IMPACT OF ORGAN AND NON-ORGAN-SPECIFIC AUTOANTIBODIES ON THE TREATMENT OUTCOME OF
PATIENTS WITH HEPATITIS D VIRUS INFECTION
1Department of Gastroenterology, Hepatology and Endocrinology, Hanover Medical School, Hanover, Germany, 2Department of Medicine and Research
Laboratory of Internal Medicine, Medical School, University of Thessaly, Larissa, Thessaly, Greece, 3University of Ankara Medical School, Gastroenterology
Section, Ankara, Turkey, 4Institute of Pathology, University of Cologne, Cologne, Germany
Zachou Kalliopi1,2, Yurdaydin Cihan3, Drebber Uta4, Schlaphoff Verena1, DienesHans Peter4, Manns Michael1, Wedemeyer Heiner1, Dalekos GN2
for the HIDT-1 Study Group
INTRODUCTION
Chronic hepatitis delta virus (HDV) infection has been
associated with the production of autoantibodies.
More specifically, anti-LKM-3 autoantibodies (against
UGT1.1) have been detected in around 13% of patients
with chronic HDV infection
Buti et al, J Hepatol 1989
Strassburg et al, Gastroenterology 1996
Obermayer-Straub et al, J Autoimmun 2001
INTRODUCTION
It is well known that autoantibodies are also commonly found
in chronic HCV infection. We have shown that the presence of
some of them (ANA, PCA and SMA) before treatment or their
increase during IFN-α therapy may predict a worse response,
suggesting the need for a more intensive follow up during
treatment of HCV patients positive for these autoantibodies.
Gatselis et al, WJG 2005
We re-evaluated the production of organ and non-
organ specific autoantibodies in a large cohort of
patients with chronic HDV infection who participated
in the Hep-Net/ International Delta Hepatitis
Intervention Trial (HIDIT-1), as well as their impact
on treatment outcome.
AIM
PATIENTS & METHODS
87 HDV patients
PegIFN + AdefovirN= 30
PegIFN + PlaceboN= 29
AdefovirN= 28
48 weeks
PATIENTS & METHODS
Age (years) 38 (17-62)
Male /Female (%) 53 (61)/ 34 (39)
Hb (g/dl) 14.5 ± 1.61
WBC (109/L) 5.6 ± 1.63
PLT (109/L) 166.8 ± 54.1
AST (U/L, UNL:35 U/L) 82 ± 59
ALT (U/L, UNL:35 U/L) 120 ± 93
gGT (U/L, UNL:55 U/L) 80 ± 94
ALP (U/L, UNL:104 U/L) 89 ± 56
Bilirubin (mg/dl) 0.95 ± 1.5
Albumin (g/dl) (n=66) 4 ± 0.5
HDVRNA (copies/ml) 7.6 E5 (1080 -8.4 E7)
HBVDNA (IU/ml) 20 (0-18.9 E6)
HBsAg (IU/ml) 11798 (67-79590)
Baseline characteristics of the 87 patients included in the study
We investigated the presence of: • antinuclear Abs (ANA) • antimitochodrial Abs (AMA) • anti-smooth muscle Abs (SMA) • anti-liver kidney microsomal Abs (anti-
LKM) • anti-parietal cell Abs (PCA)
• anti-LKM-3
IIF: -HEp2 cells/ - rat liver-kidney-stomach sections (in-house method)
WB: - recombinant UGT 1.1
At baseline and at week 48 of treatment, in the sera of 87 patients with chronic HDV infection.
PATIENTS & METHODS
Quantitative determination of: • HDV-RNA (real-time PCR in-house)• HBV-DNA (Cobas TaqMan HBV test)• HBsAg (the Architect HBsAg assay)
PATIENTS & METHODS
At baseline, week 48 (end of treatment) and week 72 of treatment
Biopsies were available in 70 patients at baseline and 60 patients at w48
At baseline: • ANA→ 29/87 (33%)• SMA→ 24/87 (27%) • AMA→ 2/87 (2.3%) • anti-LKM→ 3/87 (3.4%)• PCA→ 4/87 (4.6%)
• anti-LKM-3→ 21/87 (24%)
• At least 1 autoantibody→ 56/87 (64.4%)
RESULTS
Week 48: • ANA→ 29/74 (39%)• SMA→ 20/74 (27%)• AMA→ 3/74 (4%)• anti-LKM→ 5/74 (7%)• PCA→ 18/74 (24%)
• anti-LKM-3→ 20/74 (27%)
• At least 1 autoantibody→ 54/74 (73%)
ANA
SMA
AMA
anti-LKM
PCA
anti-LKM 3
At least o
ne
0
10
20
30
40
50
60
70
80
90
100
Baseline Week 48
P < 0.001,
McNemar te
stNS
NS
NS NSNS
NS
RESULTS
RESULTS
PCA w48 was not induced by IFN therapy
P= 0.004
No correlation was found between baseline
epidemiologic, biochemical and histological
characteristics and autoantibodies positivity.
Anti-LKM-3 Abs positivity was associated with lower
baselineHDVRNA levels
RESULTS
p= 0.029
RESULTSAt baseline: • Presence of ANA was associated with HDVRNA (-) at w72
ANA (-) ANA (+)0
5
10
15
20
25
30
HDVRNA w72 (-)HDVRNA w72 (+)
p= 0.04
N o
f ca
ses
p= 0.05
At baseline: • Absence of SMA was associated with: lower HDVRNA at w72
amelioration of fibrosis
RESULTS
SMA (-) SMA (+)0
5
10
15
20
25
30
35
Better or same fi-brosis score
Worse fibrosis score
p= 0.05
N o
f ca
ses
At baseline: • Absence of PCA was associated with: amelioration of inflammation
RESULTS
PCA (-) PCA (+)0
5
10
15
20
25
30
35
40
45
Decrease in inflamma-tion screIncrease in inflamma-tion score
N o
f ca
ses
p= 0.03
Week 48: • Absence of PCA was associated with: lower HBsAg levels at w48 and w72
RESULTS
p= 0.01 p= 0.012
Week 48: • Absence of PCA was associated with: biochemical response at w72
RESULTS
PCA w48 (-) PCA w48 (+)0
5
10
15
20
25
30
35
ALT w72< UNLALT w72> UNL
P= 0.04
N o
f ca
ses
We found increased incidence of anti-LKM-3 as well as of
other autoantibodies in patients with chronic HDV infection.
Most patients had the same autoantibody profile before
and at the end of treatment. The only autoantibodies which
seemed to be increased in frequency were PCA.
Although anti-LKM-3 antibodies do not seem to affect
response to treatment, others may play a role in the
virological, biochemical or histological response.
CONCLUSIONS
Medical SchoolUniversity of Thessaly
University of Cologne
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