HEPATOLOGY HIGHLIGHTS Hepatology highlights

Jonathan Stine, Stephen Caldwell
2016 unpublished
Castiella A, et al. Liver iron concentration is not raised in patients with dysmetabolic hyperferritinemia In this issue of Annals of Hepatology, Castiella, et al. examined the relationship between liver iron concentration (LIC), hyperferritinemia and metabolic syndrome in a Spanish cohort of patients. Metabolic syndrome is defined by the presence of at least three of the following: obesity (increased waistline circumference), atherogenic dyslipidemia (hypertriglyc-eridemia and/or low
more » ... nd/or low high-density lipoprotein), hyperten-sion or insulin resistance (elevated glucose levels or frank diabetes). 1 Metabolic syndrome is increasing in prevalence in Western societies and is on the order of 25% of the adult population. 2 Nonalcoholic fatty liver disease (NAFLD) is often observed in concert with metabolic syndrome with similar prevalence rates. 3 Hyperferritine-mia is commonly associated with both metabolic syndrome and NAFLD; a recent report from Chen, et al. found this association in the context of normal hepatic iron concentrations. 4 However, this as well as other reports has been relatively limited in accuracy by the imaging and calculation methods for determining liver iron concentration (LIC). To date, there is conflicting evidence from large-scale randomized clinical trials regarding the clinical importance of treating iron overload in improving histologic or biochemical parameters in metabolic syndrome associated with hyperferritinemia as is commonly seen in NASH/NAFLD. In this paper, the authors conducted a prospective cohort of 132 consecutive adult patients, of which 97 patients were included with complete data, over twelve months from two centers in Basque Country, Spain. Included subjects were referred for evaluation of hyperfer-ritinemia. The authors attempted to determine LIC with greater diagnostic certainty in an effort to compare patients with and without metabolic syndrome. Hyperferritinemia was defined as serum ferritin > 200 ug/L in women and > 300 ug/L in men. LIC values were extracted from magnetic resonance imaging (MRI) by one trained investigator; normal LIC was < 36 umol/g, iron overload 37-80 umol/g and high iron overload > 80 umol/g. The cohort was predominantly male (82%) and 60% (n = 54) met criteria for metabolic syndrome. Patients with metabolic syndrome were similar to those without metabolic syndrome in baseline characteristics (age, alcohol use, concurrent viral hepatitis) and reported laboratory values including ferritin, transferrin saturation index, iron hepatic index, and hemochromatosis predisposing mutations. Thirty-six patients with metabolic syndrome underwent MRI and were compared to 18 without metabolic syndrome. Interestingly, the primary end-point of LIC approached statistical significance with lower mean mean values observed in the metabolic syndrome group (28.8 ± 20.9 umol/g vs. 33.2 ± 19.6 umol/g, p = 0.067). No patients had high iron overload and the hepatic iron index was < 1.5 in all patients. This work confirms that of Chen, et al. 4 and provides further evidence that LIC may not be elevated in patients with hyperferritinemia and metabolic syndrome. Given the trend towards statistical significance, the differences in LIC in bothin the metabolic syndrome and non-metabolic syndrome patient populations should be further studied on a large scale, greater powered basis to further define this relationship. Nonetheless, this study is thought provoking in that patients with metabolic syndrome had lower levels of LIC in the setting of comparable markers of iron saturation. This points towards the importance of fer-ritin as a marker of inflammation rather than clinically important iron deposition in the liver and provides caution when interpreting these values and making subsequent clinical management decisions.