studies

750A AASLD ABSTRACTS HEPATOLOGY, October, 2015
ASV; 75.0% (398/531) achieved rapid virologic response
(RVR) and 97.0% (450/482) became undetectable until 8
week. There was no significant differences of RVR among
IL28B genotypes. 76.9% (380/494) with wild-type NS5A-Y93
achieved RVR, whereas only 54.2% (13/24) with Y93H substitution
achieved RVR. In 93Y group, there were 22 viral breakthrough
and 3 relapsers, Among these patients with treatment
failure, 40.0% (10/25) had SMV treatment history. On the
other hand, among patients with Y93H at baseline, 5 patients
(20.1%) had virologic failure and 1 patient experienced
relapse, resulting in emergence of NS5A-Y93 and NS3-D168
variants. Finally, SVR (sustained virologic response) 4 was
89.6% in Y93, whereas 45.5% in Y93H, suggesting that RVR
and SVR were higher in 93Y than 93H group. Interestingly,
multiple RAVs such as L31M/Q54H/Y93H in NS5A were
emerged by treatment failure. The number of RAVs were 0/ 1/
2/ 3=57/ 36/ 7/ 0 (%) at baseline, and 0/ 14/ 57/ 29 (%)
at the time of virologic failure; patients with multiple RAVs in
NS5A region increased from 7% to 86%. [Conclusion] History
of SMV therapy and pre-existing NS5A-Y93H substitution were
associated with breakthrough during DCV/ASV therapy, resulting
in emergence of multiple RAVs. As the multi-RAVs influence
SVR rate by DAAs therapy including NS5A inhibitors, patients
with RAVs at baseline will be required assessment for optimizing
future DAAs therapies.
Disclosures:
Yasuhito Tanaka - Grant/Research Support: Chugai Pharmaceutical CO., LTD.,
MSD, Bristol-Myers Squibb; Speaking and Teaching: janssen pharma, Bristol-Myers
Squibb
The following authors have nothing to disclose: Etsuko Iio, Noritomo Shimada,
Hiroshi Abe, Masanori Atsukawa, Kai Yoshiza, Koichi Takaguchi, Yuichiro Eguchi,
Hideyuki Nomura, Tomoyuki Kuramitsu, Jong-Hon Kang, Takeshi Matsui,
Noboru Hirashima, Atsunori Kusakabe
1098
Ribavirin levels at treatment weeks (TW) 4-6 can predict
sustained viriological response (SVR12) in HCV cirrhotic
patients treated with all oral direct–acting antiviral therapy
(DAAs).
Suman Verma 1 , Ivana Carey 1 , Kate E. Childs 1 , Andrew Ayers 1 ,
Phillip Morgan 1 , Aisling B. Considine 1 , Kath Oakes 1 , Michael
A. Heneghan 1 , Graham R. Foster 2 , Kosh Agarwal 1 ; 1 Institute of
liver studies, Kings College Hospital, London, United Kingdom;
2 The Blizard Institute, Queen Marys University of London, London,
United Kingdom
Background Ribavirin remains an important adjunct to DAAs
in end-stage cirrhotic patients (Child–Pugh(CP) B7 and above).
However ribavirin associated side-effects can be challenging
to manage in this population (CUPIC). Hence this study aimed
to investigate whether plasma ribavirin level monitoring in
this advanced liver disease population can optimise SVR12.
Method 46 patients, with CP B7-C10 cirrhosis, receiving ribavirin,
Sofosbuvir and either Ledipasvir or Daclatasvir had
serial trough plasma ribavirin measurements at TW2, 4, 6 and
8 using a validated liquid chromatography assay. At TW0,
a median of 1000mg/day (range 1000mg/day-1200mg/
day) ribavirin was administered to all patients. Despite high
inter-patient variability in ribavirin levels with the same dose,
there was low intra-patient variation with steady-state achieved
between TW4-TW6 and the median dose remained 1000mg/
day. Hence levels at this timepoint were compared between
those acheiving SVR12 vs. relapsing post treatment. All statistical
analysis was performed using SPSS. Results 37 patients
had SVR12 and 9 relapsed, but no significant difference in CP,
UKELD, MELD, prescribed ribavirin dose (median 1000mg/
day) or ribavirin dose/kg at TW0 and TW4-6 was identified
(Table 1). 25 patients with SVR12 and 2 relapsers had ribavirin
dose reduction during 12 weeks of therapy but none
required erythropoetin or blood transfusion support. Age, CP,
UKELD, MELD, and genotype showed no significant correlation
with SVR12 or relapse. However, the median plamsa ribavirin
level was higher in the SVR12 cohort vs. relapsers (2.4mg/L
and 1.4mg/L respectively (p=0.003) and levels ≥1.7mg/L at
TW4-TW6 correlated with SVR12 achievement (PPV 89.19%;
NPV 77.18%)(p=0.001 Fisher’s exact test). Ribavirin dose
reduction thereafter did not influence SVR12 development.
Conclusion Ribavirin levels at 4-6 weeks of a 12 week DAA
regimen are predictive of SVR12 in this advanced liver disease
cohort. Ribavirin plasma measurements can be a useful adjunct
in delivering optimal SVR12 and tolerability in this advanced
challenging population.
SVR12 and relapser cohort demographics (median and ranges
shown)
Disclosures:
Ivana Carey - Grant/Research Support: Gilead, Roche; Speaking and Teaching:
BMS
Graham R. Foster - Advisory Committees or Review Panels: GlaxoSmithKline,
Novartis, Boehringer Ingelheim, Tibotec, Chughai, Gilead, Janssen, Idenix,
GlaxoSmithKline, Novartis, Roche, Tibotec, Chughai, Gilead, Merck, Janssen,
Idenix, BMS; Board Membership: Boehringer Ingelheim; Grant/Research Support:
Chughai, Roche, Chughai; Speaking and Teaching: Roche, Gilead, Tibotec,
Merck, BMS, Boehringer Ingelheim, Gilead, Janssen
Kosh Agarwal - Advisory Committees or Review Panels: Gilead, Novartis,
Abbott; Grant/Research Support: Roche, MSD; Speaking and Teaching: BMS,
Astellas, Janssen
The following authors have nothing to disclose: Suman Verma, Kate E. Childs,
Andrew Ayers, Phillip Morgan, Aisling B. Considine, Kath Oakes, Michael A.
Heneghan
1099
Frequency of Renal Impairment in Patients With Hepatitis
C Infection Treated With Sofosbuvir-based Antiviral
Regimens
Saeed Almarzooqi 1 , Jagpal S. Klair 2 , Joel G. Karkada 1 , Raoel
Maan 1 , Orlando Cerocchi 1 , Matthew Kowgier 1 , Sherrie M. Harrell
2 , Kimberly Rhodes 2 , Harry L. Janssen 1 , Jordan J. Feld 1 , Andres
Duarte-Rojo 2 ; 1 Toronto Center for Liver Disease, Toronto, ON, Canada;
2 University of Arkansas for Medical Sciences, Little Rock, AR
BACKGROUND: Renal impairment (RI) was a relevant adverse
event noted in 5-7% of hepatitis C patients treated with the
protease inhibitors boceprevir/telaprevir (BOC/TPV), although
it was infrequent with peginterferon/ribavirin (PR). RI has been
very rarely reported in trials with newer direct-acting antivirals
such as simeprevir (SMV) and sofosbuvir (SOF). However, SOF
is renally cleared and it might cause RI in patients with pre-existing
kidney disease. We aimed to examine the rate of RI in
patients treated with SOF-based therapies, and to compare it
to that of BOC/TPV. METHODS: Patients treated with any SOFbased
or BOC/TPV-based therapies at two university-based
referral centers were included. Demography, presence of cirrhosis,
ascites, original MELD score, SVR12, comorbidities,
use of nephrotoxic drugs and on-treatment changes in creatinine
(Cr) were obtained from medical records. Posttransplant