Successful treatment with lomitapide in a patient with homozygous familial hypercholesterolemia and severe fatty liver disease

Abstract

Introduction and Aims: Homozygous-familial hypercholesterolemia (Ho-FH) is a rare condition due to biallelic mutations in low-density lipoprotein-receptor (LDL-R) genes characterized by high level of LDL-cholesterol (LDL-c) and huge risk of premature atherosclerotic cardiovascular disease (ASCVD), determining low quality of life and life expectancy. Lomitapide represents a therapeutic option for Ho-FH, but caution should be observed when used in fatty liver disease (FLD) and hypertransaminasemia since it is associated with onset/worsening of liver steatosis. We present a case of safe lomitapide therapy in an adult Ho-FH patient with pre-existing FLD. Case presentation: A 39-year-old man with severe hypercholesterolemia since childhood (LDL-c 405 mg/dl) and premature coronary heart disease history, was referred to our Modena Lipid Clinic. He presented an overt metabolic syndrome, FLD with hypertransaminasemia and elastosonographic significant liver fibrosis. Lipid-lowering-therapy (LLT) included rosuvastatin 20 mg, ezetimibe and evolocumab 140 mg twice a month without reaching LDL-c goal. Genetic analysis revealed homozygous pathogenic LDL-R gene mutation. Evolocumab was increased up to 420 mg twice a month and LDL-apheresis was started with quality of life worsening. Therefore, lomitapide 5 mg daily and low-fat diet were started, obtaining weight loss and lipid profile improvement. However, liver enzymes elevation higher than 5-fold was observed, leading to lomitapide discontinuation and baseline liver enzymes values restoration. After one-month wash-out, lomitapide was gradually reintroduced up to 5 mg daily without significant hypertransaminasemia recurrence, leading to LDL-c target achievement and LDL-apheresis discontinuation. Adherence to low-fat diet and weight loss resulted in FLD and fibrosis improvement. Conclusion: Ho-FH requires complex, combined treatment. Metabolic comorbidities co-existence makes Ho-FH management more difficult. Lomitapide can be safely used in Ho-FH patients with FLD and hypertransaminasemia, but strict follow-up of liver disease and a multidisciplinary approach are needed. Before lomitapide introduction, low-fat diet should be started advantageously and weight stabilization should be obtained.