Diagnostic role of transient elastography in patients with autoimmune liver diseases: A systematic review and meta-analysis

Table 1 Characteristics of studies included in this study

No.	Ref.	Country	Disease	Study time	Study design	Diagnostic model1	Sample size	Mean age in yr	Sex, F/M	Mean BMI in kg/m2	Mean, ALT in IU/mL	Treatment condition	Scoring system	Interval
1	Youssef et al[40], 2013	Egypt	AIH	NA	Retrospective	5	16	NA	NA	NA	NA	NA	Metavir	NA
2	Kim et al[41], 2014	Korea	AIH	2008-2014	Retrospective	5	47	NA	41/6	NA	NA	NA	Metavir	NA
3	Abdollahi et al[42], 2015	Iran	AIH	2011-2013	NA	1, 2, 3	80	34.75	51/29	NA	106.49	NA	Ishak	NA
4	Harrison et al[43], 2016	United Kingdom	AIH	2013-2015	Prospective	5	27	56	25/2	NA	21	Post	Ishak	The same day
5	Hartl et al[44], 2016	Germany	AIH	2007-2010	Prospective	5	34	53	28/6	NA	48.5	Post	Scheuer	Within 3 mo
	Hartl et al[44], 2016	Germany	AIH	2008-2015	Retrospective	5	60	52	50/10	NA	35	Post	Scheuer	Within 4 mo
6	Nishikawa et al45], 2016	Japan	AIH	2005-2015	Prospective	1, 2, 3, 11	84	64	69/15	NA	57.5	Pre	Scheuer	NA
7	E Anastasiou et al[46], 2016	Germany	AIH	2008-2013	Retrospective	1, 2, 3, 5	53	47.3	31/22	NA	606.42	Pre 35 + post 18	Metavir	Within 3 wk
8	Piwczyńska et al[47], 2016	Poland	AIH	NA	Prospective	4	46	14.5	33/13	NA	NA	NA	Batts-Ludwig	NA
9	Sheptulina et al[48], 2016	Russian	AIH	2008-2014	Prospective	1, 2, 3, 9	76	40	65/11	25	54.4	Pre 22 + post 54	Metavir	Within 7 d
10	Guo et al[29], 2017	China	AIH	2012-2017	Retrospective	1, 3, 5	108	46.54	88/20	23.52	146.51	NA	Metavir	Within 3 d
11	Paranagua-Vezozzo et al[49], 2016	Brazil	AIH	2012-2015	Prospective	4, 5	33	NA	28/5	28.6	NA	Post	Metavir	The same day
12	Puustinen et al[50], 2017	Finland	AIH	NA	Prospective	8	12	42.8	10/2	NA	28.5	NA	Metavir	Within 1 mo
13	Wang et al[22], 2017	China	AIH	2007-2015	Retrospective	1, 2, 3, 7	36	51.6	NA	27.7	217.4	Pre 17 + post 19	Metavir	Within 3 mo
14	Xu et al[51], 2017	China	AIH	2014-2016	Prospective	1, 3, 5	100	45	81/19	NA	131.5	Pre	Metavir	The same day
15	Zeng et al[52], 2017	China	AIH	2011-2016	Prospective	6	62	45.6	NA	21.6	78.5	Pre	Metavir	3 d
16	Liu et al[53], 2019	China	AIH	2008-2018	Retrospective	2, 3	45	54.29	37/8	NA	NA	NA	Metavir	The same day
17	Park et al[19], 2019	South Korea	AIH	2014-2017	NA	4	49	56	42/7	23.7	163	NA	Metavir	The same day
			PBC				41	55.3	35/6	25.5	45	NA
18	Li et al[54], 2020	China	AIH	2010-2019	Retrospective	1, 2, 3, 10	72	54	64/8	NA	137.55	Post	Metavir	NA
19	Wang et al[55], 2020	China	AIH	2016-2019	Retrospective	1, 3, 10	119	52.5	99/20	NA	81.6	Pre	Scheuer	Within 7 d
20	Xing et al[30], 2020	China	AIH	2016-2019	Retrospective	1, 3, 6	103	54	81/22	22.5	163	NA	Scheuer	Within 7 d
21	Janik et al[31], 2021	Poland	AIH	2015-2020	Prospective	6	63	37	15/48	23.9	130	Post	Batts-Ludwig	Within 3 mo
22	Zachou et al[20], 2021	Greece	AIH	2009-2016	Retrospective	5	78	57	54/24	NA	68	Pre 47 + post 31	Metavir	The same day
			PBC				56	52	48/8	NA	47	Pre 37 + post 19
23	Ferronato et al[56], 2022	Italy	AIH	NA	Retrospective	1, 2, 3	122	59	90/32	NA	481.8	Pre	Ishak	Within 23 d
24	Soh et al[57], 2022	Korea	AIH	2014-2021	Retrospective	6	69	59.7	60/9	NA	187.1	Pre 44 + post 25	Metavir	The same day
25	Nyblom et al[58], 2006	Sweden	PBC	1976-2000	Retrospective	2	121	54	NA	NA	189.9	NA	Metavir	NA
26	Gómez-Dominguez et al[59], 2008	Spain	PBC	NA	Prospective	5	80	54	64/16	NA	NA	Post	Metavir	Within 9 mo
27	Alempijevic et al[60], 2009	Serbia	PBC	2006	NA	1, 2	112	53.88	104/8	NA	NA	Post	Scheuer	Within 1 wk
28	Ferrara et al[61], 2009	Italy	PBC	NA	NA	1, 3	248	52	233/15	NA	NA	NA	Scheuer	The same day
29	Su et al[62], 2009	China	PBC	1985-2006	Retrospective	2	46	53.3	34/12	NA	140.6	NA	Scheuer	Within 1 mo
30	Floreani et al[63], 2011	Italy	PBC	2009	NA	5	114	58	96/24	24	44	NA	Metavir	Within 6 mo
31	Corpechot et al[64], 2012	France	PBC	2004-2010	Prospective	5	103	56	87/16	23.9	76	Post	Metavir	Within 9 mo
32	Zhang et al[34], 2014	China	PBC	2011-2013	NA	4	56	45	46/10	NA	NA	NA	Batts-Ludwig	Within 3 d
33	Sheptulina et al[21], 2015	Russian	PBC	2008-2014	Retrospective	9	82	54.5	78/4	NA	NA	NA	Metavir	NA
			PSC			3	22	38	6/16	NA	NA	NA		NA
34	Umemura et al[65], 2015	Japan	PBC	1981-2014	Retrospective	11	137	57	111/26	NA	41	Post	Metavir	The same day
35	Nishikawa et al[66], 2016	Japan	PBC	2005-2014	Prospective	1, 3, 11	57	59	49/8	NA	35	Pre	Scheuer	NA
36	Olmez et al[67], 2016	Turkey	PBC	1995-2013	Retrospective	1, 3	40	49.6	40/0	NA	54.5	NA	Scheuer	Within 1 wk
37	Wang et al[68], 2016	China	PBC	2010-2015	Retrospective	1, 3, 10	73	52.4	62/11	NA	89.3	Pre	Ludwing and Scheuer	The day before
38	Koizumi et al[23], 2017	Japan	PBC	2012-2015	Prospective	1, 2, 3, 5	44	60.5	41/3	NA	65.9	Post	Metavir	Within 1 wk
39	Wang et al[69], 2017	China	PBC	2009-2016	Retrospective	1, 3	261	52	230/31	NA	NA	NA	Metavir	NA
40	Jiang et al[70], 2018	China	PBC	2009-2015	Retrospective	3, 10	77	62.4	64/13	NA	81.2	Pre	Scheuer	NA
41	Kamal et al[71], 2018	Netherlands	PBC	1979-2010	Retrospective	1, 2, 3	85	50	75/10	NA	NA	NA	Ishak	NA
42	Meng et al[72], 2018	China	PBC	2013-2017	Retrospective	1, 3, 10	94	51.02	NA	NA	116.58	Pre	Ludwing and Scheuer	Within 1 wk
43	Milovanović et al[73], 2018	Serbia	PBC	2009-2011	Prospective	1, 2, 5	122	57.4	NA	NA	50.8	Post	Metavir	Within 1 mo
44	Wang et al[74], 2018	China	PBC	2010-2016	Retrospective	1, 3, 10	58	53.3	51/7	NA	90.4	Pre	Ludwing and Scheuer	Within 1 wk
45	Jiang et al[75], 2020	China	PBC	2008-2018	Prospective	1, 2, 3, 10	78	52	71/7	NA	NA	Pre 39 + post 39	Scheuer	Within 2 wk
	Jiang et al[75], 2020	China b	PBC	2008-2018	Retrospective	1, 3, 10	40	51	35/5	NA	NA	Pre 20 + post 20	Scheuer	Within 2 wk
46	Joshita et al[76], 2020	Japan	PBC	2015-2019	NA	5, 11	74	64	62/12	NA	48	Pre	Scheuer	The same day
47	Rossi et al[77], 2020	Italy	PBC	NA	NA	5	92	NA	NA	NA	NA	NA	Scheuer	Within 1 mo
48	Yan et al[32], 2020	China	PBC	2016-2019	Retrospective	1, 2, 3, 6	157	53	136/21	22.2	72	NA	Scheuer	NA
49	Cristoferi et al[78], 2021	Italy	PBC	2006-2019	Prospective	1, 5	126	52	114/12	22.3	52.8	Pre	Batts-Ludwig	Within 12 wk
50	Fujinaga et al[79], 2021	Japan	PBC	2000-2019	Retrospective	1, 3, 11	102	61	89/13	NA	68.4	Pre	Scheuer	NA
51	Manesis et al[80], 2021	Greece	PBC	2010-2018	Retrospective	6	53	62.6	46/7	25.7	30	Pre 30 + post 23	Scheuer	Within 3 mo
52	Osman et al[33], 2021	United States	PBC	2007-2019	Retrospective	5	63	60.95	NA	NA	31.2	NA	Batts-Ludwig	Within 1 yr
						7	98	60.21	NA	NA	36.4	NA
53	Avcioğlu et al[81], 2022	Turkey	PBC	2008-2020	Retrospective	1, 3	35	49.6	33/2	NA	50.6	Pre	Scheuer	Within 1 wk
54	Garrido et al[82], 2022	Portugal	PBC	2010-2021	NA	5	79	52	NA	NA	NA	Pre 40 + post 39	Batts-Ludwig	Within 2 mo
55	Corpechot et al[83], 2014	France	PSC	2005-20210	Prospective	5	59	40.7	24/35	NA	145.7	Post	Metavir	Within 6 mo
56	Bowlus et al[84], 2016,	France	PSC	NA	NA	5	56	43	22/34	NA	255	NA	Ishak	NA
57	Eaton et al[85], 2016	United States	PSC	2007-2013	Retrospective	1, 7	266	46.12	81/185	26	48	Pre	Batts-Ludwig	Within 1 yr
58	Ehlken et al[86], 2016	Germany	PSC	2006-2014	Retrospective	5	62	38	63/77	NA	38	NA	Scheuer	NA
59	Krawczyk et al[87], 2017	Poland	PSC	2014-2016	Prospective	5	30	33	12/18	NA	50	NA	Metavir	NA
60	Umetsu et al[88], 2018	Japan	PSC	2007-2016	Retrospective	1, 2, 3, 11	28	14	8/20	NA	56.5	NA	Batts-Ludwig	The same day

¹Diagnostic models are represented by the following numbers: 1 = Aspartate aminotransferase to platelet ratio index; 2 = caspartate aminotransferase to alanine aminotransferase ratio; 3 = Fibrosis-4 index; 4 = Acoustic radiation force impulse; 5 = Transient elastography; 6 = Shear wave elastography; 7 = Magnetic resonance elastography; 8 = Magnetic resonance spectroscopy; 9 = Platelet count to spleen diameter ratio; 10 = Red cell distribution width to platelet ratio ; 11 = Mac-2-binding protein. AIH: Autoimmune hepatitis; ALT: Alanine aminotransferase; BMI: Body mass index; F: Female; M: Male; NA: Not available; PBC: Primary biliary cholangitis; PSC: Primary sclerosing cholangitis.

Table 2 Summary sensitivities, specificities, positive likelihood ratio and negative likelihood ratio of noninvasive methods at various diagnostic thresholds for prediction of significant fibrosis, advanced fibrosis and cirrhosis in autoimmune liver diseases patients

Disease	Diagnostic model/Stage	Cutoff values	No. of patients (n)	Summary sensitivity	Summary specificity	Summary PLR	Summary NLR
AIH	APRI
	SF	0.27-0.70	2 (195)	0.80 (0.72-0.86)	0.35 (0.23-0.48)	1.46 (0.55-3.89)	0.36 (0.061-2.09)
		0.88-1.55	3 (264)	0.74 (0.68-0.80)	0.51 (0.38-0.63)	1.52 (1.18-1.96)	0.50 (0.36-0.69)
	AF	0.38-0.90	4 (379)	0.86 (0.81-0.90)	0.48 (0.41-0.56)	1.60 (1.18-2.15)	0.33 (0.24-0.47)
		1.12-3.40	6 (538)	0.80 (0.72-0.86)	0.35 (0.23-0.48)	0.57 (0.51-0.64)	0.68 (0.62-0.73)
	Cirrhosis	0.55-1.81	3 (330)	0.65 (0.56-0.74)	0.47 (0.40-0.54)	1.49 (0.93-2.39)	0.62 (0.46-0.83)
		1.85-2.00	3 (213)	0.70 (0.57-0.81)	0.73 (0.65-0.79)	2.48 (1.75-3.52)	0.42 (0.28-0.62)
	AAR
	SF	0.72-0.93	2 (129)	0.67 (0.57-0.77)	0.68 (0.49-0.83)	2.22 (1.32-3.72)	0.46 (0.23-0.90)
	AF	0.76-1.18	7 (532)	0.61 (0.54-0.68)	0.72 (0.66-0.77)	2.01 (1.59-2.53)	0.58 (0.46-0.73)
	Cirrhosis	0.94-1.40	3 (213)	0.61 (0.47-0.74)	0.83 (0.76-0.88)	3.31 (1.96-5.59)	0.49 (0.36-0.69)
	FIB-4
	SF	1.95-2.90	3 (303)	0.64 (0.58-0.71)	0.71 (0.61-0.81)	2.20 (1.48-3.27)	0.50 (0.38-0.65)
		3.20-5.07	2 (156)	0.60 (0.51-0.69)	0.77 (0.60-0.90)	2.66 (1.44-4.92)	0.52 (0.39-0.69)
	AF	1.75-2.37	6 (476)	0.66 (0.59-0.72)	0.63 (0.57-0.69)	2.05 (1.56-2.70)	0.40 (0.20-0.81)
		3.21-5.60	5 (486)	0.47 (0.41-0.54)	0.73 (0.67-0.79)	1.83 (1.24-2.71)	0.68 (0.50-0.92)
	Cirrhosis	2.21-3.40	5 (440)	0.75 (0.67-0.82)	0.56 (0.50-0.62)	2.06 (1.53-2.77)	0.37 (0.19-0.71)
		6.44	1 (103)	0.68	0.64	1.88	0.51
	TE
	SF	5.80-7.00	7 (423)	0.83 (0.78-0.87)	0.73 (0.65-0.80)	2.89 (2.23-3.76)	0.23 (0.12-0.42)
		9.10-10.05	2 (100)	0.77 (0.67-0.86)	0.94 (0.70-1.00)	7.65 (1.66-35.32)	0.18 (0.02-1.47)
	AF	8.18-9.00	3 (286)	0.80 (0.72-0.87)	0.80 (0.73-0.86)	4.09 (2.64-6.33)	0.24 (0.17-0.35)
		10.40-12.10	4 (174)	0.73 (0.60-0.83)	0.93 (0.86-0.97)	7.67 (2.89-20.31)	0.27 (0.12-0.61)
	Cirrhosis	11.00-12.67	4 (213)	0.89 (0.82-0.94)	0.88 (0.81-0.93)	6.89 (4.38-10.85)	0.14 (0.09-0.23)
		16.00-19.00	3 (147)	0.88 (0.74-0.96)	0.97 (0.92-0.99)	22.08 (5.35-91.22)	0.16 (0.08-0.33)
	2D-SWE
	SF	8.20-10.00	3 (234)	0.89 (0.83-0.93)	0.72 (0.59-0.83)	3.25 (1.67-6.32)	0.17 (0.11-0.28)
	AF	12.20-15.80	3 (234)	0.82 (0.73-0.89)	0.79 (0.72-0.86)	3.92 (2.79-5.52)	0.24 (0.13-0.44)
	Cirrhosis	14.30-19.30	4 (297)	0.83 (0.74-0.90)	0.86 (0.81-0.91)	5.85 (4.09-8.37)	0.21 (0.13-0.34)
PBC	APRI
	SF	0.26-1.20	4 (584)	0.84 (0.80-0.87)	0.63 (0.56-0.70)	1.98 (1.54-2.55)	0.34 (0.23-0.51)
	AF	0.3.0-0.75	8 (858)	0.62 (0.57-0.68)	0.54 (0.50-0.58)	1.39 (1.09-1.79)	0.68 (0.48-0.98)
		0.93-2.00	7 (731)	0.73 (0.68-0.78)	0.68 (0.64-0.72)	2.68 (1.80-3.97)	0.46 (0.36-0.58)
	Cirrhosis	0.65-1.39	6 (852)	0.75 (0.67-0.83)	0.51 (0.48-0.55)	2.19 (1.38-3.50)	0.31 (0.10-0.99)
	AAR
	SF	0.92-1.00	3 (323)	0.69 (0.61-0.76)	0.56 (0.48-0.63)	1.61 (1.33-1.95)	0.52 (0.31-0.87)
	AF	0.81-1.01	5 (559)	0.54 (0.47-0.62)	0.73 (0.68-0.77)	2.15 (1.52-3.03)	0.63 (0.44-0.91)
	Cirrhosis	1.00-1.10	4 (407)	0.81 (0.70-0.90)	0.77 (0.72-0.82)	4.55 (1.98-10.49)	0.28 (0.10-0.79)
	FIB-4
	SF	1.39-3.90	3 (462)	0.85 (0.81-0.89)	0.77 (0.69-0.83)	2.89 (2.10-3.98)	0.26 (0.10-0.66)
	AF	2.05-2.63	7 (865)	0.77 (0.72-0.81)	0.57 (0.53-0.61)	1.95 (1.51-2.52)	0.31 (0.16-0.61)
		2.81-4.60	6 (431)	0.63 (0.55-0.71)	0.80 (0.75-0.85)	3.25 (1.78-5.94)	0.49 (0.30-0.81)
	Cirrhosis	2.05-4.60	6 (852)	0.87 (0.80-0.93)	0.61 (0.58-0.65)	2.79 (1.92-4.07)	0.16 (0.05-0.52)
	TE
	SF	5.90-8.80	4 (402)	0.81 (0.76-0.85)	0.95 (0.89-0.98)	10.51 (2.03-54.36)	0.23 (0.12-0.44)
		16.00	1 (44)	0.94	0.81	4.90	0.07
	AF	6.75-7.60	4 (377)	0.80 (0.73-0.86)	0.81 (0.76-0.86)	4.19 (2.35-7.46)	0.19 (0.05-0.79)
		9.60-10.70	3 (317)	0.91 (0.84-0.95)	0.82 (0.77-0.87)	5.68 (2.55-12.69)	0.12 (0.07-0.21)
		11.90-17.90	3 (180)	0.75 (0.60-0.86)	0.94 (0.88-0.97)	11.76 (2.29-60.48)	0.22 (0.06-0.80)
	Cirrhosis	11.40-14.40	3 (256)	0.84 (0.69-0.93)	0.94 (0.90-0.97)	13.46 (7.66-23.65)	0.19 (0.10-0.38)
		15.60-25.10	3 (227)	0.90 (0.74-0.98)	0.93 (0.89-0.96)	22.8 (0.81-639.69)	0.12 (0.04-0.34)
	RPR
	AF	0.10-0.14	4 (362)	0.49 (0.40-0.58)	0.89 (0.84-0.92)	4.27 (2.22-8.22)	0.59 (0.47-0.74)
	M2BP
	AF	1.00-1.40	4 (370)	0.68 (0.59-0.77)	0.80 (0.75-0.85)	4.26 (1.82-9.96)	0.32 (0.14-0.75)
PSC	TE
	SF	8.80	2 (121)	0.76 (0.62-0.87)	0.88 (0.79-0.95)	6.34 (3.25-12.37)	0.29 (0.18-0.46)
	AF	9.60	3 (177)	0.82 (0.70-0.91)	0.83 (0.75-0.89)	4.75 (2.21-10.19)	0.15 (0.02-1.04)
	Cirrhosis	13.70-14.40	4 (207)	0.82 (0.68-0.91)	0.89 (0.83-0.94)	7.46 (3.74-14.88)	0.25 (0.15-0.43)

2D-SWE: Two-dimensional shear wave elastography; AAR: Aspartate aminotransferase to alanine aminotransferase ratio; AF: Advanced fibrosis; AIH: Autoimmune hepatitis; APRI: Aspartate aminotransferase to platelet ratio index; FIB-4: Fibrosis-4 index; M2BP: Mac-2-binding protein; NLR: Negative likelihood ratio; PLR: Positive likelihood ratio; PBC: Primary biliary cholangitis; PSC: Primary sclerosing cholangitis; RPR: Red cell distribution width to platelet ratio; SF: Significant fibrosis; TE: Transient elastography.

Table 3 Summary area under the receiver operator curve and diagnostic odds ratio of noninvasive methods for prediction of significant fibrosis, advanced fibrosis and cirrhosis in autoimmune liver diseases patients

Disease	Diagnostic model/Stage	No. of studies (patients)	AUROC (95%CI)	DOR (95%CI)
AIH	APRI
	SF	4 (383)	0.67 (0.63-0.71)	3.87 (2.1-7.3)
	AF	10 (917)	0.71 (0.67-0.75)	3.85 (2.8-5.3)
	Cirrhosis	6 (543)	0.71 (0.67-0.75)	3.77 (2.2-6.4)
	FIB-4
	SF	5 (459)	0.74 (0.70-0.78)	5.11 (3.1-8.5)
	AF	11 (962)	0.73 (0.69-0.76)	4.04 (2.4-6.8)
	Cirrhosis	6 (543)	0.72 (0.68-0.76)	5.48 (2.4-12.6)
	TE
	SF	9 (523)	0.84 (0.80-0.87)	16.83 (8.8-32.2)
	AF	7 (460)	0.88 (0.85-0.90)	25.14 (9.7-65.3)
	Cirrhosis	7 (415)	0.90 (0.87-0.92)	91.77 (40.1-201.2)
	AAR
	AF	6 (410)	0.73 (0.69-0.77)	4.94 (3.2-7.8)
	2D-SWE
	Cirrhosis	4 (297)	0.91 (0.89-0.94)	30.68 (15.7-59.9)
PBC	APRI
	SF	4 (584)	0.77 (0.73-0.80)	6.27 (3.5-11.2)
	AF	15 (1589)	0.70 (0.66-0.74)	3.67 (2.3-5.9)
	Cirrhosis	6 (852)	0.83 (0.79-0.86)	14.55 (1.9-113.8)
	FIB-4
	AF	13 (1296)	0.79 (0.75-0.82)	7.13 (4.0-12.8)
	Cirrhosis	6 (852)	0.88 (0.85-0.91)	29.79 (5.9-150.3)
	TE
	SF	5 (446)	0.93 (0.91-0.95)	74.45 (12.2-455.5)
	AF	10 (880)	0.93 (0.90-0.95)	41.84 (19.3-91.0)
	Cirrhosis	6 (483)	0.91 (0.88-0.93)	134.83 (33.0-551.8)
	AAR
	AF	6 (559)	0.74 (0.70-0.78)	4.13 (2.0-8.6)
	Cirrhosis	4 (407)	0.88 (0.84-0.90)	25.29 (9.0-70.9)
	RPR
	AF	4 (362)	0.53 (0.49-0.58)	7.98 (4.0-15.8)
	M2BP
	AF	4 (370)	0.86 (0.82-0.88)	13.17 (4.1-42.4)
PSC	TE
	Cirrhosis	4 (207)	0.95 (0.93-0.97)	70.59 (15.4-322.7)

2D-SWE: Two-dimensional shear wave elastography; 95%CI: 95% confidence interval; AAR: Aspartate aminotransferase to alanine aminotransferase ratio; AF: Advanced fibrosis; AIH: Autoimmune hepatitis; APRI: Aspartate aminotransferase to platelet ratio index; AUROC: Area under the receiver operator curve; DOR: Diagnostic odds ratio; FIB-4: Fibrosis-4 index; PBC: Primary biliary cholangitis; PSC: Primary sclerosing cholangitis; RPR: Red cell distribution width to platelet ratio; SF: Significant fibrosis; TE: Transient elastography.

Table 4 Heterogeneity of all the included studies

		Fibrosis stage	Threshold heterogeneity		Non-threshold heterogeneity
			r	P value	I2 (%)	P value
AIH	TE	SF	0.176	0.651	82.9	0
		AF	-0.429	0.337	93.8	0
		Cirrhosis	0.321	0.482	56.59	0.03
	APRI	SF	1.0	0	62.34	0.05
		AF	0.717	0.02	71.94	0
		Cirrhosis	0.714	0.111	90.93	0
	FIB-4	SF	0.70	0.188	46.81	0.11
		AF	0.627	0.039	98.29	0
		Cirrhosis	-0.029	0.957	88.98	0
	AAR	AF	0.857	0.014	36.46	0.16
	SWE	Cirrhosis	0	1.0	61.97	0.05
PBC	TE	SF	-0.10	0.873	99.99	0
		AF	0.195	0.590	100	0
		Cirrhosis	-0.726	0.027	93.77	0
	APRI	SF	1.0	0	99.9	0
		AF	0.209	0.454	100	0
		Cirrhosis	-0.657	0.156	100	0
	FIB-4	AF	0.418	0.156	100	0
		Cirrhosis	0.029	0.957	100	0
	AAR	AF	0.60	0.208	96.05	0
		Cirrhosis	0.40	0.60	95.37	0
	M2BP	AF	0	1.0	99.24	0
	RPR	AF	0	1.0	94.49	0
PSC	TE	Cirrhosis	0.80	0.20	50.07	0.11

AAR: Aspartate aminotransferase to alanine aminotransferase ratio; AF: Advanced fibrosis; AIH: Autoimmune hepatitis; APRI: Aspartate aminotransferase to platelet ratio index; FIB-4: Fibrosis-4 index; M2BP: Mac-2-binding protein; PBC: Primary biliary cholangitis; PSC: Primary sclerosing cholangitis; RPR: Red cell distribution width to platelet ratio; SF: Significant fibrosis; SWE: Shear wave elastography; TE: Transient elastography.

Table 5 Subgroup analysis of sample size and treatment status in prediction of significant fibrosis, advanced fibrosis and cirrhosis in autoimmune hepatitis and primary biliary cholangitis patients

Disease	Parameter	Stage	Subgroup	Sensitivity (95%CI)	Specificity (95%CI)	AUROC (95%CI)
AIH	Sample size	SF	n < 50	0.83 (0.55-0.95)	0.82 (0.65-0.92)	0.85 (0.82-0.88)
			n > 50	0.84 (0.73-0.91)	0.77 (0.63-0.87)	0.87 (0.84-0.90)
		AF	n < 50	0.78 (0.54-0.91)	0.91 (0.78-0.96)	0.92 (0.89-0.94)
			n > 50	0.78 (0.68-0.86)	0.87 (0.73-0.94)	0.88 (0.84-0.90)
		Cirrhosis	n < 50	0.90 (0.65-0.98)	0.92 (0.74-0.98)	0.96 (0.94-0.97)
			n > 50	0.88 (0.82-0.93)	0.93 (0.86-0.96)	0.92 (0.89-0.94)
	Treatment status	SF	Post	0.78 (0.44-0.94)	0.76 (0.60-0.86)	0.79 (0.75-0.82)
		AF	Post	0.83 (0.66-0.93)	0.96 (0.84-0.99)	0.93 (0.91-0.95)
		Cirrhosis	Post	0.91(0.77-0.97)	0.97 (0.73-1.00)	0.94 (0.91-0.95)
	Cutoff value	SF	5.80-6.27	0.87 (0.81-0.92)	0.69 (0.60-0.77)	0.86 (0.83-0.89)
			6.40-9.10	0.82 (0.75-0.88)	0.89 (0.74-0.96)	0.92 (0.89-0.94)
		AF	9.00-11.00	0.83 (0.69-0.91)	0.92 (0.73-0.98)	0.88 (0.85-0.91)
			8.18-12.10	0.77 (0.71-0.83)	0.85 (0.80-0.89)	0.88 (0.85-0.90)
		Cirrhosis	11.00-12.67	0.89 (0.82-0.94)	0.88 (0.81-0.93)	0.92 (0.94-0.96)
			11.00-19.00	0.88 (0.82-0.93)	0.92 (0.88-0.95)	0.90 (0.87-0.92)
PBC	Sample size	SF	n < 100	0.81 (0.48-0.95)	0.78 (0.60-0.89)	0.82 (0.79-0.86)
			n > 100	0.83 (0.68-0.92)	0.98 (0.74-1.00)	0.97 (0.95-0.98)
		AF	n < 100	0.90 (0.85-0.94)	0.88 (0.78-0.94)	0.91 (0.88-0.93)
			n > 100	0.81 (0.64-0.91)	0.88 (0.75-0.94)	0.91 (0.88-0.93)
		Cirrhosis	n < 100	0.82 (0.67-0.91)	0.94 (0.80-0.99)	0.86 (0.82-0.89)
			n > 100	0.91 (0.76-0.97)	0.97 (0.90-0.99)	0.94 (0.92-0.96)
	Treatment status	SF	Post	0.89 (0.70-0.97)	0.98 (0.41-1.00)	0.97 (0.95-0.98)
		AF	Post	0.85 (0.68-0.94)	0.92 (0.63-0.99)	0.93 (0.91-0.95)
		Cirrhosis	Post	0.90 (0.71-0.97)	0.96 (0.74-1.00)	0.94 (0.92-0.96)
	Cutoff value	AF	6.75-7.60	0.80 (0.73-0.86)	0.81 (0.76-0.86)	0.88 (0.85-0.91)
			9.60-10.70	0.91 (0.84-0.95)	0.82 (0.77-0.87)	0.92 (0.89-0.94)
			11.90-17.90	0.75 (0.60-0.86)	0.94 (0.88-0.97)	0.93 (0.91-0.95)
		Cirrhosis	11.40-14.40	0.84 (0.69-0.93)	0.94 (0.90-0.97)	0.96 (0.94-0.97)
			14.40-16.90	0.88 (0.72-0.97)	0.99 (0.96-1.00)	0.99 (0.98-1.00)

95%CI: 95% confidence interval; AF: Advanced fibrosis; AIH: Autoimmune hepatitis; AUROC: Area under the receiver operator curve; PBC: Primary biliary cholangitis; SF: Significant fibrosis.