Efficacy of immunosuppression monotherapy after liver transplantation: A meta-analysis

Table 1 Characteristics of randomized cohort studies included in the meta-analysis

Ref.	Year	Location	Immunosuppression		Number of patients	Drug whole-blood trough levels (ng/mL)		Steroid protocol (POT)
			Monotherapy group	Combination group		Monotherapy group	Combination group
Benítez et al[18]	2010	Spain	Tacrolimus	Tacrolimus plus prednisone	37	5–12	10-15 (3 mo POT)	20 mg/d prednisone
							7-12 thereafter	NS in monotherapy group
Boillot et al[19]	2005	Germany	Tacrolimus monotherapy	Tacrolimus plus steroids	698	10-20 (first 6 wk) and 5-15 thereafter		prednisone 1-20 mg/d during month 1, 10-15 mg/day during month 2, and 5-10 mg/d during month 3 and thereafter and NS in monotherapy group
Weiler et al[20]	2010	Germany	Tacrolimus monotherapy	Tacrolimus plus steroids	110	10-15 (first 6 wk) and 5-10 thereafter		100 mg on day 1 to 12 mg on day 14 in both groups and placebo in monotherapy group 2 wk later
Chau et al[21]	2001	Great Britain	Tacrolimus monotherapy	Triple therapy	24	5-15	NS	prednisone 1 mg/kg per day and NS in monotherapy group
Moench et al[22]	2007	Germany	Tacrolimus monotherapy	Tacrolimus plus steroids	110	10-15 (between day 0 and 42)5-10 thereafter		Methylprednisolon 100 mg at day 1, 75 mg at day 2, 48 mg at day 3 and 4, 36 mg at day 5 and 6, 24 mg at day 7 and 8, 16 mg from day 9 to 13 and 12 mg at day 14 and then placebo in monotherapy group 2 wk later
Eason et al[23]	2003	United States	Tacrolimus monotherapy + ATG	Tacrolimus plus steroids	119	10-12	NS	NS
Samonakis et al[12]	2006	Great Britain	Tacrolimus monotherapy	Tacrolimus, azathioprine, and prednisolone	56	5-14		Methylprednisolone(16 mg/d IV) until oral intake was establishedwhen 20 mg/d prednisolone and NS in monotherapy group
Margarit et al[13]	2005	Spain	Tacrolimus monotherapy	Tacrolimus plus steroids	60	10-15 over the first few weeks and between 8 and 12 thereafter		100 mg b.i.d. of methylprednisolone post-LT day 1 and decreasing to 20 mg/d by day 6 patients were weaned off prednisone, if possible, within 3 mo post-LT and NS in monotherapy group
Manousou et al[14]	2009	GreatBritain	Tacrolimus monotherapy	Tacrolimus, azathioprine, and prednisolone	103	3-26 over the first few week8 at 1 mo7 at 2 mo8 at 3 mo	2.5-14 over the first few weeks8.4 at 1 mo7.5 at 2 mo7 at 3 mo	Methylprednisolone (16 mg/d intravenously) was given until oral intake was established; then, 20 mg/d prednisolone and NS in monotherapy group
Belli et al[24]	1998	Italy	Cyclosporine monotherapy	Cyclosporine plus steroids	88	200-300 (1 mo POT)		Methylprednisolone
						150-250 thereafter		at a dose of 200 mg/d on postoperative day 1, and tapered to 20 mg/d of prednisone by postoperative day 6; 5 mg reductions every 2 wk) to a maintenance dose of 0.1 mg/kg per day and withdraw in monotherapy group 90 d later
De Carlis et al[25]	1997	Italy	Cyclosporine monotherapy	Cyclosporine plus steroids	100	200-300 (1 mo POT)150-250 thereafter		Continued with methylprednisolone at a dose of 200 mg/d on postoperative day 1, and tapered to 20 mg/d of prednisone by postoperative day 6; 5 mg reductions every 2 wk) to a maintenance dose of 0.1 mg/kg per day and withdraw in monotherapy group 3 mo later
Chau et al[21]	2001	Great Britain	Cyclosporine monotherapy	Triple therapy	26	100-300		Prednisone 1 mg/kg per day and NS in monotherapy group
Romani et al[26]	1994	Italy	Cyclosporine monotherapy	Cyclosporine plus steroids	59	200-300 (1 mo POT)		Methylprednisolone
						150-250 thereafter		at a dose of 200 mg/d on postoperative day 1 and 5 mg reductions every 2 wk) to a maintenance dose of 0.1 mg/kg per day and withdraw in monotherapy group 90 d later
Schlitt et al[27]	2001	Germany	Mycophenolate Mofetil Monotherapy	Mycophenolate Mofetil plus CNIs	28	500 mg/d in the first week; 1000 mg/d in the second week; 1500 mg/d in the third week; final dose: 2000 mg/d		CNIs dose was reduced by 25% of the initial dose every week in monotherapy group
Schmeding et al[28]	2011	Germany	Mycophenolate Mofetil Monotherapy	Mycophenolate Mofetil plus CNIs + steroids	142	500 mg/d at 1 wk; 1000-1500 mg/d at 2-3 wk; 2000 mg/d thereafter		CNI dose was withdraw completely in 12 wk later

Table 2 Methodological quality of including randomized cohort studies

Ref.	Selection criteria specified	Study design	Jadad scale score	Other causing of death report	Dropouts explained	Funding
Benítez et al[18]	Adequate	RCT	4	Adequate	Yes	Supported by grants from Fresenius Biotech GmbH, Spain
Boillot et al[19]	Adequate	RCT	4	Adequate	Adequate	Supported by Fujisawa GmbH, Munich, Germany
Weiler et al[20]	Adequate	RCT	3	Adequate	Adequate	NS
Chau et al[21]	Adequate	RCT	3	NS	NS	NS
Moench et al[22]	Adequate	RCT	6	Adequate	Adequate	Supported by Astellas Pharma Munich, Germany
Eason et al[23]	Adequate	RCT	4	NS	Adequate	Supported by unrestricted educational grants from Sangstat and Fujisawa
Samonakis et al[12]	Adequate	RCT	3	NS	Ns	Support from Fujisawa for some of the personnel involved in this investigator-led study
Margarit et al[13]	Adequate	RCT	4	Adequate	Adequate	Supported, in part, by a grant from Fujisawa GM
Manousou et al[14]	Adequate	RCT	6	Adequate	Adequate	NS
Belli et al[24]	Adequate	RCT	3	Adequate	Adequate	NS
De Carlis et al[25]	Adequate	RCT	4	Adequate	Adequate	NS
Romani et al[26]	Adequate	RCT	4	Adequate	Adequate	NS
Schlitt et al[27]	Adequate	RCT	4	Adequate	Adequate	NS
Schmeding et al[28]	Adequate	RCT	4	Adequate	Adequate	Funding for patient monitoring and laboratory diagnostics and data analysis was partially provided by Roche Pharmaceutical Company, Grenzach-Wyhlen, Germany

RCT: Randomized cohort studie; NS: Not significant.