Possible involvement of PCSK9 overproduction in hyperlipoproteinemia associated with hepatocellular carcinoma: A case report.

Herein, we describe a 69-year-old Japanese man with massive type III hyperlipoproteinemia (total cholesterol, 855 mg/dL; triglyceride, 753 mg/dL) presenting as a paraneoplastic manifestation of hepatitis B virus-associated hepatocellular carcinoma. The messenger RNA expression of sterol regulatory element-binding protein-2 and proprotein convertase subtilisin/kexin 9 in the tumor tissue was increased by 13-fold and 4-fold, respectively, compared with the non-tumor tissue. Serum level of active form of PCSK9 was 382 ng/mL (reference range: 253 ± 79 ng/mL). The non-tumor tissue had extremely low expression of low-density lipoprotein receptor and low-density lipoprotein receptor-related protein 1. Together, we speculate that marked overexpression of sterol regulatory element-binding protein-2 in the tumor may stimulate the secretion of PCSK9, which inhibits the lipoprotein receptors in the non-tumor tissue, thereby causing paraneoplastic hyperlipoproteinemia.