探索HBV相关肝衰竭诊治的新思路

杨方集; 彭亮; 高志良

doi:10.3969/j.issn.1001-5256.2017.03.041

探索HBV相关肝衰竭诊治的新思路

DOI: 10.3969/j.issn.1001-5256.2017.03.041

中山大学附属第三医院感染性疾病科

详细信息

中图分类号: R512.62;R575.3
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出版历程
- 收稿日期: 2016-10-12
- 出版日期: 2017-03-20

New strategies for diagnosis and treatment of hepatitis B virus-related liver failure

Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University

摘要

摘要: HBV相关肝衰竭患者的病死率极高,且其发病过程非常复杂,机制并未完全明了,临床诊治非常棘手。除了肝移植,肝衰竭的内科治疗尚缺乏特效药物和手段。总结了HBV相关肝衰竭诊断与治疗方面的经验和研究成果,在发病机制方面,探索宿主遗传背景和慢性乙型肝炎是否发展加重的关系,阐述肝衰竭发生过程中的"三重打击"现象及"四个时相"概念;在治疗方面,重点探讨抗病毒、抗感染、糖皮质激素和干细胞移植等在临床上的应用情况;在病情评估方面,建立一套更适合乙型肝炎肝衰竭预后评估的系统。
- 肝功能衰竭 /
- 肝炎病毒,乙型 /
- 诊断 /
- 治疗 /
- 综述
Abstract: Hepatitis B virus (HBV) -related liver failure has an extremely high mortality rate and a complex pathogenesis, and since related mechanisms are not fully understood, it has been very difficult to diagnose and treat this disease in clinical practice.Apart from liver transplantation, there is still a lack of specific and effective drugs and therapies for the medical treatment of HBV-related liver failure.This article summarizes our experience and research achievements in the diagnosis and treatment of HBV-related liver failure, explores the association between host's genetic background and development and aggravation of chronic hepatitis B, and elaborates on the phenomenon of“three attacks”and the concept of“four time phases”.In the aspect of treatment, this article focuses on the clinical application of antiviral therapy, anti-infective therapy, glucocorticoids, and stem cell transplantation;for the evaluation of patients' condition, this article establishes a suitable system for evaluating the prognosis of HBV-related liver failure.
- liver failure /
- hepatitis B virus /
- diagnosis /
- therapy /
- review

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参考文献(39)

[1]OTT JJ, STEVENS GA, GROEGER J, et al.Global epidemiology of hepatitis B virus infection:New estimates of age-specific HBsA g seroprevalence and endemicity[J].Vaccine, 2012, 30 (12) :2212-2219.

[2] Liver Failure and Artificial Liver Group of Chinese, Severe Liver Diseases and Artificial Liver Group.Guideline for diagnosis and treatment of liver failure (2012 version) [J].Chin J Clin Infect Dis, 2012, 5 (6) :321-327. (in Chinese) 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) [J].中华临床感染病杂志, 2012, 5 (6) :321-327.

[3]SARIN SK, KEDARISETTY CK, ABBAS Z, et al.Acute-on-chronic liver failure:consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL) 2014[J].Hepatol Int, 2014, 8 (4) :453-471.

[4]SHI Y, YANG Y, HU Y, et al.Acute-on-chronic liver failure precipitated by hepatic injury is distinct from that precipitated by extrahepatic insults[J].Hepatology, 2015, 62 (1) :232-242.

[5]XIE GJ, ZHANG HY, CHEN Q, et al.Changing etiologies and outcome of liver failure in Southwest China[J].Virol J, 2016, 13 (1) :1-12.

[6]ZHAO Q, PENG L, GAO ZL, et al.Rare inborn errors associated with chronic hepatitis B virus infection[J].Hepatology, 2012, 56 (5) :1661-1670.

[7]YAN H, ZHONG G, XU G, et al.Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus[J].Elife, 2012, 1:e49.

[8]WATASHI K, SLUDER A, DAITO T, et al.Cyclosporin A and its analogs inhibit hepatitis B virus entry into cultured hepatocytes through targeting a membrane transporter, sodium taurocholate cotransporting polypeptide (NTCP) [J].Hepatology, 2014, 59 (5) :1726-1737.

[9]PENG L, ZHAO Q, GAO ZL, et al.The p.Ser267Phe variant in SLC10A1, is associated with resistance to chronic hepatitis B[J].Hepatology, 2015, 61 (4) :1251-1260.

[10]HU HH, LIU J, LIN YL, et al.The rs2296651 (S267F) varian on NTCP (SLC10A1) is inversely associated with chronic hepatitis B and progression to cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis B[J].Gut, 2016, 65 (9) :1514-1521.

[11]KWON H, LOK AS.Hepatitis B therapy[J].Nat Rev Gastroenterol Hepatol, 2011, 8 (5) :275-284.

[12]VENTO S, CAINELLI F, LONGHI MS.Reactivation of replication of hepatitis B and C viruses after immunosuppressive therapy:an unresolved issue[J].Lancet Oncol, 2002, 3 (39) :333-340.

[13]ZHOU XH, GAO ZL, YAO JL.Relationship between HBV DNAserum level and acute exacerbation of the disease in chronic hepatitis B patients[J].Chin J Exp Clin Virol, 1999, 13 (4) :335-339. (in Chinese) 周小辉, 高志良, 姚集鲁.慢性乙型肝炎急性发作与血清HBVDNA含量关系[J].中华实验和临床病毒学杂志, 1999, 13 (4) :335-339.

[14]ZHANG XH, LIN GL, ZHU JY, et al.Clinical characteristics o and the related factors to the relapse of chronic hepatitis B after lamivudine withdrawal[J].Chin J Hepatol, 2004, 12 (10) :601-604. (in Chinese) 张晓红, 林国莉, 朱建芸, 等.拉米夫定停药后慢性乙型肝炎复发的临床特点及相关因素[J].中华肝脏病杂志, 2004, 12 (10) :601-604.

[15]KE WM, LI XJ, GAO ZL, et al.Etiological investigation of fatal liver failure during the course of chronic hepatitis B in southeast China[J].J Gastroenterol, 2006, 41 (4) :347-351.

[16]ZHANG XH, KE WM, GAO ZL, et al.Comparison of effects o hepatitis E or A viral superinfection in patients with chronic hepatitis B[J].Hepatol Int, 2010, 4 (3) :615-620.

[17]CHENG SH, MAI L, ZHU FQ, et al.Influence of chronic HBV infection on superimposed acute hepatitis E[J].World J Gastroenterol, 2013, 19 (35) :5904-5909.

[18]CHOW CW, TSANG SW, TSANG OT, et al.Comparison of acute hepatitis E infection outcome in patients with and without chronic hepatitis B infection:a 10 year retrospective study in three regiona hospitals in Hong Kong[J].J Clin Virol, 2014, 60 (1) :4-10.

[19]LIAO BL, LIN SW, CHEN K, et al.Analysis of epidemiologica and clinical features of 621 patients with acute hepatitis E[J].Chin J Infect Dis, 2014, 32 (9) :554-558. (in Chinese) 廖宝林, 林思炜, 陈铿, 等.621例急性戊型肝炎流行病学及临床特征研究[J].中华传染病杂志, 2014, 32 (9) :554-558.

[20]WU T, HUANG SJ, ZHU FC, et al.Immunogenicity and safety of hepatitis E vaccine in healthy hepatitis B surface antigen positive adults.[J].Hum Vaccin Immunother, 2013, 9 (11) :2474-2479.

[21] YE YN, GAO ZL.Three shock hypotheses that my induce liver failure[J].Chin J Hepatol, 2009, 22 (5) :638-640. (in Chinese) 叶一农, 高志良.乙型肝炎肝衰竭发生机制中的三重打击[J].中华肝脏病杂志, 2009, 22 (5) :638-640.

[22]ZHENG YB, HUANG ZL, GAO ZL, et al.Dynamic changes of clinical features that predict the prognosis of acute-on-chronic hepatitis B liver failure:a retrospective cohort study[J].Int J Med Sci, 2013, 10 (12) :1658-1664.

[23]LIN BL, PAN CQ, GAO ZL, et al.Entecavir improves the outcome of acute-on-chronic liver failure due to the acute exacerbation of chronic hepatitis B[J].Hepatol Int, 2013, 7 (2) :460-467.

[24]GARG H, SHIV KS, KUMAR M, et al.Tenofovir improves the outcome in patients with spontaneous reactivation of hepatitis Bpresenting as acute-on-chronic liver failure[J].Hepatology, 2011, 53 (3) :774-780.

[25]HU T, YAO L, HU A, et al.Nucleos (t) ide analogs improves the long-term prognosis in patients with chronic hepatitis B-associated liver failure[J].Hepatol Res, 2016.[Epub ahead of print]

[26]ZHANG L, HAO CQ, LIU JF, et al.Meta-analysis of the shortterm effects of lamivudine treatment for severe chronic hepatitis B[J].Virol J, 2013, 10 (1) :1-12.

[27]Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association.The guideline of prevention and treatment for chronic hepatitis B:a 2015 update[J].J Clin Hepatol, 2015, 31 (12) :1941-1960. (in Chinese) 中华医学会肝病学分会, 中华医学会感染病学分会.慢性乙型肝炎防治指南 (2015年更新版) [J].临床肝胆病杂志, 2015, 31 (12) :1941-1960.

[28]XIE DY, WU ZB, GAO ZL.Secondary infections in hepatitis B patients with acute-on-chronic liver failure and its relationship with the prognosis[J].Chin J Clin Infect Dis, 2010, 3 (2) :73-75. (in Chinese) 谢冬英, 邬喆斌, 高志良.乙型肝炎慢加急性肝功能衰竭继发感染的临床特点及其与疾病转归的关系[J].中华临床感染病杂志, 2010, 3 (2) :73-75.

[29]PAN C, GU Y, GAO Z, et al.Dynamic changes of lipopolysaccharide levels in different phases of acute on chronic hepatitis B liver failure[J].PLoS One, 2012, 7 (11) :e49460.

[30]BERNAL W, JALAN R, QUAGLIA A.Acute-on-chronic liver failure[J].Lancet, 2015, 386 (10003) :1576-1587.

[31]PENG L, XIE DY, GAO ZL.Autologous bone marrow mesenchymal stem cell transplantation in liver failure patients caused by hepatitis B:short-term and long-term outcomes[J].Hepatology, 2011, 54 (3) :820-828.

[32]WANG PP, PENG L, YU J, et al.In vitro effect of human amniotic fluid-derived mesenchymal stem cells on Th1/Th2 ratio in peripheral blood of hepatitis B patients with liver failure[J].Chin J Clin Infect Dis, 2012, 5 (3) :145-148. (in Chinese) 王培培, 彭亮, 于君, 等.人羊水间充质干细胞对乙型肝炎肝衰竭患者外周血Th1/Th2的体外调节[J].中华临床感染病杂志, 2012, 5 (3) :145-148.

[33]YU J, PENG L, LIN BL, et al.Short-term effect of allogeneic mesenchymal stem cells in patients with end stage of liver diseases due to HBV and effects on the balance of Th1/Th2 axis[J/CD].Chin J Exp Clin Infect Dis:Electronic Edition, 2012, 6 (1) :13-17. (in Chinese) 于君, 彭亮, 林炳亮, 等.异体骨髓间充质干细胞治疗乙型肝炎终末期肝病的短期疗效及对Th1/Th2的影响[J/CD].中华实验和临床感染病杂志:电子版, 2012, 6 (1) :13-17.

[34]WENG WZ, GAO ZL, LIN BL, et al.Treatment effect of allogeneic bone marrow mesenchymal stem cells transplantation to patients in different phase of hbv acute-on-chronic liver failure[J].J Sun Yat-sen Univ:Med Sci, 2013, 34 (3) :422-428. (in Chinese) 翁伟镇, 高志良, 林炳亮, 等.异体骨髓间充质干细胞治疗不同时相慢加急性乙肝肝衰竭患者的疗效[J].中山大学学报:医学科学版, 2013, 34 (3) :422-428.

[35]HOU HL, XU WX, GAO ZL, et al.The safety and therapeutic efficacy evaluation for human umbilical cord mesenchymal stem cells transplantation in patients with acute-on-chronic liver failure caused by hepatitis B virus[J].J Trop Med, 2015, 15 (12) :1625-1628. (in Chinese) 何宏亮, 许文雄, 高志良, 等.人脐带间充质干细胞治疗慢加急性乙肝肝衰竭的安全性及临床效果[J].热带医学杂志, 2015, 15 (12) :1625-1628.

[36]LI YH, XU Y, WU HM, et al.Umbilical cord-derived mesenchymal stem cell transplantation in hepatitis b virus related acute-on-chronic liver failure treated with plasma exchange and entecavir:a 24-month prospective study[J].Stem Cell Rev, 2016, 12 (6) :645-653.

[37]CHEN JF, WANG KW, GAO ZL, et al.Dexamethasone in outcome of patients with hepatitis B virus-related acute-on-chronic liver failure[J].J Gastroenterol Hepatol, 2014, 29 (4) :800-806.

[38]LI XY, LEI RX, KE WM, et al.A simple scoring system to evaluate the severity of acute-on-chronic liver failure in hepatitis B[J].Natl Med J China, 2009, 89 (47) :3353-3355. (in Chinese) 厉新妍, 雷瑞祥, 柯伟民, 等.乙型肝炎慢加急性肝衰竭严重度简易评分系统[J].中华医学杂志, 2009, 89 (47) :3353-3355.

[39]ZHENG YB, KE WM, GAO ZL, et al.A novel prognostic scoring system to predict 3-month mortality risk in patients with acute-onchronic liver failure in hepatitis B:a retrospective cohort study[J].Hepatol Int, 2012, 6 (4) :727-734.

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