慢性乙型肝炎合并代谢相关性脂肪性肝病的临床特征及预后影响因素分析

Clinical characteristics and prognosis of patients with chronic hepatitis B combined with metabolic associated fatty liver disease

目的 观察慢性乙型肝炎(CHB)患者使用富马酸替诺福韦酯(TDF)抗病毒治疗3年HBV DNA和HBsAg的动态变化。方法 回顾性收集2015年1月—2020年8月就诊于西安交通大学第二附属医院的单用TDF治疗≥3年157例的CHB患者的临床资料,按照基线HBeAg水平分为HBeAg阳性组(n=73)和HBeAg阴性组(n=84)。收集患者在治疗基线、1年、2年、3年时的血清HBV DNA定量、HBsAg定量资料并分析其动态变化。符合正态分布的计量资料两组间比较采用t检验;不符合正态分布的计量资料两组间比较采用Mann-Whitney U检验;不符合正态分布的重复测量资料先进行对数转换,组内或组间比较采用重复测量资料的方差分析;计数资料两组间比较采用χ^(2)检验或Fisher确切概率法。结果 TDF治疗第1年和2年时HBeAg阳性患者HBV DNA阴转率均显著低于HBeAg阴性患者(第1年:65.8%vs 81.0%,χ^(2)=4.676,P<0.05;第2年:87.7%vs 98.8%,P<0.05),TDF治疗3年两组HBV DNA阴转率差异无统计学意义(97.3%vs 100%,P>0.05)。HBeAg阳性和HBeAg阴性患者的基线HBsAg水平分别为10 633.6(2 084.8~24 005.7)IU/mL和1 402.8(311.0~2 863.5)IU/mL,经过TDF治疗3年后HBsAg水平分别降至1 534.9(912.7~5 885.9)IU/mL和677.8(119.4~1 974.8)IU/mL,组间差异有统计学意义(F=25.456,P<0.001)。HBeAg阳性患者第1年中位HBsAg下降值[1 856.5(158.4~12 103.1)IU/mL]显著高于第2年[879.8(130.5~2 382.5)IU/mL]和第3年[479.9(95.0~1 662.4)IU/mL](F=10.972,P<0.001),HBeAg阴性患者HBsAg下降速度前后差异无统计学意义(F=0.513,P>0.05)。此外,TDF治疗3年,59.2%的患者达到HBsAg<1500 IU/mL,HBsAg转阴率为1.3%。结论 TDF治疗3年,HBeAg阴性CHB患者HBV DNA定量全部转阴,而HBeAg阳性患者中97.3%实现HBV DNA转阴,仍然有2.7%的患者病毒定量可测及。HBsAg水平随着治疗时间延长均不断下降,且HBeAg阳性患者HBsAg水平下降速度呈现“先快后慢”的趋势特点。单用TDF治疗3年,59.2%的患者达到HBsAg<1500 IU/mL。

Objective To analyze the clinical characteristics and prognostic factors of chronic hepatitis B(CHB)patients complicated with metabolic associated fatty liver disease(MAFLD).Methods A total of 114 CHB patients and 101 CHB patients complicated with MAFLD who underwent liver biopsy between 2005 and 2018 were included.A long-term cohort was established with the time of liver puncture as the baseline,and decompensated cirrhosis,liver cancer,liver transplantation and death related to liver disease as the clinical endpoints.The patient’s NAS score,hepatitis inflammation activity(G)and fibrosis stage(S)were scored for the liver biopsy.According to fibrosis stage,patients were divided into no significant fibrosis(S0-1)and significant fibrosis(S2-4)groups.The clinical characteristics and prognosis of the CHB patients with or without MAFLD at the same fibrosis stage were compared.CHB patients with MAFLD were divided into NAS <4 and NAS≥4 groups according to NAS score,and the influence of NAS score on clinical outcomes of patients was analyzed.The independent samples t-test/Wilcoxin test was performed for comparison of continuous data and the chi-square test was used for comparison of categorical data between groups.Survival analysis was performed using Kaplan-Meier survival cure and compared using log-rank test.Cox multivariate regression analysis was used to identify prognostic factors.Results The BMI,blood glucose and TC in CHB patients with MAFLD group were significantly higher than those in CHB alone in each fibrosis stage(P < 0.05).In patients without significant fibrosis,the levels of ALT(Z =-2.249,P = 0.025),AST(Z =-2.512,P = 0.012)and GGT(Z =-5.261,P < 0.001)in the complicated group were higher than those in the CHB group.With a median follow-up time of 8.0 years,the Kaplan-Meier survival analysis revealed that the complicated MAFLD significantly reduced the liver event-free survival rate of CHB patients(χ^(2)= 7.607,P = 0.006).Cox multivariable analysis revealed MAFLD(HR = 5.76,95% CI:1.54-21.48,P = 0.009)was an independent risk factor for liver-related outcomes.In CHB patients with MAFLD,the ALT(Z =-3.139,P = 0.002),AST(Z =-2.898,P = 0.004),and GGT(Z =-2.260,P = 0.024)of patients with NAS≥4 were higher than those of patients with NAS < 4.We found that significant fibrosis(HR = 4.83,95%CI:1.23-18.91,P = 0.024)was associated with the poor prognosis of CHB patients with MAFLD.Conclusions CHB patients with MAFLD are more likely to have impaired liver function in the early stage and the disease progresses more rapidly.Complicated MAFLD will increase the risk of liver-related events in patients with CHB,and significant fibrosis is an independent risk factor for adverse outcomes in CHB patients with MAFLD.