慢性乙型肝炎患者合并脂肪肝导致单纯抗病毒治疗生物化学应答不佳诊疗分析

Analysis of diagnosis and treatment towards CHB patients complicated with fatty liver with complete virological response while biochemical suboptimal response

目的 分析慢性乙型肝炎患者经规范核苷（酸）类似物治疗获得完全病毒学应答但生物化学应答不佳的原因,并在原有治疗基础上对合并脂肪肝患者在改变生活方式的基础上加用双环醇片,观察其疗效和安全性.方法 收集40例规范核苷（酸）类似物抗病毒治疗2年以上（＞24 ～ ＜61个月）,病毒学完全应答但生物化学应答不佳的慢性乙型肝炎患者进行肝组织病理学检查,分析产生原因,对其中27例合并脂肪肝的患者在抗病毒和改变生活方式基础上加用双环醇治疗48周,观察治疗前后生物化学各项指标和肝纤维化指标的变化.患者纤维化分期危险因素的分析用二分类logistic多元回归分析;肝功能生物化学指标资料的比较采用单组重复测量设计的方差分析,不同时间点均值的两两比较采用多重比较配对的t检验进行分析. 结果 肝组织病理学检查结果显示40例患者中有不同程度肝细胞脂肪变者27例（69.23％）,发现组织中脂肪变和炎症与肝纤维化严重程度相关（x^2=4.746,P=0.029;x^2=5.072,P=0.024）,血清和组织中HBsAg水平与肝纤维化程度无相关性（x^2=0.273,P=0.601;x^2=0.020,P=0.887）.改善生活方式并加用双环醇治疗的患者,生物化学应答率显著提高,ALT水平明显下降（F=58.045,P=0.000）,血清谷胱甘肽过氧化物酶水平明显上升（t=15.109,P=0.000）,丙二醛水平明显下降（t=-10.786,P=0.000）;肝脏弹性测定硬度值下降（t=3.873,P=0.001;治疗前＜15 kPa者,t=2.255,P=0.036;治疗前＞15 kPa者,t=5.376,P=0.002）.结论 对慢性乙型肝炎患者经规范核苷（酸）类似物长期治疗后生物化学应答不佳的患者,应尽早考虑其他致病因素以便指导治疗.在改变生活方式的基础上加用双环醇对于慢性乙型肝炎合并脂肪肝导致的生物化学应答不佳的慢性乙型肝炎患者,有一定的疗效.

Objective To analyze the reason of biochemical suboptimal response in CHB patients with complete virological response after more than 2 years standard treatment with Nucleos（t）-ide analogs （NUCs）.To evaluate the efficacy and safety profiles of bicyclol tablets plus on the basis of the original treatment and lifestyle intervention.in CHB patients complicated with fatty liver.Methods In 40 patients with chronic hepatitis B meeting the inclusion criteria,the liver biopsy was conducted.And patients complicated with fatty liver were treated with bicyclol tablets（25 mg,t.i.d） additional consecutive 48 weeks.The changes of serum biochemistry indexes and liver fibrosis index were observed before and after treatment.Results Among 40 patients,27 were complicated with fatty liver（69.23%）,fatty degree in liver cell and liver inflammatory were closely related to the advanced fibrosis （x^2 =4.746,P=0.029;x^2 =5.072,P=0.024）.The expression of HBsAg in serum and liver tissue showed no correlation with the advanced fibrosis （x^2=0.273,P=0.601;x^2 =0.020,P =0.887） After bicyclol tablets treatment,serum biochemistry of patients complicated with fatty liver significantly decreased （F=58.045,P =0.000）,plasma GST-PX significantly increased （t=15.109,P =0.000）,plasma MDA significantly decreased （t=-10.786,P=0.000）;LSM significantly decreased （t=2.255,P=0.036;t =5.376,P =0.002）.Conclusion For the antiviral purpose of guide treatment,CHB patients treated with Nucleos（t）-ide analogs （NUCs） with biochemical suboptimal response,other risk factors should be considered as early as possible.Bicyclol plus lifestyle intervention was effective for chronic hepatitis B combined fatty liver patients with poor biochemical responses.