Perrillo R P, Mason A L
Section of Gastroenterology and Hepatology, Ochsner Clinic, New Orleans, Louisiana.
Gastroenterol Clin North Am. 1994 Sep;23(3):581-601.
Major advances have been made in the therapy of chronic viral hepatitis B during the past several years. This period has witnessed the publication of large, multicenter trials of recombinant interferon alfa for chronic hepatitis B in the United States and the completion of several similarly designed studies in North America, Europe and Asia. These studies have defined an initial response rate of approximately 40% to 50%. In contrast to the experience with chronic hepatitis C, loss of viral replication is generally sustained. Repeat courses of therapy are likely to result in the same type of response as that observed initially. Quantitative assessment of viral replication (HBV DNA, HBeAg) is important in predicting the likelihood of response and in monitoring patients during therapy. Perhaps the most compelling reason to treat chronic hepatitis B with interferon is the disappearance of circulating HBsAg in one third of responders with a further increase in frequency of this phenomenon as follow-up continues. Another important advantage to treatment is the striking degree of histologic improvement that is frequently observed years after a response has been achieved. Although a substantial number of patients do not respond to interferon, several promising agents that should allow for a greater degree of success, when used either alone or in combination with interferon, are under study. A short course of corticosteroids prior to interferon appears to improve response rates in patients who have low ALT levels at baseline and has been the preferred approach for these patients at our medical center. Progress is being made in the development of safer interferon regimens for patients with mild-to-moderate hepatic decompensation. Nonetheless, even patients with marginal synthetic function, as reflected by albumin levels within the low-normal range, appear to be at greater risk for complications during therapy and should preferably be referred for inclusion in research programs. Appropriate patient selection remains a critical step for maximizing the safety as well as efficacy of interferon treatment.
在过去几年中,慢性乙型病毒性肝炎的治疗取得了重大进展。在此期间,美国发表了关于重组干扰素α治疗慢性乙型肝炎的大型多中心试验,北美、欧洲和亚洲也完成了几项设计类似的研究。这些研究确定了约40%至50%的初始应答率。与慢性丙型肝炎的情况不同,病毒复制的消失通常是持续的。重复治疗疗程可能会产生与最初观察到的相同类型的应答。病毒复制的定量评估(HBV DNA、HBeAg)对于预测应答可能性以及治疗期间监测患者很重要。用干扰素治疗慢性乙型肝炎最令人信服的理由可能是,三分之一的应答者中循环HBsAg消失,且随着随访的继续,这种现象的发生率进一步增加。治疗的另一个重要优势是,在获得应答数年之后,经常能观察到显著的组织学改善。虽然相当多的患者对干扰素无应答,但有几种有前景的药物正在研究中,单独使用或与干扰素联合使用时可能会取得更大的成功。在使用干扰素之前短期使用皮质类固醇似乎能提高基线ALT水平较低的患者的应答率,这也是我们医疗中心对这些患者的首选方法。针对轻度至中度肝失代偿患者,正在开发更安全的干扰素治疗方案。尽管如此,即使是合成功能处于低正常范围(以白蛋白水平反映)的边缘患者,在治疗期间出现并发症的风险似乎也更高,最好转诊至研究项目中。适当的患者选择仍然是最大限度提高干扰素治疗安全性和疗效的关键步骤。