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