Aktuelle Leitlinien der Hepa00s Hepa00s C – Stand 2017
Prof. Dr. Stefan Zeuzem
Universitätsklinikum Frankfurt a.M.
Global burden of HCV
§  Estimated that 80 million people are living with chronic HCV worldwide
Viraemic prevalence
0.00–<0.75%
0.75–<1.25%
1.25–<1.75%
1.75–<2.5%
≥2.5%
§  Annually ~700,000 people die from HCV-related complications such
as cirrhosis and hepatocellular carcinoma
WHO. Global report on access to hepatitis C treatment – focus on
overcoming barriers. Available at: http://www.who.int/hepatitis/publications/hepc-access-report/en/ (Accessed February 2017);
Image taken from Gower J, et al. J Hepatol 2014;61:S45–57
Reprinted with permission from Elsevier. Copyright © 2014 European Association
for the Study of the Liver. Published by Elsevier Ireland Ltd
HCV Cure Decreases Mortality from Both Hepa7c and Non-­‐hepa7c Diseases 23,820 adults in Taiwan; 1095 anti-HCV positive,
69.4% with detectable HCV RNA
HCV seropositive, HCV RNA detectable
HCV seropositive, HCV RNA undetectable
HCV seronegative
Extrahepatic diseases
Hepatic diseases
20
18
p<0.001 for comparison among three groups
p<0.001 for HCV RNA detectable vs undetectable
16
14
12.8%
12
10
8
6
4
2
0
1.6%
0.7%
0
2
4
6
8
10
12
14
Follow-up (years)
Lee MH, et al. J Infect Dis 2012;206:469–77
16
18
20
Cumulative mortality (%)
Cumulative mortality (%)
20
19.8%
18
p<0.001 for comparison among three groups
p=0.002 for HCV RNA detectable
vs undetectable
16
14
12.2%
11.0%
12
10
8
6
4
2
0
0
2
4
6
8
10
12
14
Follow-up (years)
16
18
20
Replika7onszyklus des Hepa77s C Virus und Angriffspunkte der an7viralen Medikamente Rezeptorbindung
und Endozytose
Transport und Freisetzung
NS5A-Inhibitoren
(….asvir)
Fusion
NS3/4AProteaseInhibitoren
(….previr)
(+) RNA
Zusammensetzung
der Virionen
RNA Replikation
Translation und Polyprotein Prozessierung
NS5BPolymerase
Inhibitoren
(….buvir)
Zeuzem, Dtsch Ärztebl Int 2017;114:11-20
EASL recommendations 2016: all patients
should be considered for treatment of Hepatitis C
OMV/PTV/
SOF/VEL RTV + DSV OMV/PTV/ GRZ/EBV SOF + DCV SOF + SMV
± RBV
± RBV
± RBV
± RBV RTV ± RBV ± RBV
SOF
+ RBV
LDV/SOF
± RBV
GT 1
û
P
P
P
û
P
P
Suboptimal
GT 2
Suboptimal
û
P
û
û
û
P
û
GT 3
Suboptimal
û
P
û
û
û
P
û
GT 4
û
P
P
û
P
P
P
P
GT 5
û
P
P
û
û
û
P
û
GT 6
û
P
P
û
û
û
P
û
EASL. J Hepatol 2017;66:153–94
SOF + DCV ± RBV is not approved in the EU for GT 2, GT 5 or GT 6 patients.
Regimens not included in the SmPC posology table (Table 1) are shown in grey.
EASL: European Association for the Study of the Liver
Special considerations
§  In patients with GFR < 30 ml/min: limited experience with
sofosbuvir (not approved)
§  In patients with decompensated liver cirrhosis: protease
and non-nucleosidic polymerase inhibitors contraindicated
§  Consider drug-drug interactions (in particular in HIV/HCV
coinfected patients, transplanted patients, etc.)
§  Limited data in children (largest studies with SOF/LED)
§  Timing of DAA treatment under discussion in patients with
chronic hepatitis C and HCC treated with curative
intention
§  New treatment options in patients who have failed a DAA
regimen
Conclusions •  Currently approved regimens have high antiviral
activity and are safe and well tolerable
•  Sofosbuvir/Ledipasvir and 3D-regimen: 8 wks are
sufficient in non-cirrhotic, treatment-naïve patients
•  Sofosbuvir/Velpatasvir: first truly pan-genotypic
regimen
•  Glecaprevir/Pibrentasvir: second pan-genotypic
regimen
•  Grazoprevir/Elbasvir and Glecaprevir/Pibrentasvir:
highly active and safe in end-stage renal disease
•  No protease inhibitors in CPT B and C patients
•  Triple therapies as salvage treatment options in
DAA failure patients
•  Be cost-conscious !