访数据。采用靶向捕获测序方法鉴定51个药物转运蛋白基因的遗传变异。共有193名接受ADV治疗的乙肝患者入选，其中140人患有骨软化症。另53例无骨软化者为对照组。在骨软化症发生之前，ADV治疗的中位持续时间为6.5年(范围为1.5-7年)。我们发现大多数骨软化症患者存在低磷血症、高血清碱性磷酸酶水平、低尿酸血症、非糖尿病糖尿、蛋白尿。停用ADV、补充骨化三醇和补钙是有效的治疗方法。随访3-6个月，骨软化症患者的临床症状和生化指标均有明显改善。患有和不患有骨软化症的患者的阿德福韦治疗时间没有显著差异(p=0.791)。通过回归分析，我们发现年龄是骨软化症的危险因素[每1年，优势比(OR)，1.053；95%可信区间(95%CI)，1.020-1.087；p=0.015]。使用靶标捕获测序发现了1992个单核苷酸变体。然而，51个药物转运蛋白基因的遗传变异与骨软化风险的相关性可以忽略不计。长期服用治疗剂量的ADV治疗的慢性乙肝患者容易发生骨软化症。经规范治疗后，预后大多良好。我们未能找到可以预测ADV诱导的骨软化症风险的基因变异。
Adefovir dipivoxil (ADV) is widely used for chronic hepatitis B therapy in China. To explore the clinical features and prognosis of ADV-induced osteomalacia and to analyze the association between osteomalacia and genetic variants in 51 drug transporters genes. Clinical and follow-up data of the ADV-treated patients were collected. Target capture sequencing was used to identify genetic variations of 51 drug transporter genes. A total of 193 hepatitis B patients treated with ADV were enrolled, of whom 140 had osteomalacia. The other 53 without osteomalacia were included in the control group. The median duration of ADV treatment before the onset of osteomalacia was 6.5 years (range:1.5–7 years). We found that most patients with osteomalacia had hypophosphatemia, high serum alkaline phosphatase levels, hypouricemia, nondiabetic glycosuria, proteinuria. Stopping ADV administration, supplementing calcitriol and calcium were effective treatments. During 3–6 months of follow-up, the clinical symptoms and biochemical indicators of patients with osteomalacia have been significantly improved. There was no significant difference in duration of adefovir treatment in patients with or without osteomalacia (p = 0.791). Through regression analysis, we found that age was a risk factor for osteomalacia [per 1 year, odds ratio (OR), 1.053; 95% confidence interval (95% CI), 1.020–1.087; p = 0.015]. 1992 single nucleotide variants were found using target capture sequencing. However, the associations of genetic variants of 51 drug transporter genes and the risk of osteomalacia were negligible. Osteomalacia is prone to occur in patients with chronic hepatitis B treated with long-term ADV at a therapeutic dose. After standard treatment, the prognosis is mostly good. We failed to find genetic variants that can predict the risk of ADV-induced osteomalacia.
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影响因子：
1.8
作者：
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通讯作者：
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作者：
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通讯作者：
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影响因子：
158.5
作者：
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通讯作者：
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影响因子：
19.6
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