Abstracts / Digestive and Liver Disease 47S (2015) e19–e42
T-22
ROLE OF KILLER CELL IMMUNOGLOBULIN-LIKE
RECEPTORS AND THEIR HLA CLASS I LIGANDS IN
AUTOIMMUNE HEPATITIS
R. Littera 1 , C. Carcassi 1 , L. Secci 2 , S. Lai 1 ,
L. Cappai 1 , R. Porcella 1 , F. Alba 1 , R. Maddi 1 ,
M. Serra 1 , S. Cappellini 2 , C. Salustro 2 , S. Onali 2 ,
C. Balestrieri 2 , G. Serra 2 , M. Conti 2 , T. Zolfino 3 ,
R. Scioscia 2 , L. Barca 2 , L. Chessa 2
1 Medical Genetics, Department of Medical Sciences
“M.Aresu”, University of Cagliari, Italy
2 Center for the Study of Liver Diseases, Department
of Medical Sciences “M. Aresu”, University of Cagliari,
Italy
3 S.C. Gastroenterologia, AOB, Cagliari, Italy
Introduction: It is well known that CD4, and CD8 T lymphocytes
are critical protagonists of the immunopathogenetic mechanisms
of autoimmune hepatitis (AIH). However, so far, data on the
involvement and role of natural killer (NK) cells are scarce.
Aim: Killer cell immunoglobulin receptors (KIRs) represent the
major family of cell surface receptors that inhibit and activate NK
cells. The elevated expression of NK cells in liver tissue prompted
us to evaluate the impact of NK cells and KIRs on age of onset and
evolution of the disease.
Materials and Methods: We retrospectively analyzed a total
of 114 Sardinian patients diagnosed with type I AIH. Metabolic
and genetic causes of hepatopathy were excluded in all patients.
Patients and controls were typed at high resolution (4 digits) for
the alleles at the HLA-A, -B, -C and DR loci and at 15 KIR gene
loci. Patients were divided into 2 groups according to homozygosity
for KIR haplotype A (KIR genotype AA), heterozygosity or homozy-
gosity for KIR haplotype B (KIR genotype Bx).The immunogenetic
characteristics of the AIH patients were compared with those of
221 healthy individuals from the Sardinian bone marrow donor
registry.
Results: The activating KIR gene KIR2DS1 had a significantly
higher frequency in AIH patients compared to controls [57% vs
43%; HR (95% CI) = 1.7 (1.0-2.7); P = 0.03]. Also the presence of
KIR2DL1 + /KIR2DS1 + /HLA-C2 + was higher in AIH patients [47.3%
vs 35.7%; HR (95% CI) = 1.6 (1.0-2.6); P = 0.04].
Conclusions: Based on our findings, it can be hypothesized that
NK cells are involved in the pathogenetic mechanisms of type I AIH
and more specifically, that the activating KIR gene KIR2DS1 is asso-
ciated with the development of the disorder. The role of KIR2DS1
as a marker for AIH warrants further investigation.
http://dx.doi.org/10.1016/j.dld.2015.01.065
e29
T-23
SLOW ACHIEVEMENT OF HCV-RNA
UNDETECTABILITY IN CIRRHOTIC PATIENTS
TREATED WITH SOFOSBUVIR + RIBAVIRIN:
POSSIBLE CLINICAL IMPLICATIONS IN THE LIVER
TRANSPLANT LIST MANAGEMENT
I. Lenci 1 , V. Cento 2 , M. Rendina 3 , M.F. Donato 4 ,
M. Milana 1 , D. Sforza 5 , M. Manuelli 5 , M. Aragri 2 ,
V.C. Di Maio 2 , A. Abedrabbo 1 , A. Castellaneta 3 ,
F. Malinverno 4 , S. Monico 4 , M.L. Ponti 6 ,
R. Canu 6 , R. Ganga 6 , R. Alfieri 7 , L. Milanesi 7 ,
A. Di Leo 3 , G. Tisone 5 , C.F. Perno 2,8 ,
F. Ceccherini-Silberstein 2 , M. Colombo 4 ,
M. Angelico 1
1 Hepatology Unit, Policlinico Tor Vergata, Tor
Vergata University, Rome
2 Virology Chair, Tor Vergata University, Rome
3 Gastroenterology and Digestive Endoscopy,
University Hospital, Policlinico Bari
4 Gastroenterology and Liver Transplant Units, Cà
Granda Maggiore Hospital Policlinico and University
of Milan, Milan, Italy
5 Liver Transplant Centre, Policlinico Tor Vergata, Tor
Vergata University, Rome
6 Grastroenterology and Hepatology Units, Brotzu
Hospital, Cagliari, Italy
7 Institute for Biomedical Technologies-CNR, Segrate,
(Milano)
8 Virology Unit, Policlinico Tor Vergata, Tor Vergata
University, Rome
Sofosbuvir (SOF) treatment ± ribavirin (RBV) prior to LT has the
potential to change the HCV recurrence after Liver Transplantation
(LT). This approach has been reported to avoid graft reinfection
in compensated patients with hepatocellular carcinoma (HCC),
but only among those who reached and maintained undetectable
HCV-RNA (TND) before LT. Since the time to obtain this result in
decompensated cirrhotics is unknown, we sought to investigate
the early HCV-RNA decay in this setting.
Sixteen decompensated patients (M/F 12/4, median age 55.3,
CPT score ≥ B7), infected by HCV genotype 1a, 1b, 3 and 4 (2-8-
4-2), 4 of whom with HCC, were treated with SOF 400 mg/day
and RBV (200-1000 mg/day), except 2 who received SOF alone, for
a median(IQR) of 12(11-16) weeks awaiting LT. HCV-RNA levels
were measured weekly and safety and clinical parameters were
analyzed.
No serious adverse events were reported. The median(IQR)
RBV dose was 600(400-800). Despite 11/16 patients had low
baseline viremia (<600.000 IU/ml), HCV-RNA decay in the first 4
weeks of treatment was suboptimal (median[IQR] = -3.7[-4.3;-3.3]
LogIU/ml). Only 3/16 (18.7%) patients reached TND HCV-RNA at
week 4 (rapid virological response, RVR), and 5/10 (50%) evalu-
able patients were still viremic at week-12. Median(IQR) MELD
decreased from 15(13-16) at baseline to 13(12-15) at week 4,
when 14/16 (87.5%) patients returned in a compensated stage. One
patient underwent LT after 6 weeks of treatment, while HCV-RNA
was still positive (26 UI/mL). SOF was interrupted only during the