Criteria Used in Clinical Practice to Guide Immunosuppressive Treatment in Patients with Primary Sclerosing Cholangitis.
OBJECTIVE
Current guidelines recommend immunosuppressive treatment (IT) in patients with primary sclerosing cholangitis (PSC) and elevated aminotransferase levels more than five times the upper limit of normal and elevated serum IgG-levels above twice the upper limit of normal. Since there is no evidence to support this recommendation, we aimed to assess the criteria that guided clinicians in clinical practice to initiate IT in patients with previously diagnosed PSC.


METHODS
This is a retrospective analysis of 196 PSC patients from seven German hepatology centers, of whom 36 patients had received IT solely for their liver disease during the course of PSC. Analyses were carried out using methods for competing risks.


RESULTS
A simplified autoimmune hepatitis (AIH) score >5 (HR of 36, p<0.0001) and a modified histological activity index (mHAI) greater than 3/18 points (HR 3.6, p = 0.0274) were associated with the initiation of IT during the course of PSC. Of note, PSC patients who subsequently received IT differed already at the time of PSC diagnosis from those patients, who did not receive IT during follow-up: they presented with increased levels of IgG (p = 0.004) and more frequently had clinical signs of cirrhosis (p = 0.0002).


CONCLUSIONS
This is the first study which investigates the parameters associated with IT in patients with PSC in clinical practice. A simplified AIH score >5 and a mHAI score >3, suggesting concomitant features of AIH, influenced the decision to introduce IT during the course of PSC. In German clinical practice, the cutoffs used to guide IT may be lower than recommended by current guidelines.
I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Kornelius
K
Schulze
Department of Internal Medicine I, University of Bonn, Bonn, Germany; Clinic of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany.
Tobias J
TJ
Weismüller
Department of Biostatistics, Rouen University Hospital-Charles Nicolle, Rouen, France.
Michael
M
Bubenheim
I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Peter
P
Huebener
I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Roman
R
Zenouzi
Clinic of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany.
Henrike
H
Lenzen
IV. Department of Medicine, University Medical Center Heidelberg, Heidelberg, Germany.
Christian
C
Rupp
IV. Department of Medicine, University Medical Center Heidelberg, Heidelberg, Germany.
Daniel
D
Gotthardt
I. Department of Medicine, University Medical Center Frankfurt, Frankfurt am Main, Germany.
Philipp
P
de Leuw
I. Department of Medicine, University Medical Center Mainz, Mainz, Germany; Department of Medicine, University Hospital Regensburg, Regensburg, Germany.
Andreas
A
Teufel
II. Department of Medicine, Saarland University Medical Center Homburg, Homburg, Germany.
Vincent
V
Zimmer
Department of Medicine II, Liver Center Munich, University of Munich, Grosshadern Campus, Munich, Germany.
Florian P
FP
Reiter
Department of Medicine II, Liver Center Munich, University of Munich, Grosshadern Campus, Munich, Germany.
Christian
C
Rust
Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Lars
L
Tharun
Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Pathology, University Medical Center Cologne, Cologne, Germany.
Alexander
A
Quaas
Department of Pathology, University Medical Center Cologne, Cologne, Germany.
Sören A
SA
Weidemann
II. Department of Medicine, Saarland University Medical Center Homburg, Homburg, Germany.
Frank
F
Lammert
I. Department of Medicine, University Medical Center Frankfurt, Frankfurt am Main, Germany.
Christoph
C
Sarrazin
Clinic of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany.
Michael P
MP
Manns
I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Ansgar W
AW
Lohse
I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Christoph
C
Schramm
D000328:Adult; D015209:Cholangitis, Sclerosing / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*; D015331:Cohort Studies; D005260:Female; D019693:Hepatitis, Autoimmune / Q000175:diagnosis / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015212:Inflammatory Bowel Diseases / Q000150:complications; D008099:Liver / Q000473:pathology; D008107:Liver Diseases / Q000276:immunology / Q000628:therapy*; D008297:Male; D012189:Retrospective Studies; D000637:Transaminases / Q000378:metabolism*
D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000637:Transaminases