studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 257A
95
Improving liver function and delisting of patients awaiting
liver transplantation for HCV cirrhosis: do we ask
too much to DAA?
Audrey Coilly 1,2 , Georges-Philippe Pageaux 22 , Pauline Houssel-Debry
7 , Christophe Duvoux 3 , Sylvie Radenne 6 , Victor de
Ledinghen 15 , Danielle Botta-Fridlund 11 , Anaïs Vallet-Pichard 13 ,
Rodolphe Anty 9 , Vincent Di Martino 5 , Filomena Conti 10 , Marie Line
Debette-Gratien 20 , Laurent Alric 16 , Armando Abergel 17 , Camille
Besch 19 , Helene Montialoux 18 , Pascal Lebray 10 , Sebastien Dharancy
4 , Francois Durand 12 , Louis d’Alteroche 21 , Florian Charier 8 ,
Olivier Chazouillères 14 , Jérôme Dumortier 24 , Vincent Leroy 23 , Jean-
Charles Duclos-Vallee 1,2 ; 1 Centre Hepato-Biliaire, AP-HP Hopital
Paul-Brousse, Villejuif, France; 2 Unit 1193, INSERM, Villejuif,
France; 3 AP-HP Hopital Henri Mondor, Creteil, France; 4 CHRU
de Lille, Lille, France; 5 CHU Jean Minjoz, Besançon, France; 6 HCL
- Hopital Croix Rousse, Lyon, France; 7 CHU de Rennes - Hopital
Pontchaillou, Renes, France; 8 CHU de Poitiers, Poitiers, France;
9 CHU de Nice, Nice, France; 10 AP-HP Hopital Pitie-Salpetrière,
Paris, France; 11 AP-HM Hopital La Conception, Marseille, France;
12 AP-HP Hopital Beaujon, Clichy, France; 13 AP-HP Hopital Cochin,
Paris, France; 14 AP-HP Hopital Saint-Antoine, Paris, France; 15 CHU
de Bordeaux - Hopital Haut-Leveque, Pessac, France; 16 CHU de
Toulouse - Hopital Purpan, Toulouse, France; 17 CHU de Clermont-Ferrand,
Clermont-Ferrand, France; 18 CHU de Rouen, Rouen,
France; 19 CHU de Strasbourg - Hopital Hautepierre, Strasbourg,
France; 20 CHU de Limoges, Limoges, France; 21 CHU de Tours
- Hopital Trousseau, Tours, France; 22 CHU de Montpellier - Hopital
Saint-Eloi, Montpellier, France; 23 CHU de Grenoble - Hopital
Michallon, Grenoble, France; 24 HCL - Hopital Edouard Herriot,
Lyon, France
Background: Combinations of DAA have shown excellent
results to treat HCV-infection in cirrhotic patients (pts). But some
issues remain unresolved regarding efficacy in pts awaiting
liver transplantation (LT) and impact on access to LT. Methods:
This cohort study enrolled 151 pts registered in 23 centers
on French LT list (male: 79%, age 56±7 years), treated with
sofosbuvir ± ribavirin (n=84) ± daclatasvir (n=90) or simeprevir
(n=9) or ledipasvir (n=17). Meantime between listing and
starting therapy was 23±57 weeks (wks). All pts were cirrhotic.
LT indication was HCC in 85(56%) pts. 112(74%) pts were
treatment experienced including 46% of non-responders, failures
to 1rst generation protease inhibitors in 32 or sofosbuvir
in 16 pts. Majority of pts were genotype 1 (56%) and 3 (24%).
Results: Mean follow-up was 44±19 wks [12-79]. Mean baseline
MELD score (MELD), platelet count, bilirubin and albumin
levels were 10±5 [6-32], 89±50 G/L[23-347], 39±42μmol/L
[5-405], 33±7 g/L [15-47]. 73 pts (48%) were decompensated
(bilirubin > 50μmol/L in 34(23%) ± ascites in 53(35%)
± hepatic encephalopathy (HE) in 29(19%)). Indetectability
of HCV RNA was obtained at 7±4 wks [1-24]. Among 117
pts, 103(88%) achieved SVR12. Among 73 decompensated
pts, a complete response (normal bilirubin level, no ascites,
no HE) was observed in 14(19%) after 12 wks and 31(42%)
at 12 wks post-treatment. When achieving SVR12, ascites or
HE persisted in 12/44 (27%) and 7/14 (50%). Variations of
MELD are shown in Table 1. Among patients with baseline
MELD score≥20, 83% still an indication of LT at the end of treatment
(MELD≥15). 45(30%) pts were transplanted. Ten (6%) pts
were delisted because of liver function improvement. A serious
adverse event occurred in 24(19%) pts, mainly liver events
(37%), anemia (25%) and sepsis (25%). Conclusion: Among
151 cirrhotic pts awaiting LT treated with IFN-free regimens,
88% achieved SVR12. Only 6% of pts were delisted due to
liver function improvement. A complete clinical and biological
response was observed in 42%, raising hopes that more pts
could be delisted. However, major clinical improvement was
observed in a minority of patients especially when MELD score
was ≥20, suggesting that antiviral treatment might be postponed
after LT in this population. Final results will be provided
in a larger population.
Variations of MELD score in 66 pts with decompensated condition
from baseline to the end of treatment
Disclosures:
Audrey Coilly - Consulting: Novartis, Astellas, Janssen, Bristol-Myers-Squibb,
Merck Sharp & Dohme, Gilead, Roche
Georges-Philippe Pageaux - Advisory Committees or Review Panels: Roche,
Roche, Roche, Roche; Board Membership: Astellas, Astellas, Astellas, Astellas
Pauline Houssel-Debry - Speaking and Teaching: NOVARTIS, ASTELLAS, GILEAD
Christophe Duvoux - Advisory Committees or Review Panels: Novartis, Roche,
Novartis, Roche, Novartis, Roche, Novartis, Roche; Speaking and Teaching:
Astellas, Astellas, Astellas, Astellas
Victor de Ledinghen - Board Membership: Janssen, Gilead, BMS, Abbvie; Speaking
and Teaching: AbbVie, Merck, BMS, Gilead
Danielle Botta-Fridlund - Consulting: GILEAD, ABBVIE, BMS, MSD
Anaïs Vallet-Pichard - Independent Contractor: Schering Plough, Gilead, BMS,
Roche
Vincent Di Martino - Advisory Committees or Review Panels: Gilead, France,
Abbvie, BMS France; Board Membership: MSD France; Consulting: Gilead,
France; Speaking and Teaching: Janssen, BMS France, Gilead France
Laurent Alric - Board Membership: Schering Plough, Schering Plough, Schering
Plough, Schering Plough; Consulting: MSD; Speaking and Teaching: Roches,
BMS, Gilead, Roches, BMS, Gilead, Roches, BMS, Gilead, Roches, BMS, Gilead,
MSD, Abbvie
Armando Abergel - Consulting: gilead, msd, bms; Speaking and Teaching: abbvie
Pascal Lebray - Grant/Research Support: Schering-Plough, Schering-Plough, Schering-Plough,
Schering-Plough; Speaking and Teaching: Gilead, Gilead, Gilead,
Gilead
Sebastien Dharancy - Advisory Committees or Review Panels: CHIESI; Board
Membership: NOVARTIS; Speaking and Teaching: ASTELLAS
Francois Durand - Advisory Committees or Review Panels: Astellas, Novartis,
BMS; Speaking and Teaching: Gilead
Olivier Chazouillères - Consulting: APTALIS, MAYOLY-SPINDLER
Jérôme Dumortier - Board Membership: Novartis, Astellas, Roche; Consulting:
Novartis; Grant/Research Support: Novartis, Astellas, Roche, MSD, GSK
Vincent Leroy - Board Membership: Abbvie, BMS, Gilead; Consulting: Janssen,
MSD; Speaking and Teaching: Abbvie, BMS, Gilead, Janssen, MSD
The following authors have nothing to disclose: Sylvie Radenne, Rodolphe Anty,
Filomena Conti, Marie Line Debette-Gratien, Camille Besch, Helene Montialoux,
Louis d’Alteroche, Florian Charier, Jean-Charles Duclos-Vallee
96
Detecting Drug-Induced Liver Injury in Patients with
Decompensated Chronic Hepatitis C: A Review of the
SOLAR-1 and SOLAR-2 Studies
Andrew J. Muir 2 , Michael R. Charlton 5 , Phillip S. Pang 1 , Luisa
M. Stamm 1 , Diana M. Brainard 1 , John G. McHutchison 1 , Nezam
H. Afdhal 3 , Paul B. Watkins 4 ; 1 Gilead Sciences, Foster City, CA;
2 Duke University Medical Center, Durham, NC; 3 Division of Gastroenterology,
BIDMC, Boston, MA; 4 The Hamner-UNC Institute for
Drug Safety Sciences, Chapel Hill, NC; 5 Intermountain Medical
Center, Murray, UT
Background: The identification of drug-induced liver injury
(DILI) is challenging in patients with underlying liver disease,
particularly in the setting of decompensated cirrhosis which has
recently become a target population for novel therapies. Traditional
laboratory criteria (e.g., elevation in serum ALT > 5x
upper limit of normal) may not be appropriate for patients with