Min A D, Jones J L, Esposito S, Lebovics E, Jacobson I M, Klion F M, Goldman I S, Geders J M, Tobias H, Bodian C, Bodenheimer H C
Division of Liver Diseases, Mount Sinai School of Medicine, New York, New York 10029, USA.
Am J Gastroenterol. 2001 Apr;96(4):1143-9. doi: 10.1111/j.1572-0241.2001.03692.x.
Interferon combined with ribavirin has efficacy in the treatment of patients with chronic hepatitis C virus (HCV) infection. However, its utility in patients who have not responded to prior interferon therapy is not clear. Furthermore, the effect of using an increased dose of interferon in combination with ribavirin in patients with chronic hepatitis C resistant to conventional doses of interferon is not known. The aim of our study was to evaluate the effect of high-dose interferon in combination with ribavirin on the efficacy of treating patients with chronic hepatitis C resistant to interferon monotherapy in a large multicenter trial.
We randomized 154 patients with chronic hepatitis C who failed to achieve a sustained response with prior interferon therapy to receive either 3 or 5 MU of interferon alpha-2b and ribavirin (1000-1200 mg/day) for 12 months. There were 119 patients who had not responded and 35 who initially responded but relapsed after prior interferon monotherapy. Serum HCV RNA levels were measured at entry, 6, and 12 months of treatment and at the end of a 6-month follow-up period.
The mean age of the subjects was 47 yr (range 28-68 yr), and 110 (71.4%) were men. One hundred thirty-two patients (86%) had HCV genotype 1, whereas 21 (14%) had cirrhosis. Eighty-one subjects (53%) were randomized to receive 3 MU of interferon alpha-2b. Fifteen of 35 relapse subjects (43%) and 12 of 119 prior nonresponder entrants (10%) achieved a sustained virological response to the 12-month course of treatment. Overall, 11 of 81 patients (14%) receiving 3 MU, and 16 of 73 patients (22%) receiving 5 MU of interferon maintained an undetectable HCV RNA level after cessation of therapy. The difference in sustained response rates between the two interferon dosage groups did not reach statistical significance (p = 0.09). However, among the nonresponder patients alone, there was an increased sustained response in the high-dose interferon group compared with the standard interferon dose group (15.5% vs 4.9%, p = 0.055). Twenty-six patients discontinued therapy before 6 months, including 10 patients (12.3%) in the 3-MU and 16 patients (21.9%) in the 5-MU groups (p = 0.17).
Sustained virological response to combined interferon alpha-2b and ribavirin was significantly higher in relapse patients than those who did not respond to prior interferon monotherapy. Although, when all treated patients were analyzed, there was no significant difference in sustained response between subjects receiving 3 and 5 MU of interferon, among the prior nonresponder patients, treatment with 5 MU of interferon with ribavirin resulted in a slightly increased response compared with treatment with the standard interferon dosage. The tolerability of the treatment regimens was comparable.
干扰素联合利巴韦林对慢性丙型肝炎病毒（HCV）感染患者的治疗具有疗效。然而，其在先前干扰素治疗无反应患者中的效用尚不清楚。此外，对于对常规剂量干扰素耐药的慢性丙型肝炎患者，增加干扰素剂量联合利巴韦林的效果也未知。我们研究的目的是在一项大型多中心试验中评估高剂量干扰素联合利巴韦林对治疗干扰素单药治疗耐药的慢性丙型肝炎患者疗效的影响。
我们将154例先前干扰素治疗未获得持续应答的慢性丙型肝炎患者随机分为两组，分别接受3或5 MU的α-2b干扰素联合利巴韦林（1000 - 1200 mg/天）治疗12个月。其中119例患者先前无反应，35例患者先前有反应但干扰素单药治疗后复发。在治疗开始时、治疗6个月和12个月时以及6个月随访期结束时测量血清HCV RNA水平。
受试者的平均年龄为47岁（范围28 - 68岁），110例（71.4%）为男性。132例患者（86%）为HCV 1型，21例（14%）有肝硬化。81例受试者（53%）被随机分配接受3 MU的α-2b干扰素。35例复发患者中的15例（43%）和119例先前无反应患者中的12例（10%）在12个月的治疗疗程后获得持续病毒学应答。总体而言，接受3 MU干扰素的81例患者中有11例（14%），接受5 MU干扰素的73例患者中有16例（22%）在治疗停止后HCV RNA水平维持不可检测。两个干扰素剂量组之间的持续应答率差异未达到统计学意义（p = 0.09）。然而，仅在无反应患者中，高剂量干扰素组的持续应答率高于标准干扰素剂量组（15.5%对4.9%，p = 0.055）。26例患者在6个月前停止治疗，包括3 - MU组中的10例患者（12.3%）和5 - MU组中的16例患者（21.9%）（p = 0.17）。
复发患者对干扰素α-2b联合利巴韦林的持续病毒学应答显著高于先前干扰素单药治疗无反应的患者。虽然在分析所有治疗患者时，接受3 MU和5 MU干扰素的受试者之间的持续应答无显著差异，但在先前无反应患者中，5 MU干扰素联合利巴韦林治疗比标准干扰素剂量治疗导致应答略有增加。治疗方案的耐受性相当。
