studies

776A AASLD ABSTRACTS HEPATOLOGY, October, 2015
1148
Preliminary Experience Of Direct Acting Antiviral Therapy
In Hepatitis C Infected Kidney Transplant Recipients,
Who Received Grafts From Hepatitis C Positive Or Negative
Donors
Kalyan R. Bhamidimarri, David Roth, Giselle Guerra, Cynthia Levy,
Paul Martin; University of Miami-Miller School of Medicine, Miami,
FL
Background: Highly effective direct acting antiviral therapy
(DAA) is now feasible post kidney transplantation (KT) and has
also facilitated a new strategy of abbreviating time in waitlisted
patients who could accept Hepatitis C (HCV) positive
grafts. However there are no reports of treatment experience
in this group to date. Aim: We describe our preliminary experience
of HCV treatment with DAA’s in post KT patients, a
majority of whom received a graft from HCV+ donor. Methods:
Fourteen patients with chronic HCV, genotype 1, 71% males,
57% African Americans, mean age of 54 years underwent
deceased donor kidney transplantation (71% HCV+ graft).
Baseline features include 86% with genotype 1a, 50% with
fibrosis level greater than F2, mean HCV viral load of 3.4
Million IU, mean hemoglobin of 12gm/ dL and mean GFR of
60mL/ minute. Open label treatment with Sofosbuvir / Ledipasvir
was initiated in 13 patients and one patient received
Sofosbuvir plus Simeprevir. Only 65% of the patients had ribavirin
approved in their regimen and the dosage was titrated
according to their tolerance. Treatment was initiated within
a mean period of 5months since the KT (range 1-10months)
and immunosuppression was closely monitored. Results: None
of the patients developed fibrosing cholestatic hepatitis post
KT, despite receiving a graft from HCV+ donor. All patients
are at various stages of completion of their respective treatment
duration. Five patients reached end of treatment (EOT), 2
patients reached post-treatment week 4 and 1patient reached
post treatment week 12. According to per protocol analysis,
the EOT, SVR4 and SVR12 rates are 100%. Anemia was frequent
in the patients taking ribavirin which warranted frequent
dose titrations. Conclusions: Our preliminary experience shows
an evolving successful strategy of transplanting kidneys from
HCV+ donor in HCV infected recipients and the feasibility of
HCV treatment with newer DAA’s. As per protocol analysis,
all the patients had excellent virologic response and full data
awaited by AASLD Liver Meeting.
HCV Treatment in KT recipients
Disclosures:
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
David Roth - Advisory Committees or Review Panels: Merck, Sharp and Dome;
Consulting: Merck, Sharp and Dome
Paul Martin - Advisory Committees or Review Panels: BMS; Grant/Research
Support: Merck, Gilead, Janssen, Abbvie
The following authors have nothing to disclose: Giselle Guerra, Cynthia Levy
1149
IFNL4 ss469415590 Polymorphism Contributes to Treatment
Decisions in Patients with Chronic Hepatitis C virus
Genotype 1b but not 2a Infection
Ruihong Wu 1 , Xiumei Chi 1 , Haibo Sun 1 , Juan Lv 1 , Xiaomei
Wang 1 , Xiuzhu Gao 1 , Ge Yu 1 , Fei Kong 1 , Peng Zhang 2 , Mo-li
Wang 3 , Dongsheng Wang 4 , Tao Jiang 4 , Hongqin Xu 1 , Rui Hua 1 ,
Gerald Y. Minuk 5 , Jing Jiang 6 , Bing Sun 7 , Jin Zhong 7 , Yu Pan 1 ,
Junqi Niu 1 ; 1 Department of Hepatology, First hospital of JiLin University,
ChangChun, China; 2 Department of Infectious Diseases,
First hospital of Jilin University, Changchun, China; 3 Department of
Infectious Diseases, Fourth Hospital of Jilin University, Changchun,
China; 4 Hospital of HepatologyBiliary of Jilin Province, Changchun,
China; 5 Section of Hepatology, University of Manitoba, Winnipeg,
MB, Canada; 6 Department of Clinical Epidemiology, First
Hospital of Jilin University, Changchun, China; 7 Institute Pasteur
of Shanghai, Shanghai Institutes for Biological Sciences, Chinese
Academy of Sciences, Shanghai, China
Background & Aim: Recently, the dinucleotide variant
ss469415590(TT/ΔG) in the novel gene IFNL4 was identified
as a stronger predictor of hepatitis c virus (HCV) clearance in
individuals of African ancestry compared with rs12979860.
The aim of this study was to determine whether this variant
contributes to treatment decisions in a Chinese population,
predominantly infected with HCV genotype (GT) 1b and 2a.
Methods: Four hundred and forty seven chronic hepatitis c
(CHC) patients (including 328 interferon alpha-2b and ribavirin
treated), 129 individuals who had undergone spontaneous
HCV clearance (SHC) and 169 healthy controls were
retrospectively investigated. ss469415590 genotyping was
performed using a Mass spectra method (SEQUENOM).
Results: A higher proportion of SHC individuals carried TT/TT
genotype compared to CHC patients (95.3% vs. 88.8%, P =
0.027). ss469415590 variant was independently associated
with sustained virological response (SVR, OR = 3.247, 95%
CI = 1.038-10.159, P = 0.043) and on-treatment virological
responses including rapid virological response, complete early
virological response, early virological response and end of
treatment virological response with a minimal OR of 3.73.
Patients with high viral load (≥4×10 5 IU/mL) and the ΔG allele
had a higher risk of failing to achieve SVR compared to TT/
TT genotype (92.9% vs. 64%, P = 0.034). In GT-2a patients,
no significant association of ss154949590 variant with virological
response was identified. In addition, we found that
ss154949590 was in complete linkage disequilibrium with
rs12979860. Conclusions: IFNL4 ss154949590 TT/TT genotype
favours spontaneous clearance of HCV, and treatment
induced clearance in genotype 1b but not 2a infected patients.
IFNL4 ss469415590 (or rs12979860) genotyping should
be considered for patients with genotype 1b and high viral
load when making a choice between standard dual therapy
and IFN-free direct-acting antiviral regimen. If with the ΔG for
ss469415590 (or T for rs12979860), IFN-free DAA regimens
may be better options.
Disclosures:
The following authors have nothing to disclose: Ruihong Wu, Xiumei Chi, Haibo
Sun, Juan Lv, Xiaomei Wang, Xiuzhu Gao, Ge Yu, Fei Kong, Peng Zhang, Mo-li
Wang, Dongsheng Wang, Tao Jiang, Hongqin Xu, Rui Hua, Gerald Y. Minuk,
Jing Jiang, Bing Sun, Jin Zhong, Yu Pan, Junqi Niu