46
1 This enduring activity is supported by educational grants from AbbVie, Bristol-Myers Squibb, and Gilead Sciences, Inc.
1
This enduring activity is supported by educational grants from
AbbVie, Bristol-Myers Squibb, and Gilead Sciences, Inc.
2
Abstract GS01
C. Fernández-Carrillo1, S. Lens2, E. Llop1, J.M. Pascasio3, I. Fernández4, C. Baliellas5, J. Crespo6, M. Buti7, L. Castells7,
M. Romero-Gómez8, C. Pons9, J.M. Moreno10, A. Albillos11, C. Fernández-Rodríguez12, M. Prieto13, M. Fernández-Bermejo14,
J. García-Samaniego15, J.A. Carrión16, M. de laMata17, E. Badia18, J. Salmerón19, J.I. Herreros20, M. Salcedo21,
J.J. Moreno22, J. Turnes23, R. Granados24, M. Blé25, J.L. Calleja1, The Hepa-C Registry
E-mail: [email protected]
1. Digestive, Liver, Hospital Universitario Puerta de Hierro-Majadahonda,
IDIPHIM, Majadahonda, Madrid
2. Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, Barcelona
3. Digestive diseases, Hospital Universitario Virgen del Rocío, IBIS,
CIBERehd, Sevilla
4. Digestive, Hospital Universitario 12 de Octubre, Madrid
5. Digestive, Hospital Universitari de Bellvitge, L’Hospitalet de
Llobregat, Barcelona
6. Digestive, Hospital Universitario Marqués de Valdecilla, Santander;
7. Internal Medicine-Hepatology, Hospital Universitario Vall
d´Hebron, Barcelona 8. Digestive diseases, Hospital Universitario Virgen de Valme, CIBERehd,
Sevilla; Digestive, HospitalGeneral Universitario de Castellón, Castellón
de la Plana
9. Digestive, C.H.U de Albacete, Albacete
10. Digestive, Hospital Universitario Ramón y Cajal, IRYCIS, CIBERehd,
Madrid
11. Digestive, Hospital Universitario Fundación Alcorcón, Alcorcón, Madrid
12. Digestive Medicine, Hospital Universitario de La Fe, CIBERehd,
Valencia
13. Digestive, Hospital San Pedro de Alcántara, Cáceres
14. Infectious Diseases, Hospital Carlos III, CIBERehd, Madrid
15. Digestology, Hospital del Mar, IMIM, Barcelona
16. Digestive, Hospital Universitario Reina Sofía, IMIBIC, CIBERehd,
Córdoba
17. Digestive, Hepatology, Hospital Universitario de Burgos, Burgos
18. Digestive, Hospital Universitario San Cecilio, CIBERehd, Granada
19. Liver Unit, Clínica Universitaria de Navarra, IdiSNA, CIBERehd,
Pamplona
20. Liver Unit, Hospital General Universitario Gregorio Marañón. IiSGM,
Madrid
21. Internal Medicine, Hospital General de Segovia, Segovia
22. Digestive, Complejo Hospitalario de Pontevedra, Pontevedra
23. Internal Medicine, H. U. de Gran Canaria Dr. Negrín, Las Palmas de
Gran Canaria
24. Digestive, Servidigest Centre, Barcelona, Spain
5
• The study included 393/564 (70%) patients with
compensated cirrhosis (Child-Pugh A) and 171/564
(30%) patients with Child-Pugh (CPT) B/C.
• Treatment regimens (all +/- RBV):
– SMV + SOF: 292/564 (52%)
– SOF + DCV: 133/564 (24%)
– SOF/LDV: 70/564 (12%)
– OBV/PTV/r +/- DSV: 28/564 (5%)
– SMV + DCV: 12/564 (2%)
– SOF + RBV: 28/564 (5%)
6
• Overall (n=564)
– SVR: 88%
– Relapse: 10%
– Grade 3/4 AEs: 27%
• Child A (n=393)
– SVR: 95%
– Grade 3/4 AEs: 12%
– Deaths: 6
• Child B/C (n=171)
– SVR: 81%
– Grade 3/4 AEs: 61%
– Deaths: 12
7
• Baseline MELD >17 independently identified a group of
patients with 39% deaths vs. 1.5% (p
8
Abstract PS097
M.C.M. Cheung1, G.R. Foster1,W.L. Irving2, A.J.Walker3, B.E. Hudson4, S. Verma5, J. McLauchlan6,
D.J. Mutimer7, A. Brown8, W. Gelson9, D. MacDonald10, K. Agarwal5 and HCV Research UK
E-mail: [email protected]
1. Blizard Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London
2. NIHR Nottingham Digestive Diseases Biomedical Research Unit
3. Faculty of Medicine & Health Sciences, University of Nottingham, Nottingham
4. Hepatology Department, University Hospitals Bristol NHS Trust, Bristol
5. Institute of Liver Studies, King’s College London, London
6. MRC-Unviersity of Glasgow Centre for Virus Research, University of Glasgow, Glasgow
7. Centre for Liver Research, Queen Elizabeth Hospital, Birmingham
8. Department of Hepatology, St Mary’s Hospital, Imperial College London, London
9. Department of Hepatology, Cambridge University Hospitals NHS Foundation Trust, Cambridge
10. UCL Institute of Liver and Digestive Health, Royal Free London NHS Foundation, London, United Kingdom
10
HCV Research UK Database
EAP treated
(1 April 14 - 11
Nov 14)
N = 467
Untreated - enrolled with
decompensated cirrhosis 6
months before EAP start
N = 261
Decompensated
cirrhosis
N = 409
Extra-
hepatic
disease
N = 14
Baseline
liver
transplant
N = 44
SVR12 achieved
N = 329
Subsequently
treated on EAP
after 1 April 14
N = 177 SVR12:
Overall: 88%
GT1: 90%
GT3: 69%
11
0
20
40
60
80
100
G1 G3 others
SV
R1
2 %
(IT
T)
SOF/DCV
SOF/DCV/RBV
SOF/LDV
SOF/LDV/RBV
N= 4 34 13 129 5 105 5 57 3 11
23
12
Characteristics Treated decompensated
(N=409)
Untreated decompensated
(N=261)
Age, median, years 54 54
Prior HCV therapy, % 60 62
Genotype 1/ 3 HCV, % 49/ 42 49/ 35
Viral load, median, iu/mL 255,280 208,688
Bilirubin, median,
µmol/L
28 26
Albumin, median, g/L 31 32
Platelet, median, x109/L 72 70
MELD, median 12 11
Child Pugh B (%) 73
Child Pugh C (%) 10
Foster GR, Irving WL et al. J Hepatol 2016 Jan 29
13
* p< 0.05
0
10
20
30
40
% o
f p
ati
en
ts
month 0-6
month 6- 15
* *
*
14
Survival over time
0 3 6 9 12 1550
60
70
80
90
100
Treated with SVR
Treated without SVR
Untreated
Time in months
% s
urv
ival
15
0
20
40
60
80
100
MELD /=
15
CPA CPB CPC
% o
f p
ati
en
ts
Baseline liver disease
Adverse event free survival at 15
months
*
N= 71 58 61 235 30
* NS
* p< 0.05
16
0 - 6 months 0 - 15 months
(n=297) (n=77)
-20
-10
0
10
20
Ch
an
ge
in
ME
LD
sco
re
Patients without SVR, transplanted or died were excluded
Mean score change -0.86 Mean score change +0.44
p< 0.05
-20
-10
0
10
20
Ch
an
ge
in
ME
LD
sco
re
17
• Antiviral therapy in patients with CP-B cirrhosis
leads to prolonged improvement in the majority
• Only a minority of patients with CP-C cirrhosis
derive long term benefit
• Early improvement does not necessarily translate
into long term benefit
18
Abstract LBP500
A.M. Aghemo1, G. Cologni2, F. Maggiolo2, L. Pasulo2, G. Rizzardini3, C. Magni3, T. Quirino4,
L. Minoli5, G. Filice5, M. Zuin6, A. Colli7, M. Rumi8, M. Puoti9, S. Fagiuoli2, M. Colombo1 and
Lombardia Regional Network for Viral Hepatitis Working Group
E-mail: [email protected]
1. Fondazione IRCCS Ca” Granda – Ospedale Maggiore, Milano, Milano
2. A.O. Papa Giovanni Xxiii-Bergamo, Bergamo
3. A.O. “Luigi Sacco” – Milano, Milano
4. A.O. Ospedale Di Circolo – Busto Arsizio, Busto Arsizio
5. Fondazione IRCCS Policlinico S. Matteo – Pavia, Pavia
6. A.O. “San Paolo” – Milano, Milano
7. A.O. Della Provincia Di Lecco, Lecco
8. Ospedale S. Giuseppe – Milano
9. A.O. “Osp.Niguarda Ca’Granda”-Milano, Milano, Italy
19
• Large real life data of chronic Hepatitis C (HCV)
treatment are needed to assess the safety and
efficacy of directly acting antivirals (DAAs) and to
confirm results of Phase III trials.
• For this aim in May 2015 26 liver centers in the
Lombardia Region in Northern Italy created the
Regional Network for Viral Hepatitis.
20
• Patients received the following regimens, dose and
duration were dictated by EMA label: Genotype 1 patients
received either a Sofosbuvir based regimen (SOF + Riba,
SOF + Sim ± Riba, SOF + Dac ± Riba or SOF/LDV ±
Riba) or Ritonavir boosted
Paritaprevir/Ombitasvir/Dasabuvir ± Riba.
• Genotype 2 received SOF + RBV, Genotype 3 SOF +
RBV, SOF + Dac ± Riba or PR + SOF.
• Genotype 4 received either a Sofosbuvir based regimen
or Ritonavir boosted Paritaprevir/Ombitasvir/ + Riba.
• Sustained virological response was assessed at week
12 following treatment discontinuation.
21
• Overall from December 2014 to December 2015,
• N=2,432 patients received treatment.
• 81.8% of them had advanced fibrosis (14.8%) or
compensated cirrhosis (67%), decompensated cirrhosis
was present in (8%).
• HCV-1 and HCV-3 were the most prevalent genotypes
being found in 1,534 (63%) and 419 patients (17%),
respectively.
• 26 SAEs (1%) were recorded during treatment or follow-up,
15 in cirrhotics and 11 on the liver transplant (LT) waiting list
or in the post-LT period. 6 of 26 SAEs (0.2%) were deemed
related to therapy.
22
• 2 patients died during treatment (0.08%), both patients
had decompensated cirrhosis (MELD score 16 and 13).
• Death was liver related in 1, and was not attributed to
therapy in both patients.
• At the time of analysis 1,534 patients have completed
the treatment phase and 872 have been evaluated for
SVR.
• By ITT analysis overall 90.4% (788/872) patients
achieved an SVR.
• SVR rates were 92.9% in HCV-1 (498/536), 89.3% in
HCV-2 (101/113), 81.1% in HCV-3 (116/143) and
88.9% in HCV-4 (71/80).
23
Abstract LBP510
J. McCombs1, J. McGinnis1,2, S. Fox1,3, I. Tonnu-Mihara2
E-mail: [email protected]
1. Schaeffer Center for Health Policy & Economics, University of Southern California, Los Angeles
2. Veterans Health Administration, United States Department of Veterans Affairs, Long Beach
3. Keck School of Medicine, University of Southern California, Los Angeles, United States
24
• Evaluation of the effectiveness of simeprevir/sofosbuvir,
ledipasvir/sofosbuvir, and ombitasvir/paritaprevir/
ritonavir/dasabuvir within the US Veterans Health
Administration.
• Effectiveness rates were estimated across all three
treatments, and multivariate logistic analysis was employed
to explore the impact of treatment type, controlling for
patient and disease characteristics.
25
• The unadjusted rates of effectiveness were
– 87.3% for simeprevir/sofosbuvir (n=3,068)
– 93.2% for ledipasvir/sofosbuvir (n=5,524)
– 93.4% for ombitasvir/paritaprevir/ritonavir/dasabuvir (n=1,012)
• Simeprevir/sofosbuvir yielded lower effectiveness rates than the
other two study treatments (OR = 0.64 [0.49–0.85]).
• Patients with compensated and decompensated cirrhosis or HCC at
the start of treatment were less likely to achieve SVR.
• Blacks and males were less likely to achieve SVR, while co-infection
with HIV, hepatitis B, diabetes and obesity had no impact on
treatment effectiveness.
• There was some limited evidence that patients younger than 60
years of age were less likely to respond.
26
Abstract PS004
E. Zuckerman1, E. Ashkenasi1, Y. Kovalev1, E. Weitsman2, R.T. Kaspa3, M. Brown3, M. Cohen3,
T. Saadi4, Y. Baruch4, M. Carlebach5, R. Hazzan6, R. Safadi7, T. Goldberg7, R. Oren7, Y. Ashur8,
M. Carmiel9, Y. Kitay10, R. Hadari10, S.A. Mouch11, Y. Menachem12, H. Kathcman12, R. Bruk12,
O. Shibolet12
E-mail: [email protected]
1. Liver Unit, Carmel Medical Center, Haifa
2. Sheba Medical Center, Ramat Gan
3. Liver Institute, Rabin Medical Center, Petach Tikva
4. Liver Unit, Rambam Medical Center
5. Liver Unit, Bnai Zion Medical Center, Haifa
6. Liver Unit, Haemek Medical Center, Afula
7. Liver Unit, Hadassah Medical Center
8. Liver Clinic, CHS, Jerusalem
9. Liver Unit, Western Galilee Medical Center, Naharya
10. Liver Unit, Meir Medical Center, Kfar Saba
11. Liver Unit, Hillel Yaffe Medical Center, Hadera
12. Liver Unit, Tel Aviv Medical Center, Tel Aviv, Israel
27
• The paritaprevir/ritonavir/ombitasvir, dasabuvir with or without
ribavirin (3D ± R) regimen is approved in USA
and Europe for chronic hepatitis C (CHC) patients with
GT 1 and 4.
• Approved in January 2015 in Israel for GT1, CHC patients with
advanced fibrosis only (F3 and F4).
28
29
30
31
• 8 patients developed hepatic decompensation
32
Abstract PS007
S. Susser1, J. Dietz1, J. Vermehren1, K.-H. Peiffer1, S. Passmann1, D. Perner1, C. Berkowski1,
P. Ferenci2, M. Buti3, B. Müllhaupt4, B. Hunyadi5, H. Hinrichsen6, S. Mauss7, J. Petersen8,
P. Buggisch8, A. Schober9, G. Felten10, D. Hüppe10, A. Zipf11, G. Knecht12, T. Lutz12, T. Berg13,
S. Zeuzem1, C. Sarrazin1
E-mail: [email protected]
1. Medizinische Klinik1, Goethe-University Hospital,
Frankfurt, Germany
2. Department of Internal Medicine III, Medical University of
Vienna, Vienna, Austria
3. Hospital Universitario Valle Hebron and Ciberehd,
Barcelona, Spain
4. Swiss Hepato-Pancreato-Biliary Center and Department of
Gastroenterology and Hepatology, University Hospital
Zürich, Zürich, Switzerland
5. Somogy County Kaposi Mór Teaching Hospital,
Kaposvár, Hungary
6. Practice of Gastroenterology, Kiel
7. Practice of Gastroenterology, Düsseldorf
8. Institute for Interdisciplinary Medicine IFI, Hamburg
9. Practice of Hepatology, Göttingen
10. Practice of Hepatology, Herne
11. Practice of Gastroenterology, Mannheim
12. Infektiologikum, Frankfurt
13. Department of Gastroenterology and Rheumatology,
University Hospital Leipzig, Leipzig, Germany
33
• Serum samples of 3305 European HCV infected
patients were collected and population-based
sequencing of HCV NS3, NS5A and NS5B genes
was performed.
• RAVs were considered as relevant if they were
associated with treatment failure or were shown to
confer a >2-fold changed drug susceptibility in
comparison to the reference strain.
• RAVs were analysed in NS3 (positions 36, 43, 54, 55,
56, 80,122,155, 156, 158, 168, 170,175), NS5A (24,
28, 30, 31, 58, 92, 93) and NS5B (159, 282, 321, 316,
368, 411, 414, 448, 553, 554, 556, 558, 559, 561).
34
• Treatment-naïve and treatment-experienced
patients infected with HCV genotype 1a (n = 1417),
1b (n = 1300), 1c-e (n = 5), 2 (n = 49), 3
(n = 389), 4 (n = 119), 5 (n = 7), 6 (n = 1), and
2k/1b (n = 18) were studied.
35
• Pre-existing RAVs could be observed in 38% of
treatment-naive patients.
• After failure to SOF/RBV ± PEG no RAVs could be
detected.
• After DAA failure, 36-100% (depending on the
regimen)
– This may impose restrictions on effective retreatment
options with currently approved DAA regimens
36
Abstract THU-217
C. Hezode1, S. Fourati2, G. Scoazec1, A. Soulier2, A. Varaut1, M. Francois1, I. Ruiz2,
A. Mallat1, S. Chevaliez2, J.-M. Pawlotsky2
E-mail: [email protected]
1. Hepatology
2. Virology, Hôpital Henri Mondor, Créteil, France
37
• 11 patients with compensated liver disease (fibroscan: 6.6–
35.3 kPa) who failed to achieve SVR were included.
– 1a: n = 4
– 1b: n = 3
– 2: n=1
– 4: n = 2
– 6: n=1
• They had received SOF + DCV (n = 3); SOF + SMV (n = 2);
SOF + LDV (n = 1); GRZ + EBV (n = 1); mericitabine +
danoprevir + ritonavir (n = 1); without RBV for 12 weeks.
38
• SVR: n=5
• Relapse: n=3 (all GT1a, cirrhotic and previous
nonresponder to PEG/RBV, all double RAVs at
baseline)
• Pending: n=2
• Discontinued/lost to follow up: n=1
39
Abstract LBP519
N. Afdhal1, B. Bacon2, M. Curry1, D. Dieterich3, S. Flamm4, L. Guest5, K. Kowdley6, Y. Lee5,
N. Tsai7, Z. Younossi8
E-mail: [email protected]
1. Beth Israel Deaconess Medical Center, Boston, MA
2. Saint Louis University School of Medicine, Saint Louis, MO
3. Icahn School of Medicine at Mount Sinai, New York, NY
4. Northwestern University Feinberg School of Medicine, Chicago, IL
5. Trio Health Analytics, La Jolla, CA
6. Liver Care Network, Swedish Medical Center, Seattle, WA
7. Queens Medical Center, University of Hawaii, Honolulu, HI
8. Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, United States
40
• PPI use may reduce the AUC for ledipasvir
and could impact SVR in patients treated with
LDV/SOF.
• An incomplete report from the HCV TARGET network
suggested that PPI use at baseline was associated with a
5% reduction in SVR12 (Terrault, AASLD 2015); however
data regarding the actual PPI, duration of use and dosage
was not available.
• The aim of this study is to evaluate type of PPI, dose and
duration of PPI treatment on SVR in
real-world patients treated with LDV/SOF.
41
Population matching was done based on PPI use and age, gender, prior treatment, race, cirrhosis,
treatment duration, platelet count, decompensation, co-infection, practice location and use of RBV
42
• The type of PPI, PPI dose and PPI duration had no
effect on SVR.
• Twice daily PPI had an effect with reduced SVR of
91.7% in univariate analysis but not multivariate
analysis.
• Small number and wide confidence interval; however,
caution should be use with twice daily PPI.
43
Abstract GS13
M. Colombo1, A. Aghemo1, L. Liu2, R. Hyland2, C. Yun2, D. Brainard2, J. McHutchison2,
M. Bourlie re3, M. Peck-Radosavljevic4, M. Manns5, S. Pol6
E-mail: [email protected]
1. Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
2. Gilead Sciences Inc., Foster City, United States
3. Hôpital Saint Joseph, Marseilles, France
4. Medical University of Vienna, Vienna, Austria
5. Hannover Medical School, Hannover, Germany
6. Hôpital Cochin, Paris, France
44
• 5 sites in Italy, France, Austria and Germany
• Kidney transplant recipients with HCV GT 1 or 4, treatment-naïve or
-experienced, with or without cirrhosis
• Cirrhosis determined by biopsy (Metavir score =4 or Ishak score ≥5),
FibroScan® > 12.5 kPa or FibroTest >0.75 + APRI >2 (15% had
cirrhosis)
• Inclusion criteria
– >6 months from kidney transplant
– HCV RNA ≥LLOQ (15 IU/mL) at Screening
– Hemoglobin ≥10 g/dL, platelets >50 x 103/μL, CLcr ≥40 mL/min
44
LDV/SOF FDC
LDV/SOF FDC SVR12
n=57
n=57
SVR12
0 24 12 36 Week
45 45
LDV/SOF
12 weeks
n=57
LDV/SOF
24 weeks
n=57
Median eGFR, mL/min (range) 50 (37-135) 60 (35-130)
Median serum creatinine, mg/dL (range) 1.3 (0.5-2.7) 1.3 (0.8-2.4)
Median years from transplant, (range) 10 (0.5-40) 12 (0.8-42)
Use of immunosuppressants, n (%)
Corticosteroids 39 (68) 42 (74)
Others 56 (98) 55 (96)
Tacrolimus 25 (44) 30 (53)
Mycophenolate 38 (67) 31 (54)
Cyclosporine 23 (40) 21 (37)
Azathioprine 6 (11) 8 (14)
46 46
Error bars represent 95% confidence intervals.
100 100 100 96 96 100
0
20
40
60
80
100
GT 1 GT 4
SV
R1
2 (
%)
51/51 6/6 4/4
Overall
51/53 57/57 55/57
LDV/SOF 12 Weeks LDV/SOF 24 Weeks
2 LTFU
47
Abstract PS002
J. Sperl1, G. Horvath2, W. Halota3,J.A. Ruiz-Tapiador4, A. Streinu- Cercel5, L. Jancoriene6, K.Werling7, H. Kileng8,
S. Koklu9, J. Gerstoft10, S. Patel11, J. Qiu11, E. Assante-Appiah11,
J. Wahl11, B.-Y. Nguyen11, E. Barr11, H.L. Platt11.
1Institute for Clinical and Experimental Medicine, Prague, Czech Republic; 2Budai Hepatólogiai Centrum,
Budapest, Hungary; 3Wojewódzki Szpital Obserwacyjno-Zakaźny im Tadeusza Browicza, Bydgoszcz, Poland; 4Hospital Universitario Donostia, San Sebastián, Spain; 5Institutul Naţional de Boli Infecţioase “Prof. Dr. Matei
Balș”, Bucharest, Romania; 6Centre of Infectious Diseases, Vilnius University Hospital Santariskiu Klinikos,
Vilnius, Lithuania; 7Semmelweis Egyetem, Budapest, Hungary; 8UNN Universitetssykehuset Nord Norge, Tromsø,
Norway; 9Hacettepe University Medical Faculty, Ankara, Turkey; 10Department of Infectious Diseases,
Rigshospitalet, Copenhagen, Denmark; 11Merck & Co., Inc., Kenilworth, United States
E-mail: [email protected]
48
49
