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Haemochromatosis: the need for an agreed case definition
Journal of Hepatology 43 (2005) 911–912 www.elsevier.com/locate/jhep
Letters to the Editor
Haemochromatosis: the need for an agreed case definition To the Editor: We were pleased to read the editorial that accompanied the publication of our study [1]. We would like to address one comment that was made. Professor Olynyk queried our allocation of patients to treatment. We failed to explain clearly that any individuals with ferritin levels above the upper limits of normal who were not offered venesection were monitored with repeat ferritin and transferrin saturation at 3 months, followed by a recommendation to their family doctor for further monitoring or referral for treatment should there be evidence of iron accumulation. This strategy reflects the current clinical uncertainty concerning the natural history of iron overload in patients such as these. Despite attempts to reach consensus over the clinical case definition of haemochromatosis further clinical research is required to determine the prognosis of HFE mutations and iron overload. We would urge
clinicians and researchers in this area to consider this problem. Christine Patch1, Paul Roderick1, William Rosenberg2 1 Applied Clinical Epidemiology Group, University of Southampton, UK, 2 Division of Inflammation, Infection and Repair, University of Southampton, UK E-mail address: [email protected]
Reference [1] Olynyk JK, Trinder D, Milward E. Hereditary haemochromatosis: To screen or not to screen? J Hepatol 2005;43:9–10. doi:10.1016/j.jhep.2005.09.001
Liver and AIDS mortality in HIV-infected patients To the Editor: In their study of HIV patients’ mortality, Salmon et al. confirm that in France, similar to the USA, hepatitis B as much as hepatitis C is associated with substantial liver mortality in patients with HIV infection [1-3]. Previous prospective cohort studies have reported causes of death in a non competing fashion [2,3]. The French group chose to attribute death causality in a dichotomous fashion. In some cases it may have been difficult to positively ascertain whether the cause of death was only HIV- or liver-related. Patients with HCV coinfection may have been treated and that effect was not reported. This would have been important since deceased patients that were not HCV RNA positive (or had missing data) were less likely to be classified as a ‘liver death’, raising the possibility that successful treatment results in improved prognosis [1]. Indeed, the authors point out that HBV may have been partially treated by lamivudine as part of many antiretroviral regimens, and therefore the outcome of untreated HBV in HIV patients may have been even worse [2]. In addition, the authors appropriately point out the major finding that alcohol abuse, as defined, is present in greater than 50% of patients in the coinfected HCV, HCV/HBV and the HIV alone groups. This important finding for both patients and care providers, was unfortunately not stressed in the abstract.
Another noteworthy finding was that patients with the longest estimated duration of HIV infection (HIV/HCV/ HBV, 12.4 years) were those with the highest likelihood of a ‘liver’ death (44%) and the lowest ‘AIDS’ death (22%). The contrary was true for the HIV alone group that had the shorter HIV duration (5.7 years) and the lowest ‘liver deaths’ (2%) and the highest ‘AIDS’ death (60%). Thus, there were strong correlations between HIV duration and ‘AIDS’ (RZK0.92) and ‘Liver’ mortality (RZC0.89). Assuming that the estimated HIV duration was correct, it appears that patients with viral hepatitis may not have suffered an adverse prognosis in terms of ‘AIDS’ mortality. Finally, I would like to point out that while the percentage of liver deaths (the denominator being total deaths) has increased in the HAART era, the risk of liver death, adjusted for initial CD4 counts has actually significantly decreased after 1996 [3].
Maurizio Bonacini California Pacific Medical Center, 2340 Clay Street, 2nd floor, 94115 California, San Francisco, USA E-mail address: [email protected]
Letters to the Editor
Haemochromatosis: the need for an agreed case definition To the Editor: We were pleased to read the editorial that accompanied the publication of our study [1]. We would like to address one comment that was made. Professor Olynyk queried our allocation of patients to treatment. We failed to explain clearly that any individuals with ferritin levels above the upper limits of normal who were not offered venesection were monitored with repeat ferritin and transferrin saturation at 3 months, followed by a recommendation to their family doctor for further monitoring or referral for treatment should there be evidence of iron accumulation. This strategy reflects the current clinical uncertainty concerning the natural history of iron overload in patients such as these. Despite attempts to reach consensus over the clinical case definition of haemochromatosis further clinical research is required to determine the prognosis of HFE mutations and iron overload. We would urge
clinicians and researchers in this area to consider this problem. Christine Patch1, Paul Roderick1, William Rosenberg2 1 Applied Clinical Epidemiology Group, University of Southampton, UK, 2 Division of Inflammation, Infection and Repair, University of Southampton, UK E-mail address: [email protected]
Reference [1] Olynyk JK, Trinder D, Milward E. Hereditary haemochromatosis: To screen or not to screen? J Hepatol 2005;43:9–10. doi:10.1016/j.jhep.2005.09.001
Liver and AIDS mortality in HIV-infected patients To the Editor: In their study of HIV patients’ mortality, Salmon et al. confirm that in France, similar to the USA, hepatitis B as much as hepatitis C is associated with substantial liver mortality in patients with HIV infection [1-3]. Previous prospective cohort studies have reported causes of death in a non competing fashion [2,3]. The French group chose to attribute death causality in a dichotomous fashion. In some cases it may have been difficult to positively ascertain whether the cause of death was only HIV- or liver-related. Patients with HCV coinfection may have been treated and that effect was not reported. This would have been important since deceased patients that were not HCV RNA positive (or had missing data) were less likely to be classified as a ‘liver death’, raising the possibility that successful treatment results in improved prognosis [1]. Indeed, the authors point out that HBV may have been partially treated by lamivudine as part of many antiretroviral regimens, and therefore the outcome of untreated HBV in HIV patients may have been even worse [2]. In addition, the authors appropriately point out the major finding that alcohol abuse, as defined, is present in greater than 50% of patients in the coinfected HCV, HCV/HBV and the HIV alone groups. This important finding for both patients and care providers, was unfortunately not stressed in the abstract.
Another noteworthy finding was that patients with the longest estimated duration of HIV infection (HIV/HCV/ HBV, 12.4 years) were those with the highest likelihood of a ‘liver’ death (44%) and the lowest ‘AIDS’ death (22%). The contrary was true for the HIV alone group that had the shorter HIV duration (5.7 years) and the lowest ‘liver deaths’ (2%) and the highest ‘AIDS’ death (60%). Thus, there were strong correlations between HIV duration and ‘AIDS’ (RZK0.92) and ‘Liver’ mortality (RZC0.89). Assuming that the estimated HIV duration was correct, it appears that patients with viral hepatitis may not have suffered an adverse prognosis in terms of ‘AIDS’ mortality. Finally, I would like to point out that while the percentage of liver deaths (the denominator being total deaths) has increased in the HAART era, the risk of liver death, adjusted for initial CD4 counts has actually significantly decreased after 1996 [3].
Maurizio Bonacini California Pacific Medical Center, 2340 Clay Street, 2nd floor, 94115 California, San Francisco, USA E-mail address: [email protected]