studies

368A AASLD ABSTRACTS HEPATOLOGY, October, 2015
308
Tacrolimus or Mycophenylate mofetil as a second-line
therapeutic options in patients with Autoimmune Hepatitis:
An international multicentre observational study.
Cumali Efe 5 , Hannes Hagström 3 , Rahima A. Bhanji 2 , Niklas F.
Müller 1 , Qixia Wang 4 , Tugrul Purnak 5 , Luigi Muratori 6 , Mårten
Werner 7 , Hanns-Ulrich Marschall 8 , Paolo Muratori 6 , Fulya Gunsar
9 , Daniel Klintman 10 , Albert Parés 11 , Alexandra Heurgué-Berlot
12 , Thomas D. Schiano 13 , Xiong Ma 4 , Aldo J. Montano-Loza 2 ,
Thomas Berg 1 , Ersan Ozaslan 14 , Eric M. Yoshida 15 , Staffan Wahlin
3 ; 1 Universitätsklinikum Sektion Hepatologie, Klinik für Gastroenterologie
und Rheumatologie., Leipzig,, Germany; 2 University of
Alberta Division of Gastroenterology and Liver Unit., Alberta, AB,
Canada; 3 Gastroenterology and Hepatology, Karolinska Institutet,
Karolinska University Hospital., Stockholm, Sweden; 4 Department
of Hepatology, Shanghai University of Traditional Chinese Medicine,
Longhua Hospital, Shanghai,, China; 5 Department of Gastroenterology,
Hacettepe University,, Ankara, Turkey; 6 Department of
Clinical Medicine, Alma Mater Studiorum, University of Bologna,,
Bologna, Italy; 7 Departments of Medicine, Sections for Hepatology
and Gastroenterology, University Hospital of Skåne,, Malmö,
Sweden; 8 Department of Molecular and Clinical Medicine, Sahlgrenska
Academy, University of Gothenburg,, Gothenburg, Sweden;
9 Department of Gastroenterology, Ege University, Bornova,,
Izmir, Turkey; 10 Department of Molecular and Clinical Medicine,
Lund University of Hospital,, Lund, Sweden; 11 Liver Unit, Hospital
Clínic University of Barcelona C/ Villarroel 170 08036, Barcelona,
Spain; 12 Department of Hepato-Gastroenterology, CHU
Reims,, Reims, France; 13 Division of Liver Diseases, The Mount
Sinai Medical Center, New York,, NY; 14 Department of Gastroenterology,
Numune Research and Education Hospital,, Ankara, Turkey;
15 Division of Gastroenterology University of British Columbia
and Vancouver General Hospital., Vancouver, BC, Canada
Background: Autoimmune hepatitis (AIH) is a well-recognized
immune mediated liver disease. Eighty percent (80 %) of
patients respond to standard therapy, including corticosteroids
alone or combination with azathioprine (AZA). However, this
therapy is not tolerated or insufficient to control disease activity
in 20 % of patients. Second-line treatment with Tacrolimus (Tac)
or Mycophenylate mofetil (MMF) has been described in only
small case series. The aim of this study was to evaluate the outcome
of Tac and/or MMF therapy in patients with AIH who are
resistant or intolerant to standard immunosuppression. Patients
and methods: This multi-centre retrospective chart review study
evaluated data of AIH, including overlap with PBC or PSC
patients, treated with Tac and/or MMF. Initial treatment was
corticosteroids ±AZA. The patients were categorized as complete
responders to initial therapy (Group-I), partial responders
(Group-II) and lack of responders (Group-III). The IAIHG criteria
were used for the diagnosis of AIH. Results: 163 patients (121
female), mean age of 37 (9-76) years were included. Patients
were treated with Tac (n=71) and MMF (n=92) a median of
16 months (1-252 months) after standard immunosuppression.
MMF and Tac resulted in complete or partial response in all
of group-I patients. In group-II and group-III, Tac induced complete
or partial response in 75% (36/45) vs 50 % (23/46) of
MMF patients (p=0.003). Median follow up duration was 42.5
(1-2430) months after MMF and/or Tac therapy. Five and 10
years follow up rates were 37 % (34/92) and 19.6 % (18/92)
for MMF patients and 51% (36/71) and 14% (10/71) for Tac
patients. Combination of Tac and MMF was given to only 6
patients, with 4 responding to therapy. Eleven patients were
eventually transplanted. MMF and/or Tac were discontinued
due to side effects in 7 patients including, 4 Tac and 3 MMF.
Conclusions: MMF and Tac are generally effective and well tolerated
in standard treatment resistant or intolerant AIH patients.
There is no significant differences in outcomes between MMF
and Tac treatments in AIH patients who responded to conventional
therapy. However, Tac may be superior in AIH patients
who showed incomplete or non-response to standard immunosupression.
Disclosures:
Hanns-Ulrich Marschall - Consulting: Albireo
Alexandra Heurgué-Berlot - Consulting: Abbvie; Speaking and Teaching: Gilead
Thomas Berg - Advisory Committees or Review Panels: Gilead, BMS, Roche,
Tibotec, Vertex, Jannsen, Novartis, Abbott, Merck, Abbvie; Consulting: Gilead,
BMS, Roche, Tibotec; Vertex, Janssen; Grant/Research Support: Gilead, BMS,
Roche, Tibotec; Vertex, Jannssen, Merck/MSD, Boehringer Ingelheim, Novartis,
Abbvie; Speaking and Teaching: Gilead, BMS, Roche, Tibotec; Vertex, Janssen,
Merck/MSD, Novartis, Merck, Bayer, Abbvie
The following authors have nothing to disclose: Cumali Efe, Hannes Hagström,
Rahima A. Bhanji, Niklas F. Müller, Qixia Wang, Tugrul Purnak, Luigi Muratori,
Mårten Werner, Paolo Muratori, Fulya Gunsar, Daniel Klintman, Albert Parés,
Thomas D. Schiano, Xiong Ma, Aldo J. Montano-Loza, Ersan Ozaslan, Eric M.
Yoshida, Staffan Wahlin
309
Killer cell immunoglobulin-like receptors and their HLA
class I ligands in autoimmune hepatitis: a possible
pathogenetic role ?
Simona Onali 2 , Roberto Littera 1 , Carlo Carcassi 1 , Luca Secci 2 ,
Sara Lai 1 , Rita Porcella 1 , Sara Cappellini 2 , Claudia Salustro 2 ,
Cinzia Balestrieri 3 , Giancarlo Serra 3 , Maria Conti 3 , Teresa
Zolfino 4 , Francesco Figorilli 2 , Michele Casale 2 , Stefania Casu 2 ,
Maria Cristina Pasetto 2 , Laura Matta 2 , Rosetta Scioscia 2 , Lucia
Barca 2 , Luchino Chessa 2,3 ; 1 Medical Genetics, Department of
Medical Sciences “M.Aresu”, University of Cagliari, Cagliari,
Italy; 2 Center for the Study of Liver Diseases, Department of Medical
Sciences “M.Aresu”, University of Cagliari, Cagliari, Italy;
3 Department of Internal Medicine, Azienda Ospedaliero-Universitaria,
Cagliari, Cagliari, Italy; 4 S.S.D. Coordinamento Trapianti di
fegato, Azienda Ospedaliera Brotzu, Cagliari, Italy
Background: Natural killer (NK) cells are widely distributed in
hepatic tissue, but their role in the pathogenesis of autoimmune
hepatitis (AIH) has not been fully estabilished yet. Killer cell
immunoglobulin receptors (KIRs) represent the major family of
cell surface receptors that inhibit and activate NK cells. Aim:
To assess whether different type of KIRs could be involved in
pathogenesis of AIH. Methods: We analyzed all consecutive
Sardinian outpatients with type I AIH, referred to the Liver Unit
of University of Cagliari (Italy) between January and October
2014. AIH was diagnosed according to the International Autoimmune
Hepatitis Group Revised Original Scoring System and
AASLD guidelines. Patients with type II AIH, overlap syndrome
and other chronic liver diseases were excluded. The immunogenetic
characteristics of AIH patients were compared to those
of 221 healthy individuals extracted from the Sardinian bone
marrow donor registry. High resolution (4 digits) typing of HLA-
A, B, C and DR loci and 15 KIRs gene loci was performed in
both patients and controls. Subjects were divided into 2 groups
according to homozygosity for KIR haplotype A (KIR genotype
AA), heterozygosity or homozygosity for KIR haplotype B (KIR
genotype Bx). The study was approved by local ethics committee
and informed consent was obtained from all participants.
Results. 114 subjects were included: median age 55 years
(range 17-80), 87.7% females, median duration of disease 6
years (range 0.6-23). The frequency of activating KIR gene,
KIR2DS1, was significantly higher in AIH patients compared
to controls (57% vs 43%, p=0.03, HR=1.7, 95% CI=1.0-2.7),
as well as KIR2DL1+/KIR2DS1+/HLA-C2+ (47.3% vs 35.7%,
p=0.04, HR=1.6, 95% CI=1.0-2.6). When we considered the
age of onset of the autoimmune hepatitis, we found that activating
KIR gene KIR2DS1 was more frequent in patients diag-