None listed
Conditions
Brief summary
This study is assessing the utility of regular venesection (blood removal) for treatment of patients with non-alcoholic fatty liver disease and concurrent iron-overload on liver biopsy. Patients involved in this study will undergo 4-weekly venesection for up to 10-months, with a liver biopsy prior to and after the venesection schedule to assess the impact on non-alcoholic fatty liver disease and liver iron overload. We hypothesise that regular venesection will be a tolerable therapy that improves iron overload on liver biopsy and reduces severity of non-alcoholic fatty liver disease on liver biopsy.
Interventions
Patients will undergo 4-weekly venesection of 1 unit (400-500mL) of blood in the outpatient pathology centre, with experienced nursing staff performing venipuncture. Each venesection takes between 15-30 minutes. Up to a maximum of 10 venesections will be performed, with patients not undergoing their next scheduled venesection if they develop anaemia (Hb <120 g/L for women, Hb <130 g/L for men) or de-iron to a serum ferritin <200 micrograms/L. Patients who achieve a serum ferritin <200 micrograms
Patients will undergo 4-weekly venesection of 1 unit (400-500mL) of blood in the outpatient pathology centre, with experienced nursing staff performing venipuncture. Each venesection takes between 15-30 minutes. Up to a maximum of 10 venesections will be performed, with patients not undergoing their next scheduled venesection if they develop anaemia (Hb <120 g/L for women, Hb <130 g/L for men) or de-iron to a serum ferritin <200 micrograms/L. Patients who achieve a serum ferritin <200 micrograms/L prior to 10 venesections will remain in the study and continue to have 4-weekly blood tests, recommencing venesection if ferritin rises above 200 micrograms/L within 8 weeks of last venesection and if within 10 months of first venesection. The maximum total duration of the intervention is 12 months. Adherence to venesection will be monitored through view of planned blood tests on the same day as scheduled venesection. All patients will be provided with identical dietary advice and exercise advice for non-alcoholic fatty liver disease as per standard of care (this will be recommendations to reduce simple carbohydrates and saturated fats, with advice to follow the Mediterranean diet; and recommendation to undergo 30 minutes of exercise of at least moderate intensity 4-5 days per week). This advice will be provided verbally.
Sponsors
Marie Sinclair
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
- Non-alcoholic fatty liver disease evident radiologically (hepatic steatosis on ultrasonography, computed tomography or magnetic resonance of the liver, or controlled attenuation parameter >248 dB/m on transient elastography) and/or histological evidence of steatosis on liver biopsy - Serum ferritin >600 micrograms/L - Histological evidence of hepatic iron overload identified by Perl's stain for iron on liver biopsy
Exclusion criteria
• Anaemia (Hb less than 120 g/L for women, less than 130 g/L for men) • Hereditary haemochromatosis defined by C282Y homozygosity or C282Y/H63D compound heterozygosity • Alcohol consumption greater than 140 grams per week for men, or greater than 100 grams per week for women • Weight loss greater than 5% body weight 6 months prior to study inclusion • Chronic kidney disease stage 3 or greater, defined by eGFR less than 30 mL/min • Heart failure with left ventricular ejection fraction less than 40%, or ischaemic heart disease • Decompensated cirrhosis, defined by Child Pugh class B or C • Alternate cause of liver disease other than NAFLD • Concurrent use of steatogenic medications (eg. tamoxifen, methotrexate, amiodarone, prednisolone) • Inadequate venous access to facilitate regular venesection as assessed by apharesis unit • HbA1c greater than 10% • Coagulopathy such that risk of liver biopsy unacceptable • Pregnancy • Change in diabetic medication within 3 months • Those who do not speak English as a first language
Outcome results
None listed