ORIGINAL ARTICLE: Clinical Endoscopy

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Objective: To determine the diagnostic accuracy of MRCP for biliary obstruction in OLT patients.

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wwDesign: A systematic literature search identified studies primarily examining the utility of MRCP in detectingpost-orthotopic liver transplantation biliary obstruction. A meta-analysis was then performed according to theQuality of Reporting Meta-Analyses statement.

Setting: Meta-analysis of 9 studies originally performed at major transplantation centers.

Patients: A total of 382 OLT patients with clinical suspicion of biliary obstruction.

Interventions: MRCP and ERCP or clinical follow-up.

Main Outcome Measurements: Sensitivity and specificity of MRCP for diagnosis of biliary obstruction.

Results: The composite sensitivity and specificity were 0.96 (95% CI, 0.92-0.98) and 0.94 (95% CI, 0.90-0.97),respectively. The positive and negative likelihood ratios were 17 (95% CI, 9.4-29.6) and 0.04 (95% CI, 0.02-0.08),respectively.

Limitations: All but 1 included study had significant design flaws that may have falsely increased the reporteddiagnostic accuracy.

Conclusions: The high sensitivity and specificity demonstrated in this meta-analysis suggest that MRCP is apromising test for diagnosing biliary obstruction in patients who have undergone liver transplantation. However,given the significant design flaws in most of the component studies, additional high-quality data are necessarybefore unequivocally recommending MRCP in this setting. (Gastrointest Endosc 2011;73:955-62.)

Since 2004, more than 6000 orthotopic liver transplanta-ns have been performed annually in the United States.1

spite improved surgical technique, biliary complicationscur in 10% to 34% of liver transplant recipients, represent-the second leading cause of morbidity and mortality afterft rejection.2-5 Endoscopic retrograde cholangiography

(ERC) is considered the diagnostic criterion standard for post-orthotopic liver transplantation biliary obstruction4 and iscommonly performed in this patient population.2 ERC, how-ever, incurs significant risks such as pancreatitis, bleeding,infection, perforation, and sedation-related cardiopulmo-nary complications in as many as 10% of patients6-8 as well

breviations: ERC, endoscopic retrograde cholangiography; OLT, ortho-ic liver transplant; QUADAS, Quality Assessment Tool for Diagnosticuracy Systematic Review.

CLOSURE: All authors disclosed no financial relationships relevant tos publication.

pyright 2011 by the American Society for Gastrointestinal Endoscopy6-5107/$36.00:10.1016/j.gie.2010.12.014

eived August 14, 2010. Accepted December 13, 2010.

Current affiliation: Departments of Gastroenterology (J.E.J., A.K.W., M.L.V.,G.H.E., J.R.T., B.J.E.) and Radiology (M.M.A.-M.), Division of TransplantSurgery (C.J.S.), University of Michigan Health System, Ann Arbor,Michigan, Department of Gastroenterology (A.G.S.), University of TexasSouthwestern, Dallas, Texas, USA.

Reprint requests: Jennifer E. Jorgensen,MD, University ofMichiganHealthSystem, 3912 TaubmanCenter, SPC 5362, Ann Arbor, Michigan 48109-5362.

If you would like to chat with an author of this article, you may contact DrJorgensen at jjorg@umich.edu.

w.giejournal.org Volume 73, No. 5 : 2011 GASTROINTESTINAL ENDOSCOPY 955Is MRCP equivalent to ERCP for diorthotopic liver transplant recipien

Jennifer E. Jorgensen, MD, Akbar K. Waljee, MD, MChristopher J. Sonnenday, MD, MHS, Grace H. EltaAmit G. Singal, MD, MSc, Jason R. Taylor, MD, B. J

Ann Arbor, Michigan; Dallas, Texas, USA

Background: Biliary complications are the second leadtransplant (OLT) recipients. Endoscopic retrograde cholastandard for post-orthotopic liver transplantation biliaryosing biliary obstruction inA meta-analysis

Michael L. Volk, MD, MSc,, Mahmoud M. Al-Hawary, MD,h Elmunzer, MD

ause of morbidity and mortality in orthotopic livergraphy (ERC) is considered the diagnostic criteriontruction, but incurs significant risks.

as death in as many as 0.5% of patients.9 The risk profile ofdiagnostic ERC may not be justifiable in an era in whichthese

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Is MRCP equivalent to ERCP for diagnosing biliary obstruction in OLT recipients? Jorgensen et al

95accuracy of MRCP has been shown to be excellent inveral studies.9-18

The most recent National Institutes of Health Consensustement on ERCP for Diagnosis and Therapy states thatCP, EUS, and ERCP have comparable sensitivity andecificity for the diagnosis of choledocholithiasis,19 al-ugh no clear recommendations were made with re-ect to biliary strictures, particularly in orthotopic livernsplant recipients. A recent high-quality meta-analysis67 studies evaluating the diagnostic accuracy of MRCPdiagnosing biliary obstruction found that MRCP has asitivity and specificity of 97% and 98%, respectively.9

is meta-analysis, however, did not specifically evaluatest-orthotopic liver transplantation biliary obstructiond raised concerns about the accuracy of MRCP in thistting. It has been reported that in less than 40% to 50%transplant recipients with known anastomotic strictures,stream biliary dilation develops, likely secondary tonervation and fibrosis of the donor biliary system.4,20,21

e lower incidence of ductal dilation has been hypothe-ed to limit the diagnostic utility of MRCP in transplantipients.4,9 Several studies have compared MRCP withC for the diagnosis of post-transplantation biliary stric-es, but sample sizes have been small.10-18 Given theowing concerns about the risks of diagnostic ERC andcertainty regarding the accuracy of MRCP in diagnos-post-orthotopic liver transplantation biliary obstruc-

n, we performed a meta-analysis to determine theerall sensitivity, specificity, and diagnostic accuracyMRCP for post-orthotopic liver transplantation biliarystruction.

ETHODS

arch strategyThe study was conducted according to standardidelines for systematic review and meta-analysis ofgnostic studies.22,23 A computer-assisted literaturearch of EMBASE and PubMed (MEDLINE) from incep-n until September 15, 2009 was conducted to identifytentially relevant articles using the exploded medicalbject heading (MeSH) term liver transplantation ORe-text term liver transplantation AND the explodedSH term cholangiopancreatography, magnetic reso-nce OR free-text term magnetic resonance cholangio-ncreatography OR MRCP. Manual searches of referencets from potentially relevant articles were performed tontify any additional studies that may have been missedusing the computer-assisted strategy. In addition, for

ch potentially relevant article found on PubMed, thelevant article option was used to identify similaricles.6 GASTROINTESTINAL ENDOSCOPY Volume 73, No. 5 : 2011dy selectionTwo investigators (J.E.J., B.J.E.) independently reviewedes and abstracts of all citations identified by the literaturerch. Potentially relevant studies were retrieved and selec-n criteria were applied. Eligible articles were reviewed andta were abstracted in a duplicate and independent manner2 investigators (J.E.J., B.J.E.). Disagreement was re-

lved by consensus.

clusion and exclusion criteriaThe selection criteria for inclusion into the meta-alysis were (1) a study that primarily examined thelity of MRCP in diagnosing biliary obstruction afterer transplantation; (2) study that contained primarilybjects who underwent MRCP for a clinical suspicionbiliary obstruction (not for routine follow-up); (3)dy that explicitly defined the reference standard asolangiography, surgery, liver biopsy, clinical follow-, or some combination thereof; and (4) study fromich the raw numbers (true positive, false positive,e negative, false negative) necessary for meta-alysis are reported or can be calculated. Exclusionteria were (1) data duplicated in another article; (2)imal studies; and (3) articles in a language other thanglish.

ta extractionTwo independent reviewers (J.E.J., B.J.E.) extractedfollowing data from the selected studies: first au-rs name, year of publication, journal of publication,tient characteristics, type of anastomosis, MRCP tech-ue, indication for MRCP, reference standard used,ration of clinical follow-up, timing between MRCPd reference standard, blinding of radiologists anddoscopists, and outcomes (true positive, false posi-e, true negative, false negative). Two other indepen-nt reviewers (A.S., J.T.) assessed the quality of in-ded studies by extracting the 14 items in the Qualitysessment Tool for Diagnostic Accuracy Systematicview (QUADAS) guidelines.24

ta synthesis and statistical analysisThe primary outcomes of interest were the sensitivityd specificity of MRCP for biliary obstruction in pa-

Take-homeMessage

Although this meta-analysis demonstrated a highsensitivity and specificity, the overall quality of thecomponent studies was poor. A definitive high-qualitytrial would be useful before universally recommendingMRCP as the diagnostic test of choice for identifying andexcluding biliary obstruction in orthotopic liver transplantrecipients.www.giejournal.org

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TABLE 1. Patient, study design, and statistical characteristics of included studies

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Jorgensen et al Is MRCP equivalent to ERCP for diagnosing biliary obstruction in OLT recipients?

wwnts who had undergone orthotopic liver transplanta-n. We applied a bivariate mixed-effects regressiondel for synthesis of diagnostic test data assuming aomial error distribution for sensitivity and specific-.25,26 Composite sensitivity, specificity, likelihood ra-s, and diagnostic odds ratios were calculated.Heterogeneity of outcomes between included studiess evaluated graphically by a Forest plot and summaryeiver-operating characteristic curve. The 2 test of ho-geneity and the inconsistency index (I2) were used totistically assess heterogeneity.27 Publication bias wasessed with a Deeks funnel plot asymmetry test.28 TheDAS (Meta-analytical Integration of Diagnostic Accu-y Studies)29 command in Stata 10.1 (StataCorp LP, Col-e Station, Tex) was used to analyze the data by using aariate mixed-effects model.

SULTS

terature searchA total of 285 articles were retrieved by using thearch criteria described. Title and abstract review iden-

Study (year)No. ofpatients

Meanage, y

%Men

MRCPtechnique

Fulcher and Turner16

(1999)25 46 56 Thin RARE, thick

RARE24 E3

Laghi et al17 (1999) 23 46 78 3D TSE 1524-F/U

Meersshaut et al11

(2000)12 57 50 Thin TSE, thick

RARE5 ER7 cl

Boraschi et al14

(2001)113 50 80 Thin FSE, thick

FSE50 E58 wclin

Valls et al18 (2005) 63 53 75 Thin TSE, thickFSE

4122 -

Beltran et al12 (2005) 46 55 67 3D TSE 24 E30 -

Kitazono et al10

(2007)8 57 75 Multiple 3D

RAREERCMR

Maj et al13 (2007) 40 44 43 3D RARE, thickRARE

17 dfistuclin

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(2008)52 NS NS Thin FSE, thick

FSE3121 -ima

Totals 382

bx, Biopsy; 3D, 3-dimensional; ERC, endoscopic retrograde cholangiography; FN,supplied; PTC, percutaneous transhepatic cholangiogram; RARE, rapid acquisitiontrue positive; TSE, turbo spin echo.w.giejournal.org Volued 15 studies eligible for detailed review. Nine stud-were included in the meta-analysis.10-18 There was

0% agreement between reviewers regarding studyection.

cluded studiesSix studies were excluded.30-35 Zoepf et al33 was ex-ded because the primary purpose of the study was tompare ERC with various noninvasive methods such as, MRCP, and CT. The 2004 study by Boraschi et al34 wascluded because it appeared to be a subset of their 2001dy, which was included in the final analysis. Linhares et0 and Ott et al31 were excluded because most of theCPs were performed for routine follow-up and not forspicion of biliary obstruction. Bridges et al35 was ex-ded because the study was a comparison of 2 types ofCP rather than an evaluation of the diagnostic accuracyMRCP. Ward et al32 was excluded because not all in-ded subjects underwent liver transplantation, and were unable to determine the raw numbers for trans-nted patients.

Reference standard TP FP FN TN Sens Spec

TC/t tube, 1 surgery24 h toter MRCP

16 0 1 8 94 100

CP ERCP/PTC/t tube within1 - MRCP 3-10 mo clinical

15 0 0 11 100 100

C 7-18 d before or after MRCPF/U of unclear duration

12 0 0 3 100 100

5 PTC within 7 d, 11 surgeryormal MRCP findings6 mo/U US

38 6 3 74 93 93

CP direct cholangiogramPs clinical F/U for 2-48 mo

42 1 2 20 96 95

10 PTC, 5 surgeryP6 mo clinical F/U US

28 1 2 40 93 98

ll patients within 24 h of 6 1 0 2 100 67

cholangiogram, 2m, 3 path, 2 surgery, 25/U

45 1 0 5 100 83

CPs ERC or PTCPs PTC, ERC, surgery, bx,

30 1 2 19 94 95

232 11 10 182 96 94

egative; FP, false positive; FSE, fast spin echo; F/U, follow-up; N/S, notfocused echoes; Sens, sensitivity; Spec, specificity; TN, true negative; TP,tifiies10sel

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Is MRCP equivalent to ERCP for diagnosing biliary obstruction in OLT recipients? Jorgensen et al

95cluded studiesDemographics. The selected studies included 382tients with 435 MRCP readings. MRCPs were per-med 11 days to 10 years after transplantation. Thedies that reported surgery type included 299 patientso underwent choledochocholedochostomy, and 46tients who underwent choledochoenteric anastomo-.11-14,16-18 Eight articles provided specific informationout the type of strictures identified10-12,14,16-18 andluded 85 anastomotic strictures and 76 nonanasto-tic strictures. Additional patient demographics ofch included article are listed in Table 1.Diagnostic accuracy. Our independent extraction ofnsitivity and specificity matched the reported values inbut 2 studies. Kitazono et al10 reported the sensitivityd specificity of the 2 reading radiologists separately, butopted to report only the results from the less-accurateiologist. Fulcher and Turner16 reported the sensitivitycholedocholithiasis (86%) separately from stricture0%), but we combined all findings for a combinednsitivity of 94%.Statistical data for each included study are given inble 1. The composite sensitivity of MRCP for diagnos-biliary obstruction in this meta-analysis was 0.96

% CI, 0.92-0.98). The composite specificity of MRCPdiagnosing biliary obstruction in this meta-analysiss 0.94 (95% CI, 0.90-0.97). The area under the sum-ry receiver-operating characteristic curve was 0.99% CI, 0.97-0.99) (Fig. 1). The Forest plots for sensi-ity and specificity of MRCP for assessing biliary ob-uction after orthotopic liver transplantation are illus-ted in Figure 2. The diagnostic odds ratio was 378

ure 1. Summary receiver-operating characteristic (SROC) curve dem-trating composite sensitivity (SENS) and specificity (SPEC). AUC, areaer the curve.8 GASTROINTESTINAL ENDOSCOPY Volume 73, No. 5 : 2011ce of heterogeneity.

aluation of clinical utilityThe positive likelihood ratio of MRCP for biliary ob-uction was 17 (95% CI, 9.4-29.6). The negative likeli-od ratio of MRCP for biliary obstruction was 0.04 (95%0.02-0.08). Because using MRCP as the initial diagnostict is only appropriate in scenarios with low to moderatetest suspicion for obstruction, we graphed posttestbability assuming pretest probabilities of 25% and 50%.these situations, a positive MRCP results in posttestbabilities of 80% and 94%, respectively; a negativeCP results in posttest probabilities of 1% and 4%, re-ectively (Figs. 3 and 4).

sessment of study qualityThe included studies fulfilled between 5 and 14 of theQUADAS24 items for methodological quality, with aan of score of 9.7 (Table 2). Two studies had QUADASres less than 9.11,13 When these studies were excluded,mean QUADAS score increased to 10.9 and the sensi-

ity and specificity were unchanged; however, manysign flaws were noted, which may have introduced bias.

tential biasesNone of the studies used the ideal reference standard ofCP and adequate clinical follow-up. Eight of the 9 stud-did not use the same reference standard for positive

d negative MRCP results.11-18 Of the studies that re-rted which patients were followed clinically, 121 pa-nts with normal MRCPs were followed for 2 or morenths, and none of the studies reported the need forect cholangiography during the follow-up period inse patients. Table 1 provides details regarding the ref-nce standard used in each study. Other design flaws arether elucidated in the discussion.

sessment of publication biasAlthough an imperfect test for assessing publications,36 Deeks funnel plot asymmetry test was not signifi-t (P .47), nor was there a significant slope, suggest-that a large degree of publication bias was not presentg. 5).

SCUSSION

Although there is adequate scientific evidence to sup-rt the use of MRCP for diagnosing biliary obstruction inneral, it remains unclear whether these data can betrapolated to liver transplant recipients. This meta-alysis suggests that MRCP may have excellent diagnosticuracy for biliary obstruction in patients who have un-rgone orthotopic liver transplantation, with a compositesitivity of 0.96 and a composite specificity of 0.94.www.giejournal.org

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Jorgensen et al Is MRCP equivalent to ERCP for diagnosing biliary obstruction in OLT recipients?

wwhen stratified by stricture site, there was little differencesensitivity (97% for anastomotic strictures and 94% fornanastomotic strictures). The overall positive and neg-ve likelihood ratios were 17 and 0.04, respectively. Themmary results had virtually no heterogeneity, implyingt the component studies were uniform in their proce-res, patient populations, and design.All included studies adequately described the MRCP tech-ues used. Several studies used older 2-dimensional tech-ues (Table 1), and only 1 study10 used a combination ofhniques. A combination of 2- and 3-dimensional tech-ues with varying slice thickness has recently beenown to improve accuracy for diagnosing biliary compli-tions in the post-liver transplantation population.37 Eventh these differences, all study protocols were consideredod to excellent in quality by our contributing radiologist.A.). However, it should also be noted that the compo-nt studies were performed at centers with well-veloped expertise in MRCP, so the results may not beplicable to centers with less MRCP expertise.Despite these promising results, however, many of themponent studies in this meta-analysis had methodolog-l flaws that merit further discussion. First, none of thedies used the ideal reference standard of ERCP andequate clinical follow-up. This combined reference

ure 2. Forest plot for the sensitivity and specificity of MRCP for assessifidence interval.w.giejournal.org Volundard is critical because the clinical significance of aiary stricture is often not established until sufficient times passed to determine whether the ERC-guided inter-ntion (dilation or stenting) has resulted in biochemicald clinical improvement. In addition, because the idealterion standard was not used, an area under the curve of9 means only that MRCP is almost as good as ERCP inlation. Because the diagnostic accuracy of ERCP inlation of clinical follow-up has not been determined, ast area under the curve for MRCP cannot be calculatedt is likely to be significantly lower than 0.99.Second, 8 of the 9 studies did not use the same referencendard for positive and negative MRCP results.11-18 MRCPsth positive findings were often followed by direct cholan-graphy or surgery, whereas patients with negative MRCPdings were often followed clinically11-15,17,18 (Table 1).ly 2 studies provided a final diagnosis for all the patientsth negative MRCP findings who were followed clini-ly.11,17 These discrepancies may have caused a differentialrification bias and could have falsely elevated the reportedsitivities. On the other hand, a sufficiently large number oftients with negative MRCP findings who underwent onlyical follow-up seem to have done well, without the needdirect cholangiography, making it less likely that a clini-ly significant obstruction was missed.

liary obstruction in post-orthotopic liver transplantation patients. CI,stabilhaveancri0.9isoisobebu

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Is MRCP equivalent to ERCP for diagnosing biliary obstruction in OLT recipients? Jorgensen et al

96Several included studies did not report the time delaytween MRCP and the reference standard13,18 or includedignificant proportion of patients in whom the delay wasater than a week11 or a month,16 thus raising the pos-ility of disease progression (strictures) or regressionontaneously passed stones) bias. All but 1 of the studiesorted blinding of the radiologists interpreting theCPs10,12-18; however, most of studies did not specificallyte that the person performing direct cholangiography orrgery was blinded to the results of the MRCPs,10,12-18 thussing the possibility of review bias.Finally, several studies included patients who were notresentative of those who would typically be consideredMRCP in clinical practice or did not provide enoughormation to make this determination. For example, 2dies included patients with suspicion of ascendingolangitis.12,18 Another study17 reported that 11 of the 23tients had both biliary dilation and hyperbilirubinemia.clinical practice, these patients would have been re-

ure 3. Positive and negative likelihood ratios for MRCP for diagnosingary obstruction in post-orthotopic liver transplantation patients givenretest likelihood ratio (LR) of 25%. Post_Prob_Pos, posttest probabilitya positive test; Post_Prob_Neg, posttest probability of a negative test.0 GASTROINTESTINAL ENDOSCOPY Volume 73, No. 5 : 2011red directly for ERC and should not have been includeda study evaluating the utility of MRCP. Few of thedies described the patients clinical status well enoughdetermine the pretest probability of biliary obstruction,t rather imprecisely defined the inclusion criteria to benormal liver function test results.10-15,18 Only 1 study18

cluded recurrent viral hepatitis or rejection before studytry. Therefore, it is unclear whether these patients werepropriate for MRCP, suggesting the possibility of spec-m bias.On the basis of these methodological flaws in the com-nent studies, MRCP cannot be universally recom-nded as the diagnostic test of choice for post-orthotopicer transplantation biliary obstruction in the absence of afinitive high-quality study. The ideal study should pro-ectively and consecutively enroll only post-orthotopicer transplantation patients at low to moderate suspicionbiliary obstruction. Patients with cholestatic liver en-

mes and biliary ductal dilation on transabdominal US or

ure 4. Positive and negative likelihood ratios for MRCP for diagnosingary obstruction in post-orthotopic liver transplantation patients givenretest likelihood ratio (LR) of 50%. Post_Prob_Pos, posttest probabilitypositive test; Post_Prob_Neg, posttest probability of a negative test.www.giejournal.org

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TABLE 2. Quality Assessment Tool for Diagnostic Accuracy Systematic Review of quality criteria of included studies

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Jorgensen et al Is MRCP equivalent to ERCP for diagnosing biliary obstruction in OLT recipients?

wwlinical syndrome consistent with ascending cholangitisould be excluded, as these patients are most appropriateERC in clinical practice. If biliary dilation or bacterial

olangitis are absent, included patients should undergoCP followed within 24 hours by ERC or percutaneousnshepatic cholangiogram regardless of MRCP findings.

ure 5. Deeks funnel plot asymmetry test for identifying publications.

Criteria

Fulcherand

Turner16Laghiet al17

Mee

Patient spectrum representative?

Selection criteria described?

Reference standard appropriate?

Time between tests appropriate?

Uniform verification by reference standard?

Same reference test used?

Reference standard independent?

Index test described adequately?

Reference standard described adequately?

Blinding to reference standard results?

Blinding to index test results? ? ?

Appropriate clinical data available?

Uninterpretable data reported?

Withdrawals explained?

No. of criteria met out of 14 10 12

, Criteria met;, criteria not met; ?, unable to determine whether criteria werew.giejournal.org Volue reference standard should include at least 8 weeks ofnical follow-up in addition to direct cholangiographicdings to determine whether the intervention performedring ERC or percutaneous transhepatic cholangiographys resulted in biochemical and clinical improvement.e negative MRCPs should be recorded only if the directolangiogram is unremarkable and an alternative etiol-y for liver function test result abnormalities is discov-d. The time since transplantation should be recordedd evaluated to determine whether the utility of MRCPries between early and late biliary complications. Thee of ductal anastomosis should also be noted becauseower accuracy threshold may be tolerated for patientsth Roux-en-Y anatomy given the difficulty in performingC in this patient population. Endoscopists and radiolo-ts should be blinded in this study. A cost-utility andety analysis should also be performed because the highidence of biliary complications in the post-liver trans-ntation population may render MRCP cost-ineffectiveen in patients with low to moderate clinical suspicion ofiary obstruction.In summary, this meta-analysis demonstrates that MRCPy have excellent sensitivity and specificity for diagnos-biliary obstruction in patients who have undergone

hotopic liver transplantation. The aggregate positive

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and negative likelihood ratios suggest that MRCP may bean appropriate test in patients with low to moderate sus-picion for biliary obstruction, and the use of MRCP couldpotentially avoid the unnecessary risks of ERCP in thisclinical scenario. However, given the significant method-oloitivun

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18. Valls C, Alba E, CruzM, et al. Biliary complications after liver transplanta-tion: diagnosis with MR cholangiopancreatography. AJR Am J Roent-genol 2005;184:812-20.

19. Cohen S, Bacon BR, Berlin JA, et al. NIH state-of-the-science statementon endoscopic retrograde cholangiopancreatography (ERCP) for diag-nosis and therapy. NIH consensus and State-of-the-Science Statements

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Is MRCP equivalent to ERCP for diagnosing biliary obstruction in OLT recipients? Jorgensen et al

96gical flaws in most of the component studies, a defin-e high-quality clinical trial would be helpful beforeiversally recommending MRCP in this setting.

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Is MRCP equivalent to ERCP for diagnosing biliary obstruction in orthotopic liver transplant recipients? A meta-analysisMETHODSSearch strategyStudy selectionInclusion and exclusion criteriaData extractionData synthesis and statistical analysis

RESULTSLiterature searchExcluded studiesIncluded studiesDemographicsDiagnostic accuracy

Evaluation of clinical utilityAssessment of study qualityPotential biasesAssessment of publication bias

DISCUSSIONREFERENCES