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干扰素在病毒性肝炎治疗中的应用

Interferons in the management of viral hepatitis.

作者信息

Zein N N

机构信息

Department of Pediatric and Adolescent Medicine, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.

出版信息

Cytokines Cell Mol Ther. 1998 Dec;4(4):229-41.

Abstract

Since their discovery in 1957, interferons (IFNs) have been noted to have protective effects against human viral infections. The use and safety of IFNs in patients with acute or chronic hepatitis B or C infections have evolved over the last 20 years. The most studied IFN for the management of viral hepatitis is IFN-alpha, but others have recently been evaluated through controlled clinical trials. IFN treatment is not currently indicated for patients with acute hepatitis B, but has proven beneficial in chronic hepatitis B. The success of treatment in this group of patients has been measured by the normalization of liver enzymes, loss of hepatitis B e antigen and loss of detectable serum DNA of hepatitis B. It has been estimated in several clinical trials that as many as 40% of treated patients will respond to therapy, as defined above. Although only a few and limited studies have evaluated the use of IFNs in acute hepatitis C, treatment appears to decrease the likelihood of chronicity, and should be considered. In chronic hepatitis C, treatment has been effective in achieving sustained viral eradication in up to 20% of patients taking the FDA-approved dosage of three million units, three times weekly for 6-12 months. However, higher doses, longer duration of treatment or combining IFN with other antiviral agents may improve the rate of response. It has become clear during the last two decades that IFNs have beneficial effects for patients with viral hepatitis B or C. Much more effort is needed to establish the optimal dose and duration of therapy. Studies addressing the pharmacokinetics of IFNs in patients with viral hepatitis are needed, and methods to improve the bioavailability of these products to affected tissues such as the liver may improve efficacy and minimize side-effects.

摘要

自1957年被发现以来,干扰素(IFN)已被证实对人类病毒感染具有保护作用。在过去20年中,干扰素在急慢性乙型或丙型肝炎患者中的应用及安全性不断发展。用于治疗病毒性肝炎研究最多的干扰素是α干扰素,但最近也有其他类型的干扰素通过对照临床试验进行了评估。目前,急性乙型肝炎患者不建议使用干扰素治疗,但已证实其对慢性乙型肝炎有益。该组患者的治疗成功与否通过肝酶正常化、乙肝e抗原消失以及乙肝血清DNA检测不到来衡量。多项临床试验估计,多达40%的接受治疗患者会对上述定义的治疗产生反应。虽然仅有少数有限的研究评估了干扰素在急性丙型肝炎中的应用,但治疗似乎可降低慢性化的可能性,因此应予以考虑。在慢性丙型肝炎中,按照美国食品药品监督管理局(FDA)批准的剂量,即300万单位,每周三次,持续6至12个月,治疗已使高达20%的患者实现了持续病毒清除。然而,更高的剂量、更长的治疗时间或干扰素与其他抗病毒药物联合使用可能会提高反应率。在过去二十年中已明确,干扰素对乙型或丙型病毒性肝炎患者具有有益作用。还需要付出更多努力来确定最佳治疗剂量和疗程。需要开展针对病毒性肝炎患者干扰素药代动力学的研究,提高这些产品对肝脏等受影响组织的生物利用度的方法可能会提高疗效并将副作用降至最低。

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