Reichen J, Bianchi L, Bühler H, Dolivo N, Gonvers J J, Lavanchy D, Malé P J, Renner E L, Solioz M, Schmid M, Zimmermann A
Department of Clinical Pharmacology, University of Berne, Switzerland.
J Hepatol. 1996 Sep;25(3):275-82. doi: 10.1016/s0168-8278(96)80112-7.
BACKGROUND/AIM: Interferon has become the mainstay of treatment of chronic hepatitis C; however, duration of treatment and dose remain unresolved questions. The present study aimed to compare standard dose interferon with a titrated dose regimen carried out for 1 year.
This was a randomized, controlled multicenter trial. Patients with chronic hepatitis C were randomly allocated to a control group (n = 30), to a fixed dose group (n = 31) where interferon-alpha 2b 3 MU thrice weekly was given for 1 year or a titrated group (n = 34) where interferon was titrated starting at 5 MU thrice weekly to the lowest dose keeping the patient in remission as assessed by a normal ALT value. Liver biopsies were obtained before and at the end of treatment; in addition, galactose elimination capacity was measured as a measure of cytosolic function.
In the control, fixed and titrated groups a complete response was achieved in 2/29, 10/28 and 15/31, respectively (p < 0.001 in favor of treatment, p = n.s. for the two treatments). The corresponding figure for sustained response was 1/29, 5/28 and 6/ 31 (p = n.s). In the titrated group, a complete (sustained) response was achieved with 5 MU in 2 (2), with 4 MU in 1 (0), with 3 MU in 4 (0), with 2 MU in 3 (0) and with 1 MU in 5 (4). Liver biopsy score and galactose elimination capacity improved significantly in responders but not in treatment failures.
Both fixed and titrated dosing of interferon given for 1 year induced virus clearance in only a minority of treated patients. However, in a small number of patients, a complete and sustained response can be achieved with low doses of interferon. Dose titration could be an interesting approach to decreasing the cost and side effects in the treatment of chronic hepatitis C.
背景/目的：干扰素已成为慢性丙型肝炎治疗的主要手段；然而，治疗持续时间和剂量仍是尚未解决的问题。本研究旨在比较标准剂量干扰素与进行1年的滴定剂量方案。
这是一项随机对照多中心试验。慢性丙型肝炎患者被随机分配至对照组（n = 30）、固定剂量组（n = 31），固定剂量组给予α-2b干扰素3 MU，每周3次，共1年，以及滴定组（n = 34），滴定组起始剂量为5 MU，每周3次，滴定至最低剂量并保持患者缓解（通过正常ALT值评估）。在治疗前和治疗结束时获取肝活检样本；此外，测量半乳糖清除能力作为细胞溶质功能的指标。
在对照组、固定剂量组和滴定组中，完全缓解率分别为2/29、10/28和15/31（有利于治疗组，p < 0.001；两种治疗方法相比，p = 无显著性差异）。持续缓解的相应数字为1/29、5/28和6/31（p = 无显著性差异）。在滴定组中，5 MU时2例（2例）实现完全（持续）缓解，4 MU时1例（0例），3 MU时4例（0例），2 MU时3例（0例），1 MU时5例（4例）。应答者的肝活检评分和半乳糖清除能力显著改善，但治疗失败者未改善。
给予1年的干扰素固定剂量和滴定剂量方案仅在少数接受治疗的患者中诱导病毒清除。然而，在少数患者中，低剂量干扰素可实现完全和持续缓解。剂量滴定可能是降低慢性丙型肝炎治疗成本和副作用的一种有趣方法。
