In the context of our work and our mission as the international organisation representing and safeguarding the rights of multiply-transfused patients across the world, the Thalassaemia International Federation (TIF) would like to inform you regarding our recent actions on the issue of chronic hepatitis in transfusion dependent patients.
Liver disease in thalassaemia:
Multiply-transfused patients (ß-thalassaemia major and other forms that require occasional transfusions) are vulnerable to infections transmitted through the blood, including hepatitis viruses, especially C and B. Thus, TIF has proceeded to develop a paper expressing its position with regards to chronic hepatitis and more specifically at this point in time that due to the hepatitis C virus (HCV) and the need to treat infected patients promptly and appropriately.
Through this position paper (please find attached) TIF is bringing to the forefront liver disease – a medical consequence of both iron load in the liver and viral infection, mainly caused by transfusion related hepatitis viruses. Liver disease has always been an important cause of morbidity and mortality amongst multiply-transfused patients worldwide, but the high rates of iron-related cardiac complications ranking them as the first cause of morbidity and mortality in this patient population globally, has for many years, left liver disease management unattended or under-recognized as a priority.
Reliable, updated information on the percentage of patients with thalassaemia infected with HCV is still lacking or poorly known in many parts of the world including in those with high local prevalence of the virus. From the published data however, it appears that the magnitude of the problem is great and widely heterogeneous between and within countries but also very strikingly between the developed and developing parts of the world. The differences being that in Europe, North America and other industrialised countries, where the residual risk of transmission of these infections through blood has been reduced to minimal levels, new infections with hepatitis viruses are no longer occurring and the problem lies in those patients that have been infected before the 1990s (before the introduction of HCV screening). On the other hand, in many countries of the developing world these infections still occur and the problem is evident in both the young and older patient population.
With the attached paper, TIF supports the position that the EASL – AASL recommendations for antiviral treatment of HCV infections must be urgently applied to patients with thalassaemia and other transfusion dependent haemoglobin disorders as in the general population.
Experience albeit limited, has shown that ribavirin- related haemolysis and consequent increase of blood transfusion needs and readjustment of iron chelation protocols can be addressed adequately in this population. In any case and until adequate and reliable data becomes available, these patients can be treated effectively on an individual, tailor-based way, given the many other complications (endocrine, diabetes or cardiac) that must be seriously considered prior and during antiviral treatment.
It is well understood that patients with haemoglobin disorders affected by HCV are at a greater risk than those free of this infection, of developing cirrhosis and subsequently Hepatocellular Carcinoma (HCC) – a major cause of liver failure. It is thus essential to treat, as early as possible, infected patients with the best available treatment, aiming to achieve sustainable viral response. In fact on average between 4.4% and 8.54% of patients with thalassaemia are positive to antibodies of HCV. In some industrialised countries, including European ones, and especially in developing ones, the prevalence of HCV infection amongst this population reaches very high levels – between 60 – 80%.
The main goals of antiviral treatment are of course the eradication of the virus, the control of liver inflammation and the prevention of cirrhosis. Unfortunately and despite the magnitude of the problem in these patients as mentioned above, there are still considerable deviations in the majority of countries from prompt diagnosis and regular laboratory and clinical screening and observation of patients with CHC. Equally important is the fact that the greatest number of HCV infected patients with haemoglobin disorders globally do not receive appropriate antiviral treatment.
The limited attention to HCV infection in thalassaemia and the absence of participation of such patients in clinical trials with existing or upcoming new antiviral drugs, constitute important reasons for the lack of adequate information on the natural history, progression, complications and drug-to-drug interactions in this patient population and very importantly on the type of responses to the recommended by EASL – AASL established combined treatment with pegylated interferon and ribavirin.
Indeed, the paucity of a large prospective of clinical trials and the cautionary notes on the use of ribavirin in the face of haemolytic anaemia pose challenges for clinicians and health authorities to proceed to decisions on treatment. It is extremely important in terms of time, for national health authorities and the medical community to consider the treatment of HCV in these patients as an important part of their multidisciplinary care. This is particularly essential in view of the fact that in addition to the existing combined treatment with pegylated interferon and ribavirin, two new drugs have made their way through the regulatory bodies, FDA and EMA, and can now be considered as an additional option to those that do not respond adequately to the established combined treatment and who fulfil the criteria for the triple combined therapy. Already, albeit extremely few, patients are on this triple treatment, mainly those with HCV genotype I that did not respond or partially responded to the established combined therapy.
This position paper also touches on important aspects relevant to the need of the patient community to develop a productive dialogue with the national health authorities, medical community, research institutes and industry in order to promote the inclusion of patients with haemoglobin disorders into safety and clinical trials in order to better understand the profile of complications and responses of this patient population to both the established combined treatment but also to the new authorised drugs and hopefully upcoming ones that are in the pipeline of research.
We would like to see this patient population which constitute the largest group of receivers of blood as a consequence of their disease, receive appropriate treatment and attention promptly and before coming to the sad point of loosing even more patients as a result of CHC-related HCC. Their inclusion in clinical trials and the re-editing of the haemolysis associated precautionary notes on the package leaflet of ribavirin are amongst the major issues on which we would like to seek your advice and support.
TIF is committed to sending this position paper to every health authority across Europe and worldwide, as well as to our global network of medical collaborators. Very importantly TIF is committed to educate its patient members’ globally on liver disease and CHC and advise them on working closely with national health authorities to request urgently the adherence to the EASL – AASL recommendations for individuals infected with HCV.
We seek to support and initiate discussion with your medical specialists and the health authorities on this issue and we would like to kindly request that you pass on this position paper to your focal point in your ministry of health. Your comments are most welcome and we hope to hear from you as soon as possible regarding this important initiative that TIF has undertaken.
This position paper has been solely focused on HCV, as this is according to published data, the most prevalent infection in patients with haemoglobin disorders in Europe. However, there remains an equally important problem related of chronic Hepatitis B, which is widespread particularly outside Europe, in the most populous parts of the world where also haemoglobin disorders are highly prevalent (e.g. South East Asia, West Pacific Region).
TIF will focus equal attention and efforts through the preparation of another position paper, at a later point in time specifically for HBV and co-infections of HBV and HCV.
We look forward to receiving your reply and remain at your disposal for any further information and/or clarification you may require.
Dr Androulla Eleftheriou
TIF Executive Director