Saracco G, Borghesio E, Mesina P, Solinas A, Spezia C, Macor F, Gallo V, Chiandussi L, Donada C, Donadon V, Spirito F, Mangia A, Andriulli A, Verme G, Rizzetto M
Dipartimento di Gastroenterologia, Ospedale Molinette, Turin, Italy.
J Hepatol. 1997 Jul;27(1):56-62. doi: 10.1016/s0168-8278(97)80280-2.
BACKGROUND/AIMS: To examine the effect of prolonged treatment with different doses of interferon alpha-2b on the relapse rate in patients with chronic hepatitis C.
One hundred and seventy-one patients with non-cirrhotic chronic hepatitis C were enrolled in an Italian multicenter trial. All patients were treated for 3 months with 3,000,000 Units (3 MU) of interferon alpha-2b given subcutaneously three times a week (t.i.w.). Patients with abnormal alanine aminotransferase (ALT) values were given 6 MU of interferon for an additional 3 months. If ALT remained persistently abnormal, therapy was then suspended. If ALT levels were normal, therapy was continued (6 MU t.i.w.) for an additional 18 months (total=2 years). Patients with normal ALT were randomly assigned to two groups, one receiving 3 MU and the other receiving 6 MU t.i.w. for an additional 21 months (total=2 years). Follow-up continued for 2 years after therapy withdrawal.
Seven patients stopped treatment during the first 3 months. Of the remaining 164 patients, 76 (46%) showed abnormal ALT levels after 3 months of therapy: 11 of these (14%) normalized ALT values when given 6 MU and a sustained response was maintained in eight during the follow-up. Overall, 54 and 34 patients were allocated respectively to the groups receiving the 3 MU and 6 MU long-term treatment. At the end of therapy, 35/54 patients of the group 3 MU and 21/34 patients of the group 6 MU showed normal ALT levels (65% vs 62%, p=N.S.). After 2 years of follow-up, 24/35 (69%) patients of the group 3 MU and 16/21 (76%) of the group 6 MU were still in remission (p=N.S.). In an intention-to-treat analysis, 48/171 (28%) patients showed a long-term response (normal ALT values, HCV-RNA negative). About 65% of the sustained responders showed low baseline viremia compared with 33% of non-responders (p=0.005) while genotype 1b was more frequently found among non-responders than in long-term responders (84% vs 25%, p=0.0001).
About 14% of patients who do not respond to a 3-month course of 3 MU of interferon normalize ALT levels when given 6 MU. In prolonged treatment, there is no significant difference between 3 and 6 MU in inducing a sustained response. Patients with low baseline viremia and genotype 2a respond significantly better to prolonged interferon therapy than highly viremic patients with genotype 1b.
背景/目的：探讨不同剂量的干扰素α-2b长期治疗对慢性丙型肝炎患者复发率的影响。
171例非肝硬化慢性丙型肝炎患者参加了一项意大利多中心试验。所有患者接受皮下注射300万单位（3MU）干扰素α-2b治疗，每周3次，共3个月。丙氨酸氨基转移酶（ALT）值异常的患者再接受6MU干扰素治疗3个月。如果ALT持续异常，则暂停治疗。如果ALT水平正常，则继续治疗（6MU，每周3次）18个月（总计2年）。ALT正常的患者随机分为两组，一组接受3MU，另一组接受6MU，每周3次，再治疗21个月（总计2年）。治疗停药后随访2年。
7例患者在最初3个月内停止治疗。其余164例患者中，76例（46%）在治疗3个月后ALT水平异常：其中11例（14%）接受6MU治疗后ALT值恢复正常，随访期间8例维持持续应答。总体而言，分别有54例和34例患者被分配到接受3MU和6MU长期治疗的组。治疗结束时，3MU组的54例患者中有35例、6MU组的34例患者中有21例ALT水平正常（65%对62%，p=无统计学意义）。随访2年后，3MU组的24/35例（69%）患者和6MU组的16/21例（76%）患者仍处于缓解状态（p=无统计学意义）。在意向性分析中，48/171例（28%）患者显示出长期应答（ALT值正常，HCV-RNA阴性）。约65%的持续应答者基线病毒血症水平较低，而非应答者为33%（p=0.005），非应答者中基因型1b的比例高于长期应答者（84%对25%，p=0.0001）。
约14%对3MU干扰素3个月疗程无应答的患者接受6MU治疗后ALT水平恢复正常。在长期治疗中，3MU和6MU诱导持续应答的效果无显著差异。基线病毒血症水平低的患者和基因型2a患者对长期干扰素治疗的反应明显优于高病毒血症的基因型1b患者。
