乙型肝炎肝硬化抗病毒治疗的研究进展

doi:10.3969/j.issn.1672-5069.2010.04.002

摘要/Abstract

摘要： 对于乙型肝炎肝硬化患者，不论肝功能代偿或失代偿，只要证实血清HBV DNA阳性，均应给予抗病毒治疗。拉米夫定（LAM）治疗肝硬化患者安全有效，而对于对LAM耐药的患者，宜在继续应用LAM的基础上联合应用阿德福韦酯（ADV）。部分初治患者单用ADV亦可取得与LAM相似的疗效。替比夫定（LdT）和恩替卡韦（ETV）在临床上已越来越多地应用于治疗乙型肝炎肝硬化，初步结果显示不少患者可藉此获得病情改善，但其远期疗效有待进一步积累资料。对失代偿期肝硬化患者严禁应用干扰素（IFN）抗病毒治疗，但对无明显干扰素禁忌症的代偿期肝硬化患者，可谨慎尝试IFN治疗。多种联合治疗方案，特别是一种核苷/核苷酸类似物（NA）和另一种无交叉耐药的NA的联合，理论上可提高抗病毒效果和减少耐药，但其远期疗效及药物经济学有待研究。

于乐成，何长伦，汪茂荣. 乙型肝炎肝硬化抗病毒治疗的研究进展[J]. 实用肝脏病杂志, 2010, 13(4): 245-248.

参考文献

[1] LOK AS，MCMAHON BJ. The American Association for the Study of Liver Diseases（AASLD）. Chronic hepatitis B:Update 2009[J]. Hepatology，2009，50（3）:661-696.
[2] European Association for the Study of the Liver. EASL clinical practice guidelines:Management of chronic hepatitis B[J]. J Hepatol，2009，50（2）:227-242.
[3] KEEFFE EB，DIETERICH DT，HAN SB，et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States:2008 Update[J]. Clin Gastroenterol Hepatol，2008，6（12）:1315-1341.
[4] SHIHA G，SARIN KS，IBRAHIM AE，et al. Liver fibrosis:consensus recommendations of the Asian Pacific Association for the study of the liver （APASL）[J]. Hepatol Int， 2009，3（2）:323-333.
[5] LIAW YF，SUNG JJY，CHOW WC，et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease[J]. N Engl J Med，2004，351（15）:1521-1531.
[6] LIAW YF，LEUNG N，KAO JH，et al. Asian-Pacific consensus statement on the management of chronic hepatitis B:a 2008 update[J]. Hepatol Int，2008，2（3）:263-283.
[7] LIN SM，YU ML，LEE CM，et al. Interferon therapy in HBeAg positive chronic hepatitis reduces cirrhosis and hepatocellular carcinoma[J]. J Hepatol，2007，46（1）:45-52.
[8] ILOEJE UH，YANG HI，SU J，et al. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load[J]. Gastroenterology，2006，130（3）:678-686.
[9] KIM SU，HAN KH，NAM CM，et al. Natural history of hepatitis B virus-related cirrhotic patients hospitalized to control ascites[J]. J Gastroenterol Hepatol，2008，23（11）:1722-1727.
[10] CHEN YC，CHU CM，YEH CT，et al. Natural course following the onset of cirrhosis in patients with chronic hepatitis B:a longterm follow-up study[J]. Hepatol Int， 2007，1（1）:267-273.
[11] CHU CM，LIAW YF. Hepatitis B virus-related cirrhosis: natural history and treatment[J]. Semin Liver Dis，2006，26（2）:142-152.
[12] SORRELL MF，BELONGIA EA，COSTA J，et al. National Institutes of Health Consensus Development Conference Statement:Management of hepatitis B[J]. Ann Intern Med， 2009，150（2）:104-110.
[13] CHEN CJ，YANG HI，SU J，et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level[J]. JAMA，2006，295（1）:65-73.
[14] CHOU YC，YU MW，WU CF，et al. Temporal relationship between hepatitis B virus enhancer II/basal core promoter sequence variation and risk of hepatocellular carcinoma[J]. Gut，2008，57（1）:91-97.
[15] KAPOOR D，GUPTAN RC，WAKIL SM，et al. Beneficial effects of lamivudine in hepatitis B virus-related decompensated cirrhosis[J]. J Hepatol，2000，33（2）:308-312.
[16] YAO FY，TERRAULT NA，FREISE C，et al. Lamivudine treatment is beneficial in patients with severely decompensated cirrhosis and actively replicating hepatitis B infection awaiting liver transplantation:A comparative study using a matched，untreated cohort[J]. Hepatology，2001，34（2）:411-416.
[17] FONTANA RJ，KEEFFE EB，CAREY W，et al. Effect of lamivudine treatment on survival of 309 North American patients awaiting liver transplantation for chronic hepatitis B[J]. Liver Transplantation，2002，8（5）:433-439.
[18] HANN HW，FONTANA RJ，WRIGHT T，et al. A United States compassionate use study of lamivudine treatment in nontransplantation candidates with decompensated hepatitis B virus-related cirrhosis[J]. Liver Transplantation，2003，9（1）:49-56.
[19] TSENG PL，LU SN，TUNG HD，et al. Determinants of early mortality and benefits of lamivudine therapy in patients with hepatitis B virus-related decompensated liver cirrhosis[J]. J Viral Hepat，2005，12（4）:386-392.
[20] DI MARCO V，MARZANO A，LAMPERTICO P，et al. Clinical outcome of HBeAg-negative chronic hepatitis B in relation to virological response to lamivudine[J]. Hepatology，2004，40（4）:883-891.
[21] SCHIFF ER，LAI CL，HADZIYANNIS S，et al. Adefovir dipivoxil therapy for lamivudine-resistant hepatitis B in pre-and post-liver transplantation patients[J]. Hepatology，2003，38（6）:1419-1427.
[22] SCHIFF E，LAI CL，HADZIYANNIS S，et al. Adefovir dipivoxil for wait-listed and post-liver transplantation patients with lamivudine-resistant hepatitis B:final long-term results[J]. Liver Transpl，2007，13（3）:349-60.
[23] 梁静，韩涛，肖时湘，等. 替比夫定治疗乙型肝炎肝硬化的疗效观察[J]. 中华肝脏病杂志，2009，17（1）：24-27.
[24] BUSTER EH，HANSEN BE，BUTI M，et al. Peginterferon alpha-2b is safe and effective in HBeAg-positive chronic hepatitis B patients with advanced fibrosis[J]. Hepatology， 2007，46（2）:388-394.
[25] LIAW YF. Hepatitis B virus replication and liver disease progression:the impact of antiviral therapy[J]. Antivir Ther，2006，11（16）:669-679.
[26] TERRAULT NA. Benefits and risks of combination therapy for hepatitis B[J]. Hepatology，2009，49（5 S）:S122-128.