THE NEWCASTLE UPON TYNE HOSPITALS NHS FOUNDATION TRUST
HEPATITIS E-SCREENED BLOOD PRODUCTS
- HEPATITIS E BACKGROUND
Hepatitis E is a mild form of liver infection due to anon-enveloped virus. There has been an increase in reported infections within the UK and other parts of Europe. Transmission of infection is mainly by undercooked pork products from Europe. There is clear evidence that the virus may be transmitted by blood transfusion. In most patients the result is mild and usually sub-clinical. In heavily immunosuppressed patients, however, it may cause a prolonged or more serious hepatitis.
The latest study showed that about 1 in 2,500 donor units were Hepatitis E PCR positive and thus their blood potentially infective. About one in two patients receiving PCR positive blood will develop infection, though mainly subclinical. No deaths had been recorded as directly due to transfusion transmitted Hep E in the UK by mid 2015 but where a patient develops abnormal liver function tests it may either be mistaken as other disease and treatment altered inappropriately, or may affect what treatments are given because of the liver damage. Undetected, it may lead on to cirrhosis. Therefore it must be considered clinically relevant.
- SABTORULING
The DHAdvisory Committee on the Safety of Blood and Transplanted Organs (SaBTO) has ruled that solid organ transplant patients and bone marrow stem cell transplant patients should receive Hepatitis E PCR negative blood components.That the advice has been accepted and endorsed by the Minister for Health, based on the costings presented to him. NHSBlood and Transplant has additionally elected to provide the same to neonates and paediatric components, though these were not included in the original recomendation.
Extract of the minutes of an extra-ordinary meeting of SABTO July 7th 2015:
8.2.1 SaBTO recommends selective testing to provide HEV tested blood
components for patients having solid organ and allogeneic (donor) stem cell
transplants. Screening will be carried out on pools of 24 donations and donors who
test positive will have a 6 month deferral with testing for viral clearance before return
to donation. This is not expected to have a significant effect on supply of blood
components. This recommendation will be reviewed in 3 years.
- LIKELY COST TO THE TRUST
It is estimated that the numbers of blood products issued to transplant patients is 10,000 per annum. Some of these components are issued but not transfused and then returned to stock. About 2/3rds are transfused to a transplant recipient (see table below).
NHSBT and the National Commissioning group (NCG) for blood components has announced that as from 1st April 2016 they will place an additional charge of £17.18 on Hep E PCR negative components. The total cost will therefore be around £170,000 per annum for the Trust. This assumes that we are able to direct Hep E negative products at these groups only and that we are able to accurately identify those who require these components.
Further,softer guidance has now been issued by a joint working group of Sabto and the British Bone Marrow Transplantation Society. This recommends the use of Hep-E PCR negative blood in patients with a high transfusion burden who are potential allogeneic (not autologous) stem cell transplant recipients. This means that patients who are transplant eligible and who have acute leukemia or aplastic anaemia should receive Hep E negative components from diagnosis. It is likely that other clinicians within the hospital will request PCR tested components for their patients e.g. paediatric immunology patients in the lead up to transplantation, renal dialysis patients on the transplant waiting list, patients who have received rituximab (a known risk factor for various types of hepatitis) and patients with significant pre-existing liver disease. This could further increase demand and costs. We are currently evaluating possible costs on the haematology ward outside direct transplant. It is possible that a further 5-10,000 units may be required if we followed this path.
Risk of Hepatitis E from transfused blood and cost of avoidance
To put the risks in context:
Incidence of Hep E pcr positive donations 1 in 2800 unitsCost of prevention £48,000
Risk of infection 1 in 5000Cost of prevention £86,000
Risk of clinical disease*(~1 in 2 infections) 1 in 10,000Cost of prevention £172,000
Risk of significantdisease$(~? 1 in 5infs)1in25,000 Cost of prevention £428,500
Risk of death or disability£ ??1 in 100,000 Cost of prevention £1,714,000
We transfuse 27,000 red cells (least infective component), 7000 platelets and 5000 units of FFP (most infective component). Based on frequency of infection with different PCR +vecomponents (25% RCs, 50% Platelets, 100% FFP) we would expect six to seven transmissions per year in this trust. Of these, perhaps half would be to immunosuppressed patients. We might see one case of ‘clinical’ disease per year.
*Clinical disease : Symptoms or a rise in liver enzymes, Incidence based on Hewitt et al Lancet 2015.
$ Significant disease: Change in treatment or use of anti-viral
£ In the study of Hewitt et al 43 patients received PCR +ve donations. Cost of screening to prevent this would have been £2.1 million (43X2848x£17.14). No deaths or disability were ascribed to the infection. One patient had ribavirin, and one had a immunosuppressive drug dose alteration. Some patients did die during follow up with active viraemia, but not reported to be as a result of the viraemia. These 43 patients were not selected as high risk(immunosuppressed) , but of the 18 with proven transmission 4 were considered high risk and a further 5 were considered moderate risk. Ie perhaps 50% were immunosuppressed. We do not know the risk profiles of those 25 patients not developing proven infection. TargettingPCR negative components to high risk patients only will be more cost effective perhaps by a factor of about 2-3
Hepatitis E acquired through diet is currently running at a rate of around 1 in 5-600 population per year,i.e. the risk from a single unit of plasma rich component is equivalent to the risk of an unrestricted diet for about 5-6 weeks. Avoiding processed pork in the diet would however substantially reduce the dietary risk.
- NATIONAL COMMISIONING GROUP FOR BLOOD PRICES
Extract from November memo of the National Commissioning Group for Blood Components:
The risk of transfusion transmitted hepatitis E virus (HEV) infection has beenreviewed by SaBTO at two meetings during 2015. SaBTO subsequentlyrecommended the selected testing of blood donations that are used tomanufacture blood components for use by organ and stem cell transplantrecipients. The NHSBT Board agreed to implement this recommendation andextend the suggested selected testing to incorporate all neonatal bloodcomponents. This has been built into our commissioning plan in two ways:
a)For blood components that will be HEV negative as part of their standardspecification (intrauterine, neonatal and paediatric packs and granulocyteconcentrates), the costs have been built into prices as a development(£0.2m).
b)For other blood components, which would be ordered as HEV negative foradult solid organ or stem cell transplant recipients, an added valuecharge (add-val) has been incorporated into the price list (£1.1m).
- OPTIONS
Options for the Trust include the following.
(i)Absorb the costs
(ii)Complain to DH that the Trust needs recompense
(iii)Increase transplant prices by appropriate amount
(iv)After risk assessment to not use Hep E negative products in these cases.
Risks include creeping expansion of requests for Hep E PCR negative products for other patient groups, e.g.all paediatric haemato-oncology,liver failure patients. In addition, there could be criticism by CQC and/or MHRA and legal action in case of clinical cases with clinical harm if we do not follow DH/Sabto guidance.
- RECOMMENDATION
To i) receive the briefing and note the content and ii) determine whether or not to absorb the increased costs of Hepatitis E-screened blood products.
Dr Jonathan Wallis
Clinical Director – Blood Sciences
16th March 2016
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