Almasio P, Bortolini M, Pagliaro L, Coltorti M
Clinica Medica R, Università di Palermo, Italy.
Drugs. 1990;40 Suppl 3:111-23. doi: 10.2165/00003495-199000403-00011.
Recent studies have established the clinical efficacy of S-adenosyl-L-methionine (SAMe) in the treatment of cholestasis associated with hepatic diseases, pregnancy and the administration of estrogen-containing oral contraceptives. In 4 clinical trials involving a total of 639 patients with cholestasis due to acute or chronic liver disease, SAMe in an intravenous dose of 800 mg/day or an oral regimen of 1.6 g/day for 2 weeks was superior to placebo in relieving the symptom of pruritus and in restoring serum total bilirubin and serum alkaline phosphatase towards normal. The drug is also effective in intrahepatic cholestasis of pregnancy (ICP), with intravenous administration of 800 mg/day for 2 weeks producing a substantial reduction in pruritus and an improvement in abnormal liver function indices. Moreover, SAMe treatment decreases the incidence of premature labour. SAMe appears to be the first safe and effective approach to the treatment of this syndrome, and also protects against the adverse hepatic effects of small doses of estrogen in patients with a history of ICP by normalising liver biochemistry and the oversaturated biliary lipid composition of the gallbladder bile. In animal models, SAMe reverses the pathological liver changes induced by xenobiotics such as taurolithocholate and alpha-naphthyl-isothiocyanate (ANIT) and the antipsychotic chlorpromazine. Several cooperative mechanisms appear to underlie the anticholestatic action of SAMe, the most important being the restoration of normal hepatocyte membrane fluidity and Na+, K+ ATPase activity, through a reversal of the reduction in phospholipid methylation produced by hepatotoxic agents. In addition, SAMe may act by promoting trans-sulphuration pathway reactions and consequently improving the detoxifying capacity of this metabolic system.
近期研究已证实S-腺苷-L-蛋氨酸（SAMe）在治疗与肝脏疾病、妊娠及含雌激素口服避孕药服用相关的胆汁淤积方面具有临床疗效。在4项临床试验中，总计639例因急性或慢性肝病导致胆汁淤积的患者参与其中，静脉注射剂量为每日800毫克的SAMe或口服剂量为每日1.6克、持续2周的SAMe在缓解瘙痒症状以及使血清总胆红素和血清碱性磷酸酶恢复正常方面优于安慰剂。该药物在妊娠肝内胆汁淤积症（ICP）中也有效果，静脉注射每日800毫克、持续2周可使瘙痒显著减轻，肝功能异常指标得到改善。此外，SAMe治疗可降低早产发生率。SAMe似乎是治疗该综合征的首个安全有效的方法，还可通过使肝生化指标及胆囊胆汁中过饱和胆汁脂质成分正常化，预防有ICP病史患者小剂量雌激素的肝脏不良影响。在动物模型中，SAMe可逆转由牛磺石胆酸和α-萘基异硫氰酸酯（ANIT）等外源性物质以及抗精神病药物氯丙嗪诱导的肝脏病理变化。SAMe的抗胆汁淤积作用似乎有几种协同机制，其中最重要的是通过逆转肝毒性药物导致的磷脂甲基化减少，恢复正常的肝细胞膜流动性和Na+、K+ - ATP酶活性。此外，SAMe可能通过促进转硫途径反应起作用，从而提高该代谢系统的解毒能力。
