Evaluating the association of serum ferritin and hepatic iron with disease severity in non‐alcoholic fatty liver disease

Abstract

Background & Aims: Hyperferritinemia, with or without increased hepatic iron, represents a common finding in non-alcoholic fatty liver disease (NAFLD). However, it is unclear whether it reflects hepatic inflammation or true iron-overload and, in case the latter is confirmed, whether this influences disease progression. We therefore explored the association between serum ferritin, degree and pattern of hepatic iron deposition and liver disease severity in patients with NAFLD. Methods:We selected 468 patients with biopsy-proven NAFLD from 2 European centres. Iron, hepatic and metabolic parameters were collected at the time of liver biopsy. Iron deposits in hepatocytes and reticuloendothelial cells were assessed and graded. Diagnosis of non-alcoholic steatohepatitis (NASH) and fibrosis staging were performed.Results: A total of 122 (26%) patients had hyperferritinemia, whereas stainable hepatic iron was found in 116 (25%) patients (38% predominantly in hepatocytes, 20% in reticuloendothelial cells and 42% in both). Subjects with stainable hepatic iron, particularly those with a mixed pattern, had higher serum ferritin and transaminases but only a mixed pattern of iron deposition was among the variables significantly associated with presence of NASH. Serum ferritin was not associated with presence of NASH, however it increased with worsening fibrosis stage (F3 compared to F0-F1), and significantly decreased in stage F4. Conclusions:A mixed pattern of hepatic iron deposition is associated with the presence of steatohepatitis, while serum ferritin increases with worsening fibrosis up to pre-cirrhotic stage. In individual NAFLD patients, serum ferritin could be evaluated as part of non-invasive diagnostic panels but not on its own.

Mesenchymal iron deposition is associated with adverse long‐term outcome in non‐alcoholic fatty liver disease

“…Italian study found that the mixed pattern was linked to NASH. 17 Thus, our findings are in support of the relevance of the mesenchymal pattern of iron deposition to be detected in a NAFLD patient.…”

“…6 However, the contribution of excess iron in the aimed to assess disease severity and iron with inconclusive and conflicting results. 8,14,15,17,18 Interventional studies, ie iron depletion via phlebotomies, are few and observational, while one well-designed…”

“…16 Among stainable hepatic iron, the proportions of the various patterns range between 22% and 36% for parenchymal, 21% and 31% for mesenchymal and 43% and 50% for mixed iron distribution. 14,15,17 With regard to the clinical relevance of iron in NAFLD, most studies have examined the link of intrahepatic iron deposition and/or SF concentrations in NAFLD or non-alcoholic steatohepatitis (NASH) with histological characteristics and have obtained conflicting findings. 8,18 Similarly, phlebotomies have been linked to improved clinical findings for various endpoints such as T2DM, insulin resistance or hypertension, while no clear benefit on NAFLD histological severity has been reported.…”

Pathophysiological, Molecular and Therapeutic Issues of Nonalcoholic Fatty Liver Disease: An Overview

“…Moreover, further studies are warranted to understand the real prognostic value of iron deposits at liver biopsy. Interestingly, hyperferritinemia, which probably identifies NAFLD patients with major hepatic iron deposition, has also been demonstrated to be an independent predictor, not only of liver steatosis, but also of fibrosis [199,200,201]. However, it should be mentioned that clinical trials examining the potential therapeutic role of phlebotomy in NAFLD have shown contrasting results regarding any benefits in terms of reduction of liver damage [202,203].…”

Association between Different Animal Protein Sources and Liver Status in Obese Subjects with Non-Alcoholic Fatty Liver Disease: Fatty Liver in Obesity (FLiO) Study

“…However, in inflammatory conditions ferritin concentrations are increased and it is synthesized as an acute phase protein, acting as a pro-inflammatory molecule capable of inducing liver damage. [33,35,36,37]. The potential anti-inflammatory effect and antioxidant capacity of omega-3 PUFAs [38], might ameliorate ferritin pro-oxidant and pro-inflammatory activity, although the exact molecular pathways are yet to be elucidated.…”