studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 751A
patients were excluded. RI was defined as an increase in Cr
≥50% from baseline while on-treatment. Mann-Whitney U,
Kruskal-Wallis, chi-square, and logistic regression were used
for analysis. RESULTS: A total of 456 patients (55±9 years,
61% males, cirrhotic 50%, HIV 3%) were included (G1: 78%,
G2: 13%, G3: 7%, G4&6: 2%). BOC/TPV was used in 224
patients (50%); SOF+PR in 76 (17%); SOF+R in 75 (17%);
SMV/SOF±RBV in 66 (15%); and LDV/SOF in 11 (2%).
Patients on PR-based therapies were less likely cirrhotic (44% vs
60%, p=0.001) and had lower MELD scores when compared
to those on all-oral therapies (4 [2-6] vs 6 [3-9], p=0.0001). In
total, 95% had a baseline eGFR ≥60 mL/min (Cr 0.83±0.16
mg/dL). Among them, RI was noted in 7% of patients (n=15)
on BOC/TPV, 5% of SOF-PR (n=3), and 4% of all-oral regimens
(n=5), (p=0.4). On-treatment CrMax in patients on BOC/
TPV was 1.4 (1.2-2) mg/dL, on SOF-PR 2 (1.2-2), and on alloral
regimens 2 (1.35-3.2) (p=0.04). Although cirrhosis and
MELD were linked to RI on univariate analysis, only ascites
(OR=3.16 [1.14-8.92]) and preexisting proteinuria (OR=5.74
[2.04-16.15]) remained significant in multivariate models. In
all cases, serum Cr returned to baseline after stopping therapy.
SVR12 did not differ between those who did or did not
develop RI (88% vs 86%, p=0.9). CONCLUSIONS: Reversible
RI in SOF-based therapies was seen in 4-5% in this cohort with
a high prevalence of cirrhosis, similar to rates reported with
BOC/TPV-based regimens. RI was more frequent in patients
with advanced liver disease, mainly in the presence of ascites
and in those with preexisting kidney injury. Monitoring of
renal function and standard nephroprotective measures are
suggested when considering SOF-based regimens.
Disclosures:
Raoel Maan - Consulting: AbbVie
Harry L. Janssen - Consulting: AbbVie, Bristol Myers Squibb, GSK, Gilead Sciences,
Innogenetics, Merck, Medtronic, Novartis, Roche, Janssen, Medimmune,
ISIS Pharmaceuticals, Tekmira; Grant/Research Support: AbbVie, Bristol Myers
Squibb, Gilead Sciences, Innogenetics, Merck, Medtronic, Novartis, Roche,
Janssen, Medimmune
Jordan J. Feld - Advisory Committees or Review Panels: Merck, Janssen, Gilead,
AbbVie, Theravance, Bristol Meiers Squibb; Grant/Research Support: AbbVie,
Boehringer Ingelheim, Janssen, Gilead, Merck
Andres Duarte-Rojo - Advisory Committees or Review Panels: Gilead Sciences;
Grant/Research Support: Vital Therapies; Speaking and Teaching: Roche
The following authors have nothing to disclose: Saeed Almarzooqi, Jagpal S.
Klair, Joel G. Karkada, Orlando Cerocchi, Matthew Kowgier, Sherrie M. Harrell,
Kimberly Rhodes
1100
Prospective Study for The Efficacy of Sofosbuvir and
Simeprevir ± Ribavirin in Hepatitis C Genotype 1 and
4 Compensated Cirrhotic Patients. Single Center Study
and Real Life Experience
Zeid Kayali 1,2 , Cory Amador 2 , Andrew Lowe 2 , Besher Ashouri 1,2 ,
Katherine Lam 2 , Warren N. Schmidt 3 ; 1 Inland Empire Liver Foundation,
Rialto, CA; 2 Arrowhead Regional Medical Center, Colton,
CA; 3 University of Iowa Hospital and Clinics, Iowa City, IA
Sofosbuvir (SOF) and simeprevir (SMV) ± ribavirin (RBV)
have been used widely to treat hepatitis C genotype 1 and 4
patients and showed 94% SVR12 in patients with stage 3 and
4 fibrosis (COSMO study). The efficacy of this regimen, however,
has never been validated in a large number of cirrhotic
patients from a community, multiracial setting. The goal of this
study was to investigate the performance of this regimen in a
large, diverse group of difficult to treat cirrhotic patients. Methods:
This was a prospective, open-label single center study.
Enrolled subjects were consecutive patients with cirrhosis, genotype
1 and 4, including both naïve and treatment experienced
patients. Cirrhosis (Stage 4 fibrosis) was diagnosed based on
biopsy and/or Fibrosure test. Decompensated cirrhotics, HIV
co-infected, hepatocellular carcinoma, and active substance
abuse patients were excluded. Duration of treatment was either
24 weeks without RBV or 12 weeks with ribavirin. Primary
end point was SVR12. Secondary end points were safety and
relapse. Results: One hundred eight patients were enrolled.
Mean age 54 year, 63 (58%) were male, 36 (33%) Caucasians,
25 (21%) Black and 50 (46%) Hispanics. mean BMI 33,
86 (79.6%) patients had HCV GT1a, and 7 (7%) had GT4,
mean baseline viral load was 2.2 x 10 6 IU/ml, 59 (54%) were
treatment naive. All patients completed treatment. No Grade 4
adverse events were reported. HCV RNA was undetected in 90
patients (83%) at end of treatment. Eighty-four patients (77%)
achieved SVR12 and 24 patients (23%) relapsed. There was
no change in MELD score or worsening decompensation at end
of treatment. Univariate regression analysis showed that BMI
(33) and Black race were independent factors associated with
relapse (p=0.004,95%CI 1-1.22) and (p=0.025,95%CI 0.03-
0.23) respectively. Duration of treatment, sex, age, baseline
viral load, Geno1 subtypes and MELD score were not independent
factors that predict relapse. Conclusion: In this large
study of difficult to treat compensated cirrhotics patients, SOF
and SMV ± RBV regimen was well tolerated but had lower SVR
12 than previously reported. Surprisingly Black race and BMI
were independent factors for relapse and these variables need
to be considered when deciding the best regimen for difficult
to treat patients.
Disclosures:
Zeid Kayali - Consulting: Abbvie; Grant/Research Support: Merck, Gilead
Warren N. Schmidt - Consulting: gilead
The following authors have nothing to disclose: Cory Amador, Andrew Lowe,
Besher Ashouri, Katherine Lam
1101
Sofosbuvir + Ledispasvir Combination Therapy for
Recurrent Hepatitis C in Liver Transplant Recipients: A
Real-Life Multicenter Experience
Ryan M. Kwok 1 , Suzanne Robertazzi 1 , Helen S. Te 2 , Joshua Wiegel
3 , Joseph Ahn 3 , Janet Gripshover 4 , Darryn R. Potosky 4 , Amber
Tierney 5 , Mohamed A. Hassan 5 , Rohit Satoskar 1 , Coleman I.
Smith 1 ; 1 Transplant Institute, Medstar Georgetown University Hospital,
Washington, DC; 2 Medicine, University of Chicago, Chicago,
IL; 3 Oregon Health and Science University, Portland, OR;
4 Division of Gastroenterology and Hepatology, University of Maryland
School of Medicine, Baltimore, MD; 5 Gastroenterology Division,
University of Minnesota Medical School, Minneapolis, MN
Background Recurrent hepatitis C (HCV) after liver transplant
(LT) is associated with significant morbidity and mortality.
Second generation direct acting antiviral medications such as
sofosbuvir / ledipasvir (SOF/LDV) have a high rate of sustained
virologic response in treating non-cirrhotic and pretransplant
HCV. Data on the efficacy and safety of SOF/LDV in the post-LT
patient are limited. Aim: To evaluate the safety and efficacy of
the SOF/LDV therapy in patients with HCV recurrence after LT.
Methods All post-LT patients with recurrent HCV . previously or
currently being treated with SOF/LDV with or without ribavirin
for 12-24 weeks were identified at five centers. Sustained
virologic response at 12 weeks (SVR12) after treatment was
determined. On-treatment response, graft function, changes in
immunosuppression, adverse events (AE), and survival were
recorded. Results 128 patients were included: 76% male,
65% Caucasian with a mean age of 60.9 ±6.8 years. 70% of
patients were genotype (GT) 1a, 23% GT 1b, 1 patient was
a GT 2, 2 patients were GT 4, 1 patient had both GT 1a/4.
10% had kidney transplant, 52% had failed prior therapy, and