恩替卡韦抗病毒治疗慢性乙型肝炎合并非酒精性脂肪性肝病患者病毒学应答情况分析

Would the coincidence of nonalcoholic fatty liver diseases impact the antiviral response to enticavir therapy in patients with chronic hepatitis B?

目的 评价抗病毒治疗慢性乙型肝炎(CHB)合并非酒精性脂肪性肝病(NAFLD)患者的疗效。方法 2016年1月~2020年6月我院收治的CHB合并NAFLD患者125例和同期CHB患者120例,均接受恩替卡韦治疗48 w。使用FibroScan 502型肝脏弹性成像仪检测肝脏受控衰减参数(CAP)。常规检测血清HBeAg和HBV DNA。采用COX比例风险回归模型分析影响疗效的因素。结果 在基线资料方面,本研究纳入的CHB合并NAFLD组血小板(PLT)计数、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、甘油三酯(TG)、总胆固醇(TC)、LDL和CAP分别为189.0(156.0,212.0)×109/L、78.0(40.0,138.0)U/L、72.0(26.0,98.0)U/L、4.4(3.0,5.8)mmol/L、 5.9(4.9,7.3)mmol/L、3.8(2.7,4.5)mmol/L和290.0(245.0,315.0)dB/m,显著不同于CHB组[分别为154.0(127.0,184.0)×109/L、198.0(43.0,160.0)U/L、121.0(29.0,105.0)U/L、1.7(1.2,3.2)mmol/L、4.9(4.4,5.4)mmol/L、2.9(2.5,3.6)mmol/L和194.0(170.0,232.0)dB/m,P<0.05];在治疗24 w和48 w末,两组血清HBV DNA均大部或全部转阴(P>0.05),血清HBeAg阴转率都很低(P>0.05),但CHB合并NAFLD组血清ALT复常率则分别为44.8%和66.4%,显著低于CHB组的95.8%和100.0%(P<0.05);经多因素COX比例风险回归模型分析显示,CAP值是影响ALT复常的独立危险因素(HR:0.996,95%CI:0.994~0.999,P<0.05),即CAP值较高的患者血清ALT复常率较低。结论 合并NAFLD将影响接受恩替卡韦治疗的CHB患者血生化学应答,因此在抗病毒治疗的同时还需要针对性地处理肝脂肪变。

Objective The aim of this study was to investigate the impact of nonalcoholic fatty liver diseases(NAFLD) on antiviral response to entecavir in patients with chronic hepatitis B(CHB). Methods 125 patients with CHB and concomitant NAFLD and 120 patients with CHB at the same time were recruited in our hospital between January 2016 and June 2020, and all received entecavir therapy for 48 weeks. The controlled attenuation parameter(CAP) of the liver was determined by FibroScan 502, and serum HBV DNA and HBeAg were detected routinely. The COX proportional risk regression model was applied to multivariate correlation analysis. Results The blood platelet(PLT) counts, alanine aminotransferase(ALT), aspartate aminotransferase(AST), triglyceride(TG), total cholesterol(TC), low density lipoprotein cholesterol(LDL) and CAP in patients with CHB and NAFLD were 189.0(156.0,212.0)×10~9/L, 78.0(40.0, 138.0)U/L, 72.0(26.0, 98.0)U/L, 4.4(3.0, 5.8)mmol/L, 5.9(4.9,7.3)mmol/L, 3.8(2.7, 4.5)mmol/L and 290.0(245.0, 315.0)dB/m, all significantly different compared to [154.0(127.0, 184.0)×10~9/L, 198.0(43.0, 160.0)U/L, 121.0(29.0, 105.0)U/L, 1.7(1.2, 3.2)mmol/L, 4.9(4.4, 5.4)mmol/L, 2.9(2.5, 3.6)mmol/L and 194.0(170.0, 232.0)dB/m, respectively, P<0.05] in patients with CHB;at the end of 24 week and 48 week treatment, almost all patients in the two groups had their serum HBV DNA transferred to negative and few patients in the two groups had their serum HBeAg transferred to negative(P>0.05), but serum ALT normalization rates in patients with CHB and NAFLD were 44.8% and 66.4%, both significantly lower than 95.8% and 100.0%(P<0.05) in patients with CHB;the multivariate COX analysis showed that the CAP was the independent risk factor for serum ALT normalization(HR:0.996, 95%CI:0.994-0.999, P<0.05), suggesting that the more high the CAP, the more lower the ALT normalization rates. Conclusion The concomitant NAFLD might frustrate the biochemical response to entecavir antiviral therapy in patients with CHB, which warrants simultaneously appropriate management of hepatic steatosis.