Lindsay K L, Davis G L, Schiff E R, Bodenheimer H C, Balart L A, Dienstag J L, Perrillo R P, Tamburro C H, Goff J S, Everson G T, Silva M, Katkov W N, Goodman Z, Lau J Y, Maertens G, Gogate J, Sanghvi B, Albrecht J
Department of Medicine, University of California, Los Angeles, USA.
Hepatology. 1996 Nov;24(5):1034-40. doi: 10.1002/hep.510240509.
To evaluate response rates to 3, 5, or 10 million units (MU) of interferon alfa-2b, given thrice weekly, and to determine whether higher doses of interferon increase the likelihood or durability of the response, a multicenter, randomized trial was performed at nine academic medical centers in the United States. Two hundred forty eight patients with chronic hepatitis C were randomized to receive 3, 5, or 10 MU of interferon alfa-2b thrice weekly for 12 weeks. Based on the alanine aminotransferase (ALT) response at treatment-week 12, the patients were rerandomized to additional therapy at the same or at increased doses for an additional 12 to 36 weeks; in the case of no response to the highest dose, the patients were discontinued from the study. Serum ALT concentrations and liver histology were measured. The overall complete response rates to 3, 5, or 10 MU were not different at treatment-week 12 (31% vs. 42% vs. 40%, not significant). The majority of week-12 responders continued to respond during additional treatment. When the treatment was discontinued, 15.4% to 19.0% of patients maintained their response. Of the nonresponders to 3 MU at week 12, who were continued on 3 MU for an additional 12 weeks, none responded. However, response to additional therapy occurred in 12% of week-12 nonresponders, whose dose was escalated from 3 or 5 MU to 10 MU. The only baseline features associated with the treatment response were the absence of fibrosis or cirrhosis on the pretreatment liver biopsy and viral genotype. We conclude that the initial response to interferon in patients with chronic hepatitis C is not increased by treatment with higher doses of the drug. Patients who do not respond to 3 MU by treatment-week 12 will not respond with continued therapy at that dose; however, a proportion of patients who do not respond to 12 weeks of treatment with 3 or 5 MU may respond to higher doses. Although the long-term sustained response rates are marginally increased with interferon doses above 3 MU three times per week, the side effects are difficult to tolerate. The analysis of baseline factors in relation to response identified no single baseline factor associated with a low-enough response rate to warrant withholding interferon therapy from patients with chronic hepatitis C.
为评估每周三次给予300万、500万或1000万单位（MU）的干扰素α-2b的缓解率，并确定更高剂量的干扰素是否会增加缓解的可能性或持续性，在美国9家学术医疗中心进行了一项多中心随机试验。248例慢性丙型肝炎患者被随机分为三组，分别接受每周三次、每次300万、500万或1000万MU的干扰素α-2b治疗，疗程为12周。根据治疗第12周时的丙氨酸氨基转移酶（ALT）反应，患者被重新随机分组，接受相同剂量或增加剂量的额外治疗，持续12至36周；如果对最高剂量无反应，则患者退出研究。测量血清ALT浓度和肝脏组织学。在治疗第12周时，300万、500万或1000万MU的总体完全缓解率无差异（分别为31%、42%和40%，无统计学意义）。大多数第12周有反应的患者在额外治疗期间继续有反应。当治疗停止时，15.4%至19.0%的患者维持了反应。在第12周时对300万MU无反应且继续接受300万MU额外治疗12周的患者中，无人有反应。然而，在第12周无反应且剂量从300万或500万MU增加到1000万MU的患者中，12%出现了对额外治疗的反应。与治疗反应相关的唯一基线特征是治疗前肝活检无纤维化或肝硬化以及病毒基因型。我们得出结论，更高剂量的药物治疗不会增加慢性丙型肝炎患者对干扰素的初始反应。在治疗第12周时对300万MU无反应的患者，继续使用该剂量治疗不会有反应；然而，一部分对300万或500万MU治疗12周无反应的患者可能对更高剂量有反应。虽然每周三次使用高于300万MU的干扰素时，长期持续缓解率略有提高，但副作用难以耐受。与反应相关的基线因素分析未发现单一基线因素与低到足以保证不对慢性丙型肝炎患者进行干扰素治疗的反应率相关。
