studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 753A
1104
Real Life Experience of Direct Acting Anti-Viral Therapy
for Hepatitis C infection in North East of Scotland
Pauline Dundas, Shirley English, Lorna Bailey, Ashis Mukhopadhya,
Balasubramaniam Vijayan, Andrew Fraser, Lindsay
McLeman; Gastroenterology, Aberdeen Royal Infirmary, Aberdeen,
United Kingdom
There have been several clinical trials reported for new direct
acting antiviral (DAA) drugs for hepatitis C (HCV) infection,
but very few reports on ‘real life data’. We report our single
centre experience of 140 patients initiated on the current generation
of DAA agents in the North East of Scotland between
October 2014 and May 2015. The choice and duration of
regimen was decided according to local guidelines taking into
consideration genotype, stage of disease, viral load, HIV coinfection,
drug interaction, previous treatment and drug licences.
Regimens included Simeprevir, Sofosbuvir, Daclatasvir and
Sofosbuvir/Ledipasvir combinations. Sustained viral response
(SVR) 4 week data will be available by September 2015 and
12 week by November 2015. The regimens and patient characteristics
are described in table 1. We report on 142 patient
episodes of which 116 (82%) were initiated on an IFN free
regimen. The mean age was 47 years (SD 10.9, range 20-79)
and 109 (77%) were male. Eight (6%) patients were co-infected
with HIV and 3 (2%) had an Orthotopic Liver Transplant
(OLT). Prior to initiation of therapy; mean MELD score was 9
(SD 4.96, range 6-29) and 53 (37%) had a Fibroscan score of
> 12.5 kpa. The majority (91,64%,) had genotype 1 infection
and 75 (53%) were treatment naïve. Patients who had failed
first generation protease inhibitors were included. Opiate substitution
therapy was prescribed in 42 (30%) patients. To date
101/109 (93%) planned patient episodes are complete and
33 remain on treatment. Of the 8 patient episodes where treatment
was incomplete, 2 patients receiving peg/simeprevir/
ribavirin switched to sofosbuvir/ledipasvir due to intolerable
IFN related side effects however completed the all oral regimen,
2 receiving daclatasvir/sofosbuvir died from end stage
liver disease and 2 developed non resectable/transplantable.
Treatment was incomplete in 2 patients who received sofosbuvir/ledipasvir
+ ribavirin, one due to suicidal ideation after 1
week, the other developed renal failure after 3 weeks. The new
treatment regimens are well tolerated; to date 93% of patients
have completed their planned course; the majority who failed
to complete had advanced liver disease. No-one has been lost
to follow up. We would hope that SVR rates will be comparable
to those reported in clinical trials.
TABLE 1
Disclosures:
The following authors have nothing to disclose: Pauline Dundas, Shirley English,
Lorna Bailey, Ashis Mukhopadhya, Balasubramaniam Vijayan, Andrew Fraser,
Lindsay McLeman
1105
Asian Patients with Genotype 1 HCV Infection Achieve
99% Sustained Virologic Response with 12 Weeks of
Ledipasvir/Sofosbuvir Single Tablet Regimen: Integrated
analysis of Phase 3 Multicenter Studies
Masashi Mizokami 2 , Wan-Long Chuang 3 , Kwang-Hyub Han 4 ,
Young-Suk Lim 5 , Jenny C. Yang 1 , Shampa De-Oertel 1 , Bing
Gao 1 , Hongmei Mo 1 , Phillip S. Pang 1 , Steven J. Knox 1 , John G.
McHutchison 1 , Masao Omata 6 , Jia-Horng Kao 7 ; 1 Gilead Sciences,
Foster City, CA; 2 National Center for Global Health and Medicine,
Tokyo, Japan; 3 Kaohsiung Medical University, Kaohsiung, Taiwan;
4 Yonsei University College of Medicine, Seoul, Korea (the Republic
of); 5 University of Ulsan College of Medicine, Asan Medical Center,
Seoul, Korea (the Republic of); 6 Yamanashi Prefectural Hospital
Organization, Yamanashi, Japan; 7 National Taiwan University
College of Medicine, Taipei, Taiwan
Introduction: Similar to the United States and Europe, the majority
of patients with chronic HCV infection in Japan, Korea, and
Taiwan are infected with HCV genotype (GT) 1. However,
important differences in viral and host characteristics exist
between the infected populations in these regions, including
age, BMI, IL28B genotype and HCV GT1 subtype. The aim of
this integrated analysis is to evaluate the efficacy and safety
of LDV/SOF in a large cohort of Asian patients with chronic
GT1 HCV infection. Methods: This analysis combines data
from subjects enrolled in two Phase 3 trials: GS-US-337-0113
(Japan) and GS-US-337-0131 (Korea and Taiwan) evaluating
12 weeks of LDV/SOF (90mg/400mg) in treatment-naïve and
treatment-experienced adults with chronic GT1 HCV infection.
Eligibility criteria: no upper age limit restriction, inclusion of
subjects with compensated cirrhosis, platelet count ≥50,000/
mL and no restriction on neutrophil values. HCV NS5A and
NS5B resistance associated variants (RAV) were evaluated by
deep sequencing (cutoff of 1%). The primary efficacy endpoint
was SVR12. Results: Overall, 349 subjects were enrolled in
Korea, Taiwan, and Japan, 67 (19%) had cirrhosis. The majority
were female (58%), treatment-experienced (51%), GT1b
infected (94%), and IL28B CC (62%). The mean age (range)
was 57 (18-80) years old, BMI 24 (17-38) kg/m 2 , and HCV
RNA was 6.6 (3.7-7.6) log 10
IU/mL. HCV NS5A RAVs were
detected in 23% (80/343) of subjects at baseline. The overall
SVR12 rate was 99% (346/349); 2 subjects relapsed and 1
subject prematurely discontinued treatment. All treatment-experienced
subjects with cirrhosis (45/45) achieved SVR12.
NS5A RAVs were detected at the time of relapse but no NS5B
RAVs were detected. Serious AE and treatment discontinuations
were rare (