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.