Thébaut A, Debray D, Gonzales E
Hépatologie et transplantation hépatique pédiatrique, hôpital Bicêtre, université Paris-Sud-11, Assistance Publique-Hôpitaux de Paris, 78, rue du Général-Leclerc, 94270 Le-Kremlin-Bicêtre, France; Inserm UMR-S-1174, Université-Paris-Sud-11, Orsay, France.
Hépatologie pédiatrique, hôpital Necker-Enfants-Malades, 149, rue de Sèvres, 75015 Paris, France; Inserm UMR-S-938, centre de recherche Saint-Antoine, Paris cedex 12, France.
Clin Res Hepatol Gastroenterol. 2018 Apr;42(2):103-109. doi: 10.1016/j.clinre.2017.08.007. Epub 2017 Oct 12.
Pruritus is a disabling symptom accompanying chronic cholestasis. In extreme cases, the refractory nature of pruritus can result in a need for invasive therapies including liver transplantation. The pathogenesis of pruritus in cholestatic disease is poorly understood. It may involve a specific neural pathway (similar to that associated with pain) regulated by several pruritogenic substances such as bile acids, opioids, serotonin, and the more recently identified lysophosphatidic acid. While the therapeutic management of cholestatic pruritus is well established in adults, there is no consensus in children, in light of the difficulty of conducting controlled clinical studies. The currently recommended strategy to manage cholestatic pruritus in children is based on several lines of specific therapies that should be associated with skin hydration and with non-specific treatment of cholestasis including ursodeoxycholic acid. Pruritus should be assessed as objectively as possible between each line of therapy. Rifampicin, a potent CYP3A4 inducer, is the first-line treatment of cholestatic pruritus. Second-line therapies require evaluation of the child in an expert center and are discussed on a case-by-case basis depending on the underlying disease and the experience of the center. These include inhibitors of serotonin reuptake (sertraline), opioid antagonists (naloxone), or ASBT inhibitors. Invasive therapies such as biliary diversion or liver transplantation can also be proposed in the most severe cases. The aim of the current update is to review the physiopathologic mechanisms implicated in cholestatic pruritus and to propose potential therapeutic strategies in children.
瘙痒是慢性胆汁淤积伴发的一种使人丧失能力的症状。在极端情况下，瘙痒的难治性可能导致需要包括肝移植在内的侵入性治疗。胆汁淤积性疾病中瘙痒的发病机制尚不清楚。它可能涉及一条特定的神经通路（类似于与疼痛相关的通路），该通路由几种致痒物质调节，如胆汁酸、阿片类药物、5-羟色胺，以及最近发现的溶血磷脂酸。虽然胆汁淤积性瘙痒在成人中的治疗管理已很成熟，但由于进行对照临床研究存在困难，儿童中尚无共识。目前推荐的儿童胆汁淤积性瘙痒管理策略基于几种特定疗法，这些疗法应与皮肤保湿以及胆汁淤积的非特异性治疗（包括熊去氧胆酸）相结合。在每一轮治疗之间，应尽可能客观地评估瘙痒情况。利福平是一种强效的CYP3A4诱导剂，是胆汁淤积性瘙痒的一线治疗药物。二线治疗需要在专家中心对患儿进行评估，并根据潜在疾病和中心的经验逐案讨论。这些治疗包括5-羟色胺再摄取抑制剂（舍曲林）、阿片类拮抗剂（纳洛酮）或ASBT抑制剂。在最严重的情况下，也可考虑如胆汁转流或肝移植等侵入性治疗。本次更新的目的是回顾胆汁淤积性瘙痒所涉及的病理生理机制，并提出儿童潜在的治疗策略。
