Venesection for nonalcoholic fatty liver disease unresponsive to lifestyle counselling - a propensity score-adjusted observational study

Background/Aim: To test the short-term clinical usefulness of venesection associated with lifestyle counselling as against counselling alone on insulin resistance and liver enzymes in subjects with non-alcoholic fatty liver disease (NAFLD), using a propensity score approach. Methods: We carried out a 6- to 8-month observational analysis of 198 NAFLD patients in three Italian referral centres (79 venesection and 119 counselling alone). Insulin resistance was measured by the homeostasis model assessment (HOMA) method. Logistic regression was used to identify factors associated with normal HOMA and normal alanine aminotransferase (ALT) at the end of observation. The results were adjusted for the propensity score to be enrolled in the venesection programme, based on clinical and laboratory data, including common HFE polymorphisms and liver biopsy (available in 161 cases). Results: After adjustment for propensity and changes in BMI, venesection was significantly associated with normal HOMA [all cases: odds ratio (OR) 3.00; 95% confidence interval (CI) 1.51–5.97; cases with histology: OR 2.29; 95% CI 1.08–4.87] and ALT within normal limits (all cases: OR 2.56; 95% CI 1.29–5.10; cases with histology: OR 2.81; 95% CI 1.20–5.24). The results were confirmed in an analysis of 57 pairs matched for propensity, where venesection similarly increased the probability of normal HOMA (OR 3.27; 95% CI 1.16–7.84) and normal ALT (OR 5.60; 95% CI 2.09–15.00). Similar data were obtained in the subset of cases with normal basal ferritin (<350 ng/ml). Conclusion: Iron depletion by venesection favours the normalization of insulin resistance and raised liver enzymes in non-haemochromatosis patients with NAFLD.