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

Table 6 Summary of outcome data relating to prespecified symptoms and consequences of cholestasis

Parameter	Study	Scale / scoring system	Disease	Inter-vention	Baseline		After treatment		Statistical method	P value
					AdoMet	Control	AdoMet	Control
Fatigue
Fatigue (cm)	Frezza et al[33], 19901	10 cm visual analog scale: 0 = lack of symptom to 10 = maximal severity	Chronic liver disease with IHC (N = 220)	AdoMet (n = 110) vs placebo (n = 110)	5.5 ± 0.3 (mean ± SE)	5.3 ± 0.3	3.5 ± 0.2 (Week 1), 2.6 ± 0.2 (Week 2)	5.0 ± 0.3 (Week 1), 4.8 ± 0.3 (Week 2)	Fisher’s exact test	P < 0.01 vs placebo at Weeks 1 and 2
Fatigue (% patients)	Virukalpattigopalratnam et al[36], 20132	NR	IHC due to chronic NAFLD (N = 250)	AdoMet	75.8	-	32.5	-	McNemar's test	P < 0.0001 vs baseline at Week 6
Fatigue (% patients)	Perlamutrov et al[31], 20142	Two-degree scale: 0 = absent; 1 = present	DILI with IHC (N = 105)	AdoMet	81.0	-	29.5 (Day 14), 11.4 (Day 42)	-	NR	NR
Fatigue (% patients)	Larionova et al[30], 20152,3	NR	DILI due to CT and evidence of IHC (N = 99)	AdoMet	42.4	-	25.3 (Day 14), 17.2 (Day 42)	-	NR	NR
Fatigue (% patients without)	Ivashkin et al[35], 2018	Six-point scale: 0 = no symptoms to 5 = maximal symptoms	IHC due to ALD (N = 72)	AdoMet	18.1	-	49.2	-	NR	NR
Depressed mood
Asthenic syndrome4 (% patients)	Podymova et al[34], 19982,3	Four-degree scale: 0 = absent to 3 = severe	Chronic liver disease with IHC (N = 32)	AdoMet	100%	-	50 (Day 17), 46 (Day 33)	-	NR	NR
Depressed mood (% patients without)	Perlamutrov et al[31], 20142	Four-degree scale: 0 = absent to 3 = severe	DILI with IHC (N = 105)	AdoMet	12.4%	-	50.5 (Day 14), 74.3 (Day 42)	-	x2 test	P < 0.001 vs baseline at Days 14 and 42
Low mood (No. patients)	Larionova et al[30], 20152,3	NR	DILI due to CT and evidence of IHC (N = 99)	AdoMet	NR	-	No. of patients without low mood increased on Days 14 and 42	-	NR	NR
Depressed mood (% patients without)	Ivashkin et al[35], 20182	Six-point scale: 0 = no symptoms to 5 = maximal symptoms	IHC due to ALD (N = 72)	AdoMet	16.7	-	73.0	-	NR	NR
Pruritus
Pruritus (cm)	Frezza et al[33], 19901	10 cm visual analog scale: 0 = lack of symptom to 10 = maximal severity	Chronic liver disease with IHC (N = 220)	AdoMet (n = 110) vs placebo (n = 110)	5.3 ± 0.3 (mean ± SE)	5.3 ± 0.3	3.5 ± 0.3 (Week 1), 2.7 ± 0.2 (Week 2)	4.8 ± 0.2 (Week 1), 4.1 ± 0.2 (Week 2)	Fisher’s exact test	P < 0.01 vs placebo at Weeks 1 and 2
Pruritus (% patients)	Podymova et al[34], 19982,3	Four-degree scale: 0 = absent to 3 = severe	Chronic liver disease with IHC (N = 32)	AdoMet	63	-	53 (Day 17), 41 (Day 33)	-	NR	NR
Pruritus (% patients)	Virukalpattigopalratnam et al[36], 20132	NR	IHC due to chronic NAFLD (N = 250)	AdoMet	38.9	-	17.3	-	McNemar's test	P < 0.0001 vs baseline at Week 6
Pruritus (% patients)	Perlamutrov et al[31], 20142	Two-degree scale: 0 = absent; 1 = present	DILI with IHC (N = 105)	AdoMet	81.0	-	42.9 (Day 14), 6.7 (Day 42)	-	NR	NR
Pruritus (% patients)	Larionova et al[30], 20152,3	NR	DILI due to CT and evidence of IHC (N = 99)	AdoMet	24.2	-	7.1 (Day 14), 6.1 (Day 42)	-	NR	NR
Pruritus (% patients without)	Ivashkin et al[35], 20182	Six-point scale: 0 = no symptoms to 5 = maximal symptoms	IHC due to ALD (N = 72)	AdoMet	45.8	-	88.9	-	NR	NR

¹Randomized studies;

²Observational studies;

³Published studies translated to English from original language;

⁴Typically involving irritability, weakness, fatigue, and unstable mood. AdoMet: S-adenosylmethionine; ALD: Alcoholic liver disease; CT: Chemotherapy; DILI: Drug-induced liver injury; IHC: Intrahepatic cholestasis; NAFLD: Non-alcoholic fatty liver disease; NR: Not reported; SE: Standard error.