Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5985839 | Journal of Clinical Lipidology | 2014 | 6 Pages |
âºMipomersen therapy reduces LDL cholesterol in the absence of LDL receptors.âºMipomersen therapy commonly leads to hepatic steatosis.âºLiver biopsies on mipomersen-treated patients primarily revealed simple hepatic steatosis.
BackgroundMipomersen is an antisense oligonucleotide that inhibits apolipoprotein B synthesis and lowers plasma low-density lipoprotein cholesterol even in the absence of low-density lipoprotein receptor function, presumably from inhibition of hepatic production of triglyceride-rich very low-density lipoprotein particles. By virtue of this mechanism, mipomersen therapy commonly results in the development of hepatic steatosis. Because this is frequently accompanied by alanine aminotransferase elevations, concern has arisen that mipomersen could promote the development of steatohepatitis, which could in turn lead to fibrosis and cirrhosis over time.ObjectiveThe objective of this study was to assess the liver biopsy findings in patients treated with mipomersen.MethodsWe describe 7 patients who underwent liver biopsy during the mipomersen clinical development programs. Liver biopsies were reviewed by a single, blinded pathologist.ResultsThe histopathological features were characterized by simple steatosis, without significant inflammation or fibrosis.ConclusionThese findings suggest that hepatic steatosis resulting from mipomersen is distinct from nonalcoholic steatohepatitis.