Meta-Analysis
Copyright ©The Author(s) 2023.
World J Hepatol. Sep 27, 2023; 15(9): 1060-1083
Published online Sep 27, 2023. doi: 10.4254/wjh.v15.i9.1060
Table 1 Characteristics of eligible studies
Ref.Type of studyDeviceFormulaPatients, nControls, nFemale ratioAlcoholic etiology ratioChild-Pugh
MELD scoreAge in yrQTc
A, n
B, n
C, n
Prolongation ratio
Controls
Females
Viral etiology
Acohol etiology
Child-Pugh A
Child-Pugh B
Child-Pugh C
Tx pre
Tx post
Wang et al[62], 2023REB10220.095152.6 ± 11.60.107
Bilous et al[10], 2023PHB330.3948141148.0 ± 12.0393.7 ± 35.0
Barutcu et al[37], 2023REB1001000.44032343416 ± 860.0 ± 42.2446.3 ± 49.3439 ± 33410 ± 23455 ± 39473 ± 53
Lu et al[46], 2022REB35290.2330.18255.0 ± 11.00.158
Wang et al[63], 2022REB1890.783102563159.4 ± 11.8435.9 ± 46.10.243433 ± 45439 ± 47439 ± 47
Li et al[27], 2021PEF2740.4561081224412 ± 461.8 ± 12.80.328
Ou et al[40], 2021REB1670.2810.16870811611 ± 452.9 ± 10.80.665
Ko et al[25], 2021REB4080.2360.09357.1 ± 12.0452.0 ± 31.00.650452 ± 31430 ± 32
Héla et al[36], 2020PHB420.4290.09512151560.0 ± 13.2435.9 ± 21.80.476423 ± 19429 ± 17453 ± 17
Abrahamovych et al[64], 2020RHB870.276144.5 ± 4.3443.8 ± 34.4
Ibrahim et al[65], 2020PEB500.58003812052.0 ± 12.0415.8 ± 24.4
Hussain et al[66], 2020PEB87870.4600.31647.0 ± 13.3470.0 ± 50.00.218400 ± 50
Kim et al[35], 2020REB3100.2740.2741059411146.0 ± 17.0450.0 ± 43.0460 ± 44417 ± 29452 ± 34480 ± 38
Toma et al[67], 2020PEB630.508018202556.2 ± 13.5452.5 ± 27.70.460453 ± 28445 ± 27451 ± 23459 ± 31
Bhardwaj et al[68], 2020PEB1001000.1500.5304356149.8 ± 13.6458.5 ± 27.0424 ± 28
Gaafar et al[69], 2019PEB1120424.4 ± 36.6
Kazankov et al[28], 2019REB915415.0 ± 30.0
Moaref et al[70], 2019PEB300.36716 ± 541.0 ± 6.6
Santeusanio et al[71], 2019REB2580.3370.09718 ± 1059.5 ± 9.7454.4 ± 27.90.403
Biselli et al[72], 2019REF4740.3520.23613 ± 561.7 ± 12.6438.0 ± 42.0
Tieranu et al[45], 2018PEB600.4336282659.4 ± 7.3457.8 ± 23.9456 ± 27452 ± 26462 ± 20
Lee et al[39], 2018REB2830.2470.11317 ± 1155.1 ± 7.7449.9 ± 31.60.636450 ± 32435 ± 32
Hajiaghamohammadi et al[73], 2018PEB370.43212121358.8 ± 11.5418.5 ± 41.9
Główczyńska et al[44], 2018REB1510.3710.17950732812 ± 549.0 ± 12.3426.3 ± 41.60.338426 ± 41432 ± 45423 ± 38424 ± 46438 ± 34
Tahata et al[74], 2018PEB1040.6541040071.1 ± 8.4415.9 ± 30.6416 ± 31
Tsiompanidis et al[75], 2018PEB510.3730.33322181128 ± 1955.2 ± 14.2428.1 ± 31.00.431437 ± 31419 ± 30419 ± 30435 ± 30
Yap et al[43], 2018REB1480.5270.1551757972.4 ± 14.0440.3 ± 45.6464 ± 63432 ± 33448 ± 63
Kim et al[76], 2017REB4060.4040.38918 ± 956.4 ± 9.0454.5 ± 27.80.510
Rimbaş et al[18], 2018PEB46460.3480.5222316713 ± 557.0 ± 9.0436.0 ± 30.00.413404 ± 21438 ± 35
Salgado et al[42], 2016PEB670.4780.23925261654.0 ± 12.9418.7 ± 26.60.224415 ± 34418 ± 21426 ± 22
Naqvi et al[34], 2016PEB890.438017294351.5 ± 12.4475.1 ± 73.30.461420 ± 36459 ± 56508 ± 78
Zhao et al[38], 2016REB12680.3470.2534975281406 ± 756.0 ± 12.10.382
Sonny et al[77], 2016REB1060.2800.17917 ± 855.0 ± 9.0453.0 ± 28.0453 ± 28442 ± 29
Barbosa et al[17], 2016CEB260.1540.76917819 ± 554.6 ± 10.4460.0 ± 23.00.769
Carvalheiro et al[78], 2016REF1060.1980.65123245917 ± 854.8 ± 8.50.189
Pourafkari et al[79], 2016REB690.3480.21714282717 ± 756.8 ± 16.0452.2 ± 46.00.507453 ± 52455 ± 40449 ± 50
Barakat et al[80], 2015PEB740.324019 ± 26473.1 ± 25.1
Voiosu et al[81], 2015PEF740.3780.37843121913 ± 558.0 ± 11.0418.3 ± 26.8
Cichoż-Lach et al[82], 2015REB122320.3440.66428405442.1 ± 12.7447.5 ± 29.9394 ± 23465 ± 50443 ± 7438 ± 35434 ± 40476 ± 40
Peter et al[83], 2014PEB780.1540.53815 ± 551.2 ± 11.9424.0 ± 10.2
Moaref et al[15], 2014PEB800.375008041.0 ± 14.0490.0 ± 51.0490 ± 51
Josefsson et al[84], 2014REB2020.30722918917 ± 652.0 ± 11.00.262
Karagiannakis et al[14], 2014PEB450.2670.4442615312 ± 457.2 ± 12.4428.0 ± 27.5
Yataco et al[41], 2014REB170.4710.235011629 ± 757.9 ± 7.9461.4 ± 37.40.529461 ± 38459 ± 31479 ± 42
Bhatti et al[85], 2014CEB1660.422022697557.1 ± 12.0429.9 ± 45.10.247
Møller et al[86], 2012PEB100.50055.6 ± 10.0450.0 ± 20.0
Trevisani et al[87], 2012REF700.3290.18616 ± 161.7 ± 12.5415.9 ± 36.00.243
Zamirian et al[24], 2012PEB2430.3800.049446.9 ± 12.50.432483 ± 20478 ± 25447 ± 13383 ± 49
Kim et al[88], 2011PEB1000.14018483414 ± 852.3 ± 8.3
Shin et al[89], 2011PEB500.20014191752.0 ± 7.0433.2 ± 32.70.440
Mozos et al[33], 2011PEB380.5000.3951613958.0 ± 12.0493.0 ± 46.00.711481 ± 51527 ± 50462 ± 25493 ± 62520 ± 45
Vuppalanchi et al[90], 2011PEB140.2860.50011 ± 253.9 ± 9.6
Møller et al[91], 2010PEB430.32611718811 ± 357.4 ± 9.1453.0 ± 31.0
Zurick et al[23], 2010REB2690.3722150.9448.3 ± 41.30.502449 ± 11449 ± 41417 ± 41
Lossnitzer et al[13], 2010PEB200.4500.60015 ± 652.4 ± 9.40.250
Genovesi et al[32], 2009PHB400.0000.4502615756.1 ± 11.2439.3 ± 30.20.525425 ± 24452 ± 30465 ± 24
Zambruni et al[31], 2008PEB300.1670.2331510513 ± 158.8 ± 11.0455.4 ± 26.80.367459 ± 38450 ± 38440 ± 16466 ± 26486 ± 20
Henriksen et al[92], 2007PEB480.3540.91715191452.1 ± 11.1450.0 ± 33.90.563441 ± 53441 ± 39470 ± 76
Kosar et al[93], 2007REB330.455915953.0 ± 11.0412.5 ± 89.6405 ± 51411 ± 46427 ± 64
Hansen et al[12], 2007PHB230.2610.609610755.0 ± 8.6441.0 ± 31.70.478420 ± 53438 ± 48461 ± 45
Zuberi et al[94], 2007CEB780.2696195334.4438.0 ± 15.00.192
Zambruni et al[47], 2007PEB100530.3700.21034392757.2 ± 7.6465.2 ± 33.30.520416 ± 24
Ytting et al[7], 2005PEB800.2630.48833331451.0 ± 10.4447.0 ± 42.30.513
Adigun et al[21], 2005PEB1830.3660.16471433347.7 ± 7.4419.6 ± 31.80.279419 ± 35436 ± 21421 ± 21
Henriksen et al[95], 2004PEB240.1251312958.3 ± 11.0462.0 ± 40.30.583462 ± 40
Bal and Thuluvath[26], 2003REB4090.4400.196027313649.0 ± 14.2439.4 ± 36.40.396456 ± 42434 ± 31451 ± 43450 ± 39429 ± 29
Trevisani et al[6], 2003PEB190.47461.2 ± 6.5465.0 ± 26.20.842
Mimidis et al[30], 2005REB520.2500.55823191061.3 ± 11.1466.6 ± 37.80.596468 ± 15466 ± 43468 ± 15446 ± 27480 ± 39489 ± 36
Henriksen et al[11], 2002PEB24170.1251312958.3 ± 11.0462.0 ± 40.30.375410 ± 41462 ± 40
Puthumana et al[29], 2001REB1300.46942533552.0 ± 10.0442.7 ± 29.30.446432 ± 23443 ± 29455 ± 33
Quera et al[96], 2000REB47460.0 ± 30.00.723
Bernardi et al[3], 1998PEB94370.2770.07424452553.1 ± 13.6440.3 ± 31.00.468394 ± 36444 ± 25453 ± 25
Finucci et al[4], 1998PEB75240.3600.45323371557.0 ± 11.0452.0 ± 33.00.600414 ± 28463 ± 31449 ± 31415 ± 26
C: Case-control; NOS: Newcastle-Ottawa scale; P: Prospective; R: Retrospective; E: Electrocardiography; B: Bazett’s formula; H: Holter; F: Fridericia’s formula; QTc: Corrected QT; MELD: Model for end-stage liver disease; Tx: Transplantation.
Table 2 Newcastle-Ottawa risk of bias assessment tool for all eligible studies
Ref.
Type
NOS selection
NOS comparability
NOS exposure1 or outcome of interest2
Risk of bias
Wang et al[62], 2023Retrospective study******Intermediate
Bilous et al[10], 2023Prospective study******Intermediate
Barutcu et al[37], 2023Retrospective study********Low
Lu et al[46], 2022Retrospective study*******Low
Wang et al[63], 2022Retrospective study*******Low
Li et al[27], 2021Prospective study*********Low
Ou et al[40], 2021Retrospective study********Low
Ko et al[25], 2021Retrospective study*********Low
Héla et al[36], 2020Prospective study*******Low
Abrahamovych et al[64], 2020Retrospective study*******Low
Ibrahim et al[65], 2020Prospective study********Low
Hussain et al[66], 2020Prospective study*******Low
Kim et al[35], 2020Retrospective study********Low
Toma et al[67], 2020Prospective study********Low
Bhardwaj et al[68], 2020Prospective study*******Low
Gaafar et al[69], 2019Prospective study*******Low
Kazankov et al[28], 2019Retrospective study********Low
Moaref et al[70], 2019Prospective study*******Low
Santeusanio et al[71], 2019Retrospective study********Low
Biselli et al[72], 2019Retrospective study*******Low
Tieranu et al[45], 2018Prospective study********Low
Lee et al[39], 2018Retrospective study*********Low
Hajiaghamohammadi et al[73], 2018Prospective study******Intermediate
Główczyńska et al[44], 2018Retrospective study********Low
Tahata et al[74], 2018Prospective study********Low
Tsiompanidis et al[75], 2018Prospective study********Low
Yap et al[43], 2018Retrospective study*******Low
Kim et al[76], 2017Retrospective study******Intermediate
Rimbaş et al[18], 2018Prospective study********Low
Salgado et al[42], 2016Prospective study*********Low
Naqvi et al[34], 2016Prospective study********Low
Zhao et al[38], 2016Retrospective study*******Low
Sonny et al[77], 2016Retrospective study********Low
Barbosa et al[17], 2016Case-control study*******Low
Carvalheiro et al[78], 2016Retrospective study*******Low
Pourafkari et al[79], 2016Retrospective study********Low
Barakat et al[80], 2015Prospective study******Intermediate
Voiosu et al[81], 2015Prospective study*******Low
Cichoż-Lach et al[82], 2015Retrospective study*******Low
Peter et al[83], 2014Prospective study******Intermediate
Moaref et al[15], 2014Prospective study******Intermediate
Josefsson et al[84], 2014Retrospective study*******Low
Karagiannakis et al[14], 2014Prospective study*******Low
Yataco et al[41], 2014Retrospective study********Low
Bhatti et al[85], 2014Case-control study******Intermediate
Møller et al[86], 2012Prospective study*******Low
Trevisani et al[87], 2012Retrospective study********Low
Zamirian et al[24], 2012Prospective study******Intermediate
Kim et al[88], 2011Prospective study********Low
Shin et al[89], 2011Prospective study*******Low
Mozos et al[33], 2011Prospective study********Low
Vuppalanchi et al[90], 2011Prospective study******Intermediate
Møller et al[91], 2010Prospective study*******Low
Zurick et al[23], 2010Retrospective study*********Low
Lossnitzer et al[13], 2010Prospective study*******Low
Genovesi et al[32], 2009Prospective study*********Low
Zambruni et al[31], 2008Prospective study********Low
Henriksen et al[92], 2007Prospective study*********Low
Kosar et al[93], 2007Retrospective study*********Low
Hansen et al[12], 2007Prospective study*******Low
Zuberi et al[94], 2007Case-control study******Intermediate
Zambruni et al[47], 2007Prospective study********Low
Ytting et al[7], 2005Prospective study*******Low
Adigun et al[21], 2005Prospective study********Low
Henriksen et al[95], 2004Prospective study*******Low
Bal and Thuluvath[26], 2003Retrospective study*********Low
Trevisani et al[6], 2003Prospective study*******Low
Mimidis et al[30], 2005Retrospective study********Low
Henriksen et al[11], 2002Prospective study*******Low
Puthumana et al[29], 2001Retrospective study********Low
Quera et al[96], 2000Retrospective study******Intermediate
Bernardi et al[3], 1998Prospective study*********Low
Finucci et al[4], 1998Prospective study*********Low
1For case-control studies.
2For cross-sectional studies.
NOS: Newcastle-Ottawa scale.
Table 3 GRADE assessment of evidence certainty (quality) for every endpoint
Endpoint
Risk of bias
Imprecision
Inconsistency
Indirectness
Publication bias
Effect size
Quality
Cirrhosis effect (patients vs controls) on QTcNo important risk of biasNo important imprecisionNo important inconsistencyNo important indirectnessNo important publication biasVery largeVery high
QTc prolongation in cirrhosis (QTc vs 440 ms)No important risk of biasNo important imprecisionNo important inconsistencyNo important indirectnessNo important publication biasVery largeVery high
Sex effect on QTc in cirrhosisNo important risk of biasNo important imprecisionSerious inconsistencyNo important indirectnessNo important publication biasTrivialVery low
Etiology of cirrhosis (alcohol vs viral) effect on QTcNo important risk of biasNo important imprecisionSerious inconsistencyNo important indirectnessNo important publication biasTrivialVery low
Child-Pugh stage (C vs B vs A) effect on QTcNo important risk of biasNo important imprecisionNo important inconsistencyNo important indirectnessNo important publication biasMedium with dose-response gradientHigh
MELD score effect on QTc prolongationNo important risk of biasNo important imprecisionNo important inconsistencyNo important indirectnessNo important publication biasMediumLow
β-blockers effect on QTcNo important risk of biasNo important imprecisionNo important inconsistencyNo important indirectnessNo important publication biasMediumLow
Acute gastrointestinal bleeding effect on QTcNo important risk of biasNo important imprecisionSerious inconsistencyNo important indirectnessNo important publication biasVery largeHigh
Liver transplantation effect on QTcNo important risk of biasNo important imprecisionNo important inconsistencyNo important indirectnessNo important publication biasLargeHigh
QTc prolongation effect on overall survival in cirrhosisNo important risk of biasNo important imprecisionNo important inconsistencyNo important indirectnessNo important publication biasMediumLow
MELD: Model for end-stage liver disease; QTc: Corrected QT.