The incidence of inherited porphyrias in Europe

Abstract

Retrospective estimates of the prevalence of porphyrias have been reported but there has been no large scale prospective study of their incidence. The European Porphyria Network collected information prospectively over a 3 year period about the number of newly diagnosed symptomatic patients with an inherited porphyria (335 patients from 11 countries). Prevalence was calculated from the incidence and mean disease duration. The incidence of hepato-cellular carcinoma (HCC) in acute hepatic porphyria and the prevalence of patients with recurrent acute attacks of porphyria were also investigated. The incidence of symptomatic acute intermittent porphyria (AIP) was similar in all countries (0.13 per million per year; 95 % CI: 0.10 - 0.14) except Sweden (0.51; 95 % CI: 0.28-0.86). The incidence ratio for symptomatic AIP: variegate porphyria: hereditary coproporphyria was 1.00:0.62: 0.15. The prevalence of AIP (5.4 per million; 95 % CI: 4.5-6.3) was about half that previously reported. The prevalence of erythropoietic protoporphyria (EPP) was less uniform between countries and, in some countries, exceeded previous estimates. Fourteen new cases of HCC (11 from Sweden) were reported in patients with acute porphyria. Sixty seven patients (3 VP; 64 AIP: 53 females, 11 males) with recurrent attacks of acute porphyria were identified. The estimated percentage of patients with AIP that will develop recurrent acute attacks was 3-5 %. In conclusion, the prevalence of symptomatic acute porphyria may be decreasing, possibly due to improved management, whereas the prevalence of EPP may be increasing due to improved diagnosis and its greater recognition as a cause of photosensitivity.

Occurrence of Malignant Tumours in the Acute Hepatic Porphyrias

“…In this respect, it is important to state that our data showed an incidence of AHP in our cohort that is similar to that encountered in other European countries (Elder et al 2013). In contrast to most epidemiological studies on the incidence of tumours, which are usually carried out on large cohorts from the general population, this work focuses on a small group of rare hereditary metabolic diseases, which affect only a few individuals.…”

“…Since the first report on the concomitant occurrence of HCC and AIP in 1984, several studies have shown an association between this type of primary liver cancer and the AHPs in Europe (Lithner and Wetterberg 1984;Hardell et al 1984;Bengtsson and Hardell 1986;Tidman et al 1989;Grabczynska et al 1996;Andersson et al 1996;Linet et al 1999;Andant et al 2000;Schneider-Yin et al 2009;Innala and Andersson 2011;Elder et al 2013;Sardh et al 2013). However, some of the aforementioned studies linking HCC to AHP certainly include cases in which there were further risk factors.…”

“…The incidence of AHP in our cohort was calculated as the ratio of the number of symptomatic patients who were first diagnosed between January 2007 and December 2009 to the number of patient-years corresponding to the reference population in that period, according to Elder et al (2013). The prevalence was calculated as the product of the incidence rate and the mean duration of disease.…”

“…The prevalence was calculated as the product of the incidence rate and the mean duration of disease. As mean duration of disease, 45 years was used for AIP and 40 years for VP, in accordance with Elder et al (2013) To calculate confidence intervals, a Poisson distribution was assumed for the observed cases (Ulm 1990). The relative risk for developing HCC was measured by the ratio of the observed number of HCC cases among porphyric patients to the number of expected HCC cases to be among them (Kauppinen and Mustajoki 1988;Andant et al 2000).…”

“…Well-known risk factors for the development of HCC include alcohol ingestion, hepatitis B and C virus infection and liver cirrhosis (Hardell et al 1984;Fattovich et al 2004). Several mortality and case-control studies have demonstrated an association between this type of liver cancer and the AHPs in Europe (Lithner and Wetterberg 1984;Bengtsson and Hardell 1986;Kauppinen and Mustajoki 1988;Andersson et al 1996;Linet et al 1999;Andant et al 2000;Schneider-Yin et al 2009;Innala and Andersson 2011;Elder et al 2013;Sardh et al 2013). Concerning other malignant tumour entities, however, systematic studies on their occurrence in AHP patients have not yet been conducted.…”