Systematic Reviews
Copyright ©The Author(s) 2023.
World J Gastroenterol. Oct 21, 2023; 29(39): 5503-5525
Published online Oct 21, 2023. doi: 10.3748/wjg.v29.i39.5503
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
1Youssef et al[40], 2013EgyptAIHNARetrospective516NANANANANAMetavirNA
2Kim et al[41], 2014KoreaAIH2008-2014Retrospective547NA41/6NANANAMetavirNA
3Abdollahi et al[42], 2015IranAIH2011-2013NA1, 2, 38034.7551/29NA106.49NAIshakNA
4Harrison et al[43], 2016United KingdomAIH2013-2015Prospective5275625/2NA21PostIshakThe same day
5Hartl et al[44], 2016GermanyAIH2007-2010Prospective5345328/6NA48.5PostScheuerWithin 3 mo
Hartl et al[44], 2016GermanyAIH2008-2015Retrospective5605250/10NA35PostScheuerWithin 4 mo
6Nishikawa et al45], 2016JapanAIH2005-2015Prospective1, 2, 3, 11846469/15NA57.5PreScheuerNA
7E Anastasiou et al[46], 2016GermanyAIH2008-2013Retrospective1, 2, 3, 55347.331/22NA606.42Pre 35 + post 18MetavirWithin 3 wk
8Piwczyńska et al[47], 2016PolandAIHNAProspective44614.533/13NANANABatts-LudwigNA
9Sheptulina et al[48], 2016RussianAIH2008-2014Prospective1, 2, 3, 9764065/112554.4Pre 22 + post 54MetavirWithin 7 d
10Guo et al[29], 2017ChinaAIH2012-2017Retrospective1, 3, 510846.5488/2023.52146.51NAMetavirWithin 3 d
11Paranagua-Vezozzo et al[49], 2016BrazilAIH2012-2015Prospective4, 533NA28/528.6NAPostMetavirThe same day
12Puustinen et al[50], 2017FinlandAIHNAProspective81242.810/2NA28.5NAMetavirWithin 1 mo
13Wang et al[22], 2017ChinaAIH2007-2015Retrospective1, 2, 3, 73651.6NA27.7217.4Pre 17 + post 19MetavirWithin 3 mo
14Xu et al[51], 2017ChinaAIH2014-2016Prospective1, 3, 51004581/19NA131.5PreMetavirThe same day
15Zeng et al[52], 2017ChinaAIH2011-2016Prospective66245.6NA21.678.5PreMetavir3 d
16Liu et al[53], 2019ChinaAIH2008-2018Retrospective2, 34554.2937/8NANANAMetavirThe same day
17Park et al[19], 2019South KoreaAIH2014-2017NA4495642/723.7163NAMetavirThe same day
PBC4155.335/625.545NA
18Li et al[54], 2020ChinaAIH2010-2019Retrospective1, 2, 3, 10725464/8NA137.55PostMetavirNA
19Wang et al[55], 2020ChinaAIH2016-2019Retrospective1, 3, 1011952.599/20NA81.6PreScheuerWithin 7 d
20Xing et al[30], 2020ChinaAIH2016-2019Retrospective1, 3, 61035481/2222.5163NAScheuerWithin 7 d
21Janik et al[31], 2021PolandAIH2015-2020Prospective6633715/4823.9130PostBatts-LudwigWithin 3 mo
22Zachou et al[20], 2021GreeceAIH2009-2016Retrospective5785754/24NA68Pre 47 + post 31MetavirThe same day
PBC565248/8NA47Pre 37 + post 19
23Ferronato et al[56], 2022ItalyAIHNARetrospective1, 2, 31225990/32NA481.8PreIshakWithin 23 d
24Soh et al[57], 2022KoreaAIH2014-2021Retrospective66959.760/9NA187.1Pre 44 + post 25MetavirThe same day
25Nyblom et al[58], 2006SwedenPBC1976-2000Retrospective212154NANA189.9NAMetavirNA
26Gómez-Dominguez et al[59], 2008SpainPBCNAProspective5805464/16NANAPostMetavirWithin 9 mo
27Alempijevic et al[60], 2009SerbiaPBC2006NA1, 211253.88104/8NANAPostScheuerWithin 1 wk
28Ferrara et al[61], 2009ItalyPBCNANA1, 324852233/15NANANAScheuerThe same day
29Su et al[62], 2009ChinaPBC1985-2006Retrospective24653.334/12NA140.6NAScheuerWithin 1 mo
30Floreani et al[63], 2011ItalyPBC2009NA51145896/242444NAMetavirWithin 6 mo
31Corpechot et al[64], 2012FrancePBC2004-2010Prospective51035687/1623.976PostMetavirWithin 9 mo
32Zhang et al[34], 2014ChinaPBC2011-2013NA4564546/10NANANABatts-LudwigWithin 3 d
33Sheptulina et al[21], 2015 RussianPBC2008-2014Retrospective98254.578/4NANANAMetavirNA
PSC322386/16NANANANA
34Umemura et al[65], 2015JapanPBC1981-2014Retrospective1113757111/26NA41PostMetavirThe same day
35Nishikawa et al[66], 2016JapanPBC2005-2014Prospective1, 3, 11575949/8NA35PreScheuerNA
36Olmez et al[67], 2016TurkeyPBC1995-2013Retrospective1, 34049.640/0NA54.5NAScheuerWithin 1 wk
37Wang et al[68], 2016ChinaPBC2010-2015Retrospective1, 3, 107352.462/11NA89.3PreLudwing and ScheuerThe day before
38Koizumi et al[23], 2017 JapanPBC2012-2015Prospective1, 2, 3, 54460.541/3NA65.9PostMetavirWithin 1 wk
39Wang et al[69], 2017ChinaPBC2009-2016Retrospective1, 326152230/31NANANAMetavirNA
40Jiang et al[70], 2018ChinaPBC2009-2015Retrospective3, 107762.464/13NA81.2PreScheuerNA
41Kamal et al[71], 2018NetherlandsPBC1979-2010Retrospective1, 2, 3855075/10NANANAIshakNA
42Meng et al[72], 2018ChinaPBC2013-2017Retrospective1, 3, 109451.02NANA116.58PreLudwing and ScheuerWithin 1 wk
43Milovanović et al[73], 2018SerbiaPBC2009-2011Prospective1, 2, 512257.4NANA50.8PostMetavirWithin 1 mo
44Wang et al[74], 2018ChinaPBC2010-2016Retrospective1, 3, 105853.351/7NA90.4PreLudwing and ScheuerWithin 1 wk
45Jiang et al[75], 2020ChinaPBC2008-2018Prospective1, 2, 3, 10785271/7NANAPre 39 + post 39ScheuerWithin 2 wk
Jiang et al[75], 2020China bPBC2008-2018Retrospective1, 3, 10405135/5NANAPre 20 + post 20ScheuerWithin 2 wk
46Joshita et al[76], 2020JapanPBC2015-2019NA5, 11746462/12NA48PreScheuerThe same day
47Rossi et al[77], 2020ItalyPBCNANA592NANANANANAScheuerWithin 1 mo
48Yan et al[32], 2020ChinaPBC2016-2019Retrospective1, 2, 3, 615753136/2122.272NAScheuerNA
49Cristoferi et al[78], 2021ItalyPBC2006-2019Prospective1, 512652114/1222.352.8PreBatts-LudwigWithin 12 wk
50Fujinaga et al[79], 2021JapanPBC2000-2019Retrospective1, 3, 111026189/13NA68.4PreScheuerNA
51Manesis et al[80], 2021GreecePBC2010-2018Retrospective65362.646/725.730Pre 30 + post 23ScheuerWithin 3 mo
52Osman et al[33], 2021United StatesPBC2007-2019Retrospective56360.95NANA31.2NABatts-LudwigWithin 1 yr
79860.21NANA36.4NA
53Avcioğlu et al[81], 2022TurkeyPBC2008-2020Retrospective1, 33549.633/2NA50.6PreScheuerWithin 1 wk
54Garrido et al[82], 2022PortugalPBC2010-2021NA57952NANANAPre 40 + post 39Batts-LudwigWithin 2 mo
55Corpechot et al[83], 2014FrancePSC2005-20210Prospective55940.724/35NA145.7PostMetavirWithin 6 mo
56Bowlus et al[84], 2016, FrancePSCNANA5564322/34NA255NAIshakNA
57Eaton et al[85], 2016United StatesPSC2007-2013Retrospective1, 726646.1281/1852648PreBatts-LudwigWithin 1 yr
58Ehlken et al[86], 2016GermanyPSC2006-2014Retrospective5623863/77NA38NAScheuerNA
59Krawczyk et al[87], 2017PolandPSC2014-2016Prospective5303312/18NA50NAMetavirNA
60Umetsu et al[88], 2018JapanPSC2007-2016Retrospective1, 2, 3, 1128148/20NA56.5NABatts-LudwigThe same day
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
AIHAPRI
SF0.27-0.702 (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)
0.88-1.553 (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)
AF0.38-0.904 (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)
1.12-3.406 (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)
Cirrhosis0.55-1.813 (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)
1.85-2.003 (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
SF0.72-0.932 (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)
AF0.76-1.187 (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)
Cirrhosis0.94-1.403 (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
SF1.95-2.903 (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)
3.20-5.072 (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)
AF1.75-2.376 (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)
3.21-5.605 (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)
Cirrhosis2.21-3.405 (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)
6.441 (103)0.680.641.880.51
TE
SF5.80-7.007 (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)
9.10-10.052 (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)
AF8.18-9.003 (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)
10.40-12.104 (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)
Cirrhosis11.00-12.674 (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)
16.00-19.003 (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
SF8.20-10.003 (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)
AF12.20-15.803 (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)
Cirrhosis14.30-19.304 (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)
PBCAPRI
SF0.26-1.204 (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)
AF0.3.0-0.758 (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)
0.93-2.007 (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)
Cirrhosis0.65-1.396 (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
SF0.92-1.003 (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)
AF0.81-1.015 (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)
Cirrhosis1.00-1.104 (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
SF1.39-3.903 (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)
AF2.05-2.637 (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)
2.81-4.606 (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)
Cirrhosis2.05-4.606 (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
SF5.90-8.804 (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)
16.001 (44)0.940.814.90 0.07
AF6.75-7.604 (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)
9.60-10.703 (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)
11.90-17.903 (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)
Cirrhosis11.40-14.403 (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)
15.60-25.103 (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
AF0.10-0.144 (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
AF1.00-1.404 (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)
PSCTE
SF8.802 (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)
AF9.603 (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)
Cirrhosis13.70-14.404 (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)
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)
AIHAPRI
SF4 (383)0.67 (0.63-0.71)3.87 (2.1-7.3)
AF10 (917)0.71 (0.67-0.75)3.85 (2.8-5.3)
Cirrhosis6 (543)0.71 (0.67-0.75)3.77 (2.2-6.4)
FIB-4
SF5 (459)0.74 (0.70-0.78)5.11 (3.1-8.5)
AF11 (962)0.73 (0.69-0.76)4.04 (2.4-6.8)
Cirrhosis6 (543)0.72 (0.68-0.76)5.48 (2.4-12.6)
TE
SF9 (523)0.84 (0.80-0.87)16.83 (8.8-32.2)
AF7 (460)0.88 (0.85-0.90)25.14 (9.7-65.3)
Cirrhosis7 (415)0.90 (0.87-0.92)91.77 (40.1-201.2)
AAR
AF6 (410)0.73 (0.69-0.77)4.94 (3.2-7.8)
2D-SWE
Cirrhosis4 (297)0.91 (0.89-0.94)30.68 (15.7-59.9)
PBCAPRI
SF4 (584)0.77 (0.73-0.80)6.27 (3.5-11.2)
AF15 (1589)0.70 (0.66-0.74)3.67 (2.3-5.9)
Cirrhosis6 (852)0.83 (0.79-0.86)14.55 (1.9-113.8)
FIB-4
AF13 (1296)0.79 (0.75-0.82)7.13 (4.0-12.8)
Cirrhosis6 (852)0.88 (0.85-0.91)29.79 (5.9-150.3)
TE
SF5 (446)0.93 (0.91-0.95)74.45 (12.2-455.5)
AF10 (880)0.93 (0.90-0.95)41.84 (19.3-91.0)
Cirrhosis6 (483)0.91 (0.88-0.93)134.83 (33.0-551.8)
AAR
AF6 (559)0.74 (0.70-0.78)4.13 (2.0-8.6)
Cirrhosis4 (407)0.88 (0.84-0.90)25.29 (9.0-70.9)
RPR
AF4 (362)0.53 (0.49-0.58)7.98 (4.0-15.8)
M2BP
AF4 (370)0.86 (0.82-0.88)13.17 (4.1-42.4)
PSCTE
Cirrhosis4 (207)0.95 (0.93-0.97)70.59 (15.4-322.7)
Table 4 Heterogeneity of all the included studies
Fibrosis stageThreshold heterogeneity
Non-threshold heterogeneity
r
P value
I2 (%)
P value
AIHTESF0.1760.65182.90
AF-0.4290.33793.80
Cirrhosis0.3210.48256.590.03
APRISF1.0062.340.05
AF0.7170.0271.940
Cirrhosis0.7140.11190.930
FIB-4SF0.700.18846.810.11
AF0.6270.03998.290
Cirrhosis-0.0290.95788.980
AARAF0.8570.01436.460.16
SWECirrhosis01.061.970.05
PBCTESF-0.100.87399.990
AF0.1950.5901000
Cirrhosis-0.7260.02793.770
APRISF1.0099.90
AF0.2090.4541000
Cirrhosis-0.6570.1561000
FIB-4AF0.4180.1561000
Cirrhosis0.0290.9571000
AARAF0.600.20896.050
Cirrhosis0.400.6095.370
M2BPAF01.099.240
RPRAF01.094.490
PSCTECirrhosis0.800.2050.070.11
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)
AIHSample sizeSFn < 500.83 (0.55-0.95)0.82 (0.65-0.92)0.85 (0.82-0.88)
n > 500.84 (0.73-0.91)0.77 (0.63-0.87)0.87 (0.84-0.90)
AFn < 500.78 (0.54-0.91)0.91 (0.78-0.96)0.92 (0.89-0.94)
n > 500.78 (0.68-0.86)0.87 (0.73-0.94)0.88 (0.84-0.90)
Cirrhosisn < 500.90 (0.65-0.98)0.92 (0.74-0.98)0.96 (0.94-0.97)
n > 500.88 (0.82-0.93)0.93 (0.86-0.96)0.92 (0.89-0.94)
Treatment statusSFPost0.78 (0.44-0.94)0.76 (0.60-0.86)0.79 (0.75-0.82)
AFPost0.83 (0.66-0.93)0.96 (0.84-0.99)0.93 (0.91-0.95)
CirrhosisPost0.91(0.77-0.97)0.97 (0.73-1.00)0.94 (0.91-0.95)
Cutoff valueSF5.80-6.270.87 (0.81-0.92)0.69 (0.60-0.77)0.86 (0.83-0.89)
6.40-9.100.82 (0.75-0.88)0.89 (0.74-0.96)0.92 (0.89-0.94)
AF9.00-11.000.83 (0.69-0.91)0.92 (0.73-0.98)0.88 (0.85-0.91)
8.18-12.100.77 (0.71-0.83)0.85 (0.80-0.89)0.88 (0.85-0.90)
Cirrhosis11.00-12.670.89 (0.82-0.94)0.88 (0.81-0.93)0.92 (0.94-0.96)
11.00-19.000.88 (0.82-0.93)0.92 (0.88-0.95)0.90 (0.87-0.92)
PBCSample sizeSFn < 1000.81 (0.48-0.95)0.78 (0.60-0.89)0.82 (0.79-0.86)
n > 1000.83 (0.68-0.92)0.98 (0.74-1.00)0.97 (0.95-0.98)
AFn < 1000.90 (0.85-0.94)0.88 (0.78-0.94)0.91 (0.88-0.93)
n > 1000.81 (0.64-0.91)0.88 (0.75-0.94)0.91 (0.88-0.93)
Cirrhosisn < 1000.82 (0.67-0.91)0.94 (0.80-0.99)0.86 (0.82-0.89)
n > 1000.91 (0.76-0.97)0.97 (0.90-0.99)0.94 (0.92-0.96)
Treatment statusSFPost0.89 (0.70-0.97)0.98 (0.41-1.00)0.97 (0.95-0.98)
AFPost0.85 (0.68-0.94)0.92 (0.63-0.99)0.93 (0.91-0.95)
CirrhosisPost0.90 (0.71-0.97)0.96 (0.74-1.00)0.94 (0.92-0.96)
Cutoff valueAF6.75-7.600.80 (0.73-0.86)0.81 (0.76-0.86)0.88 (0.85-0.91)
9.60-10.700.91 (0.84-0.95)0.82 (0.77-0.87)0.92 (0.89-0.94)
11.90-17.900.75 (0.60-0.86)0.94 (0.88-0.97)0.93 (0.91-0.95)
Cirrhosis11.40-14.400.84 (0.69-0.93)0.94 (0.90-0.97)0.96 (0.94-0.97)
14.40-16.900.88 (0.72-0.97)0.99 (0.96-1.00)0.99 (0.98-1.00)