Factors associated with response to therapy and outcome of patients with primary biliary cirrhosis with features of autoimmune hepatitis.
OBJECTIVE
For patients with primary biliary cirrhosis (PBC) with features of autoimmune hepatitis (AIH), treatment with ursodeoxycholic acid (UDCA) alone or in combination with immunosuppression is controversial. Little is known about the factors associated with initial response to therapy or outcome. We performed a retrospective analysis of treatment strategies and factors associated with outcomes of patients with PBC-AIH.


METHODS
We analyzed data from 88 patients who were diagnosed with PBC-AIH according to Paris criteria, from 7 centers in 5 countries. First-line therapies included UDCA alone (n = 30) or a combination of UDCA and immunosuppression (n = 58).


RESULTS
Of patients who received UDCA alone as the first-line therapy, 37% did not respond to treatment. Severe interface hepatitis was independently associated with lack of response to treatment (P = .024; odds ratio, 0.05; 95% confidence interval, 0.004-0.68). The combination of UDCA and immunosuppression was effective in 73% of patients who had not been previously treated or had not responded to UDCA. The presence of advanced fibrosis was associated with lack of response to the combination of UDCA and immunosuppression (P = .003; odds ratio, 0.13; 95% confidence interval, 0.03-0.48). Second-line immunosuppressive agents (cyclosporine, tacrolimus, and mycophenolate mofetil) led to biochemical remission in 54% of patients who did not respond to initial immunosuppression. Liver transplants were given to 4 patients with PBC-AIH. Five patients died during follow-up (3 from liver-related causes).


CONCLUSIONS
In a retrospective study of a large cohort of patients with PBC-AIH, UDCA alone did not produce a biochemical response in most patients with severe interface hepatitis; these patients require additional therapy with immunosuppression. Second-line immunosuppressive agents are effective in controlling disease activity in patients who do not respond to conventional immunosuppression.
Department of Gastroenterology, Numune Research and Education Hospital, Ankara, Turkey.
Ersan
E
Ozaslan
Department of Gastroenterology, Hacettepe University, Ankara, Turkey. Electronic address: drcumi21@hotmail.com.
Cumali
C
Efe
Department of Hepato-Gastroenterology, CHU Reims, Reims, France.
Alexandra
A
Heurgué-Berlot
Department of Gastroenterology, Hacettepe University, Ankara, Turkey.
Taylan
T
Kav
Department of Clinical Medicine, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
Chiara
C
Masi
Department of Gastroenterology, Numune Research and Education Hospital, Ankara, Turkey.
Tugrul
T
Purnak
Department of Clinical Medicine, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
Luigi
L
Muratori
Department of Gastroenterology, Zonguldak Karaelmas University Hospital, Zonguldak, Turkey.
Yücel
Y
Ustündag
Department of Hepatology, Besançon, France.
Solange
S
Bresson-Hadni
Department of Hepato-Gastroenterology, CHU Reims, Reims, France.
Gérard
G
Thiéfin
Division of Liver Diseases, The Mount Sinai Medical Center, New York, New York.
Thomas D
TD
Schiano
Department of Gastroenterology and Hepatology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Staffan
S
Wahlin
Department of Clinical Medicine, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
Paolo
P
Muratori
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D019693:Hepatitis, Autoimmune / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008105:Liver Cirrhosis, Biliary / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*; D055815:Young Adult
D002756:Cholagogues and Choleretics; D007166:Immunosuppressive Agents; D014580:Ursodeoxycholic Acid
Autoimmunity; Malignancy; Mycophenolate-Mofetil; Paris Criteria