162 Poster Sessions
Results: The combined endpoint ’death or liver transplantation’ occurred
in 7/97 (7.2%) patients in the UDCA group vs. 11/101 (10.9%) patients in
the placebo group (p=0.368). Occurrence of liver transplantation as a sin-
gle endpoint showed a similar advatage of UDCA treatment (5/97 (5.2%)
vs. 8/101 (7.9%)). Three UDCA and 4 placebo patients died from cholan-
giocarcinoma, one placebo patient died from liver failure. ALP and ALT
tended to decrease during the first 6 months. There were no differences be-
tween the two groups in symptoms, or Quality of life as recorded by SF-36.
Conclusion: No statistically significant benefit from 20 mg/kg bw UDCA
in PSC was demonstrated. However, there was a tendency to improved sur-
vival in the UDCA treated patients. Furthermore, we had estimated before
the study that based on a type I error of =5%,and a type II error of =20%, at
least 346 patients was required for detection of a difference in events of at
least =50%, a goal we did not reach within the predetermined recruitment
time of 15 months. Therefore,the study may have been undernumbered to
exclude a significant beneficial effect on survival.
552 PRIMARY BILIARY CIRRHOSIS (PBC) SPECIFIC
ANTINUCLEAR ANTIBODIES (ANA) HAVE PROGNOSTIC
VALUE AND A DISTINCT IMMUNOGLOBULIN ISOTYPE
PROFILE
E.I. Rigopoulou 1 , E.T. Davies 2 , D.P. Bogdanos 3 , G. Koukoulis 4 ,
G.N. Dalekos 1 , D. Vergani 3 . 1 Academic Liver Unit, Dept. of Internal
Medicine, Medical School, University of Thessaly, Larissa, Greece;
2
Department of Immunology, King’s College, London, UK; 3 Institute of
Liver Studies, King’s College Hospital, London, UK; 4 Department of
Pathology, Medical School, University of Thessaly, Larissa, Greece
Background/aim: PBC is characterized by anti-mitochondrial (AMA) and
disease-specific ANA generating a rim-like/membranous (RL/M) or multi-
ple nuclear dot (MND) pattern by indirect immunofluorescence (IIF). The
aim of the present study was to investigate the prevalence and clinical sig-
nificance of the isotypes of PBC-specific ANA and their relation to the
AMA isotypes.
Methods: PBC-specific ANA and AMA were investigated by conventional
IIF on triple rodent tissue and on HEp-2010 cells in 44 Greek PBC patients.
Revealing reagents comprised antisera targeting IgG or IgA or IgM or
individual IgG (1-4) subclasses.
Results: Thirty-seven of 44 (84%) PBCs tested positive for IgM and/or
IgG (class or subclasses) PBC-specific ANA, 27 (61.4%) being positive
for RL/M and 21 (47.7%) for the MND pattern. The prevailing isotype
was IgG1 for anti-RL/M and IgG3 for anti-MND reactivity. PBC patients
positive for either RL/M or MND had a histologically more advanced
liver disease and were more frequently cirrhotic compared to those ANA
negative. In addition, PBC-specific ANAs of the IgG3 subclass were sig-
nificantly associated with more severe disease and higher frequency of
cirrhosis. AMA belonging to any isotype were present in 41 (93.2%) PBC
patients, the prevailing isotype pattern comprising IgG1, 2 and 3 subclass.
Comparison of AMA and ANA revealed identical Ig isotype profile in only
8 PBC patients.
Conclusions: PBC-specific ANAs, especially of the IgG3 isotype, are as-
sociated with a more advanced disease. The different isotypes profiles of
MND, RL/M and AMA suggest that distinct antigen driven mechanisms
are responsible for their production.
553 PREVALENCE OF RO/SSA AUTOANTIBODIES IN
AUTOIMMUNE HEPATITIS AND ASSOCIATION WITH
UNEXPLAINED PREGNANCY LOSS
C. Schramm, J. Herkel, J.-P. Modrow, I. Ernst, S. Kanzler, P.R. Galle,
A.W. Lohse. I. Department of Medicine, University of Mainz, Mainz,
Germany
Introduction: Ro/SSA autoantibodies have been associated with unex-
plained pregnancy loss in rheumatic diseases. We therefore determined the
prevalence of Ro/SSA antibodies in autoimmune liver disease and assessed
the risk of pregnancy loss in a cohort of patients with AIH.
Patients and Methods: Test sera were obtained from 293 consecutive pa-
tients attending our liver outpatient clinic. 29 pregnancies in 14 patients
with known Ro/SSA status and autoimmune hepatitis were reviewed ret-
rospectively and patients were specifically asked about miscarriages in a
questionnaire.
Results: 14% of the patients with AIH (n=96) and 20% of the patients
with an AIH/PBC overlap syndrome (n=20) manifested autoantibodies to
the Ro/SSA antigen. In contrast, Ro/SSA autoantibodies were absent in
all of the 120 patients with viral hepatitis, PSC, NASH, toxic hepatitis
and also in the 57 PBC patients. There was no difference in the clinical
characteristics of AIH patients with and without Ro/SSA autoantibodies.
Five pregnancy losses occurred in four patients with autoantibodies to the
Ro/SSA molecule, whereas only one unexplained pregnancy loss occurred
in a patient without Ro/SSA autoantibodies. Thus, the odds ratio for an
unexplained pregnancy loss in the presence of Ro/SSA autoantibody was
14 (95% confidence interval: 0.94 to 207.74).
Conclusions: Ro/SSA autoantibodies might be an additional marker for
AIH and the AIH/PBC overlap syndrome. Moreover, Ro/SSA autoantibod-
ies seem to be associated with unexplained pregnancy loss in patients with
AIH. A prospective study seems to be warranted and testing for Ro/SSA
antibody should be included in the counselling of young female patients
with AIH.
554 HLA DR7 POSITIVE PATIENTS WITH TYPE 2 AUTOIMMUNE
HEPATITIS ARE CHARACTERISED BY A PROLONGED
CLINICAL COURSE
J. Underhill 1 , D.P. Bogdanos 1 , M.S. Longhi 1 , S. Bansal 2 ,
G. Mieli-Vergani 1,2 , D. Vergani 1 , Y. Ma 1 . 1 Institute of Liver Studies,
King’s College Hospital, London, UK; 2 Department of Child Health,
King’s College Hospital, London, UK
Background: HLA-DRB1∗07 (DR7) is over-represented in LKM1+ au-
toimmune hepatitis (AIH-2) (J Hepatol 2002;36:S1, 156), DR7+ patients
having a broader and more vigorous cellular immune response to CYP2D6
– the target of LKM1 – than those DR7- (J Hepatol 2003;38:S2, 719).
Aim: To compare the clinical features of DR7+ and DR7- AIH-2 patients.
Patients and Methods: Thirty-five patients with AIH-2 were investigated
(6 male, median age 6.8 yrs, range 1 to 15.4). Class II genotyping for HLA-
DRB was performed by PCR/SSO using oligonucleotide probes (BSHI,
Bristol, UK).
Results: 20 patients (57%) were HLA-DR7 positive. Of 15 DR7-, 9 were
DR3 (26%, p<0.01), 1 DR4 (3%, p<0.001) and 5 had other allotypes
(DR1, 13, 14 and 15; 17%, p<0.001). Age at diagnosis (6 vs 9 yrs), mode
of presentation (chronic/acute: 6/14 vs 2/13), biochemical (AST: 321 vs
449 IU/l; Bilirubin: 49 vs 33 micromol/l) and histological (HAI: 7 vs 8)
disease severity were similar, while male sex was more frequent (6/20,
30% vs 0/15, 0% p=0.02) in DR7+ than in DR7- patients. DR7+ patients
required longer time to achieve remission (12 vs 7 months, p=0.05) and
tended to relapse more often than DR7- patients (10/15, 67% vs 4/12, 33%,
p=0.08). The frequency of patients who died or required transplantation,
however, was similar (5/20, 25% vs 3/15, 20%).
Conclusion: DR7+ patients have a relatively more severe course of liver
disease, possibly a consequence of their broader and stronger cellular im-
mune response to CYP2D6.