Angulo P, Larson D R, Therneau T M, LaRusso N F, Batts K P, Lindor K D
Department of Health Sciences Research, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Am J Gastroenterol. 1999 Nov;94(11):3310-3. doi: 10.1111/j.1572-0241.1999.01543.x.
The aim of this study was to determine the time course over which patients with primary sclerosing cholangitis (PSC) progress through the histological stages of the disease.
One hundred seven patients with PSC who had at least two liver biopsies were identified. The stage information from two consecutive biopsies formed one observation and a continuous time Markov model was used to describe the rate of progression between biopsies.
Three hundred seven liver biopsies were performed in the 107 patients giving a total of 200 observations. At 1 yr, 42% of patients in stage II disease progress, 66% at 2 yr, and 93% at 5 yr; whereas 14% of patients in stage III progress at 1 yr, 25% at 2 yr, and 52% at 5 yr. The frequency of progression of stage I disease could not be determined because of the small number of patients in stage I. Regression of histological stage was observed in 30 of 200 total observations (15%), and in 30 of 85 observations (35%) in which there was a change in stage.
These data regarding histological progression in PSC may be potentially helpful in determining the number of patients and length of time necessary to appreciate a treatment effect in clinical trials. However, the high degree of sampling variability in PSC may restrict the usefulness of serial liver biopsies as a means of evaluating treatment efficacy.
本研究的目的是确定原发性硬化性胆管炎（PSC）患者在疾病组织学阶段的进展时间过程。
确定了107例至少进行过两次肝活检的PSC患者。来自连续两次活检的阶段信息构成一次观察，并使用连续时间马尔可夫模型来描述活检之间的进展率。
107例患者共进行了307次肝活检，总共200次观察。在1年时，处于II期疾病的患者中有42%进展，2年时为66%，5年时为93%；而处于III期的患者在1年时进展的比例为14%，2年时为25%，5年时为52%。由于I期患者数量较少，无法确定I期疾病的进展频率。在总共200次观察中有30次（15%）观察到组织学阶段的逆转，在阶段有变化的85次观察中有30次（35%）观察到组织学阶段的逆转。
这些关于PSC组织学进展的数据可能有助于确定临床试验中评估治疗效果所需的患者数量和时间长度。然而，PSC中高度的抽样变异性可能会限制连续肝活检作为评估治疗疗效手段的实用性。
