CARE AND TREATMENT OF CHRONIC HBV AND HCV -December 2016- GEORGE PAPATHEODORIDIS, MD PROFESSOR IN MEDICINE AND GASTROENTEROLOGY ATHENS UNIVERSITY MEDICAL SCHOOL HARRY JANSSEN, MD PROFESSOR OF MEDICINE, TORONTO WESTERN AND TORONTO GENERAL HOSPITAL, UNIVERSITY HEALTH NETWORK, TORONTO, CANADA ANGELOS HATZAKIS, MD PROFESSOR OF EPIDEMIOLOGY AND PREVENTIVE MEDICINE ATHENS UNIVERSITY MEDICAL SCHOOL
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CARE AND TREATMENT OF CHRONIC HBV AND HCV … · Chronic HBV and HCV are treatable or curable HBV Treatment HCV Treatment Interferon alfa-2b Interferon-alfa-2a/2b ± ribavirin Lamivudine
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CARE AND TREATMENT
OF CHRONIC HBV AND HCV - D e c e m b e r 20 1 6 -
GEORGE PAPATHEODORIDIS, MD
PROFESSOR IN MEDICINE AND GASTROENTEROLOGY ATHENS UNIVERSITY MEDICAL SCHOOL
HARRY JANSSEN, MD PROFESSOR OF MEDICINE, TORONTO WESTERN AND TORONTO GENERAL HOSPITAL,
UNIVERSITY HEALTH NETWORK, TORONTO, CANADA
ANGELOS HATZAKIS, MD PROFESSOR OF EPIDEMIOLOGY AND PREVENTIVE MEDICINE
Papatheodoridis et al. Hepatology 2002,36:219-26; Hadziyannis et al. Gastroenterology 2006,131:1743-51; Liaw YF et al. Gastroenterology 2009,136:486-95; Wang Y et al. AASLD 2009, Abstr. 482;
Tenney D et al. APASL 2008, Abstr. PL02; Marcellin P et al. AASLD 2014
29
HBeAg- HBeAg- HBeAg-
First-line
Resistance to oral antiviral agents in naive CHB patients Data from different studies with different patients characteristics and methodology
Han S et al. AASLD 2008. Shouval et al. AASLD 2008.
Pat
ien
ts w
ith
HB
V D
NA
<3
00
cp
/mL
(%)
55%
Year 1
83%
Year 2
89%
Year 3
67%
n/ N
236/ 354
Year 4
91%
80/ 146
116/ 140
116/ 131
98/ 108
Year 5
88/ 94
94%
Year 1
ETV-022
0
20
40
60
80
100
ETV-901
Long-term ETV therapy in naive HBeAg(+)/(-) CHB
HBeAg(+) HBeAg(-)
Year 1
91%
Year 2 95%
Year 3
94%
93/99 84/90
67/74 54/57
93%
Year 1
ETV-027
0
20
40
60
80
100
ETV-901
Marcellin P et al. AASLD 2011, 2012
HBeAg(-): 5 year - 6 years
ΙΤΤ: 83%- 81%
Per protocol*: 99%- 100%
HBeAg(+): 5 years - 6 years
ΙΤΤ: 65%- 62%
Per protocol*: 97%- 99%
Patients with HBV DNA <400 cp/mL at 5-6 years under TDF
*missing = exclusion
Resistance to ETV or TDF in CHB with LAM resistance P
atie
nts
wit
h r
esi
stan
ce (
%)
6 0 0 0 0
Years 1 2 3 4 5 6 1 2 3 4
Entecavir (ETV) Tenofovir (TDF)
These trials included different populations, different exclusion criteria and different endpoints
15
31
47 51
Although licensed, ETV (1.0 mg) is not recommended for patients with LAM resistance by almost all guidelines
57
Tenney D et al. EASL 2009, Abstr. 20; Van Bommel F et al. Hepatology 2010, 51: 73-80
Ishak Fibrosis Scores
Pe
rce
nta
ge o
f p
atie
nts
0
10
20
30
40
50
60
70
80
90
100
Baseline Year 1 Year 5
39%
38%
12%
P < 0.001
P < 0.001
63%
0
10
20
30
40
50
60
70
80
90
100
Baseline Year 1 Year 5
39%
38%
12%
P < 0.001
P < 0.001
63%
6
5
4
3
2
1
0
6
5
4
3
2
1
0
Patients with cirrhosis (Ishak score ≥5): 28% at baseline, 8% at year 5
Fibrosis Is Reversible Liver Fibrosis Regression over 5 Yrs of Tenofovir Therapy
Marcellin P et al. Lancet 2013
348 patients with paired biopsies at baseline & year 5
HCC in CHB patients under LAM
Patients with HCC,
%
LAM Untreated
Patients n: 779 534
HBeAg(-) 49% 54%
Comp. Ci: 29% 39%
FUP (mos): 32-90 32-108
• Liaw et al, NEJM 2004
• Papatheodoridis et al, HEP 2005
• Yuen et al, AVT 2007
P=0.003
P=0.015
P=0.016
All VR BR/BTH Untreated pts LAM treated pts N 779 353 426 534
Papatheodoridis GV et al. J Hepatol 2010;53:348-56
Patients with HCC,
%
No cirrhosis
Cirrhosis
Virological remission
No virological remission
Patients NA naive LAM resistance NA naive LAM resistance
No 2233 / 1054 241 / 170 982 / 852 320 / 91
P<0.001 P<0.001 P<0.001 P=NS
HCC incidence in CHB patients under NA(s) for a median of 4 years
Papatheodoridis GV et al. J Hepatol 2010;53:348-56
0,5%
1,0%
0,7%
0,1%
0,5%
0,0%
0,5%
1,0%
1,5%
2,0%
Tx-naive Tx-naive and/or tx-experienced Tx-naive
Papathe- odoridis N=212
Yang N=202
Wong N=984
Wong N=813
Yang N=314
Hosaka N=237
Lampe- rtico
N=213
Arends N=580
An
nu
al H
CC
In
cid
en
ce
Lim N=878
Cho N=933
Wu N=18748
Lampe- rtico
N=243
Papathe- odoridis N=1231
ETV TDF ETV or TDF
Yamada N=402
Prior exposure
NR
Tx-naive and/or tx-experienced
Asians Caucasians
ETV or TDF for non-cirrhotic CHB patients
HCC rates per year
Papatheodoridis GV et al. J Hepatol 2015;62:956-67
1,4%
2,8%
5,4%
2,0%
4,1%
3,3%
0,9%
5,4%
2,6%
5,1%
2,2%
4,5%
3,9%
0,0%
1,0%
2,0%
3,0%
4,0%
5,0%
6,0%
Yang N=121
Wong N=482
Wong
N=247
Hosaka N=79
Chen
N=239
Kim
N=324
Yang
N=152
Chen N=143
Papa theo- dori dis
N=69
Lamp- etico
N=155
Are- nds
N=164
Koklü N=77
2,8%
4,2%
1,8%
3,3%
2,5%
5,2%
1,5%
0,0%
1,0%
2,0%
3,0%
4,0%
5,0%
6,0%
Lim N=860
Cho
N=445
Su N=666
Wu N=2847
Lamp- ertico
N=131
Papa theo- dori dis
N=1231
Koklü N=72
Yama- da
N=94
ETV or TDF for cirrhotic CHB patients HCC rates per year
ETV TDF ETV or TDF
Tx-naive Tx-naive and/or tx-experienced Tx-naive
Prior exposure
NR
Tx-naive and/or tx-experienced
Asians Caucasians
Papatheodoridis GV et al. J Hepatol 2015;62:956-67
PAGE-B represents a simple to use HCC risk score for the first 5 years of ETV/TDF in Caucasian CHB patients
Construction of the PAGE-B risk score for HCC
Age (years) Gender Platelets
(/mm3)
16–29: 0 Female:
0 ≥200,000: 0
30–39: 2 Male: 6 100,000–
199,999: 6
40–49: 4 <100,000: 9
50–59: 6
60–69: 8
≥70: 10
Papatheodoridis GV et al. J Hepatol 2016;64:800-6
Patients with
durable HBeAg
serocon- version,
%
At 6 12 24 months after NA(s) discontinuation
GV Papatheodoridis et al. Hepatology 2016; 63:1481-92.
Rates of durable HBeAg seroconversion after NAs discontinuation Systematic review: 6 studies, 289 initially HBeAg+ patients
Patients with
HBV DNA <20,000 IU/mL,
%
At 6 12 24 36 months after NA(s) discontinuation
Rates of virological remission after NAs discontinuation 14 studies, 733 initially HBeAg+ patients
Pooled HBsAg loss: 1%; Durable biochemical remission: 76%
GV Papatheodoridis et al. Hepatology 2016; 63:1481-92.
Patients with
HBV DNA <20,000 IU/mL,
%
At 6 12 24 36 months after NA(s) discontinuation
Rates of virological remission after NAs discontinuation 17 studies, 967 HBeAg- patients
Pooled HBsAg loss: 1.7%; Durable biochemical remission: 57%
GV Papatheodoridis et al. Hepatology 2016; 63:1481-92.
Patients with VR
at 12 mos after NAs
discontin., %
Rates of virological remission at 12 mos after NAs discontinuation in HBeAg-neg. CHB patients in relation to several factors
VR: virological remission
HBV DNA (IU/mL) <200 <2,000 <20,000 <12 12-24 >24 mos
VR definition Duration of on-NAs VR
P=0.513 P=0.017
GV Papatheodoridis et al. Hepatology 2016; 63:1481-92.
Main advantages and disadvantages of Peg-IFN & nucleos(t)ide analogues (NAs) in CHB
Peg-IFN NAs
Advantages Finite duration
Higher rates of anti-HBe &
anti-HBs seroconversion
with 12 mos of therapy
Absence of resistance
Potent antiviral effect
Good tolerance
Oral administration
Disadvantages Moderate antiviral effect
Inferior tolerability
Risk of adverse events
Subcutaneous injections
Long-term (indefinite?) duration
Unknown long-term safety
Risk of resistance
EASL HBV CPGs. J Hepatol 2012
HBV treatment modifies the outcome of the disease
Sustained response after pegIFN or long-term ETV/TDF monotherapy
Improvement/Stabilization of liver disease in practically all patients
Often regression of histological cirrhosis
Improvement/Disappearance of portal hypertension and liver decompensation
No need for liver transplantation due to liver failure
Rapid virological response (RVR) - at 4 weeks of therapy
undetectable HCV RNA (<50 IU/mL)
Early virological response (EVR) – at 12 weeks of therapy
complete: undetectable HCV RNA (<600 IU/mL)
partial: detectable HCV RNA but ≥2 log decrease from baseline
PEG-IFN+RBV in CΗC: HCV Genotype & SVR
PEG-ΙFN-2b (1.5μg/Kg/wk) + RBV 0.8g
PEG-ΙFN-2a (180μg/wk) + RBV 1-1.2g
x 48 weeks
SVR
, %
Manns et al. Lancet 2001 Fried et al . Ν Engl J Med 2002
2/3 1 2/3 1
HCV genotype HCV genotype
• 22 studies, 2891 G4 patients (12-308 patients per study)
PEG-IFN+RBV in CHC-G4
SVR, %
Khattab MA et al. J Hepatol 2011;54:1250-62
All patients F3-F4 patients
Unresolved issues with Peg-IFNa+RBV
Treatment contraindications
(all patients needed treatment most)
Low SVR rates mostly in G1 (& G4) patients
Poor chance of SVR in treatment failures
Side effects – Poor quality of life
Adherence problems
SOVALDI®
Sofosbuvir NS5B polymerase
Inhibitor Gilead
OLYSIO® Simeprevir
NS3/4A protease Inhibitor Janssen
DAKLINZA® Daclatasvir
NS5A Inhibitor
BMS
400 mg/24h
Genotypes 1-6
High genetic barrier
150 mg/24h with food
Genotypes 1,4
Low genetic barrier
60 mg/24h
Genotypes 1,2,3,4
Low genetic barrier
January 17, 2014 May 16, 2014 August 28, 2014 November 18, 2014
90+400 mg/24h
Genotypes 1,3,4
High genetic barrier
HARVONI® Ledipasvir
NS5A inhibitor +Sofosbuvir
NS5B polymerase Inhibitor Gilead
Anti-HCV agents approved by ΕMA in 2014
VIEKIRAX® Ombitasvir
NS5A inhibitor +Paritaprevir
NS3/4A protease inhibitor/ Ritonavir
EXVIERA® Dasabuvir
Non-nucleos(t)ide NS5B polymerase
inhibitor
[75/50+12.5 mg] x2 /24h with food
Genotypes 1, 4
Genetic barrier dependent on genotype
250 mg/12h
Genotype 1
Low genetic barrier
January 16, 2015
Anti-HCV agents approved by ΕMA in 2015
Abbvie
EPCLUSA® Velpatasvir
NS5A inhibitor +Sofosbuvir
NS5B polymerase Inhibitor Gilead
100+400 mg/24h
Genotypes 1-6
High genetic barrier
July 8, 2016
ZEPATIER®
Elbasvir NS5A inhibitor +Grazoprevir
NS3/4A protease inhibitor
MSD
50+100 mg /24h
Genotypes 1, 4
Genetic barrier dependent on genotype
July 28, 2016
Anti-HCV agents approved by ΕMA in 2016
Simeprevir
Ribavirin
IFNa-containing combinations – Main strategies Not recommended by most current guidelines
+
+
PegIFNa
Ribavirin
+
PegIFNa
+
Ribavirin
+
PegIFNa
+
Ribavirin
+
PegIFNa
Boceprevir
Telaprevir
Sofosbuvir Daclatasvir
Nucleotide inhibitor of NS5B polymerase
NS3/4 protease inhibitor
NS5A inhibitor
?
PegIFNa +Ribavirin is still used in
several countries for easy to treat
patients without access to
IFNa-free regimens
PegIFNa +Ribavirin +Sofosbuvir
bay be still used for genotype 2 or 3
patients in some countries
without access to all current DAAs
Sofosbuvir
Simeprevir Daclatasvir
Paritaprevir/ritonavir
Dasabuvir Ribavirin
IFNa-Free combinations – Main strategies
Sofosbuvir
Ribavirin
+ + Ombitasvir
Ribavirin
±
±
± ±
Ledipasvir
Sofosbuvir
Ribavirin
±
Sofosbuvir
Ribavirin
+
Nucleotide inhibitor of NS5B polymerase
Non-nucleos(t)ide inhibitor of NS5B polymerase
NS3/4 protease inhibitor
NS5A inhibitor
Velpatasvir
Sofosbuvir
Ribavirin
±
Elbasvir
Grazoprevir
Ribavirin
±
Sofosbuvir + Simeprevir (±Ribavirin)
Sofosbuvir + Daclatasvir (±Ribavirin)
IFNa-free regimens for genotype 1
Sofosbuvir/Ledipasvir (±Ribavirin)
Paritaprevir/r/Ombitasvir ±Dasabuvir (±Ribavirin)
Sofosbuvir/Velpatasvir
Grazoprevir/Elbasvir (±Ribavirin)
OPTIMIST-1: SΜV+SOF x8-12 weeks in HCV GT-1 non-cirrhotics SV
R1
2 (
%)
112/115
Treatment-naive Treatment-experienced
97% (94.0;100)
88/103 38/40 40/52
85% (78.1;92.7)
95% (87.0;100)
77% (64.5;89.3)
SMV+SOF 12 weeks SMV+SOF 8 weeks
Kwo P et al. Hepatology 2016;64:370-80.
OPTIMIST-2: SΜV+SOF x12 weeks in HCV GT-1 cirrhotics SV
R1
2 (
%)
44/50
Treatment-naive Treatment-experienceda
88 (95% CI: 78.0; 98.0)
42/53
79 (95% CI: 67.4; 91.1)
CI, confidence interval; aTreatment-experienced patients included prior relapsers, prior non-responders, IFN-intolerant and other patients Lawitz E et al. Hepatology 2016;64:360-9
SVR
12
(%
)
60/72
GT1a GT1a with Q80K
GT1a without Q80K
GT1b
25/34 35/38 26/31
83 (95% CI: 74.0; 92.6)
74 (95% CI: 57.2; 89.8)
92 (95% CI: 82.2; 100)
84 (95% CI: 69.3; 98.4)
Lawitz E et al. EASL 2015, LB-Poster 04
OPTIMIST-2: SΜV+SOF x12 weeks in HCV GT-1 cirrhotics
Welzel T et al. EASL Special Conference September 23–24 2016. Poster presentation #163.
GARNET: Efficacy of 8-Week Paritaprevir/r/Ombitasvir+Dasabuvir (PRV/OBV+DSV) in Treatment-Naïve Non-cirrhotic GT1b Patients
162 166
160 162
2 relapses, 1 discontinuation
160 163
ITT: all patients who received at least one dose of study drug; mITT-GT: ITT modified to exclude 3 patients without GT1b (1a, 1d, 6); mITT-GT-VF: mITT-GT modified to exclude non-virologic failures (1 patient discontinued prematurely due to noncompliance).
Fibrosis was the only significant predictor of SVR12 identified:
(F3 86.7% [13/15] vs F0–F2 99.3% [147/148])
TURQUOISE-II: SVR12 rates in GT1 treatment-naive and experienced cirrhotic patients
SOF/VEL 12wks (+RBV σε RAS*+) naive, 24wks +RBV σε αποτυχ.
12wks (+RBV σε RAS*+) ή 24wks
-
*NS5A RAS Y93H
Naive or PegIFNa±RBV experienced, non-cirrhotics with GT3
Sofosbuvir + Simeprevir (±Ribavirin)
Sofosbuvir + Daclatasvir (±Ribavirin)
IFNa-free regimens for genotype 4
Sofosbuvir/Ledipasvir (±Ribavirin)
Paritaprevir/r/Ombitasvir ±Dasabuvir (±Ribavirin)
Sofosbuvir/Velpatasvir
Grazoprevir/Elbasvir (±Ribavirin)
Ruane PJ et al. Hepatology 2015, Epud ahead of print
Virologic ResponseSOF + RBV in Treatment of GT4 Patients of Egyptian Ancestry
11/14 11/14 14/14 10/17 10/17 14/15
Treatment-naive Treatment-experienced
SYNERGY Trial: LDV/SOF for 12 wks in patients with G4
• Single-center, open-label phase 2a trial
• 38% of patients were TE; all were naive to DAAs; 33% had cirrhosis
• No deaths, SAEs, or grade 4 laboratory events; 1 D/C
GT4 HCV (N=21)
SOF/LDV
12 wks SVR12, %
95
Kapoor R et al. AASLD 2014, Abstract #240
French cohort
GT4 HCV (N=44)
SOF/LDV
12 wks SVR12, %
93
Abergel A et al. EASL 2015, Abstr. O56
Experienced: 22 (50%), Cirrhosis: 10 (23%)
PEARL-I: Paritaprevir/r/Ombitasvir ± RBV x12 wks in non-cirrhotic naive/experienced patients with GT4
SVR
(%
)
Hezode C et al. Lancet 2015; 385:2502-9.
No RBV +RBV +RBV (N=44) (N=42) (N=49)
SVR4
SVR12
P=0.086
Error bars indicate 95% confidence intervals.
Arm A: 12 weeks (N = 59)
Arm B: 16 weeks (N = 61)
Non-responses, n (%) 2 (3) 1 (2)
Virologic failure 1 (2) 0
Relapse 0 0
Premature study drug D/C 1 (2) 0
Missing SVR12 data 0 1 (2)
1 2 w e e k 1 6 w e e k
0
2 5
5 0
7 5
1 0 0V
iro
log
ic R
es
po
ns
e,
% P
ati
en
ts
5 9
5 7
5 8
5 7
6 0
6 0
9 8 1 0 09 7 9 8
O B V / P T V / r + R B V T r e a t m e n t D u r a t io n
6 1
6 0
S V R 1 2 (s e n s it iv ity a n a ly s is )
SVR12 Rates by Treatment Arm (Sensitivity Analysis)
The sensitivity analysis excluded patients who prematurely discontinued study drug (with no on-treatment virologic failure) or who were missing follow-up data in the SVR12 window
AGATE-I: Paritaprevir/r/Ombitasvir + RBV x12 wks in cirrhotic naive/experienced patients with GT4
Asselah T et al. DDW 2016
SV
R1
2 (
%)
18/18 n/N =
GT 4
100% 100
75
50
25
0
SV
R1
2 (
%)
32/37 7/9 8/8 n/N =
Overall 12 weeks 16 weeks + RBV
87 79 100 100
75
50
25
0
Elbasvir/Grazoprevir for GT4 patients
Zeuzem Z et al. Ann Intern Med 2015;163:1-13. Kwo P et al. Gastroenterology 2016.
Naive
Treatment experienced
ASTRAL-1: SOF/VEL STR for 12 Weeks in GT4, GT5, GT6 Patients
Feld JJ et al. N Engl J Med. 2015;373:2599-607.
116/116 34/35 41/41
SVR12, %
AASLD (09/2016)
EASL (09/2016)
PegIFNa+RBV (PR) NO NO
PR+SMV – PR NO 24 (12-12)wks in naive/RR, 48 (12-36)wks in PR/NR
PR+SOF NO 12wks
SOF+RBV NO NO
SOF +SMV NO 12wks in naive, 12wks +RBV or 24wks in experienced
SOF +DCV NO 12wks in naive, 12wks +RBV or 24wks in experienced
SOF/LDV 12wks 12wks in naive, 12wks +RBV or 24wks in experienced
PRV/r/OBV 12wks +RBV 12wks +RBV
SOF/VEL 12wks 12wks
EBR/GZR 12wks σε naive/RR, 16wks +RBV σε PR/NR
12wks in naïve or in experienced with HCVRNA ≤800,000 IU/ml,
16wks +RBV in experienced with HCVRNA >800,000 IU/ml
Naive or PegIFNa±RBV experienced, non-cirrhotics with GT4
AASLD (09/2016)
EASL (09/2016)
PegIFNa+RBV (PR) NO NO
PR+SMV – PR NO 48 (12-36)wks
PR+SOF NO 12wks
SOF+RBV NO NO
SOF +SMV NO 12wks in naive, 12wks +RBV or 24wks in experienced
SOF +DCV
NO 12wks in naive, 12wks +RBV or 24wks in experienced
SOF/LDV 12wks in naive, 12wks +RBV or 24wks in experienced
12wks in naive, 12wks +RBV or 24wks in experienced
PRV/r/OBV 12wks +RBV 12wks +RBV
SOF/VEL 12wks 12wks
EBR/GZR 12wks in naive/RR, 16wks +RBV σε PR/NR
12wks in naïve or in experienced with HCVRNA ≤800,000 IU/ml,
16wks +RBV in experienced with HCVRNA >800,000 IU/ml
Naive or PegIFNa±RBV experienced, cirrhotics with GT4
AASLD (09/2016)
EASL (09/2016)
PegIFNa+RBV (PR) NO NO
PR+SOF NO 12wks
SOF +RBV NO NO
SOF +DCV NO 12wks in naive, 12wks +RBV or 24wks in experienced
SOF/LDV 12wks 12wks in naive, 12wks +RBV or 24wks in experienced
SOF/VEL 12wks 12wks
Naive or PegIFNa±RBV experienced, (non-)cirrhotics with GT5/6
SOLAR-1: SVR12 and safety according to CTP score in decompensated cirrhosis
100
80
60
40
20
0
SVR
12
(%
)
Overall CTP B CTP C
LDV/SOF + RBV 12 wks LDV/SOF + RBV 24 wks
87 89
45/52 42/47
87 89 86 90
26/30 24/27 19/22 18/20
3 relapses 1 death 1 relapse
2 deaths
1 relapse 1 death 1 LTFU 1 relapse
1 death
Patients n (%)
CTP B CTP C
12 Wks
(n=30)
24 Wks
(n=29)
12 Wks
(n=23)
24 Wks
(n=26)
AE 29 (97) 27 (93) 23 (100) 26 (100)
SAE 3 (10) 10 (34) 6 (26) 11 (42)
Treatment-emergent, -related
SAEs 2 (7) 0 0 2 (8)
Treatment D/C due to AEs 0 1 (3) 0 2 (8)
Charlton M et al. Gastroenterology 2015;149:649-59.
SOLAR-2: SOF/LDV+RBV in HCV decompensated cirrhotics and transplant patients
M Manns et al. Lancet Infect Dis 2016;16:685-97.
SOLAR-2: SOF/LDV+RBV in HCV decompensated cirrhotics and transplant patients
MELD score change from baseline to follow-up week-4
M Manns et al. Lancet Infect Dis 2016;16:685-97.
aBased on all treated patients who have reached PT Week 12 b1 HCV RNA > LLOQ but discontinuation before week 12.
Welzel T et al. EASL 2015 Abstr P772
EU multicentre Compassionate Use Program
Total n = 482 72% GT-1; CP-A: 57%, CP-B: 36%, CP-C: 6%
Safety: DC due to AE: 28 (6%)
DCV + SOF ± RBV, 24 weeks
Interim resultsa - DCV + SOF ± RBV in GT1 patients with decompensated cirrhosis in early access programme
52
55 95
100 147 155
21b
22 27 27
48b 49
ASTRAL-4: SOF/VEL ± RBV in HCV Patients with Decompensated Liver Disease