From the Guidelines
MAFLD can indeed cause increased iron stores in some patients, as evidenced by the association between hepatic iron accumulation and insulin resistance in non-alcoholic fatty liver disease 1. The relationship between MAFLD and iron accumulation appears bidirectional, with excess iron potentially worsening insulin resistance and liver damage, while the metabolic dysfunction in MAFLD can alter iron metabolism. Key points to consider include:
- The mechanism involves increased intestinal iron absorption, decreased hepcidin production, and inflammatory processes that disrupt normal iron handling.
- Elevated iron levels can exacerbate liver injury by increasing oxidative stress and promoting fibrosis progression.
- Clinically, patients with MAFLD and elevated iron may present with higher serum ferritin levels, though this doesn't always correlate with actual liver iron content.
- For MAFLD patients with confirmed iron overload, therapeutic phlebotomy may be considered alongside lifestyle modifications targeting the underlying metabolic dysfunction, as suggested by the improvement in NAS score without worsening fibrosis in patients undergoing phlebotomy 1. However, it's essential to note that the most recent guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD) do not specifically address the issue of iron overload 1, highlighting the need for further research in this area.
From the Research
MAFLD and Iron Stores
- MAFLD has been associated with increased iron stores, which can contribute to the progression of the disease 2
- A study using Mendelian randomization analysis found that genetically predicted increased liver iron was associated with an increased risk of MAFLD 2
- Another study found that MAFLD was significantly associated with increased serum ferritin levels, which is a marker of iron stores 2
- Iron metabolism dysfunction has been implicated in the pathogenesis of MAFLD, and iron depletion therapy has been shown to be effective in reducing serum aminotransferase levels and improving insulin sensitivity in patients with NAFLD, a precursor to MAFLD 3
Mechanisms of Iron Overload in MAFLD
- Iron overload in MAFLD may be due to a combination of factors, including increased iron absorption and decreased iron excretion 2
- The sub-cellular location of iron deposition in hepatocytes or RES cells may play a role in the impact of iron on the progression of MAFLD 3
- Iron may potentiate the onset and progression of MAFLD by increasing oxidative stress and altering insulin signaling and lipid metabolism 3
Treatment of Iron Overload in MAFLD
- Iron chelation therapy, such as deferasirox, has been shown to be effective in reducing iron burden in patients with iron overload 4, 5
- Phlebotomy has also been shown to be effective in reducing iron burden in patients with iron overload 5
- However, more research is needed to determine the best approach for managing iron overload in patients with MAFLD 2, 6