Shiratori Y, Imazeki F, Moriyama M, Yano M, Arakawa Y, Yokosuka O, Kuroki T, Nishiguchi S, Sata M, Yamada G, Fujiyama S, Yoshida H, Omata M
Department of Internal Medicine, University of Tokyo and Nihon University School of Medicine, Japan.
Ann Intern Med. 2000 Apr 4;132(7):517-24. doi: 10.7326/0003-4819-132-7-200004040-00002.
Short-term histologic improvement in hepatitis C-related hepatic fibrosis has been noted in studies with more than 2 years of follow-up, but the long-term effects of interferon therapy on hepatic fibrosis remain unclear.
To assess changes in hepatic fibrosis after interferon therapy in patients with chronic hepatitis C.
Retrospective cohort study.
7 university hospitals and 1 national hospital in Japan.
593 patients with chronic hepatitis C who underwent a paired liver biopsy from 1987 to 1997. Of these, 487 patients received interferon therapy and 106 patients were untreated.
Patients in the treatment group received a 2- to 6-month course of interferon within 6 months after the initial biopsy.
Fibrosis and inflammatory activity in paired biopsy samples obtained a median of 3.7 years apart (range, 1 to 10 years) were graded by using the criteria of Desmet and colleagues (F0 to F4) and those of the French METAVIR Cooperative Study Group (A0 to A3), respectively. Changes in fibrosis staging and activity scores and yearly rates of fibrosis progression and regression were calculated.
183 of the 487 interferon-treated patients showed a sustained virologic response. Activity grade was unchanged in most of the untreated patients and improved in 89% (CI, 83% to 93%) of patients with a sustained virologic response. A sustained response to interferon was associated with a mean (+/-SE) reduction in fibrosis score of -0.60+/-0.07 at less than 3 years of follow-up and -0.88+/-0.08 at 3 years or more of follow-up. The rate of fibrosis progression was -0.28+/-0.03 unit/y (regression) in patients with sustained response, 0.02+/-0.02 unit/y in patients with nonsustained response (P< 0.001), and 0.10+/-0.02 unit/y in untreated patients.
Although the time between biopsies partly affected the patient's clinical course, the differences observed here suggest that in patients with chronic hepatitis C, regression of fibrosis is associated with sustained virologic response to interferon therapy.
在随访超过2年的研究中,已注意到丙型肝炎相关肝纤维化的短期组织学改善,但干扰素治疗对肝纤维化的长期影响仍不清楚。
评估慢性丙型肝炎患者接受干扰素治疗后肝纤维化的变化。
回顾性队列研究。
日本的7所大学医院和1所国立医院。
593例慢性丙型肝炎患者,于1987年至1997年接受了配对肝活检。其中,487例患者接受了干扰素治疗,106例患者未接受治疗。
治疗组患者在初次活检后6个月内接受了2至6个月疗程的干扰素治疗。
分别使用Desmet及其同事的标准(F0至F4)和法国METAVIR合作研究组的标准(A0至A3),对中位间隔3.7年(范围1至10年)获取的配对活检样本中的纤维化和炎症活动进行分级。计算纤维化分期和活动评分的变化以及纤维化进展和消退的年率。
487例接受干扰素治疗的患者中有183例显示出持续病毒学应答。大多数未治疗患者的活动分级未改变,而在89%(可信区间,83%至93%)有持续病毒学应答的患者中活动分级得到改善。对干扰素的持续应答与随访不到3年时纤维化评分平均(±标准误)降低-0.60±0.07以及随访3年或更长时间时降低-(-0.88±0.08相关。有持续应答的患者纤维化进展率为-0.28±0.03单位/年(消退),无持续应答的患者为0.02±0.02单位/年(P<0.001),未治疗患者为0.10±0.02单位/年。
虽然活检间隔时间部分影响了患者的临床病程,但此处观察到的差异表明,在慢性丙型肝炎患者中,纤维化的消退与对干扰素治疗的持续病毒学应答相关。