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

Table 4 Summary of outcome data relating to prespecified biochemical liver parameters (randomized studies)

Parameter	Study	Disease	Intervention	Baseline		After treatment		Statistical method	P value
				AdoMet	Placebo / comparator	AdoMet	Placebo / comparator
ALT
ALT (μkat/L)	Frezza et al[33], 1990	Chronic liver disease with IHC (N = 220)	AdoMet (n = 110) vs placebo (n = 110)	3.3 ± 0.4 (mean ± SE)	2.8 ± 0.3	2.3 ± 0.2 (Week 1), 1.5 ± 0.1 (Week 2)	2.4 ± 0.2 (Week 1), 2.2 ± 0.2 (Week 2)	Split-plot analysis	Not reported at Week 1, P < 0.05 vs placebo at Week 2
ALT (μkat/L)	Manzillo et al[38], 1992	IHC (N = 343)	AdoMet (n = 180) vs placebo (n = 163)	1.2 (1.1, 1.4) (mean, 95% CI)	1.2 (1.1, 1.4)	0.8 (0.7, 0.9)	1.0 (0.9, 1.2)	Split-plot analysis (MANOVA)	P < 0.01 treatment-to-time interaction vs placebo at Week 2
ALT (U/L)	Qin et al[37], 20001	Intrahepatic cholestatic viral hepatitis (N = 30)	AdoMet (n = 15) vs potassium magnesium aspartate (n = 15)	198.5 ± 75.2 (mean ± SD)	190.6 ± 71.2	127.0 ± 47.5 (Week 2), 48.2 ± 43.5 (Week 4)	130.2 ± 47.2 (Week 2), 67.7 ± 27.2 (Week 4)	x2 test for comparison of rates; t test for comparison of means	NS at Week 2 P < 0.05 vs comparator at Week 4
AST
AST (μkat/L)	Frezza et al[33], 1990	Chronic liver disease with IHC (N = 220)	AdoMet (n = 110) vs placebo (n = 110)	2.4 ± 0.2 (mean ± SE)	2.1 ± 0.2	1.8 ± 0.1 (Week 1), 1.3 ± 0.1 (Week 2)	1.8 ± 0.2 (Week 1), 1.7 ± 0.2 (Week 2)	Split-plot analysis	NS vs placebo at Weeks 1 and 2
AST (μkat/L)	Manzillo et al[38], 1992	IHC (N = 343)	AdoMet (n = 180) vs placebo (n = 163)	1.4 (1.2, 1.6) (mean, 95% CI)	1.3 (1.2, 1.5)	0.9 (0.9, 1.1)	1.0 (0.9, 1.2)	Split-plot analysis (MANOVA)	P < 0.05 treatment-to-time interaction vs placebo at Week 2
AST (U/L)	Qin et al[37], 20001	Intrahepatic cholestatic viral hepatitis (N = 30)	AdoMet (n = 15) vs potassium magnesium aspartate (n = 15)	127.0 ± 60.7 (mean ± SD)	118.2 ± 58.7	84.6 ± 33.8 (Week 2), 45.6 ± 28.2 (Week 4)	78.3 ± 38.5 (Week 2), 52.7 ± 25.3 (Week 4)	x2 test for comparison of rates; t test for comparison of means	NS at Week 2 P < 0.05 vs comparator at Week 4
ALP
ALP (μkat/L)	Frezza et al[33], 1990	Chronic liver disease with IHC (N = 220)	AdoMet (n = 110) vs placebo (n = 110)	4.5 ± 0.3 (mean ± SE)	4.7 ± 0.3	3.7 ± 0.3 (Week 1), 3.2 ± 0.2 (Week 2)	4.6 ± 0.3 (Week 1), 4.4 ± 0.3 (Week 2)	Split-plot analysis	P < 0.05 vs placebo at Week 1, P < 0.01 vs placebo at Week 2
ALP (μkat/L)	Manzillo et al[38], 1992	IHC (N = 343)	AdoMet (n = 180) vs placebo (n = 163)	4.8 (4.2, 5.5) (mean, 95% CI)	4.9 (4.3, 5.7)	3.9 (3.4, 4.4)	4.0 (3.4, 4.7)	Split-plot analysis (MANOVA)	NS vs placebo at Week 2
ALP (U/L)	Qin et al[37], 20001	Intrahepatic cholestatic viral hepatitis (N = 30)	AdoMet (n = 15) vs potassium magnesium aspartate (n = 15)	203.2 ± 39.5 (mean ± SD)	202.8 ± 39.4	93.5 ± 33.7 (Week 2), 85.6 ± 20.6 (Week 4)	97.5 ± 33.0 (Week 2), 89.1 ± 27.8 (Week 4)	x2 test for comparison of rates; t test for comparison of means	NS vs comparator at Weeks 2 and 4
γGT
γGT (μkat/L)	Frezza et al[33], 1990	Chronic liver disease with IHC (N = 220)	AdoMet (n = 110) vs placebo (n = 110)	2.5 ± 0.3 (mean ± SE)	2.2 ± 0.2	1.9 ± 0.3 (Week 1), 1.5 ± 0.2 (Week 2)	1.9 ± 0.1 (Week 1), 1.7 ± 0.1 (Week 2)	Split-plot analysis	NS at Week 1 or Week 2
γGT (μkat/L)	Manzillo et al[38], 1992	IHC (N = 343)	AdoMet (n = 180) vs placebo (n = 163)	1.9 (1.6, 2.2) (mean, 95% CI)	1.8 (1.6, 2.2)	1.2 (1.0, 1.3)	1.3 (1.1, 1.6)	Split-plot analysis (MANOVA)	P < 0.05 treatment-to-time interaction vs placebo at Week 2

¹Published studies translated to English from original language. AdoMet: S-adenosylmethionine; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; CI: Confidence interval; γGT: Gamma-glutamyl transferase; IHC: Intrahepatic cholestasis; MANOVA: Multivariate analysis of variance; NS: Not significant; SD: Standard deviation; SE: Standard error.