studies

726A AASLD ABSTRACTS HEPATOLOGY, October, 2015
SOF therapy, respectively. Additional virologic response data,
including SVR12 responses, will be reported. CONCLUSIONS:
We found high preliminary EOT and SVR4 rates for patients
with HCV GT 1 treated with LDV/SOF-based therapy of 94 to
100% which are very comparable to the 94 to 100% virologic
responses reported in the published ION study series.
Disclosures:
The following authors have nothing to disclose: Jennifer B. Lai, David J. Witt
1054
Hepatitis C Cure Could Avoid Liver Transplant In Some
Cirrhotic Patients On Dialysis Listed for Simultaneous
Liver Kidney Transplantation
Frank Czul, David Roth, Rodrigo M. Vianna, Cynthia Levy, Paul
Martin, Kalyan R. Bhamidimarri; Hepatology, University of Miami-
Miller School of Medicine, Miami, FL
Background: Simultaneous liver kidney transplant (SLKT) is recommended
in Hepatitis C (HCV) infected dialysis patients with
cirrhosis but isolated kidney transplant (KT) can be considered
in a subset that have early cirrhosis without portal hypertension.
HCV cure could potentially avoid the need for liver transplantation
in some patients listed for SLKT. Aim: To report our new
strategy in SLKT wait-listed patients, whereby liver transplant
(LT) was avoided in those who achieved HCV cure and did not
demonstrate portal hypertension. Methods We describe our
experience of 9 HCV infected patients with cirrhosis and end
stage renal disease (ESRD) on hemodialysis who were initially
listed for SLKT at the Miami Transplant Institute from 2011 to
2014. Of the 9 patients, 6 (67%) were male with a mean age
of 59.8 (+/-5.9) infected with HCV genotype 1 (78% GT1a).
All of them underwent liver biopsy which confirmed the presence
of cirrhosis, 8 (89%) Child A and 1 (11%) Child B, 1
decompensated by small esophageal varices (EV) and 1 by EV
+ ascites. The patients underwent HCV treatment, 2 (22%) with
Pegylated interferon, Ribavirin and Boceprevir and 7 (78%)
with Simeprevir and half dose Sofosbuvir. Results Among them,
8 patients (89%) underwent trans-jugular liver biopsy with portal
pressures measurements and 1 underwent percutaneous
biopsy (see table). Seven (78%) patients achieved SVR12 and
given the absence of portal hypertension, they were delisted
from LT and were considered only for KT. The 2 patients who
did not achieve SVR continued to be listed for SLKT. At the
end of treatment there was a significant decrease on mean
AST and ALT from 32.1 to 18.1 (p=0.047) and 31.6 to 15
(p=0.0099). No other statistically significant differences were
appreciated in the laboratory data. Conclusion HCV treatment
could be offered to dialysis patients after they undergo KT.
However, SLKT wait-listed patients could derive a huge benefit
by pre-transplant HCV cure as LT could be avoided in those
with compensated cirrhosis and devoid of portal hypertension.
Characteristics of SLKT wait-listed patients
Paul Martin - Advisory Committees or Review Panels: BMS; Grant/Research
Support: Merck, Gilead, Janssen, Abbvie
Kalyan R. Bhamidimarri - Advisory Committees or Review Panels: Gilead, Abb-
Vie, Janssen; Grant/Research Support: Bristol Squibb Myers, Biotest, Synageva,
Salix, Vital Therapies, Ocera Inc
The following authors have nothing to disclose: Frank Czul, Rodrigo M. Vianna,
Cynthia Levy
1055
Association of polymorphisms in the hepatitis C virus
NS5B polymerase with reduced virologic response to
sofosbuvir-based treatment
Johannes Vermehren 1 , Simone Susser 1 , Christoph P. Berg 2 , Martin
W. Welker 1 , Bernd Kronenberger 1 , Caterina Berkowski 1 , Stefan
Zeuzem 1 , Christoph Sarrazin 1 ; 1 Medizinische Klinik 1, Klinikum
der J. W. Goethe-Universität, Frankfurt am Main, Germany; 2 Universitätsklinikum
Tübingen, Tübingen, Germany
Background Sofosbuvir (SOF) is a nucleotide inhibitor of the
hepatitis C virus (HCV) RNA polymerase NS5B that has been
approved for the treatment of chronic HCV infection. SOF
binds to the highly conserved active site of NS5B. Therefore,
SOF has shown pangenotypic activity and a high barrier to
resistance in vitro and in vivo. However, the importance of a
number of minor variants within the HCV NS5B polymerase for
treatment outcome of SOF-based therapy without other DAAs
is unknown. Methods All consecutive patients with HCV GT1
infection who received a SOF-based therapy with SOF being
the only DAA were included in the study. Patients received
either SOF in combination with PEG-IFN and ribavirin (RBV)
or SOF in combination with RBV alone. Baseline samples were
tested for the presence of resistance associated variants (RAVs)
at positions L159, S282, C316, V321 und S368 of the NS5B
polymerase by direct sequencing. The presence of these variants
was tested for associations with treatment outcome. Results
In total, 54 patients with HCV GT1 infection (24 with HCV
GT1b) were treated with a SOF-based regimen (SOF+RBV:
n=18; SOF+PEG-IFN+RBV: n=38). In patients with HCV GT1a
and available follow-up data, 23/28 (82%) achieved a sustained
virologic response (SVR) whereas only 14/23 (62%)
patients with GT1b achieved an SVR. The C316N RAV was
detected in 2 GT1a patients, both of whom did not achieve an
SVR (1 relapse, 1 treatment discontinuation due to side effects).
C316N was detected in 12 patients with GT1b, of whom 6
achieved an SVR and 6 did not (all with relapse). In GT1b
patients, SVR rates were significantly higher in patients without
RAVs compared to patients in whom C316N was present
(87.5% vs. 50%; p