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

Table 5 Summary of outcome data relating to prespecified biochemical liver parameters (non-randomized studies)

Parameter	Study	Disease	Intervention	Baseline	After treatment	Statistical method	P value
ALT
ALT (IU)	Podymova et al[34], 19981	Chronic liver disease with IHC (N = 32)	AdoMet	109.3 ± 26.4 (mean ± SD)	74.4 ± 167.0 (Day 17), 40.5 ± 14.5 (Day 33)	NR	P > 0.1 vs baseline at Day 17, P > 0.05 vs baseline at Day 33
ALT (U/L)	Fiorelli[32], 1999	IHC complicating chronic liver disease (N = 640)	AdoMet im or iv	im: 96 ± 6.1, iv: 92 ± 5.6 (mean ± SE)	im: 84 ± 5.3 (Day 7), 76 ± 5.6 (Day 15), iv: 84 ± 4.3 (Day 7), 76 ± 3.6 (Day 15)	Friedman non-parametric test	P < 0.01 vs baseline at Days 7 and 15 for both im and iv
ALT (U/L)	Virukalpattigo-palratnam et al[36], 2013	IHC due to chronic NAFLD (N = 250)	AdoMet	124.4 (mean)	62.1	Wilcoxon signed-rank test	P < 0.05 vs baseline at Week 6
ALT (U/L)	Perlamutrov et al[31], 2014	DILI with IHC (N = 105)	AdoMet	NR	NR	Spearman’s correlation coefficient	P < 0.05 vs baseline at Weeks 2 and 6
ALT (U/L)	Larionova et al[30], 20151	DILI due to CT and evidence of IHC (N = 99)	AdoMet	137.3 (median)	68.5 (Day 14), 55.2 (Day 42)	NR	P < 0.001 vs baseline at Days 14 and 42
AST
AST (IU)	Podymova et al[34], 19981	Chronic liver disease with IHC (N = 32)	AdoMet	105.9 ± 21.5 (mean ± SD)	66.4 ± 13.9 (Day 17), 32.5 ± 10.0 (Day 33)	NR	P > 0.1 vs baseline at Day 17 P > 0.01 vs baseline at Day 33
AST (U/L)	Fiorelli[32], 1999	IHC complicating chronic liver disease (N = 640)	AdoMet im or iv	im: 104 ± 4.2, iv: 116 ± 5.7 (mean ± SE)	im: 96 ± 4.4 (Day 7), 88.0 ± 4.8 (Day 15), iv: 100 ± 4.1 (Day 7), 92.0 ± 4.1 (Day 15)	Friedman non-parametric test	P < 0.01 vs baseline at Days 7 and 15 for both im and iv
AST (U/L)	Virukalpattigo-palratnam et al[36], 2013	IHC due to chronic NAFLD (N = 250)	AdoMet	130.8 (mean)	61.6	Wilcoxon signed-rank test	P < 0.05 vs baseline at Week 6
AST (U/L)	Perlamutrov et al[31], 2014	DILI with IHC (N = 105)	AdoMet	NR	NR	Spearman’s correlation coefficient	P < 0.05 vs baseline at Weeks 2 and 6
AST (U/L)	Larionova et al[30], 20151	DILI due to CT and evidence of IHC (N = 99)	AdoMet	103.3 (median)	49.7 (Day 14), 41.0 (Day 42)	NR	P < 0.001 vs baseline at Days 14 and 42
ALP
ALP (U/L)	Podymova et al[34], 19981	Chronic liver disease with IHC (N = 32)	AdoMet	676.9 ± 154.8 (mean ± SD)	596.5 ± 144.2 (Day 17), 446.2 ± 175.1 (Day 33)	NR	P > 0.1 vs baseline at Day 17, P > 0.1 vs baseline at Day 33
ALP (U/L)	Fiorelli[32], 1999	IHC complicating chronic liver disease (N = 640)	AdoMet im or iv	im: 259.5 ± 10.8, iv: 276.5 ± 13.7 (mean ± SE)	im: 217.0 ± 10.5 (Day 7), 191.5 ± 10.2 (Day 15), iv: 234.0 ± 14.3 (Day 7), 208.5 ± 13.6 (Day 15)	Friedman non-parametric test	P < 0.01 vs baseline at Days 7 and 15 for both im and iv
ALP (U/L)	Virukalpattigo-palratnam et al[36], 2013	IHC due to chronic NAFLD (N = 250)	AdoMet	230.6 (mean)	165.3	Wilcoxon signed-rank test	P < 0.05 vs baseline at Week 6
ALP (U/L)	Perlamutrov et al[31], 2014	DILI with IHC (N = 105)	AdoMet	NR	NR	Spearman’s correlation coefficient	P < 0.05 vs baseline at Week 2, P < 0.05 vs baseline at Week 6
ALP (U/L)	Ivashkin et al[35], 2018	IHC due to ALD (N = 72)	AdoMet	241.2	167.9 (Week 2), 152.2 (Week 8)	ANCOVA	P < 0.0001 vs baseline at Weeks 2 and 8
γGT
γGT (IU)	Podymova et al[34], 19981	Chronic liver disease with IHC (N = 32)	AdoMet	153.5 ± 36.1 (mean ± SD)	145.1 ± 50.1 (Day 17), 51.8 ± 16.1 (Day 33)	NR	P > 0.1 vs baseline at Day 17, P > 0.05 vs baseline at Day 33
γGT (U/L)	Fiorelli[32], 1999	IHC complicating chronic liver disease (N = 640)	AdoMet im or iv	im: 240.7 ± 20.0, iv: 303.4 ± 36.1	im: 195.1 ± 16.0 (Day 7), 160.9 ± 10.0 (Day 15), iv: 218.0 ± 17.7 (Day 7), 189.4 ± 17.3 (Day 15)	Friedman non-parametric test	P < 0.01 vs baseline at Days 7 and 15 for both im and iv
γGT (U/L)	Virukalpattigo-palratnam et al[36], 2013	IHC due to chronic NAFLD (N = 250)	AdoMet	151.5 (mean)	90.8 (mean)	Wilcoxon signed-rank test	P < 0.05 vs baseline at Week 6
γGT (U/L)	Perlamutrov et al[31], 2014	DILI with IHC (N = 105)	AdoMet	NR	NR	Spearman’s correlation coefficient	P < 0.05 vs baseline at Week 2, P < 0.05 vs baseline at Week 6
γGT (U/L)	Ivashkin et al[35], 2018	IHC due to ALD (N = 72)	AdoMet	NR	Mean change ± SD: -197.0 ± 403.5 (Week 2), -233.8 ± 407.1 (Week 8)	ANCOVA	P < 0.0001 vs baseline at Weeks 2 and 8

¹Published studies translated to English from original language. AdoMet: S-adenosylmethionine; ALD: Alcoholic liver disease; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; ANOVA: Analysis of variance; ANCOVA: Analysis of covariance; AST: Aspartate aminotransferase; CI: Confidence interval; CT: Chemotherapy; DILI: Drug-induced liver injury; γGT: Gamma-glutamyl transferase; IHC: Intrahepatic cholestasis; im: Intramuscular; iv: Intravenous; NAFLD: Non-alcoholic fatty liver disease; NR: Not reported; SD: Standard deviation; SE: Standard error.