Time course of histological progression in primary sclerosing cholangitis.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Angulo
P
P
Department of Health Sciences Research, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Larson
D R
DR
Therneau
T M
TM
LaRusso
N F
NF
Batts
K P
KP
Lindor
K D
KD
D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D002756:Cholagogues and Choleretics / Q000627:therapeutic use; D015209:Cholangitis, Sclerosing / Q000145:classification / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006505:Hepatitis / Q000473:pathology; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008103:Liver Cirrhosis / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000473:pathology; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D009336:Necrosis; D010396:Penicillamine / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use
D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid; D010396:Penicillamine