抗病毒治疗慢性乙型肝炎合并非酒精性脂肪性肝病的效果观察

Efficacy of antiviral therapy for chronic hepatitis B with nonalcoholic fatty liver disease

目的分析合并非酒精性脂肪性肝病(NAFLD)对慢性乙型肝炎(CHB)抗病毒疗效的影响,为此类患者的临床治疗提供参考。方法选取2011年1月—2017年12月在深圳市第三人民医院就诊的患者187例,分为CHB组(43例)、NAFLD组(41例)、CHB合并NAFLD组(103例)。所有患者在入组和随访的不同时间点行身高、体质量、ALT、AST、血脂四项、肝纤维化四项、APRI、HBsAg、HBeAg、抗-HBe、HBV DNA定量检查,比较进行抗病毒治疗的CHB患者和CHB合并NAFLD患者在使用抗病毒药物12、24、48、72、96周的治疗效果。符合非正态分布的计量资料多组间比较采用Kruskal-Wallis H检验,两组间比较采用Wilcoxon秩和检验;计数资料组间比较采用χ2检验。结果基线时CHB组和CHB合并NAFLD组的PLT、ALT、GGT、ALP水平和右叶斜径均显著低于NAFLD组(P值均<0.05),CHB合并NAFLD组的BMI、TC、TG水平显著高于CHB组(P值均<0.05),其脾脏厚度显著低于CHB组(P<0.05),两组中的其他指标水平在基线期差异均无统计学意义(P值均>0.05)。抗病毒治疗12周时,CHB组和CHB合并NAFLD组患者的肝纤维化指标及炎症指标差异均无统计学意义(P值均>0.05),24、48周时CHB组的ALT(Z值分别为-2.128、-3.055,P值均<0.05)、GGT(Z值分别为-2.025、-1.631,P值均<0.05)水平下降更明显,48周时CHB组(Z=-6.445,P<0.001)和CHB合并NAFLD组(Z=-4.415,P<0.001)的HBV DNA水平均较治疗前显著降低,但CHB组的降低水平更明显。CHB合并NAFLD组在抗病毒治疗的不同时间点,HBV DNA转阴率均显著低于CHB组(χ2值分别为14.237、13.961、15.226、10.462、13.030,P值均<0.05)。抗病毒治疗48周时,CHB合并NAFLD组的HBeAg转阴率显著低于CHB组(χ2=5.309,P=0.021),但96周时两组间的转阴率差异无统计学意义(χ2=0.117,P=0.732)。抗病毒治疗24、48、72、96周,CHB合并NAFLD组的ALT复常率均显著低于CHB组(χ2值分别为12.049、5.287、11.407、11.375,P值均<0.05)。结论合并NAFLD降低了CHB患者的抗病毒治疗效果,使抗病毒治疗时间延长。

Objective To investigate the influence of nonalcoholic fatty liver disease(NAFLD)on the antiviral response of patients with chronic hepatitis B(CHB),and to provide a reference for clinical treatment of such patients.Methods A total of 187 patients who attended Shenzhen Third People’s Hospital from January 2011 to December 2017 were enrolled and divided into CHB group with 43 patients,NAFLD group with 41 patients,and CHB+NAFLD group with 103 patients.Related indices were measured at enrollment different time points of follow-up,including body height,body weight,alanine aminotransferase(ALT),aspartate aminotransferase,four blood lipid parameters,four indicators of liver fibrosis,aspartate aminotransferase-to-platelet ratio index,HBsAg,HBeAg,anti-HBe,and HBV DNA quantification,and the CHB patients and the CHB+NAFLD patients receiving antiviral therapy were compared in terms of treatment outcome at weeks 12,24,48,72,and 96 of antiviral therapy.The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups,and the Wilcoxon rank-sum test was used for comparison between two groups;the chi-square test was used for comparison of categorical data between groups.Results Compared with the NAFLD group at baseline,the CHB group and the CHB+NAFLD group had significantly lower platelet count,ALT,gamma-glutamyl transpeptidase(GGT),alkaline phosphatase,and right lobe of liver oblique diameter(all P<0.05),and compared with the CHB group,the CHB+NAFLD group had significantly higher body mass index,total cholesterol,and triglyceride and a significantly lower spleen thickness(all P<0.05),while there were no significant differences in the other indicators between the two groups at baseline(all P>0.05).At week 12 of antiviral therapy,there were no significant differences in liver fibrosis markers and inflammatory indices between the CHB group and the CHB+NAFLD group(all P>0.05);compared with the CHB+NAFLD group at weeks 24 and 48,the CHB group had significantly greater reductions in ALT(Z=-2.128 and-3.055,both P<0.05)and GGT(Z=-2.025 and-1.631,both P<0.05);at week 48,the CHB group and the CHB+NAFLD group had a significant reduction in HBV DNA(Z=-6.445 and-4.415,both P<0.001),and the CHB group had a significantly greater reduction.The CHB+NAFLD group had a significantly lower HBV DNA clearance rate than the CHB group at different time points of antiviral therapy(χ2=14.237,13.961,15.226,10.462,and 13.030,all P<0.05).At week 48 of antiviral therapy,the CHB+NAFLD group had a significantly lower HBeAg clearance rate than the CHB group(χ2=5.309,P=0.021),while there was no significant difference between the two groups at week 96(χ2=0.117,P=0.732).At weeks 24,48,72,and 96 of antiviral therapy,the CHB+NAFLD group had a significantly lower ALT normalization rate than the CHB group(χ2=12.049,5.287,11.407,and 11.375,all P<0.05).Conclusion NAFLD reduces the antiviral response of CHB patients and prolongs the duration of antiviral therapy.