1. Clinical outcome after SVR: Veterans Affairs
Design
Observational cohort (Veterans Affairs Registry)
All patients treated with DAA, separated in 2 groups
No advanced liver disease: FIB-4 ≤ 3.25 and absence of cirrhosis, liver decompensation, HCC or liver transplant
Advanced liver disease: FIB-4 > 3.25
Overall all-cause mortality and incident HCC: rate per 100 patient-years of follow-up
1 year-mortality and incident HCC after end of treatment (censoring date May 31, 2016)
Kaplan-Meier curves of survival and of HCC-free survival by SVR compared with log-rank tests
Mortality and incident HCC rates compared with Exact Poisson test
One-year mortality and HCC rates compared with proportion tests
Cox proportional hazard models to identify predictors of mortality and the impact of SVR
Veterans Affairs
Backus L, AASLD 2017, Abs. 78

2. Clinical outcome after SVR: Veterans Affairs
Baseline characteristics
Advanced liver disease
No advanced liver disease
No SVR
N = 1 067
SVR
N =
N = 1 308
N =
Mean age, years 62
63.2 *
60.3
61.2 *
Female, % 2 3 4
African American / Caucasian, %
28 / 56
31 / 55
43 / 45
38 / 52 *
History of decompensation, % 35
25 * -
Alcohol abuse, % 30
21 * 27
Hard drug use, % 16
11 * 21
14 *
Albumin (g/dL), mean
3.4
3.6 *
3.9
4.0 *
Platelet count (x 109/L), mean
105
116 *
220
LDV/SOF regimen, % 58 60 64 65
Mean follow-up, days
542
595 *
458
499 *
Death during follow-up, %
18.3
4.3
3.6
1.6
* p < vs no SVR
Veterans Affairs
Backus L, AASLD 2017, Abs. 78 2

3. Clinical outcome after SVR: Veterans Affairs
Survival curves for patients with advanced liver disease
with and without SVR
SVR
No SVR
All-cause mortality free survival
HCC disease free survival
0.4
0.6
0.8
1.0
0.5 1
1.5 2
Log rank p-value < 0.001
0.7
0.8
0.9
1.0
0.5 1
1.5 2
Log rank p-value < 0.001
Years since end of DAA treatment
Years since end of DAA treatment
No SVR
SVR
1 067
13 992
923
12 939
650
9 521
326
5 437
105
1 875
No SVR
SVR
1 067
13 992
923
12 939
650
9 521
326
5 437
105
1 875
Veterans Affairs
Backus L, AASLD 2017, Abs. 78

4. Clinical outcome after SVR: Veterans Affairs
All cause-mortality for patients with no advanced liver disease
with and without SVR
SVR
No SVR
Overall
FIB-4 :
FIB-4 < 1.45
0.5 1
1.5 2
Years since end of DAA treatment
0.9
0.925
0.95
0.975
p < 0.001
Years since end of DAA treatment
0.5 1
1.5 2
0.9
0.925
0.95
0.975
p < 0.001
0.5 1
1.5 2
Years since end of DAA treatment
0.9
0.925
0.95
0.975
p < 0.026
No SVR
SVR
1 306
29 918
1 209
38 143
741
25 126
406
15 308 91
8 537
No SVR
SVR
819
25 457
745
24 412
404
16 808
242
10 084 55
5 530
No SVR
SVR
489
14 461
448
13 737
196
9 318 90
5 221
-inf
3 007
Veterans Affairs
Backus L, AASLD 2017, Abs. 78

5. Clinical outcome after SVR: Veterans Affairs
Mortality and incident HCC rates in patients with advanced liver disease
No SVR
N = 1 067
SVR
N =
Reduction with SVR p
Deaths/100 patient-years (95% CI)
Total
Genotype 1a
Genotype 1b
Genotype 2
Genotype 3
No HCC prior to DAA
HCC prior to DAA
12.3 ( )
12.8 ( )
11.2 ( ) 9.9 ( )
12.8 ( )
10.1 ( )
21 ( )
2.6 ( ) 2.6 ( )
2.5 ( )
2.7 ( )
3.3 ( )
2.3 ( )
7.5 ( )
78.9% -
77.2% 64.3%
< 0.001
1-year mortality rate (95% CI)
11.3 ( )
2.3 ( )
79.6%
HCC/100 patient-years (95% CI) *
11.5 ( )
1.9 ( )
83.5%
1-year HCC rate (95% CI)
9.4 ( )
1.9 ( )
79.8%
* Excludes patients with HCC prior to DAA initiation and HCC diagnosis while on DAA or ≤12 weeks after DAA completion
Veterans Affairs
Backus L, AASLD 2017, Abs. 78 5

6. Clinical outcome after SVR: Veterans Affairs
Mortality rates in patients with no advanced liver disease
No SVR
N = 1 308
SVR
N =
Reduction
with SVR p
Deaths/100 patient-years (95% CI)
Total
Genotype 1a
Genotype 1b
Genotype 2
Genotype 3
FIB-4 < 1.45
FIB
2.87 ( )
2.21 ( )
2.90 ( )
6.44 ( )
3.12 ( )
2.08 ( )
3.36 ( )
1.18 ( )
1.14 ( )
1.27 ( )
1.32 ( )
0.91 ( )
1.13 ( )
1.21 ( )
58.9% -
45.7%
64.0%
< 0.001
0.04
Multivariate model of all-cause mortality after SVR, HR (95% CI)
Advanced liver disease p
No advanced liver disease
0.27 ( )
< 0.001
0.44 ( )
Variables selected a priori : age, gender, race/ethnicity, BMI, HIV, comorbidities, albumin, eGFR, genotype and SVR status
Advanced liver disease model included history of liver decompensation
Non-advanced liver disease model included FIB-4 strata and achievement of HCV RNA < LLOQ on treatment
Veterans Affairs
Backus L, AASLD 2017, Abs. 78 6

7. Clinical outcome after SVR: Veterans Affairs
Conclusions
SVR after DAA was associated with
Significant lower all-cause mortality, regardless of genotype
Reduction of risk of 78.9% in patients with advanced chronic liver disease
Reduction of risk of 58.9% in patients with non-advanced chronic liver disease
Significant lower incidence of HCC
Reduction of risk of 83.5%
Veterans Affairs
Backus L, AASLD 2017, Abs. 78