Surgical Unit, Gastroenterologia, Azienda Ospedaliera Pisana, Ospedale Cisanello, Pisa, Italy.
Clin Drug Investig. 1998;15(4):271-7. doi: 10.2165/00044011-199815040-00002.
In an attempt to determine the best therapeutic protocol for the treatment of chronic hepatitis C with interferon (IFN), we reported our experience comparing the efficacy of IFN at the usual dose and duration, i.e. 3 million units (MU) three times weekly for 6 months, with the immediate and long-term effects of different types, dosages and duration of IFN therapy. 300 patients with chronic hepatitis C were randomly assigned to five groups of 60 subjects each and treated as follows: group A - recombinant IFN alpha (rIFNalpha) 3MU three times weekly for 6 months; group B - rIFNalpha 6MU three times weekly for 6 months; group C - rIFNalpha 3MU 3 times weekly for 12 months; group D - lymphoblastoid IFN (L-IFN) 6MU three times weekly for 6 months; group E - L-IFN 3MU three times weekly for 12 months. The diagnosis of hepatitis was based on clinical, serological and histological data in all patients. A 'biochemical response' was defined as the normalisation of alanine aminotransferase (ALT) values, and a 'complete response' as the normalisation of ALT with disappearance of serum hepatitis C virus (HCV)-RNA. A 'sustained response' was defined as the persistence of ALT normalisation and undetectable viraemia 2 years after the end of treatment. The five groups were homogeneous. The incidence of dropouts was 8%, and IFN treatment was interrupted for adverse effects in 11% of the patients. In group A, 55% of the patients showed a 'biochemical response' and 31% of the subjects demonstrated a 'complete response'. In group B, a 'biochemical response' was observed in 61% and a 'complete response' in 36% of the cases. In group C, 77% of the subjects showed a 'biochemical response', with a 'complete response' seen in 40%. In group D, we observed a 'biochemical response' in 55% of the patients and a 'complete response' in 33%. In group E, 79% of the subjects had a 'biochemical response', and a 'complete response' was seen in 38%. At the end of the treatment-free follow-up the percentage of patients with a sustained response was 24% in group A, 28% in group B, 35% in group C, 27% in group D and 33% in group E. Therefore, a longer period of IFN treatment seems to provide higher percentages of sustained response than the usual 6-month duration, independently of the type of IFN. Moreover, the patients treated with a higher dosage (6MU 3 times weekly) for 6 months showed a slightly better sustained response rate compared with the usual dose. In conclusion, even if the differences among the response rates in the five groups were not statistically significant, we recommend a 12-month regimen, possibly using higher dosages at least in the first 4 to 6 months of treatment.
为了确定治疗慢性丙型肝炎的最佳治疗方案，我们报告了使用干扰素（IFN）的经验，比较了常规剂量和持续时间（即每周 3 次，每次 300 万单位，持续 6 个月）与不同类型、剂量和持续时间的 IFN 治疗的即时和长期效果。我们将 300 例慢性丙型肝炎患者随机分为 5 组，每组 60 例，分别接受以下治疗：A 组 - 重组 IFNα（rIFNalpha）每周 3 次，每次 3MU，持续 6 个月；B 组 - rIFNalpha 每周 3 次，每次 6MU，持续 6 个月；C 组 - rIFNalpha 每周 3 次，每次 3MU，持续 12 个月；D 组 - 淋巴母细胞 IFN（L-IFN）每周 3 次，每次 6MU，持续 6 个月；E 组 - L-IFN 每周 3 次，每次 3MU，持续 12 个月。所有患者的诊断均基于临床、血清学和组织学数据。“生化反应”定义为丙氨酸氨基转移酶（ALT）值正常化，“完全反应”定义为 ALT 正常化且血清丙型肝炎病毒（HCV）-RNA 消失。“持续反应”定义为治疗结束后 2 年内 ALT 正常化和病毒血症不可检测。这 5 组是同质的。失访率为 8%，因不良反应中断 IFN 治疗的患者为 11%。在 A 组中，55%的患者出现“生化反应”，31%的患者出现“完全反应”。在 B 组中，61%的患者出现“生化反应”，36%的患者出现“完全反应”。在 C 组中，77%的患者出现“生化反应”，其中 40%出现“完全反应”。在 D 组中，我们观察到 55%的患者出现“生化反应”，33%的患者出现“完全反应”。在 E 组中，79%的患者出现“生化反应”，38%的患者出现“完全反应”。在无治疗随访结束时，A 组持续反应的患者比例为 24%，B 组为 28%，C 组为 35%，D 组为 27%，E 组为 33%。因此，与常规的 6 个月持续时间相比，较长时间的 IFN 治疗似乎提供更高比例的持续反应，而与 IFN 的类型无关。此外，6 个月内接受较高剂量（每周 3 次，每次 6MU）治疗的患者与常规剂量相比，持续反应率略高。总之，尽管五组之间的反应率差异没有统计学意义，但我们建议采用 12 个月的方案，至少在前 4 至 6 个月的治疗中使用较高剂量。
