1 / 17

Liver Disease and Thalassaemia

Liver Disease and Thalassaemia. George Constantinou. IRON OVERLOAD. VIRUS C INFECTION VIRUS B INFECTION and/or Other infections Hepatotropic agents, e.g. HGV, GBVC, TTV. Causes of liver damage in thalassaemic patients. Iron overload resulting from Blood Transfusions and Hepatitis

cynara
Download Presentation

Liver Disease and Thalassaemia

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Liver Disease and Thalassaemia George Constantinou

  2. IRON OVERLOAD VIRUS C INFECTION VIRUS B INFECTION and/or Other infections Hepatotropic agents, e.g. HGV, GBVC, TTV Causes of liver damage in thalassaemic patients Iron overload resulting from Blood Transfusions and Hepatitis ⇒ SAFE BLOOD AND EFFECTIVE CHELATION ARE ESSENTIAL Limassol 25 October 2012

  3. Progression of Liver Disease FIBROSIS HEALTHY LIVER CIRRHOSIS Limassol 25 October 2012

  4. Clinical course of virus related liver disease CompensatedCirrhosis Resolution Stabilisation Liver Cancer AcuteHepatitis ChronicHepatitis Cirrhosis DecompensatedCirrhosis (Death) 20 - 40 Years Limassol 25 October 2012

  5. HCV Infection: Worldwide Prevalence WHO. Wkly Epidemiol Rec. 2005 Limassol 25 October 2012

  6. Prevalence of HCV serum markers in cohorts of patients with transfusion-dependent thalassaemia born before 1990 (V. Di Marco, M. Capra, et al,) Limassol 25 October 2012

  7. Hepatitis virus infections in thalassaemic patients Prevalence depends on the quality and safety of the blood as well as, on how endemic the virus is at the local and/or regional level Limassol 25 October 2012

  8. Hepatitis C Virus (HCV) infection • Hepatitis C virus is the most common viral infection. • Worldwide 20%-90% of patients with thalassaemia are seropositive for anti-HCV antibodies (Variation is based on the country’s blood service policy) • Chronic HCV infection is more common in patients who had a large number of blood transfusions before 1990. Limassol 25 October 2012

  9. HCV Infection: “The Facts” Estimated global prevalence  3% (170 million persons) Risk of chronicity (variable) 75% - 85% (2) Early fibrosis progression rate : Low Risk of cirrhosis: Up to 10% within 20 years; 20% within 30 years (2) Cirrhosis-related mortality: 1% - 5%/year (3) Incidence of HCC (Carcinoma)1% - 4%/year (2) in patients with cirrhosis: WHO. Hepatitis C. Fact sheet no. 164. 2. CDC. MMWR. 1998;47(RR-19):1-39. 3. CDC. Hepatitis C slide kit. Limassol 25 October 2012

  10. HCV Infection: ‘The Facts’ Estimated global prevalence Risk of chronicity (variable) Early fibrosis progression rate: Risk of cirrhosis: Cirrhosis-related mortality: Incidence of HCC in patients with cirrhosis: ~3% (170 million persons) 75%-85% (2) Low Up to 10% within 20 years; 20%within 30 years (2) 1%-5%/year (3) 1%-4%/year (2) WHO. Hepatitis C. Fact sheet no. 164. 2. CDC. MMWR. 1998;47(RR-19):1-39. 3. CDC. Hepatitis C slide kit.

  11. Comparison of virological response p= 0.04 80 77% 77% 70 64% 60 54% 54% 50 48% 46% 40 46% Virological Response (%) 30 20 10 0 PEG-IFN PEG-IFN plus Ribavirin 48 weeks End of treatment Virologic response ETR Early Virologic Response EVR 4 weeks Sustained Virologic Response SVR Rapid Virologic Response RVR 72 weeks 12 weeks Limassol 25 October 2012

  12. Interferon Once per week - 48 weeks Ribavirin Twice a day - 48 weeks Telaprevir Three times a day - 12 weeks (Boceprevir) New Triple Combination Therapy Limassol 25 October 2012

  13. The new triple treatment was not available to Thalassaemia patients during the clinical trials, as the pharmaceutical companies enrolled patients without additional problems; such as transfusion dependent We set up a group, whose aim was to overcome the pharmaceutical’s exclusion of thalassaemia patients, as the side effects of the drugs relating to anaemia could be well managed. As a result the 1st patients enter the treatment under the company’s ‘Compassionate Use Programme’ Thanks to UK Health Professionals & UKTS Limassol 25 October 2012

  14. RNA is non detectable (less than 140 IU/ml) within 4 -8 weeks of treatment If this does not occur, then the treatment is stopped, as it will not work This is good news, as you will not have to endure 48 weeks of treatment, if it is not working (unless you are unlucky and the virus develops resistance to Interferon, which will be revealed at the end of the treatment) Objective of treatment Limassol 25 October 2012

  15. Patients who had relapsed from previous therapy (Interferon + Ribavirin) Genotype 1 (Genotype 2 was also included, and it worked) Patients able to tolerate the many side effects Candidates for the early access programme: triple therapy Limassol 25 October 2012

  16. Increase in transfusion frequency (50%-70% more) Requiring increase in iron chelation (30%-50% more) Loss of weight Fatigue / Extreme tiredness Interference with sugar levels if you are diabetic. Min 2+ days after the interferon injection, you feel as if you are getting the worse cold of your life. (actually more like having been run over by a lorry!) Psychological anxieties are increased to intolerance levels Intolerance to daily minor problems increases to frightening levels Impacts aspects of everyday life due to above Side effects Limassol 25 October 2012

  17. Success rate: Sustained Viral Response(SVR) of non Thalassaemia patients is 65-85 % (Studies?) So far, 2 Thalassaemia patients have been treated in the UK and a 3rd has just started The side effects, are as close to intolerable as can be (similar to the double combination therapy) Future therapies (such as) Daclatasvir & GS-7977 Clinical Trial This is an only, oral therapy, not using Interferon and/or Ribivirin Conclusion BUT WHAT IS THE ALTERNATIVE ?? Limassol 25 October 2012

More Related