The pathogenesis and treatment of pruritus and fatigue in patients with PBC.

摘要: The pathogenesis of the pruritus that complicates cholestasis in patients with primary biliary cirrhosis (PBC) is uncertain. limited and inconsistent efficacy conventional empiric therapies, such as anion exchange resins rifampicin, has led to inconclusive trials invasive experimental plasmapheresis, charcoal haemoperfusion partial external diversion bile. However, some double-blind, placebo-controlled used a subjective end-point (the perception pruritus) have suggested certain drugs affect metabolism many compounds, for example may be efficacious. potential mechanisms by which mediate beneficial effect not been determined. There paucity data indicate whether peripheral events, accumulation bile acids interstitial fluid skin, initiate neural events this form pruritus. Recent findings suggest central brain, specifically an increase neurotransmission/ neuromodulation mediated endogenous opioid agonists (increased opioidergic tone), implicated. This hypothesis supported three lines evidence. (1) Opioid receptor ligands agonist properties (e.g. morphine) (2) Endogenous opioid-mediated neurotransmission/neuromodulation nervous system (CNS) increased cholestasis. (3) Controlled shown opiate antagonists induce ameliorations behavioural consequence (scratching activity). In trials, measurements scratching activity independent limb movements constituted objective quantitative end-point. Potent antagonists, are bioavailable when given mouth, nalmefene naltrexone, place long-term management PBC. Evidence serotoninergic neurotransmission also contributes at present less strong than implicating involvement system, further investigation needed determine specific serotonin subtype treatment evidence suggests CNS fatigue origin, but there causal relationship between altered profound occurs PBC currently