Hepatitis C and Haemoglobinopathies · Case presentation III November 2014 12 week regimen of...
Transcript of Hepatitis C and Haemoglobinopathies · Case presentation III November 2014 12 week regimen of...
Hepatitis C and Haemoglobinopathies
8th Larissa International Congress of Internal Medicine Satellite Symposium: “Chronic Hepatitis C: Managing Special Populations”
Larissa, March 18, 2016
Manolis Sinakos Lecturer in Internal Medicine & Hepatology, Aristotle University of Thessaloniki
4th Department of Internal Medicine, Hippokratio Hospital
Conflict of interest: Speaker: AbbVie, BMS, Janssen Advisory Board: AbbVie, BMS, Gilead Sponsorship: AbbVie, BMS, Gilead, Janssen
Is this association significant?
Prevalence of hepatitis C
Di Marco et al, Blood 2010
Prevalence of hepatitis C in Greece
Causes of death in patients with thalassaemia
Ann Hematol 2012;91:1451–1458
Causes of death in patients with thalassaemia
Ann Hematol 2012;91:1451–1458
Main mechanisms of liver disease
Liver fibrosis progression
Agelucci et al, Blood 2002
What are the main characteristics of patients with hepatitis C and haemoglobinopathy?
Case presentation I
• Female, 48 years
• BMI 19,5
• History of diabetes type II treated with insulin
• Chelation therapy: deferoxamine+deferiprone
• Genotype 1b infection
• Two previous courses of antiviral treatment
(last with PegIFN+Ribavirin)
Prevalence of HCV genotypes
Di Marco et al, Blood 2010
Kuduras et al, Liver Int 2012
Treatment efficacy
Di Marco et al, Blood 2010
Ribavirin in patients with thalassaemia
• Patients with genotype 1 infection significantly benefit from the addition of ribavirin.
• Using ribavirin is associated with a 30-40% increase in transfusion rates.
Alavian et al, J Viral Hepat 2010
What are the current treatment options?
Treatment recommendations
EASL
Greek guidelines
Prioritization of new treatment regimens (interferon-free) should include patients with haemoglobinopathy.
GENOTYPE 1 Treatment regimen Duration (wks)
PegIFN+Ribavirin 48 or 24
PegIFN+Ribavirin+Sofosbuvir 12
PegIFN+Ribavirin+Simeprevir x12/12 or 36
Sofosbuvir+Ribavirin 24
Sofosbuvir+Simeprevir 12
Sofosbuvir+Daclatasvir (add ribavirin in tx experienced cirrhotics)
12
Sofosbuvir+Ledipasvir (add ribavirin in tx experienced cirrhotics)
12
Paritaprevir/ritonavir+Ombitasvir+Dasabuvir (add ribavirin in subtype 1a)
12
www.keelpno.gr
Sofosbuvir+Daclatasvir+Ribavirin S
VR
12
,
%a
Post-transplant Advanced cirrhosis
Post-transplant Advanced cirrhosis
All Patients GT 1 (Primary Endpoint)
ALLY-1 study
Poordad et al. Hepatology 2016
Sofosbuvir+Ledipasvir
Pooled results from 7 clinical trials in patients with cirrhosis
Reddy et al. Hepatology 2015
211/21
7
12 Weeks 24 Weeks
LDV/SOF + RBV
211/214 212/217
SV
R12 (
%)
215/217
LDV/SOF + RBV LDV/SOF LDV/SOF
64/71 152/159 98/100 22/22
Καταγραφή TARGET
Sofosbuvir+Simeprevir
Paritaprevir/ritonavir+Ombitasvir+Dasabuvir
Feld et al. J Hepatol 2016
Naïve or treatment experienced patients with genotype 1b and compensated cirrhosis
Case presentation II
• Cirrhosis (biopsy proven) – Child-Pugh A
• No ascites or encephalopathy
• HCV RNA 28500 IU/mL
• Hb 8,5 g/dL
• AST 79 IU/mL
• ALT 66 IU/mL
• Creatinine 0,44 mg/dL
• Ferritin 700 ng/mL
GENOTYPE 1 Treatment regimen SVR 12 (%)
PegIFN+Ribavirin
PegIFN+Ribavirin+Sofosbuvir
PegIFN+Ribavirin+Simeprevir
Sofosbuvir+Ribavirin
Sofosbuvir+Simeprevir ~90
Sofosbuvir+Daclatasvir (add ribavirin in tx experienced cirrhotics)
~90
Sofosbuvir+Ledipasvir (add ribavirin in tx experienced cirrhotics)
96
Paritaprevir/ritonavir+Ombitasvir+Dasabuvir (add ribavirin in subtype 1a)
100
www.keelpno.gr
Case presentation III
November 2014
12 week regimen of sofosbuvir+simeprevir was initiated
No concomitant treatment modification
What are the available data in patients with thalassaemia?
Sofosbuvir+Ledipasvir in patients with sickle-cell disease
• 24 patients
• Gen 1 (83%), cirrhosis (33%)
• Mild side effects
• SVR 12: 92%
Basu et al, AASLD 2015
Interferon-free regimens
Sinakos et al, AASLD 2015
N 30
Age, years 45 (35-57)
Male, n (%) 17 (57)
BMI 23.7 (19-27)
PLT*, /mm3 260 (102-561)
Serum albumin, g/dL 3.85 (2.3-4.5)
AST, IU/mL 84 (22-213)
ALT, IU/mL 98 (24-203)
HCV RNA, IU/mL 808,000 (2,000-6,110,000)
Genotype, n (%) 1a 1b
2 3 4
5 (17)
12 (40) 1 (3)
6 (20) 6 (20)
Ferritin, ng/ml 545 (156-1900
LIC**, mg 1.68 (0.87-4.82)
Treatment experience, n (%) 25 (83)
Interferon-free regimens
Sinakos et al, AASLD 2015
Sofosbuvir+Ribavirin (24 weeks) 3 (10)
Sofosbuvir+Simeprevir (12 weeks) 13 (43)
Sofosbuvir+Daclatasvir (12 weeks) 12 (40)
Sofosbuvir+Daclatasvir+Ribavirin (12 weeks) 2 (7)
Results
• No major adverse events or drug-drug interactions.
• Slight increase in transfusion rates in patients receiving ribavirin.
• SVR rates 90% (27/30).
Sinakos et al, AASLD 2015
Interferon-free regimens
Arvaniti et al
Pts Gen Treatment regimen Duration Transfusion AEs
1 1b Ombitasvir/ paritaprevir/ ritonavir + dasabuvir + Riba
12w -
2 1b Sofosbuvir + simeprevir 12w -
3 1b Sofosbuvir + simeprevir + Riba 12w ↑ -
4 1b Sofosbuvir + Daclatasvir 12w Arthralgia
5 3 Sofosbuvir + Daclatasvir 24w -
6 3 Sofosbuvir +Daclatasvir 24w ↑ -
7 3 Sofosbuvir + Daclatasvir 24w -
8 1a Ombitasvir/ paritaprevir/ ritonavir + dasabuvir + Riba
12w
-
9 1a Sofosbuvir + Daclatasvir + Riba 12w -
10 2 Sofosbuvir + Riba 12w ↑ -
Interferon-free regimens
Arvaniti et al
Pts Gen Treatment regimen EOT SVR 12
1 1b Ombitasvir/ paritaprevir/ ritonavir + dasabuvir + Riba
Yes pending
2 1b Sofosbuvir + simeprevir Yes Yes
3 1b Sofosbuvir + simeprevir + Riba Yes Yes
4 1b Sofosbuvir + Daclatasvir Yes pending
5 3 Sofosbuvir + Daclatasvir Yes Yes
6 3 Sofosbuvir +Daclatasvir Yes Yes
7 3 Sofosbuvir + Daclatasvir Yes Yes
8 1a Ombitasvir/ paritaprevir/ ritonavir + dasabuvir + Riba
Yes
Yes
9 1a Sofosbuvir + Daclatasvir + Riba Yes pending
10 2 Sofosbuvir + Riba Yes Yes
Case presentation IV
• Treatment completed.
• No adverse events.
• SVR 12.
Conclusions
• Hepatitis C is a significant cause of liver related morbidity and mortality in patients with haemoglobinopathy.
• Genotype 1b is the predominant genotype.
• The majority of patients are treatment experienced and many of them have advanced liver disease.
• These patients should be prioritized for interferon/ribavirin free regimens.
• The combination of paritaprevir/ritonavir+ombitasvir+dasabuvir for 12 weeks (3D)
seems the most appropriate regimen for these patients.