恩替卡韦治疗男性慢性乙型病毒性肝炎对生殖功能影响的临床研究

目的:探讨恩替卡韦治疗男性慢性乙型病毒性肝炎后对其生殖功能影响。方法:收集2015~2018年慢性乙型肝炎男性患者接受初始恩替卡韦治疗56例,年龄18~45(33.14±5.38)岁;收集健康志愿者24例作为正常对照组近期有怀孕生育史,21~45(32.62±5.94)岁]。观察乙肝治疗组和正常对照组在年龄、BMI、生殖激素水平、勃起功能(勃起功能国际问卷IIEF-5)及精液质量参数之间的差异。初始恩替卡韦治疗(0. 5 mg/d抗HBV治疗24周)后比较治疗前后乙肝治疗组BMI、生殖激素水平、勃起功能及精液质量参数之间的差异。结果:乙肝治疗组与正常对照组比较:年龄、BMI、生活习惯及生殖激素水平等因素中除了FSH水平和E2水平组间存在显著差异FSH(3.92±1.29) mIU/ml vs(3.08±0.85) mIU/ml,P=0.003;E2(35.79±7.49) pg/ml vs(28.25±7.09) pg/ml,P<0.0001],其余均无明显差异。各项精液参数(精子总活动率、前向运动精子百分率、精子浓度及精子总数),乙肝治疗组均明显低于正常对照组精子总活动率(37.75±13.33)%vs(49.58±9.27)%,P=0.004;前向运动精子百分率(30.70±10.03)%vs(42.46±8.90)%,P<0.0001;前向运动精子百分率(30.70±10.03)%vs(42.46±8.90)%,P<0.0001;精子浓度(51.51±19.50)×10^6/ml)vs(70.33±30.62)×10^6/ml,P=0.007及精子总数(160.2±51.8)×10^6)vs(225.91±97.97)×10^6,P=0.002]。乙肝治疗组IIEF-5评分显著低于正常对照组(19.32±2.34 vs 21.25±2.35,P=0.0006)。恩替卡韦治疗24周后,与治疗前的精液参数,精液量、精液pH、禁欲天数均比较无显著性差异。精子总活动率、前向运动精子百分率、精子浓度及精子总数较治疗前均有显著提升分别为精子总活动率(37.75±13.33)%vs(44.1±11.89)%,P=0.004;前向运动精子百分率(30.70±10.03)%vs(38.30±7.42)%,P<0.0001;精子浓度(51.51±19.50)×10^6/mlvs(62.00±24.64)×10^6/ml,P=0.007及精子总数(160.21±51.8)×10^6vs(207.65±81.69)×10^6,P=0.0002)。同时治疗后乙肝治疗组IIEF-5评分较治疗前显著升高(20.13±1.82 vs 19.32±2.34,P=0.02)。结论:恩替卡韦治疗慢性乙型病毒性肝炎时,肝功能改善明显,勃起功能及精液质量明显提高。

Entecavir improves the reproductive function of male patients with chronic hepatitis B

Objective: To study the effect of entecavir on the reproductive function of male patients with chronic hepatitis B(CHB). Methods: This study included 56 CHB male patients(aged 18-45 33.14 ± 5.38] years) initially treated with entecavir at 0.5 mg/d for 24 weeks from 2015 to 2018 and another 24 healthy fertile male volunteers(aged 21-45 32.62 ± 5.94] years) as normal controls. We obtained the body mass index(BMI), reproductive hormone levels, semen parameters and IIEF-5 scores from the subjects and compared them between the two groups before and after treatment. Results: There were no statistically significant differences between the CHB and normal control groups in age, BMI, lifestyle and baseline reproductive hormone levels except in the levels of FSH(3.92 ± 1.29] vs 3.08 ± 0.85] mIU/ml, P = 0.003) and E2(35.79 ± 7.49] vs 28.25 ± 7.09] pg/ml, P < 0.01). The semen parameters were significantly lower in the CHB patients than in the normal controls, including total sperm motility(37.75 ± 13.33]% vs 49.58 ± 9.27]%, P = 0.004), the percentage of progressively motile sperm(PMS)(30.70 ± 10.03]% vs 42.46 ± 8.90]%, P < 0.01), sperm concentration(51.51 ± 19.50] vs 70.33 ± 30.62) ×10^6/ml, P = 0.007), and total sperm count(160.2 ± 51.8] vs 225.91 ± 97.97] ×10^6, P = 0.002), and so were the IIEF-5 scores(19.32 ± 2.34 vs 21.25 ± 2.35, P = 0.0006). After 24 weeks of entecavir treatment, the CHB patients showed no significant difference from the baseline in the semen volume, semen pH and days of abstinence, but remarkable improvement in total motility(37.75 ± 13.33] vs 44.1 ± 11.89]%, P = 0.004), PMS(30.70 ± 10.03] vs 38.30 ± 7.42]%, P < 0.01), sperm concentration(51.51 ± 19.50] vs 62.00 ± 24.64] ×10^6/ml, P = 0.007), total sperm count(160.21 ± 51.8] vs 207.65 ± 81.69] ×10^6, P = 0.0002), and IIEF-5 score(20.13 ± 1.82 vs 19.32 ± 2.34, P = 0.02). Conclusion: CHB patients have lower sexual function and semen quality than normal males. Entecavir can significantly improve the liver function, sexual function and semen quality of the CHB patients, but whether it directly improves the sexual function and semen quality of the patients or indirectly through liver function improvement needs to be further studied.