As shown in Fig. 1, we identified 590 articles, of which 252 were duplicates and were hence removed. Fifty-five articles were excluded based on title and abstract screening. Other studies that did not fulfil the eligibility criteria, i.e. review articles, systematic reviews, abstracts, poster presentations, and studies not reporting full or partial economic evaluation of HH, were also excluded (n = 244). Of 590 identified records, 39 were selected for inclusion in our systematic review.

PRISMA flow diagram of the literature search and selection of articles included in this systematic review. PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analyses, HH hereditary hemochromatosis

A summary of the study characteristics of all the articles included in this current study is reported in Tables 1, 2, and 3. The studies were variable and the study design included population, intervention, comparator, intervention duration, outcomes, perspectives, and ICER; the QALYs were heterogeneous.

Thirty-three percent of the studies evaluated the modeled screening programs over a lifetime [19,20,21,22,23,24,25,26,27,28,29,30,31]. Six studies were conducted in Canada [7, 19,20,21, 23, 35], 13 in the US [24, 25, 30, 34, 37, 39, 40, 45, 48, 49, 52, 53, 55], 3 in Germany [22, 31, 47], 2 in Norway [32, 33], 3 in The Netherlands [29, 50, 51], 4 in the UK [28, 36, 38, 41], 6 in Australia [26, 27, 42,43,44, 46], 1 in Switzerland [54], and 1 in Italy [56]. The timeline of publications was from 1992 to 2020, and the currency evaluated was €, Canadian dollars (CAN$), US dollars (US$), Australian dollars (AUS$), and Great Britain pounds (£). Other than the original cost values in the original currency (outcome, ICER), we also added two additional columns reporting all the current cost values in the original currency, as well as the cost values in the current currency (€). Taking into consideration the heterogeneity of all the economic published data, we expressed the cost data in the same year using the standard inflator for the country on which the analysis is focused. The average daily exchange rates for the period from 1 January 2023 to 30 June 2023 were taken into consideration when calculating the cost values in the current (€) currency.

The majority of the studies reported both phenotype screening, including TS, serum ferritin, and liver biopsy, and genotype screening (HFE screening, C282Y mutation) [7, 20,21,22,23, 25,26,27, 29, 30, 32, 35, 36, 38, 42]. A few studies reported on phlebotomy and erythrocytapheresis treatment [50,51,52,53,54,55,56].

Of the 39 papers accepted, most studies used a cost-effectiveness analysis (n = 20) [7, 19, 21,22,23,24,25,26,27, 29, 31, 32, 34, 36,37,38, 41, 48, 49]; 23.1% of studies used a decision tree (n = 9) [17, 18, 21, 24, 25, 30, 35, 37, 40]. There were eight non-experimental screened studies that included a cost description [28, 30, 42, 43, 45, 47, 52, 53]. Four studies employed a cost-utility analysis [19, 20, 33, 44], and a Markov model was applied in four studies [22, 24, 27, 33].

Overall, 12.8% of studies reported an annual discount rate of 3%, while other studies reported a discount rate of 5% [31] or 0–7% [27]. No discounting of costs was reported in 80.5% of screening studies [7, 21, 28,29,30, 32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,