服用核苷(酸)类似物停药后乙型肝炎相关慢加急性肝衰竭患者的临床特点分析

目的分析乙型肝炎不同发病阶段停药后慢加急性肝衰竭患者的临床特点,观察治疗后的病情变化,进一步增强规范用药意识。方法选取东部战区总医院淮安医疗区2005年5月至2020年10月期间,停用口服核苷(酸)类似物的慢性乙型肝炎(CHB)及肝硬化(CIR)患者40例,分析停药种类和发生乙型肝炎相关慢加急性肝衰竭(ACLF)的关系,停药发生ACLF后经积极综合治疗的病情转归。结果引起ACLF的停药种类中,停用恩替卡韦的比例最高(52.5%)。乙型肝炎组患者停药后引起ACLF的患者中,停用恩替卡韦的比例最高(65.2%),乙型肝炎肝硬化组患者停药后引起ACLF的患者中,停用阿德福韦酯(41.2%)的比例最高。40例停药患者中,乙型肝炎组患者的CHE[(7235±825.2)U/L]、AFP[(156.7±34.0)ng/L]水平显著高于乙型肝炎肝硬化组患者的CHE[(5534±900.4)U/L]、AFP[(30.8±12.6)ng/L]水平(P<0.05),乙型肝炎组的TBA[(52.7±11.4)μmol/L]、TBil[(95.6±17.5)μmol/L]、DBil[(62.7±8.6)μmol/L]、PT[(14.7±9.5)s]水平显著低于乙型肝炎肝硬化组TBA[(67.5±15.5)μmol/L]、TBil[(349.7±62.2)μmol/L]、DBil[(214.0±18.7)μmol/L]、PT[(30.5±12.9)s]水平(P<0.05)。治疗有效组患者的ALB(30.3±7.2)、CHE[(7005±890.4)U/L]、AFP[(139.5±28.7)ng/L]水平显著高于未愈组患者的ALB(25.3±9.4)、CHE[(5021±976.4)U/L]、AFP[(29.8±4.7)ng/L]水平(P<0.05),治疗有效组的TBA[(40.7±18.2)μmol/L]、TBil[(96.5±15.3)μmol/L]、DBil[(53.5±7.2)μmol/L]、PT[(15.4±8.9)s]水平显著低于未愈组的TBA[(50.9±20.4)μmol/L]、TBil[(350.6±50.8)μmol/L]、DBil[(218.0±20.7)μmol/L]、PT[(29.7±11.4)s]水平(P<0.05)。乙型肝炎组和乙型肝炎肝硬化组,治疗有效组和未愈组在病情转归上比较,发生失代偿肝硬化的病例差异有统计学意义(P<0.05)。结论服用核苷(酸)类似物停药停药后发生ACLF病情较重,对病情的预后影响较大,停药需慎重。

The clinical characteristics of HBV related acute on chronic liver failure patients with hepatitis B after withdrawal of nucleoside(acid)analogues

Objective To analyze the clinical characteristics of acute on chronic liver failure(ACLF)patients with hepatitis B after stopping anti-viral drugs,and to emphasize the awareness of standardized medication.Methods Forty ACLF patients with chronic hepatitis B(CHB)and CHB related liver cirrhosis(CHB-cirrhosis)who stopped taking oral nucleoside(acid)analogues were selected in this study.The association between the types of withdrawal drugs and the occurrence of ACLF,and the prognosis of these patients after active comprehensive treatment were analyzed.Results Among the types of withdrawal drugs resulting in ACLF,the proportion of entecavir was the highest(52.5%).In CHB group,the proportion of entecavir discontinuation associated ACLF was the highest(65.2%).In CHB-cirrhosis group,the proportion of adefovir dipivoxil withdrawal associated ACLF was the highest(41.2%).In 40 patients who had stopped taking anti-viral medicine,the levels of cholinesterase(CHE)(7235±825.2 U/L)andα-fetoprotein(AFP)(156.7±34.0 ng/L)in hepatitis B group were significantly higher than those of CHE(5534±900.4 U/L)and AFP(30.8±12.6 ng/L)in CHB-cirrhosis group(P<0.05).The levels of total bile acid(TBA)(52.7±11.4μmol/L),total bilirubin(TBil)(95.6±17.5μmol/L),direct bilirubin(DBil)(62.7±8.6μmol/L)and prothrombin time(PT)(14.7±9.5s)in CHB group were significantly lower than those of TBA(67.5±15.5μmol/L),TBil(349.7±62.2μmol/L),DBil(214.0±18.7μmol/L),PT(30.5±12.9 s)in CHB-cirrhosis group(P<0.05).The levels of ALB(30.3±7.2),CHE(7005±890.4 U/L)and AFP(139.5±28.7 ng/L)in the effective treatment group were significantly higher than those of ALB(25.3±9.4),CHE(5021±976.4 U/L)and AFP(29.8±4.7 ng/L)in the ineffective treatment group(P<0.05).The levels of TBA(40.7±18.2μmol/L),TBil(96.5±15.3μmol/L),DBil(53.5±7.2μmol/L),PT(15.4±8.9 s)in the effective treatment group were significantly lower than those of TBA(50.9±20.4μmol/L),TBil(350.6±50.8μmol/L),DBil(218.0±20.7μmol/L),PT(29.7±11.4 s)in the ineffective treatment group(P<0.05).In the CHB group and the CHB-cirrhosis group,the difference in the prognosis between effective and the ineffective treatment groups was statistically significant(P<0.05).Conclusion ACLF occurs after withdrawal of nucleoside(acid)analogues in CHB and CHB-cirrhosis patients and imposes a great impact on their prognosis.Cautious should be taken for discontinuing anti-viral agents.