探讨西藏地区恩替卡韦治疗对非酒精性脂肪肝合并慢性乙型肝炎患者肝纤维化程度的影响

Exploring the effects of entecavir treatment on the degree of liver fibrosis in patients with non-alcoholic fatty liver combined with chronic hepatitis B in Tibet region

目的:探讨西藏地区非酒精性脂肪性肝病(NAFLD)合并慢性乙型肝炎(CHB)患者用恩替卡韦抗病毒治疗的疗效及肝纤维化程度。方法:回顾分析经恩替卡韦治疗自2018年1月—2019年12月在西藏自治区人民医院感染科门诊就诊或住院的HBeAg阳性的CHB患者。140例CHB研究对象中,45例经超声诊断为CHB合并NAFLD(A组),95例为单纯CHB(B组)。所有患者均给予恩替卡韦0.5 mg空腹口服1次/d,疗程48周,比较两组患者在治疗第12、24、48周时的HBeAg阴转率、血糖、血脂、肝功能以及肝纤维化程度,评估病毒学应答情况。运用SPSS 19.0统计学软件对数据进行处理,计量资料以均数±标准差(xˉ±s)表示,采用描述性统计分析,用t检验;计数资料以百分率(%)表示,运用χ^(2)检验,以P<0.05为差异有统计学意义。结果:治疗48周后,B组的HBeAg阴转率与HBV DNA阴转率显著优于A组的28.9%HBV DNA转阴率比较,B组(阴转率为83.2%)显著高于A组(阴转率为64.4%),差异有统计学意义(P<0.05)。单纯CHB患者的丙氨酸转氨酶水平下降程度明显高于CHB合并NAFLD患者。两组患者治疗后天冬氨酸转氨酶/血小板比值指数都比治疗前有显著性的降低,其中B组下降更为明显。A组患者的肝脏硬度值均显著低于B组,其中A组受脂肪衰减因素的影响,治疗前肝脏硬度值比B组值高,经治疗后差值为3.50±4.66;而B组未受脂肪衰减因素的影响,其治疗前、后的差值为2.05±2.53,故A组的肝脏硬度值下降幅度更明显,差异有统计学意义。两组患者血糖与血脂水平在治疗前后的差异均无统计学意义。结论:NAFLD对CHB患者抗病毒治疗及肝纤维化具有一定的影响,即单纯CHB患者抗病毒治疗效果较好而合并NAFLD时效果较差;在给予抗病毒治疗时,CHB合并NAFLD患者肝脏硬度值的下降程度明显高于单纯CHB患者。故在抗病毒治疗时,需根据不同个体的实际情况,对与NAFLD相关的风险因素进行积极干预,从而提高临床疗效。

Objective To explore the efficacy of entecavir antiviral therapy on the degree of liver fibrosis in patients with non-alcoholic fatty liver disease(NAFLD)combined with chronic hepatitis B(CHB)in Tibet region.Methods HBeAg-positive CHB patients who were treated with entecavir in the outpatient and inpatient Department of Infectious Diseases of the Tibet Autonomous Region people's Hospital between January 2018 to December 2019 were retrospectively analyzed.Among the 140 subjects with CHB,95 cases were CHB alone,and the other 45 cases were diagnosed as CHB combined with NAFLD by ultrasound.All patients were given entecavir 0.5 mg orally once daily on an empty stomach for 48 weeks.HBeAg negative conversion rate,blood glucose,blood lipid,liver function and the degree of liver fibrosis were compared between the two groups at the 12th,24th and 48th weeks of treatment to evaluate the virological response.SPSS 19.0 statistical software was used to process the data.Measurement data were expressed as mean±standard deviation(x¯x¯±s).Descriptive statistical analysis was used for t-test,and the categorical variables were expressed as percentage(%)andχ^(2) test.A p-value<0.05 was considered as statistically significant.Results After 48 weeks of treatment,the HBeAg and HBV DNA negative conversion rate were significantly better in patients with CHB alone(group B)than CHB combined with NAFLD(group A),that is to say,HBeAg negative conversion rate in group A and B patients were 28.90%and 40%,respectively,and group B was better than group A.HBV DNA negative conversion rate was significantly elevated in group B(83.2%)than group A(64.4%),with statistical significance(P<0.05),and the difference between the both groups was statistically significant.Alanine aminotransferase level was significantly decreased in patients with CHB alone than patients with CHB combined with NAFLD.Aspartate aminotransferase/platelet ratio index was significantly decreased after treatment than before treatment in both group of patients,and the depletion was more pronounced in CHB alone group.Liver stiffness values were significantly decreased in patients with CHB combined with NAFLD than CHB alone group.Moreover,liver stiffness values was higher in group A than group B before treatment under the influence of fat attenuation factors,and the differences before treatment and after treatment were 3.50±4.66 and 2.05±2.53,respectively;however,group B was not affected by fat attenuation factors,so LSM value reduction in group A was more obvious,and the differences were statistically significant.There was no statistically significant difference in blood glucose and blood lipids levels before and after treatment between the two groups.Conclusion NAFLD has a certain effect on antiviral therapy and liver fibrosis in patients with CHB,i.e.,the effect of antiviral therapy in patients with CHB alone is better than patients with CHB combined with NAFLD.Patients with CHB combined with NAFLD when treated with antiviral therapy had a significantly greater degree of liver stiffness reduction than patients with CHB alone.Therefore,it is necessary to actively intervene the risk factors associated with NAFLD according to the actual situation of different individuals to improve clinical efficacy of antiviral therapy.