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Het nut van het behalen van een SVR
Raoel Maan, MD
Erasmus MC, Rotterdam
Department of Gastroenterology and Hepatology
Het nut van het behalen van een SVR
Disclosures
Honoraria for consulting: AbbVie
• Chronic infection with the hepatitis C virus (HCV) may cause
hepatic fibrosis, and eventually cirrhosis
• The incidence of HCV-induced cirrhosis is increasing1,2
• In case of cirrhosis
– Liver failure
– Hepatocellular carcinoma (HCC)
Liver transplantation / death
• Extra-hepatic symptoms already before advanced liver disease
HCV infection as health problem
1Davis Gastroenterology 2010, 2Buti J Hepatol 2005
Natural History of HCV-infection
• R.E.V.E.A.L. study from
Taiwan
• N=19 636
• Mean follow-up: 16.2y
• Chronic HCV infection
was associated with
increased risk of
all-cause mortality
1Lee J Infect Dis 2012
Antiviral therapy
• Antiviral therapy may clear the viral infection:
Sustained Virological Response (SVR)
1Swain Gastroenterology 2010
• SVR reached with IFN-therapy has
long-term durability1
• Marker of successful therapy in
and out of clinical trials
SVR rates have increased!
Recent advances: who needs interferon anymore?
0
10
20
30
40
50
60
70
80
90
100
company1
company2
company3
company4
Overall
IFN-experienced
Cirrhotics
SVR (%)
Interferon-free regimens
• SVR is not the goal of antiviral therapy
• We treat patients in order to:
− Increase health-related quality of life
−Reduce liver-related morbidity
− Improve life expectancy
The goal of antiviral therapy
Randomized placebo-controlled trials showing a clear clinical
benefit of antiviral therapy are lacking
• Fatigue as most common physical complaint
– N=161 patients who attained SVR with PegIFN and RBV1
– Proportion with fatigue decreased from 53% at baseline to 33% 24 weeks
post treatment (p<0.001)
• Health-related quality of life (HR-QOL)
– Systematic review of 9 studies2
– The HR-QOL improved among patients with SVR, but not among patients
without SVR
Patient-reported outcome measures
1Sarkar J Hepatol 2012, 2Spiegel Hepatology 2005
All-cause mortality according to response
Mortality according to response
0 2 4 6 8 100
10
20
30
years
Perc
en
t d
eceased
p<0.001
Time - years
Cumulative mortality (%)
Without SVR
With SVR
30
8.9%(95%CI 3.3-14.5)
26.0%(95%CI 20.2-28.4)
Van der Meer JAMA 2012
• 530 patients with Ishak F4-6 • Median Follow-up: 8.4 years
0 1 2 3 4 5 6 7 8 9 100
10
20
30
Time - in years
Liv
er
Failu
re (
%)
Adjusted HR of SVR:
0.07 (95%CI 0.03-0.20)
p<0.001
0 1 2 3 4 5 6 7 8 9 100
10
20
30
Time - in years
HC
C (
%)
Adjusted HR of SVR:
0.19 (95%CI 0.08-0.44)
p<0.001
Without SVR
With SVR
Without SVR
With SVR
p<0.001
p<0.001
Liver failure and HCC
Van der Meer JAMA 2012
Van der Meer JAMA 2014
100
90
80
70
60
2 3 4 5 6 7 8 9 1010Time - Years
Cumulative survival (%)
Comparing to the general population
Matched Dutch Population
SVR
91%(95%CI 86-97)
p=0.571
non-SVR
p<0.00174%(95%CI 72-80)
Hsu et al. Gut 2015
Extrahepatic manifestations
• 1000 SVR patients with advanced fibrosis followed for a median of 5.7 years
Van der Meer AASLD 2013
Meta-analyses based on individual patient data
0 1 2 3 4 5 6 7 80
2
4
6
8
10
12
14
years
Perc
en
t d
eceased
0 1 2 3 4 5 6 7 80
2
4
6
8
10
12
14
years
Perc
en
t d
eceased
p=0.006
9.7%
2.6%
>60 years
45-60 years
<45 years
12.2%
Time – years
Cirrhosis (85%)
Severe Fibrosis (15%)
p=0.064
8.5%
1.8%
Time – years
Cumulative HCC occurrence (%) Cumulative HCC occurrence (%)
• SVR is likely to result in a beneficial clinical outcome, with a
prolonged overall survival as most important endpoint
• SVR results in a lower incidence of extrahepatic manifestations
and improves quality of life
• Achievement of SVR does not dismiss a cirrhotic patient from
HCC surveillance!
Conclusions
Het nut van het behalen van een SVR
Raoel Maan, MD
Erasmus MC, Rotterdam
Department of Gastroenterology and Hepatology
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