Phase 3 clinical trial and long‐term extension study of lomitapide in patients with 
NAFLD, beta‐carotene, fibrosis
LIVER FIBROSIS, COLD, FIBROSIS, CHRONIC LIVER DISEASE
The details of phase 3 clinical trial and its long‐term extension have been published before.Data from the clinical trial programme were used to evaluate mean liver transaminase levels and instances of Hy's law. For biomarker analysis, stored serum samples from the phase 3 trial were analysed by Pacific Biomarkers Inc (PBI). Measurements were conducted on cytokeratin‐18 (CK‐18), CK‐18 fragments, tissue inhibitor of metalloproteinase 1 (TIMP‐1), amino‐terminal propeptide of type III procollagen (P3NP) and hyaluronic acid (HA). Upper and lower limits of quantitation for the assays were determined by PBI. For CK‐18 and CK‐18 fragments, duplicate tests were conducted on matching aliquots 6 months apart to assess the stability of the samples in cold storage.Values for TIMP‐1, P3NP and HA can be used to calculate an individual patient's enhanced liver fibrosis (ELF) score. The ELF score correlates with the degree of fibrosis in chronic liver disease.In the present study, ELF was calculated using the formula provided by Guha et alELF scores derived by this method have a negative value. For NAFLD, indication of some degree of fibrosis is suggested by values greater than −0.6415. For ELF scores, above this figure, there is a 72% positive and 66% negative predictive value for fibrosis with a sensitivity of 80% and a specificity of 56%.Values for HA, P3NP, TIMP‐1 and ELF during lomitapide treatment were compared to those at baseline using a paired t‐test.Fat‐soluble vitamins and essential fatty acids were also measured as patients receiving lomitapide need to be on a low‐fat diet with <20% energy from fat due to the inhibitory effect of lomitapide on chylomicron formation in the intestine. It is important that these micronutrients are maintained at or above the normal level. Vitamins A, vitamin D and beta‐carotene were assessed by measuring serum concentrations of the individual nutrients. Vitamin E was reported as the ratio of vitamin E/total lipids (total cholesterol plus triglycerides). Levels of vitamin K were assessed directly by measuring the ratio of uncarboxylated osteocalcin/total osteocalcin. The fatty acid profile included serum levels of all essential fatty acids. All patients receiving lomitapide also received vitamin E and essential fatty acid supplements (daily amounts: vitamin E 400 IU, eicosapentaenoic acid [EPA] 110 mg, docosahexaenoic acid [DHA] 80 mg, alpha‐linolenic acid 220 mg and linoleic acid 200 mg).