Early treatment efficacy of S-adenosylmethionine in patients with intrahepatic cholestasis: A systematic review

Table 1 Overview of the included studies

Study	Country	Study design	Disease	Intervention and dose		Duration of treatment	Available parameters
Randomized studies
Frezza et al[33], 1990	Italy	Multicenter, randomized, double-blind, placebo-controlled study	Chronic liver disease with IHC (N = 220)	AdoMet 1600 mg oral daily (n = 110)	Placebo (n = 110)	2 wk	ALT, AST, ALP, γGT, fatigue
Manzillo et al[38], 1992	Italy	Multicenter, randomized, double-blind, placebo-controlled study	IHC (N = 343)	AdoMet 800 mg iv daily (n = 180)	Placebo (n = 163)	2 wk	ALT, AST, ALP, γGT
Qin et al[37], 20001	China	Randomized, parallel-group, comparator-controlled study	Intrahepatic cholestatic viral hepatitis (N = 30)	AdoMet 1000 mg iv daily (n = 15)	Potassium magnesium aspartate 20 mL daily (n = 15)	4 wk	ALT, AST, ALP
Non-randomized studies
Podymova et al[34], 19981	Russia	Observational, baseline-controlled study	Chronic liver disease with IHC (N = 32)	AdoMet 800 mg iv daily for 16 d (first phase), then 1600 mg oral daily for 16 d (second phase)		32 d	ALT, AST, ALP, γGT, asthenic syndrome2
Fiorelli[32], 1999	Italy	Multicenter, baseline-controlled, open-label study	IHC complicating chronic liver disease (N = 640)	AdoMet 500 mg im (n = 338) or 800 mg iv (n = 302) daily		15 d	ALT, AST, ALP, γGT
Virukalpattigo-palratnam et al[36], 2013	India	Multicenter, observational, baseline-controlled study	IHC due to chronic NAFLD (N = 250)	AdoMet 800-1200 mg daily for 239/243 (98.4%) patients3		6 wk	ALT, AST, ALP, γGT, fatigue
Perlamutrov et al[31], 2014	Russia	Multicenter, observational, baseline-controlled study	DILI with IHC (N = 105)	AdoMet 400-800 mg iv or im daily for 2 wk (first phase), then 800-1600 mg oral daily for 4 wk (second phase)		6 wk	ALT, AST, ALP, γGT, fatigue, depressed mood
Larionova et al[30], 20151	Russia	Multicenter, observational, baseline-controlled study	DILI due to CT and evidence of IHC (N = 99)	AdoMet 400-800 mg iv or im daily for 2 wk (first phase), then 800-1600 mg oral daily for 4 wk (second phase)		6 wk	ALT, AST, fatigue, low mood
Ivashkin et al[35], 2018	Russia	Multicenter, baseline-controlled, open-label study	IHC due to ALD (N = 72)	AdoMet 1500 mg oral daily or 500/800 mg iv daily for 2 wk, then 1500 mg oral daily for 6 wk		8 wk	ALP, γGT, fatigue, depressed mood

¹Published studies translated to English from original language;

²Typically involving irritability, weakness, fatigue, and unstable mood;

³4/243 patients (1.6%) received doses < 800 mg/d. AdoMet: S-adenosylmethionine; ALD: Alcoholic liver disease; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; CT: Chemotherapy; DILI: Drug-induced liver injury; γGT: Gamma-glutamyl transferase; IHC: Intrahepatic cholestasis; im: Intramuscular; iv: Intravenous; NAFLD: Non-alcoholic fatty liver disease.