恩替卡韦初治慢性乙型肝炎患者发生低磷血症的危险因素

肝脏 ›› 2025, Vol. 30 ›› Issue (1): 78-82.

恩替卡韦初治慢性乙型肝炎患者发生低磷血症的危险因素

王亮, 余燕青, 邬小萍, 马仕鹏, 刘丽萍, 蔡天盼, 李小鹏, 葛善飞

330000 江西南昌大学第一附属医院感染科(王亮,邬小萍,马仕鹏,刘丽萍,李小鹏,葛善飞),病理科(余燕青),信息处(蔡天盼)

收稿日期:2023-11-25 出版日期:2025-01-31 发布日期:2025-03-10
通讯作者: 葛善飞,Email: geshanfei2010@163.com
基金资助:
江西省卫生健康委科技计划(202310304)

Risk factors associated with hypophosphatemia in chronic Hepatitis B patients treated with Entecavir of initial therapy

WANG Liang¹, YU Yan-qing², WU Xiao-ping¹, MA Shi-peng¹, LIU Li-ping¹, CAI Tian-pan², LI Xiaopeng¹, GE Shan-fei¹

1. Department of Infectious Diseases, the First Affiliated Hospital of Nanchang University, Jiangxi 330000, China;
2. Department of Pathology, the First Affiliated Hospital of Nanchang University, Jiangxi 330000, China;
3. Information Center, the First Affiliated Hospital of Nanchang University, Jiangxi 330000, China

Received:2023-11-25 Online:2025-01-31 Published:2025-03-10
Contact: GE Shan-fei, Email:geshanfei2010@163.com

摘要/Abstract

摘要： 目的探讨恩替卡韦(ETV)初治慢性乙型肝炎(CHB)患者发生低磷血症的危险因素及动态变化。方法选取2020年1月至2023年6月于南昌大学第一附属医院感染科接受ETV治疗的CHB患者148例。采用Cox回归风险模型分析CHB患者发生低磷血症的危险因素,运用受试者工作特征曲线下面积(AUC)评估CHB患者发生低磷血症的效能。采用Kaplan-Meier分析低磷血症累积发生率,并应用Log-rank检验进行比较。相关性采用Spearman Correlation进行分析。动态观察治疗期间血磷和eGFR变化。结果 148例患者中发生低磷血症17例(11.5%)。Cox单因素分析结果显示,性别、血磷的差异有统计学意义(P<0.05);多因素Cox风险模型分析显示,基线血磷(HR=0.001,95%CI: 0~0.021,P<0.001)是CHB患者发生低磷血症的独立影响因素。基线血磷预测发生低磷血症的AUC为0.7786,预测效能较好,敏感度、特异度分别为88.2%,60.3%。基线血磷≤1.03 mmol/L的CHB患者发生低磷血症累积发生率明显高于基线血磷＞1.03 mmol/L的患者(HR=81.79,95%CI:18.581~360.057, P<0.001)。低磷血症患者与eGFR无相关性(r=-0.084,P=0.749)。同时存在低磷血症及eGFR异常的患者,低磷血症的发生时间在eGFR异常后0~1.17年。CHB患者的血磷、eGFR水平呈现下降的趋势。低血磷组患者的血磷水平在随访期间始终低于血磷正常组。结论基线低血磷水平的ETV初治的CHB患者更易发生低磷血症。

关键词: 乙型肝炎慢性, 低磷血症, 恩替卡韦

Abstract: Objective To investigate the risk factors associated with hypophosphatemia and their dynamic changes in chronic Hepatitis B (CHB) patients treated with Entecavir of initial treatment. Methods 148 CHB patients treated with Entecavir of initial ireatment in the Department of infectious Diseases of the First Affiliated Hospital of Nanchang University from January 2020 to June 2023 were selected. Patients were divided into normal phosphorus group (n=131) and low phosphorus group (n=17) according to serum phosphorus. The Multivariate Cox regression analysis was performed to analyze the independent risk factors of hypophosphatemia in CHB patients. The efficacy of predicting hypophosphatemia in patients with CHB was evaluated with the receiver operating characteristic(ROC) curve. The cumulative incidence of hypophosphatemia was analyzed by Kaplan-Meier analysis and was compared by the Log-rank test. Spearman Correlation was used for correlative analysis. Serum phosphorus and estimated glomerular filtration rate (eGFR) were dynamically observed during treatment. Methods Of all 148 patients, 17 experienced hypophosphatemia, resulting in hypophosphatemia rate of 11.5%, The results of univariate analysis showed that sex and serum phosphorus at baseline were statistically significant (P<0.05) between the normal group and the low phosphorus group. The multivariate cox regression analysis showed that baseline serum phosphorus (HR=0.001, 95%CI: 0~0.021, P＜0.001) was an independent influencing factor for hypophosphatemia in CHB patients. The area under ROC curve of baseline serum phosphorus was 0.7786, indicating a good prediction efficiency. The optimal cut-off point was 1.03, and the sensitivity and specificity were 88.2% and 60.3% respectively. The cumulative incidence of hypophosphatemia in CHB patients with baseline serum phosphorus ≤ 1.03 mmol/L was significantly higher than that in patients with baseline serum phosphorus > 1.03 mmol/L(HR=81.79, 95%CI:4.127~28.550, P<0.001). There was no correlation between hypophosphatemia and eGFR (r=-0.084, P=0.749). For all patients with both hypophosphatemia and abnormal eGFR, hypophosphatemia occurs no earlier than eGFR abnormalities, occurring 0 to 1.17 years(median 0.58 years). The levels of blood phosphorus and eGFR in CHB patients showed a decreasing trend. The levels of serum phosphorus in hypophosphatemia group were always lower than those in normal group during follow-up. Conclusion For the CHB patients treated with entecavir of initial treatment, lower baseline phosphorus level are more likely to develop hypophosphatemia. Dynamic monitoring of serum phosphorus has great significance for the safe use of entecavir.

Key words: Chronic hepatitis B, Hypophosphatemia, Entecavir

王亮, 余燕青, 邬小萍, 马仕鹏, 刘丽萍, 蔡天盼, 李小鹏, 葛善飞. 恩替卡韦初治慢性乙型肝炎患者发生低磷血症的危险因素[J]. 肝脏, 2025, 30(1): 78-82.

WANG Liang, YU Yan-qing, WU Xiao-ping, MA Shi-peng, LIU Li-ping, CAI Tian-pan, LI Xiaopeng, GE Shan-fei. Risk factors associated with hypophosphatemia in chronic Hepatitis B patients treated with Entecavir of initial therapy[J]. Chinese Hepatolgy, 2025, 30(1): 78-82.

/ 推荐

参考文献

[1] 中华医学会肝病学分会, 中华医学会感染病学分会. 慢性乙型肝炎防治指南(2022年版). 中华肝脏病杂志, 2022, 30(12): 1309-1331.
[2] MartinP, Nguyen MH, Dieterich DT, et al. Treatment algorithm for managing chronic hepatitis B virus infection in the United States: 2021 Update. Clin Gastroenterol Hepatol, 2022,20(8):1766-1775.
[3] EuropeanAssociation for the Study of the Liver. EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol, 2017, 67(2): 370-398.
[4] LauG, Yu ML, Wong G, et al. APASL clinical practice guideline on hepatitis B reactivation related to the use of immunosuppressive therapy. Hepatol Int, 2021, 15(5): 1031-1048.
[5] YangX, Yan H, Zhang X, et al. Comparison of renal safety and bone mineral density of tenofovir and entecavir in patients with chronic hepatitis B: a systematic review and meta-analysis. Int J Infect Dis, 2022, 124: 133-142.
[6] NotsumataK, Nomura Y, Tanaka A, et al. Early changes in tubular dysfunction markers and phosphorus metabolism regulators as a result of switching from entecavir to tenofovir alafenamide fumarate nucleoside analog therapy for chronic hepatitis B patients. Hepatol Res, 2020, 50(3): 402-404.
[7] FujiiT, Kawasoe K, Ohta A, et al. A case of entecavir-induced Fanconi syndrome. CEN Case Rep, 2019, 8(4): 256-260.
[8] YuG, Cheng J, Jiang Y, et al. Serum phosphorus and calcium levels, and kidney disease progression in immunoglobulin A nephropathy. Clin Kidney J, 2021, 14(9): 2108-2113.
[9] FlorenzanoP, Cipriani C, Roszko KL, et al. Approach to patients with hypophosphataemia. Lancet Diabetes Endocrinol, 2020, 8(2): 163-174.
[10] InkerLA, Schmid CH, Tighiouart H, et al. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med, 2012, 367(1): 20-29.
[11] WagnerCA. The basics of phosphate metabolism. Nephrol Dial Transplant, 2023, gfad188.
[12] 上海市肾内科临床质量控制中心专家组. 慢性肾脏病早期筛查、诊断及防治指南(2022年版). 中华肾脏病杂志, 2022, 38(05): 453-464.
[13] MegapanouE, Florentin M, Milionis H, et al. Drug-induced hypophosphatemia: current insights. Drug Saf, 2020, 43(3): 197-210.
[14] YangX, Ma Z, Zhou S, et al. Multiple drug transporters are involved in renal secretion of entecavir. Antimicrob Agents Chemother, 2016, 60(10): 6260-6270.
[15] TienC, Xu JJ, Chan LS, et al. Long-term treatment with tenofovir in Asian-American chronic hepatitis B patients is associated with abnormal renal phosphate handling. Dig Dis Sci, 2015, 60(2): 566-572.
[16] HuangPY, Chiu S YH, Chang KC, et al. A novel evidence of serial changes of bone mineral density in chronic hepatitis B patients treated with entecavir. Hepatol Int, 2021, 15(2): 310-317.
[17] TebbenPJ. Hypophosphatemia: a practical guide to evaluation and management. Endocr Pract, 2022, 28(10): 1091-1099.
[18] HendrixRJ, Hastings MC, Samarin M, et al. Predictors of hypophosphatemia and outcomes during continuous renal replacement therapy. Blood Purif, 2020, 49(6): 700-707.
[19] DecruyenaereA, Kortbeek K, Delanghe S, et al. Incidence, evolution and risk factors of hypophosphatemia in patients with solid tumors receiving ferric carboxymaltose: a retrospective cohort study. Acta Clin Belg, 2023, 78(4): 298-307.