Gish Robert G, Perrillo Robert P, Jacobson Ira M
Division of Hepatology and Complex GI, Physicians Foundation, California Pacific Medical Center, 2340 Clay Street, San Francisco, CA 94115, USA.
Semin Liver Dis. 2007 Aug;27 Suppl 1:9-17. doi: 10.1055/s-2007-984695.
As of October 2006, 6 medications are approved in the United States for the management of chronic hepatitis B virus (HBV) infection: 2 formulations of interferon and 4 oral nucleos(t)ide analogues. For the treating practitioner, tailoring the pharmaceutical regimen according to patient features and clinical circumstances can be a challenge. First-line therapeutic regimens for the management of HBV infection include monotherapy with a U.S. Food and Drug Administration-approved agent that has potent on-treatment viral response and low rates of resistance; in the future, these regimens may include a combination of more than one nucleos(t)ide analogue or a combination of a nucleos(t)ide analogue and pegylated interferon. The oral nucleos(t)ide analogues are generally better tolerated than interferon; however, they can be expensive when administered for lengthy periods and can also lead to medication resistance. Lamivudine, the first approved nucleoside analogue for the treatment of HBV infection, has a very high resistance profile; in fact, lamivudine exposure increases viral resistance to other commercially available nucleos(t)ide analogues: entecavir, telbivudine, and adefovir. For these reasons, the 2007 American Association for the Study of Liver Diseases (AASLD) guidelines no longer recommend lamivudine as first-line therapy for the management of HBV infection. A satellite symposium conducted during the 57th Annual Meeting of the AASLD in Boston, Massachusetts, presented approaches to customizing the management of chronic HBV infection. The presentation highlighted recent findings suggesting that early, profound, and sustained viral suppression improves the probability of sustained virologic response and reduces the likelihood of nucleos(t)ide resistance.
截至2006年10月,美国有6种药物被批准用于治疗慢性乙型肝炎病毒(HBV)感染:2种干扰素制剂和4种口服核苷(酸)类似物。对于治疗医生而言,根据患者特征和临床情况调整药物治疗方案可能是一项挑战。HBV感染的一线治疗方案包括使用一种经美国食品药品监督管理局批准的药物进行单药治疗,该药物具有有效的治疗期病毒反应且耐药率低;未来,这些方案可能包括一种以上核苷(酸)类似物的联合使用,或核苷(酸)类似物与聚乙二醇化干扰素的联合使用。口服核苷(酸)类似物通常比干扰素耐受性更好;然而,长期使用时费用可能较高,并且还可能导致耐药。拉米夫定是首个被批准用于治疗HBV感染的核苷类似物,其耐药性很高;事实上,接触拉米夫定可增加病毒对其他市售核苷(酸)类似物(恩替卡韦、替比夫定和阿德福韦)的耐药性。出于这些原因,2007年美国肝病研究协会(AASLD)指南不再推荐拉米夫定作为HBV感染管理的一线治疗药物。在马萨诸塞州波士顿举行的AASLD第57届年会期间举办的一次卫星研讨会上,介绍了针对慢性HBV感染进行个体化管理的方法。该报告强调了近期的研究结果,表明早期、深度和持续的病毒抑制可提高持续病毒学应答的概率,并降低核苷(酸)耐药的可能性。