Noureddin Mazen, Sander-Struckmeier Suntje, Mato José M
Division of Digestive and Liver Diseases, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States.
Gastroenterology/Hepatology, Abbott Laboratories GmbH, Hannover 30173, Germany.
World J Hepatol. 2020 Feb 27;12(2):46-63. doi: 10.4254/wjh.v12.i2.46.
S-adenosylmethionine (AdoMet) is a metabolically pleiotropic molecule used to treat intrahepatic cholestasis (IHC) and chronic liver diseases. While the efficacy of AdoMet has been demonstrated previously, it has not been systematically investigated within the early weeks of treatment.
To systematically review the early treatment efficacy of AdoMet in adult patients with IHC.
Studies reporting the efficacy of intravenous, intramuscular, or oral forms of AdoMet within 8 wk of treatment initiation were considered; three randomized and six non-randomized studies were eligible for inclusion (PROSPERO registration number CRD42018090936). Of the three randomized studies, two were double-blind and placebo-controlled, and one was comparator-controlled with unclear blinding and a relatively high risk of bias. Mean serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (γGT) following AdoMet treatment placebo, comparator, or baseline were summarized to determine differences in liver enzymes. Changes in patient-reported clinical symptoms of cholestasis were also summarized.
Both placebo-controlled randomized studies reported significant reductions in serum ALT levels with AdoMet placebo within 2 wk. One of these also reported significant ALP reductions, and the other reported significant AST and γGT reductions within 2 wk. The comparator-controlled randomized study, which had a number of notable limitations, reported significant reductions in serum ALT and AST levels with AdoMet potassium magnesium aspartate within 4 wk, but not within2 wk. All of the non-randomized studies (4/4) that investigated ALT, AST, ALP and/or γGT reported significant reductions in at least two of these parameters within 2 wk. Of the five studies that evaluated fatigue, reductions were observed within 2 wk in one randomized and two non-randomized studies. The remaining two non-randomized studies reported improvements in fatigue within 6 and 8 wk. Of the four studies reporting symptoms of depression, two non-randomized studies observed improvements within 2 wk and the other two observed improvements within 17 d and 8 wk.
Data from both randomized and non-randomized studies suggest that AdoMet improves some biochemical liver parameters and symptoms of cholestasis within 2 wk, with further improvements observed in some studies after 4 and 8 wk of treatment.
S-腺苷甲硫氨酸（AdoMet）是一种具有多种代谢功能的分子，用于治疗肝内胆汁淤积症（IHC）和慢性肝病。虽然AdoMet的疗效此前已得到证实，但在治疗的最初几周内尚未进行系统研究。
系统评价AdoMet对成年IHC患者的早期治疗效果。
纳入报告治疗开始8周内静脉、肌肉或口服AdoMet疗效的研究；三项随机研究和六项非随机研究符合纳入标准（PROSPERO注册号CRD42018090936）。三项随机研究中，两项为双盲安慰剂对照研究，一项为对照药物对照研究，设盲情况不明且偏倚风险较高。汇总AdoMet治疗后（与安慰剂、对照药物或基线相比）丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、碱性磷酸酶（ALP）和γ-谷氨酰转移酶（γGT）的平均血清水平，以确定肝酶的差异。还汇总了患者报告的胆汁淤积临床症状的变化。
两项安慰剂对照随机研究均报告，AdoMet治疗组在2周内血清ALT水平较安慰剂组显著降低。其中一项研究还报告2周内ALP显著降低，另一项研究报告2周内AST和γGT显著降低。对照药物对照随机研究存在一些显著局限性，该研究报告AdoMet治疗组在4周内血清ALT和AST水平较门冬氨酸钾镁组显著降低，但2周内未出现显著降低。所有调查ALT、AST、ALP和/或γGT的非随机研究（4/4）均报告在2周内至少两项参数显著降低。在五项评估疲劳的研究中，一项随机研究和两项非随机研究在2周内观察到疲劳减轻。其余两项非随机研究报告在6周和8周内疲劳有所改善。在四项报告抑郁症状的研究中，两项非随机研究在2周内观察到症状改善，另外两项研究在17天和8周内观察到症状改善。
随机研究和非随机研究的数据均表明，AdoMet在2周内可改善一些肝脏生化指标和胆汁淤积症状，在治疗4周和8周后，一些研究观察到进一步改善。
