Dyslipidemia in liver cirrhosis: Pathophysiology and emerging therapeutic approaches

Table 2 Efficacy and safety of emerging non-statin lipid-lowering agents in compensated and advanced cirrhosis

Therapy	Main mechanism of action	Use in compensated cirrhosis	Main risk in cirrhosis (advanced/decompensated)
Ezetimibe	Inhibits intestinal cholesterol absorption (NPC1 L1 transporter)	Possible, with caution	Increased drug exposure in Child-Pugh B/C, higher risk of hepatotoxicity
Fibrates	Activate PPAR-α to ↓triglycerides, ↑HDL	Possible, under monitoring	Elevation of liver enzymes, cholestasis, rhabdomyolysis (especially if combined with statins)
PCSK9 inhibitors (alirocumab, evolocumab)	Monoclonal antibodies inhibiting PCSK9 to ↑LDL receptor recycling, ↓LDL-C	Data limited; theoretically safer since not hepatically metabolized	Limited clinical data in cirrhosis, safety in advanced liver disease not established
Bempedoic acid	Inhibits ATP-citrate lyase (upstream of HMG-CoA reductase)	Potential option, but limited data in cirrhosis	No robust studies in advanced liver disease; potential risk of hepatotoxicity
Inclisiran	Small interfering RNA targeting hepatic PCSK9 synthesis, leading to sustained LDL receptor upregulation and LDL-C reduction	Potential option; limited but favorable pharmacologic profile given minimal hepatic metabolism	Very limited clinical data in cirrhosis; safety in Child-Pugh B/C not established

PCSK9: Proprotein convertase subtilisin/kexin type 9; NPC1 L1: Niemann-Pick C1-like 1 transporter; PPAR: Peroxisome Proliferator-activated receptor; HDL: High-density lipoprotein; LDL: Low-density lipoprotein; LDL-C: Low-density lipoprotein cholesterol; ATP: Adenosine triphosphate; HMG-CoA: 3-hydroxy-3-methylglutaryl coenzyme A.