Impact of iron on insulin resistance in people with hepatitis associated with

INTERVENTION: Therapeutic venesection in non‐alcoholic steatohepatitis study participants who have iron overload. 'Visit 1 (Screening) ‐ Obtain informed consent ‐ Inclusion and exclusion criteria ‐ Record medical history including alcohol, dietary and lifestyle ‐ Return within 2 weeks Visit 2( Baseline‐month 0) ‐ Inclusion/exclusion criteria ‐ Physical examination including vital signs, waist and hips measurement ‐ Alcohol and lifestyle questionnaires ‐ Fasting blood test, urine sample ‐ Dietary and lifestyle counselling ‐ Ferriscan ‐ Randomisation Visit 3 (month 3‐ for both groups) ‐ Physical examination including vital signs, waist and hips measurement ‐ Alcohol and lifestyle questionnaires ‐ Fasting blood test, urine sample ‐ Dietary and lifestyle counseling Visit 4 (month 18‐ for both groups) ‐ Physical examination including vital signs, waist and hips measurement ‐ Alcohol and lifestyle questionnaires ‐ Fasting blood test, urine sample ‐ Dietary and lifestyle counseling ‐ Liver biopsy ‐ Ferriscan Liver biopsy and Ferriscan will be performed in two major tertiary teaching hospitals. For the venesection (intervention) group: ‐ Visits will be initially scheduled for 1 month after randomisation, then 3 monthly if necessary ‐ Fortnightly venesection until serum ferritin level is <50 ug/L ‐ Skip one session of venesection if anaemia (Hb <115g/L (female) <135g/L (male) ‐ Further maintenance on a three monthly basis or as frequently as required to keep ferritin level <50ug/L ‐ Iron studies will be performed prior to each venesection ‐ Vital signs and any adverse events will be recorded at each visit. Duration of each visit: Visits 1, 2, 3 and 4 (final visit)‐ between 1‐ 1.5 hours. Ferriscan visits‐ 1 hour Venesection visits‐ This can varies between one hour or more depending if there are any adverse events post venesection. Standard dietary and lifestyle counselling‐ advice will be given at each visit by the research nurse who is experienced in counselling type 2 diabetics and NAFLD patients, on a generally low fat and low glycaemic index diet, and regular exercise of moderate to high intensity of minimal 60‐90 minutes a day. The session will be of approximately 30 minutes duration. Period of overall intervention is 18 months CONDITION: Insulin resistance Iron overload Non‐alcoholic fatty liver disease (NAFLD) non‐alcoholic steatohepatitis (NASH) PRIMARY OUTCOME: Histological inprovement in NASH as determined by a two point inprovement in the NAS score (NAFLD Activity Score) SECONDARY OUTCOME: Fibrosis stage as measured by Brunt histological scoring scheme Necroinflammatory grade as measured by Brunt histological scoring scheme Steatosis grade as measured by Brunt histological scoring scheme. INCLUSION CRITERIA: Biopsy demonstrating NASH within six months of trial entry.