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

Area of Science:

• Hepatology
• Internal Medicine
• Pathology

Background:

• Non-alcoholic fatty liver disease (NAFLD) affects a significant portion of the population.
• Approximately one-third of NAFLD patients exhibit mild-to-moderate iron overload.
• The clinical impact of hepatic iron deposition in NAFLD remains unclear.

Purpose of the Study:

• To investigate the long-term clinical impact of histological iron deposition in patients with biopsy-proven NAFLD.
• To determine the association between different patterns of hepatic iron deposition and patient outcomes.

Main Methods:

• Retrospective study of 299 patients with biopsy-proven NAFLD.
• Patients categorized into four groups based on hepatic iron distribution: NONE, exclusively reticuloendothelial (xRES), exclusively hepatocellular (xHC), and mixed (HC/RES).
• Long-term analysis of overall survival, hepatic, cardiovascular, and extrahepatic-malignant events using multivariate Cox proportional hazards models.

Main Results:

• Reticuloendothelial (RES) iron deposition was associated with increased fatal and non-fatal hepatic events.
• The xRES pattern showed a significantly higher risk for combined hepatic and cardiovascular events (csHR 3.2).
• The mixed HC/RES iron pattern also demonstrated a higher rate of combined hepatic events (csHR 3.6), while xHC iron showed no association with adverse events.

Conclusions:

• Hepatic iron deposition, particularly in reticuloendothelial cells, is linked to adverse long-term outcomes in NAFLD.
• Reticuloendothelial-accentuated iron patterns correlate with an elevated risk of both liver-related and cardiovascular events.
• These findings highlight the prognostic significance of iron distribution in NAFLD pathogenesis and progression.