Effect of venesection on insulin resistance and oxidative stress in people with non-alcoholic fatty liver disease.

Therapeutic venesection in NAFLD patients with hepatic steatosis and hyperferritinaemia. a) Participants will be randomised into either the intervention group and non-intervention group. b) For the intervention group, fortnightly venesection will be performed by the haematologist until serum ferritin level has reached 50 ug/L. Haemoglobin and iron studies will be checked in between venesection sessions and all adverse events either related or not related to the venesection will be captured. c) Removal of iron by venesection in patients with NAFLD has a number of parallel effects on iron metabolism, oxidative stress, insulin resistance and subsequent liver damage. Specifically, venesection reduces circulating and intracellular iron. This reduces serum free fatty acid (FFA) levels and oxidative stress thereby improving insulin sensitivity independent of changes in adiponectin or body fat mass. This results in an improvement in hepatic steatosis, inflammation and fibrosis. Hepcidin and hepatocyte and adipocyte intracellular iron content modulates insulin sensitivity. d) Duration of the study is 6 months. Frequency of venesection will depend on the participant's haemoglobin and ferritin levels. It is likely that partcipants will need fortnightly venesection initially and taper towards longer intervals between sessions gradually.