Objective: To investigate the changes of bone mineral density and its related influencing factors in chronic hepatitis B patients treated with long-term entecavir monotherapy. Methods: 211 cases with chronic hepatitis B treated with entecavir monotherapy in the Department of Infectious Diseases of Henan Provincial People's Hospital from June 2018 to September 2019 were retrospectively collected. Age, gender, body mass index, number of years of medication use, presence or absence of liver cirrhosis and current bone mineral density level (using dual-energy X-ray detection, taking lumbar L1 ~ 4 and left femur as observation region) and other related data were collected. 211 cases general situation was descriptively analyzed by case-control study design. Two independent sample t-tests were used to compare the differences in serum calcium, phosphorus, and renal function levels in patients with different medication durations. Univariate logistic regression was used to screen the influencing factors of bone mineral density level. Significant variables of univariate analysis were included in multivariate logistic regression to obtain the independent influencing factors leading to the decrease of bone mineral density level. The test level was set as α = 0.05. Results: The average age of 211 cases with chronic hepatitis B was (42.36 ± 11.10) years. The average medication time use was (2.52 ± 1.94) years. The body mass index (23.95 ± 3.11), and male-to-female ratio was 2.25/1. The incidence of liver cirrhosis was 35.5%. The incidence of low bone mass in the two observation sites (lumbar spine L1~4 and left femur) was 24.6% and 29.4%, respectively. There were statistically significant differences in serum calcium, phosphorus and renal function levels among patients with different entecavir treatment duration (≥3 years and < 3 years) (P < 0.05). Univariate analysis result showed that the influencing factors of BMD were age, the number of years of medication use, gender, liver cirrhosis (L1~4 of the lumbar spine region) and age, the number of years of medication, and gender (left femoral region). The variables that entered the two models after the multivariate analysis were age (L1~4 region of lumbar spine: OR = 2.225, left femur OR = 1.660), gender (L1~4 region of lumbar spine: OR = 3.048, left femur OR = 2.496), number of years of medication use (L1~4 region of lumbar spine: OR = 1.387, left femur OR = 1.276). Conclusion: Age, gender, and the number of years of medication use are independent factors that influence the bone mineral density of patients with chronic hepatitis B treated with long-term entecavir. Low bone mass risk at the two observation sites is 2.225 and 1.66 times the normal level for every 10 years of age increase. Compared with men, the risk of low bone mass at the two observation sites is 3.048 and 2.496 times for women, and for every additional year of medication use, the risk of low bone mass at the two observation sites is 1.387 and 1.276 times the normal level. Female patients with older age and prolonged medication use are at high risk of developing bone mineral density reduction.
目的： 探讨长期应用恩替卡韦单药治疗的慢性乙型肝炎患者骨密度变化情况及其相关影响因素。 方法： 回顾性收集2018年6月至2019年9月就诊于河南省人民医院感染科的211例应用恩替卡韦单药治疗的慢性乙型肝炎患者，收集年龄、性别、人体质量指数、用药年数、有无肝硬化以及目前骨密度水平（利用双能X线检测，取腰椎L1～4与左侧股骨为观察部位）等相关资料。采用病例对照研究设计，对211例患者的一般情况进行描述性分析。采用两独立样本t检验比较不同用药时长患者血清钙、磷及肾功能水平差异；利用单因素logistic回归筛选骨密度水平相关影响因素，将单因素分析有意义的变量纳入多因素logistic回归，获得导致患者骨密度水平降低的独立影响因素，检验水准取α= 0.05。 结果： 211例慢性乙型肝炎患者年龄（42.36±11.10）岁、用药（2.52±1.94）年、人体质量指数（23.95±3.11）、男女比例2.25/1、肝硬化发生率35.5%、两个观察部位（腰椎L1～4与左侧股骨）低骨量的发生率分别为24.6%与29.4%。不同恩替卡韦经治时长（≥3年和< 3年）患者血清钙、磷及肾功能水平差异有统计学意义（P值均< 0.05）；单因素分析结果显示影响骨密度的因素分别为年龄、用药年数、性别、有无肝硬化（腰椎L1～4部位）和年龄、用药年数、性别（左侧股骨部位）。纳入多因素分析后进入两个模型的变量分别为年龄（腰椎L1～4部位：OR = 2.225，左股骨OR = 1.660）、性别（腰椎L1～4部位：OR = 3.048，左股骨OR = 2.496）、用药年数（腰椎L1～4部位：OR = 1.387，左侧股骨OR = 1.276）。 结论： 年龄、性别、用药年数是影响长期应用恩替卡韦治疗慢性乙型肝炎患者骨密度水平的独立影响因素。年龄每增加10岁，两个观察部位发生低骨量的风险分别是原先的2.225倍和1.660倍；女性相比于男性，两个观察部位发生低骨量的风险分别为3.048倍和2.496倍；用药年数每增加1年，两个观察部位发生低骨量的风险分别是原先的1.387倍和1.276倍。年龄越大、用药时间越长的女性患者是发生骨密度降低的高危人群。.
Keywords: Antiviral therapy; Bone mineral density; Chronic hepatitis B; Entecavir; Influencing factors.