Tacrolimus and mycophenolate mofetil as second-line treatment in autoimmune hepatitis: Is the evidence of sufficient quality to develop recommendations?

Table 1 Baseline characteristics and summary of findings of the 21 studies included in our meta-analysis of second-line treatments for autoimmune hepatitis refractory patients

Ref.	Year	Country	Patients (n)	Female	Mean age	Design	Biochemical remission (%)	Follow-up	Mean dose2
Tacrolimus
Zolfino et al[29]	2002	United Kingdom	5	3/5	28.4 ± 12.26	Retrospective	2/5 (40)	NR	2-4
Aqel et al[30]	2004	United States	11	10/11	63	Retrospective	10/11 (91)	161	3.0
Chatur et al[31]	2005	Canada	3	NR	NR	Retrospective	0/3 (0)	26.5 (10–54)	2-4
Larsen et al[32]	2007	Denmark	9	8/9	36 ± 16.06	Retrospective	9/9 (100)	21.25 ± 8.37	2 (2-4)
Yeoman et al[33]	2011	United Kingdom	9	5/9	39.5 ± 18.07	Retrospective	7/9 (77.8)	NR	NR
Tannous et al[34]	2011	United States	13	10/13	40.6 ± 12.5	Retrospective	12/13 (92.3)	1-65	2-6
Than et al[35]	2016	German, United Kingdom	17	11/17	34.5 ± 15.03	Retrospective	9/17 (53)	84 ± 53.45	2 (0.5-5)1
Efe et al[36]	2017	Europe, United States, Canada, and China	80	60/80	34.7 ± 11.78	Retrospective	58/80 (72.5)	85.75 ± 37.83	3 (0-6)1
Pape et al[17]	2020	Belgium, Netherlands	10	8/10	38 ± 13.67	Retrospective	5/10 (50)	14.5 ± 6.47	3.5 ± 1.72
MMF
Richardson et al[37]	2000	United Kingdom	7	6/7	27.28 ± 10.45	Retrospective	5/7 (71.4)	43 ± 13.92	2
Zolfino et al[29]	2002	United Kingdom	2	1/2	17.5 ± 2.12	Retrospective	0/2 (0)	NR	2
Devlin et al[38]	2004	Canada	5	4/5	54 ± 2.10.83	Retrospective	5/5 (100)	NR	1-2
Chatur et al[31]	2005	Canada	11	NR	NR	Retrospective	7/11 (63.6)	26.5 (10–54)	0.5-2
Czaja et al[39]	2005	United States	7	NR	NR	Retrospective	0/7 (0)	19 ± 7	0.5-3
Inductivo-Yu et al[40]	2007	United States	15	11/15	60 ± 15	Retrospective	11/15 (73.3)	41	2
Hlivko et al[41]	2008	United States	12	NR	NR	Retrospective	8/12 (66.7)	NR	0.5-2
Hennes et al[42]	2008	Germany	36	28/36	41.5 ± 13.24	Retrospective	14/36 (39)	35.38 ± 21.4	1.75 (0.5-3)1
Wolf et al[43]	2009	United States	16	NR	NR	Retrospective	12/16 (75)	NR	1-2
Sharzehi et al[44]	2010	United States	17	13/17	50	Retrospective	8/17 (48)	12	0.5-2
Yeoman et al[33]	2011	United Kingdom	2	1/2	31.5 ± 19.51	Retrospective	1/2 (50)	NR	NR
Baven-Pronk et al[45]	2011	The Netherlands	30	24/30	NR	Retrospective	14/30 (46.7)	39.5 ± 22.51	0.5-3
Jothimani et al[46]	2014	India, United Kingdom	19	16/19	52.25 ± 16.52	Retrospective	14 /19 (73.6)	45.4 ± 21.13	1-2
Roberts et al[47]	2018	Australia	105	92/105	52.5 ± 3.65	Retrospective	63/105 (60)	38.75 ± 10.14	2.0 (1.0-2.0)1
Efe et al[36]	2017	Europe, United States, Canada, and China	121	96/121	41.25 ± 13.45	Retrospective	84/121 (69.4)	66.25 ± 31.77	1 (0-2)1
Giannakopoulos et al[18]	2019	Sweden	22	12/22	50 ± 12.57	Retrospective	10/22 (45.5)	71 (10-54)1	2.0 (1.0–2.5)1

¹Median.

²Mean dose in tacrolimus studies is defined as mg/d and in mycophenolate mofetil studies is defined as g/d. NR: Not reported; MMF: Mycophenolate mofetil.