Elsevier

Journal of Hepatology

Volume 33, Issue 3, September 2000, Pages 496-504
Journal of Hepatology

EASL International Consensus Conference on Haemochromatosis: Part III. Jury Documen,

https://doi.org/10.1016/S0168-8278(01)80875-8Get rights and content

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Preamble

This document summarises the conclusions of a Consensus Panel (hereafter called “the Panel”) convened by the European Association for the Study of the Liver in the framework of an International Meeting on Haemochromatosis held in Sorrento (Italy) on May 23–29, 1999. This panel was assembled as an independent group of experts from various disciplines, including: genetics, epidemiology, health services research, health educators, clinical pharmacologists, clinicians and a patient advocate.

These

1.1 General definition

Haemochromatosis (HC) is a condition in which iron loading of the liver, pancreas, heart, and other organs impairs the function and damages the structure of these organs1. Hereditary HC - synonymous with primary iron overload or primary HC - is a disorder due to inappropriately increased iron absorption in which iron loading of parenchymal cells in the liver, pancreas, heart and other organs impairs the function and damages the

2.1. Epidemiology

According to a recent review of epidemiologic data carried out by the French Agency for Accreditation and Technology Assessment (ANAES) the worldwide prevalence of hereditary HC in people aged 18–70 is between 1.5 and 3 per thousand. In more recent studies these values have been somewhat higher, ranging between 1.6 and 5.9 per thousand. The male/female ratio is 2.2 to 1; women may develop symptoms at a later age and in a milder form, probably due to repeated blood losses from menstruation and

3. What is the Clinical Course of Hereditary HC?

There are no inception cohort studies that can determine the course of hereditary HC in any population. The best available information was cited in the Expert Group's review document and is derived from the account of the long-term case series from Düsseldorf reported by Niederau and colleagues (4). This cohort of 251 patients was compared with age- and sex-matched control subjects but contained a high proportion of patients with cirrhosis and diabetes. Life expectancy in those patients who

4. What is the Best Diagnostic Strategy?

The Panel considered papers presented by the Expert Group and additional information concerning diagnostic tests in the investigation of the individual diagnosis of hereditary HC.

5. What are the Priorities for the Education of Patients and Health Care Providers?

The Panel agreed that underdiagnosis of hereditary HC is a problem that should be addressed through the education of physicians in primary care practice. The Panel also agreed that a significant barrier to conveying this message effectively was that physicians believe that they rarely encounter cases of hereditary HC in their practices. Therefore, it is suggested that a message be crafted which will persuade primary care physicians of the advantage of maintaining a high index of suspicion with

6. What are the Ethical, Social and Policy Issues in Population Screening for Hereditary HC?

The central ethical and policy questions are whether the benefits of screening outweigh the costs to a sufficient degree to justify general screening on public health grounds, and whether and how to allow individuals to make informed choices about participating in screening, either for research or therapeutic reasons.

As with any other test for genetic susceptibility, informed consent is considered necessary before beginning the testing process. In addition, whether or not mutation analysis is

7. Is Population Screening Warranted?

The majority of the Panel believes that there is today insufficient evidence to recommend universal, population-based screening for hereditary HC using haematological indices. As far as genetic testing is concerned, the Panel is aware that screening programmes are going to be implemented based on consideration of the high prevalence of the predisposing gene in certain populations. It should be clear that if such programmes were introduced at present, this would be in the absence of good

8. What are the Research Priorities?

The Panel believes that it should be a priority to conduct population studies that attempt to avoid ascertainment bias in order to establish the overall health impact of hereditary HC. These studies should:

  • Determine the prevalence of hereditary HC in defined populations.

  • Determine in the same populations the frequency of the heterozygous and homozygous states for C282Y and H63D mutations.

  • Derive age-specific penetrance.

  • Describe the spectrum of clinical manifestations and the variability of

Future Directions

The Panel expressed the view that it would be unethical to conduct a trial that would randomise hereditary HC patients to no treatment. However, information about the course of untreated and treated disease could be obtained from future studies that employ screening methods. These might include cross-sectional studies of the spectrum of disease in a range of patients at different stages of disease, identified through screening programmes. Carefully designed pilot screening programmes which

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Co-sponsored by the World Health Organization

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The views expressed in the jury document are not necessarily those of the WHO Secretariat.

Supported by the National Institutes of Health and the Centers for Disease Control and Prevention (USA)

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The views expressed in the jury document are not necessarily those of the WHO Secretariat.

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Members of the Panel: Alessandro Liberati (Chairperson, methodologist), Jean P. Benhamou (Hepatologist), Albert Berg (Methodologist), Suzanne Braga (Medical geneticist), Dorit Carmelli (Genetic epidemiologist), Timothy Cox (Internist), Janet Fernau (Haemochromatosis Association), Norman Fost (Bioethicist), Lucio Luzzatto (Haematologist-Geneticist), Nicola Magrini (Clinical pharmacologist), Michael Manns (Hepatologist), Nancy Press (Social scientist), William Rosenberg (Clinical epidemiologist and hepatologist), Juan Rodés (Hepatologist), Gilbert H. Welch (Health policy and Screening). Writing Committee: Albert Berg, Timothy Cox, Norman Fost, Alessandro Liberati, Lucio Luzzatto, Nancy Press and William Rosemberg.

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