慢性乙型肝炎再激活所致慢加急性肝衰竭影响因素及疗效评价

摘要/Abstract

摘要： 目的探究影响慢性乙型肝炎(CHB)再激活所致慢加急性肝衰竭(ACLF)预后的因素以及疗效评价。方法选取2018年10月至2020年10月连云港市第二人民医院收治的CHB再激活ACLF患者68例(男37例、女31例),年龄(45.1±6.0)岁。给予个体化综合治疗方案,以此为基础上单独或联合应用抗病毒药物恩替卡韦、拉米夫定及阿德福韦酯,观察治疗前后患者主要指标变化。logistic回归分析不同结局ACLF患者影响因素。结果 68例ACLF患者中治疗好转48例(治疗好转组)、无效死亡20例(无效死亡组)。比较一般资料可知,治疗好转组年龄[(41.4±10.2)岁]显著低于无效死亡组[(50.2±9.7)岁,P<0.05];治疗好转组中肝炎、肝硬化代偿期及肝硬化失代偿期分别为21例(43.7%)、17例(35.4%)及10例(20.8%),均显著高于无效死亡组[3例(15.0%)、1例(5.0%)及16例(80.0%),P<0.05];前者腹水、上消化道出血、肝性脑病、肝肾综合征分别为19例(39.6%)、2例(4.2%)、2例(4.2%)及4例(8.3%),均显著低于后者[16例(80.0%)、6例(30.0%)、7例(35.0%)及8例(40.0%),P<0.05];治疗好转组中PTA、血氨及血肌酐分别为(38.6±7.8)%、(38.2±9.0)μmol/L及(62.4±13.2)μmol/L,与无效死亡组[(27.0±6.6)%、(63.4±15.6)μmol/L及(82.4±17.0)μmol/L]比较差异有统计学意义(P<0.05)。此外年龄、PTA、血氨及血肌酐被验证为预测ACLF治疗无效死亡的独立危险因素(P<0.05)。与治疗前相比,治疗后ALT、HBV DNA均显著下降(P<0.05),治疗12、24周后TBil均显著下降(P<0.05),治疗24周后PTA显著下降(P<0.05)。结论年龄、PTA、血氨及血肌酐是影响CHB再激活ACLF预后的独立危险因素,应用抗病毒药物能够显著改善患者主要指标。

关键词: 慢性乙型肝炎, 慢加急性肝衰竭, 乙型肝炎病毒, 预后

Abstract: Objective To analyze the prognostic impact factors and therapeutic effect evaluation of patients with acute-on-chronic liver failure (ACLF) induced by chronic hepatitis B (CHB) reactivation.Methods From October 2018 to October 2020, sixty-eight patients (including 37 males and 31 females) with ACLF due to CHB reactivation were selected, with an average age of (45.1±6.0) years. All patients were given individualized comprehensive treatment. On this basis, antiviral drugs including entecavir, lamivudine and adefovir dipivoxil were used alone or in combination. The changes of main indexes of the ACLF patients were observed before and after treatment. The patients were divided into treatment improvement group and ineffective death group based on their different outcomes. Logistic regression analysis was used to indentify the influencing factors of the patients’ outcomes.Results Among 68 patients with ACLF, 48 cases improved after treatment (treatment improvement group) and 20 cases died after ineffective treatment (ineffective death group). According to the general data, the age of treatment improvement group [(41.4±10.2) years] was significantly younger than that of ineffective death group [(50.2±9.7) years (P<0.05). In the treatment improvement group, there were 21 cases (43.7%), 17 cases (35.4%) and 10 cases (20.8%) of hepatitis, compensated cirrhosis and decompensated cirrhosis, respectively, which were significantly more than those of 3 cases (15.0%), 1 case (5.0%) and 16 cases (80.0%) in the ineffective death group (P<0.05). Ascites, upper gastrointestinal bleeding, hepatic encephalopathy and hepatorenal syndrome in the treatment improvement group were 19 cases (39.6%), 2 cases (4.2%), 2 cases (4.2%) and 4 cases (8.3%), respectively, which were significantly lower than those of 16 cases (80.0%), 6 cases (30.0%) in the ineffective death group (P<0.05). The prothrombin time activity (PTA), blood ammonia and serum creatinine levels in the treatment improvement group were (38.6±7.8)%, (38.2±9.0) μmol/L and (62.4±13.2) μmol/L, respectively, which were significantly higher than those of [(27.0±6.6)% and (63.4±15.6) μmol in the ineffective death group (P<0.05). In addition, age, PTA, blood ammonia and serum creatinine levels were verified as independent risk factors to predict death in the ACLF patients due to ineffective treatment (P<0.05). Alanine transaminase (ALT) and HBV DNA decreased significantly after treatment, similarly, Total bilirubin (TBil) level decreased significantly after 12 and 24 weeks of treatment (P<0.05), and PTA decreased significantly before and after 24 weeks of treatment (P<0.05).Conclusion Age, PTA, blood ammonia and serum creatinine levels in this study are independent risk factors that affecting the prognosis of ACLF patients caused by CHB reactivation. Antiviral drugs can significantly improve the condition of the ACLF patients induced by CHB reactivation.

Key words: Chronic hepatitis B, Acute-on-chronic liver failure, Hepatitis B virus, reactivation, Prognosis

邵松泽, 朱勇, 林丽. 慢性乙型肝炎再激活所致慢加急性肝衰竭影响因素及疗效评价[J]. 肝脏, 2022, 27(12): 1305-1308.

SHAO Song-ze, ZHU Yong, LIN Li. The prognostic impact factors and therapeutic effect evaluation of patients with acute-on-chronic liver failure induced by chronic hepatitis B reactivation[J]. Chinese Hepatolgy, 2022, 27(12): 1305-1308.

参考文献

[1] Loomba R, Liang TJ. Hepatitis B reactivation associated with immune suppressive and biological modifier therapies: current concepts, management strategies, and future directions. Gastroenterology, 2017, 152(6):1297-1309.
[2] Smalls DJ, Kiger RE, Norris LB, et al. Hepatitis B virus reactivation: risk factors and current management strategies. Pharmacotherapy, 2019, 39(12):1190-1203.
[3] Mücke MM, Backus LI, Mücke VT, et al. Hepatitis B virus reactivation during direct-acting antiviral therapy for hepatitis C: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol, 2018, 3(3):172-180.
[4] Wu T, Li J, Shao L, et al. Development of diagnostic criteria and a prognostic score for hepatitis B virus-related acute-on-chronic liver failure. Gut, 2018, 67(12):2181-2191.
[5] Sun Z, Liu X, Wu D, et al. Circulating proteomic panels for diagnosis and risk stratification of acute-on-chronic liver failure in patients with viral hepatitis B. Theranostics, 2019, 9(4):1200-1214.
[6] Liu H, Zhang Q, Liu L, et al. Effect of artificial liver support system on short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure. Artif Organs, 2020, 44(10):E434-E447.
[7] Wu FL, Shi KQ, Chen YP, et al. Scoring systems predict the prognosis of acute-on-chronic hepatitis B liver failure: an evidence-based review. Expert Rev Gastroenterol Hepatol, 2014, 8(6):623-632.
[8] 中华医学会感染病学分会肝衰竭与人工肝学组, 中华医学会肝病学分会重型肝病与人工肝学组. 肝衰竭诊治指南(2012年版). 实用肝脏病杂志,2013,16(3):210-21.
[9] Karvellas CJ, Francoz C, Weiss E. Liver transplantation in acute-on-chronic liver failure. Transplantation, 2021, 105(7):1471-1481.
[10] Sundaram V, Jalan R, Wu T, et al. Factors associated with survival of patients with severe acute-on-chronic liver failure before and after liver?transplantation. Gastroenterology, 2019, 156(5):1381-1391.e3.
[11] Gao R, Li Y, Cao Y, et al. Glucocorticoid versus traditional therapy for hepatitis B virus-related acute-on-chronic liver failure: A systematic review and meta-analysis. Medicine (Baltimore), 2020, 99(25):e20604.
[12] Philips CA, Sarin SK. Potent antiviral therapy improves survival in acute on chronic liver failure due to hepatitis B virus reactivation. World J Gastroenterol, 2014, 20(43):16037-16052.
[13] Rui F, Yang H, Guo Z, et al. Derivation and validation of prognostic models for predicting survival outcomes in Acute-on-chronic liver failure patients. J Viral Hepat, 2021, 28(12):1719-1728.
[14] Picon RV, Bertol FS, Tovo CV, et al. Chronic liver failure-consortium acute-on-chronic liver failure and acute decompensation scores predict mortality in Brazilian cirrhotic patients. World J Gastroenterol, 2017, 23(28):5237-5245.
[15] Lai J, Yan Y, Mai L, et al. Short-term entecavir versus lamivudine therapy for HBeAg-negative patients with acute-on-chronic hepatitis B liver failure. Hepatobiliary Pancreat Dis Int, 2013, 12(2):154-159.