Cholangitis Definition and Treatment after Kasai Hepatoportoenterostomy for Biliary Atresia: A Delphi Process and International Expert Panel

Ana M Calinescu, Omid Madadi-Sanjani, Cara Mack, Richard A Schreiber, Riccardo Superina, Deirdre Kelly, Claus Petersen, Barbara E Wildhaber, Ana M Calinescu, Omid Madadi-Sanjani, Cara Mack, Richard A Schreiber, Riccardo Superina, Deirdre Kelly, Claus Petersen, Barbara E Wildhaber

Abstract

(1) Background: Acute cholangitis during the first year after Kasai hepatoportoenterostomy (HPE) has a negative impact on patient and native liver survival. There are no consistent guidelines for the definition, treatment, and prophylaxis of cholangitis after HPE. The aim of this study was to develop definition, treatment, and prophylaxis guidelines to allow for expeditious management and for standardization in reporting. (2) Methods: the Delphi method, an extensive literature review, iterative rounds of surveys, and expert panel discussions were used to establish definition, treatment, and prophylaxis guidelines for cholangitis in the first year after HPE. (3) Results: Eight elements (pooled into two groups: clinical and laboratory/imaging) were identified to define cholangitis after HPE. The final proposed definitions for suspected and confirmed cholangitis are a combination of one element, respectively, two elements from each group; furthermore, the finding of a positive blood culture was added to the definition of confirmed cholangitis. The durations for prophylaxis and treatment of suspected and confirmed cholangitis were uniformly agreed upon by the experts. (4) Conclusions: for the first time, an international consensus was found for guidelines for definition, treatment, and prophylaxis for cholangitis during the first year after Kasai HPE. Applicability will need further prospective multicentered studies.

Keywords: Kasai; biliary atresia; cholangitis; hepatoportoenterostomy.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
First Delphi questionnaire (a) Clinical signs following Kasai hepatoportoenterostomy included in the definition of cholangitis according to the 1st Delphi questionnaire. (b) Laboratory and imaging elements following Kasai hepatoportoenterostomy included in the definition of cholangitis according to the 1st Delphi questionnaire.
Figure 2
Figure 2
Definition of suspected cholangitis according to the 2nd Delphi questionnaire.
Figure 3
Figure 3
Treatment duration of suspected cholangitis according to the 2nd Delphi questionnaire.
Figure 4
Figure 4
Definition of confirmed cholangitis according to the 2nd Delphi questionnaire.
Figure 5
Figure 5
Treatment duration of confirmed cholangitis according to the 2nd Delphi questionnaire.
Figure 6
Figure 6
Peroral prophylaxis duration after Kasai hepatoportoenterostomy according to the 2nd Delphi questionnaire.
Figure 7
Figure 7
Working group proposal for cholangitis definitions, prophylaxis, and treatment.

References

    1. Nio M., Wada M., Sasaki H., Tanaka H., Okamura A. Risk factors affecting late-presenting liver failure in adult patients with biliary atresia. J. Pediatr. Surg. 2012;47:2179–2183. doi: 10.1016/j.jpedsurg.2012.09.003.
    1. Koga H., Wada M., Nakamura H., Miyano G., Okawada M., Lane G.J., Okazaki T., Yamataka A. Factors influencing jaundice-free survival with the native liver in post-portoenterostomy biliary atresia patients: Results from a single institution. J. Pediatr. Surg. 2013;48:2368–2372. doi: 10.1016/j.jpedsurg.2013.08.007.
    1. Chen S.Y., Lin C.C., Tsan Y.T., Chan W.C., Wang J.D., Chou Y.J., Lin C.H. Number of cholangitis episodes as a prognostic marker to predict timing of liver transplantation in biliary atresia patients after Kasai portoenterostomy. BMC Pediatr. 2018;18:119. doi: 10.1186/s12887-018-1074-2.
    1. Hung P.Y., Chen C.C., Chen W.J., Lai H.S., Hsu W.M., Lee P.H., Ho M.C., Chen T.H., Ni Y.H., Chen H.L., et al. Long-term prognosis of patients with biliary atresia: A 25 year summary. J. Pediatr. Gastroenterol. Nutr. 2006;42:190–195. doi: 10.1097/01.mpg.0000189339.92891.64.
    1. Li D., Chen X., Fu K., Yang J., Feng J. Preoperative nutritional status and its impact on cholangitis after Kasai portoenterostomy in biliary atresia patients. Pediatr. Surg. Int. 2017;33:901–906. doi: 10.1007/s00383-017-4118-z.
    1. Liu J., Dong R., Chen G., Dong K., Zheng S. Risk factors and prognostic effects of cholangitis after Kasai procedure in biliary atresia patients: A retrospective clinical study. J. Pediatr. Surg. 2019;54:2559–2564. doi: 10.1016/j.jpedsurg.2019.08.026.
    1. Ryon E.L., Parreco J.P., Sussman M.S., Quiroz H.J., Willobee B.A., Perez E.A., Sola J.E., Thorson C.M. Drivers of Hospital Readmission and Early Liver Transplant after Kasai Portoenterostomy. J. Surg. Res. 2020;256:48–55. doi: 10.1016/j.jss.2020.06.019.
    1. Decharun K., Leys C.M., West K.W., Finnell S.M. Prophylactic Antibiotics for Prevention of Cholangitis in Patients With Biliary Atresia Status Post-Kasai Portoenterostomy: A Systematic Review. Clin. Pediatr. 2016;55:66–72. doi: 10.1177/0009922815594760.
    1. Bu L.N., Chen H.L., Chang C.J., Ni Y.H., Hsu H.Y., Lai H.S., Hsu W.M., Chang M.H. Prophylactic oral antibiotics in prevention of recurrent cholangitis after the Kasai portoenterostomy. J. Pediatr. Surg. 2003;38:590–593. doi: 10.1053/jpsu.2003.50128.
    1. Wu E.T., Chen H.L., Ni Y.H., Lee P.I., Hsu H.Y., Lai H.S., Chang M.H. Bacterial cholangitis in patients with biliary atresia: Impact on short-term outcome. Pediatr. Surg. Int. 2001;17:390–395. doi: 10.1007/s003830000573.
    1. Gunadi, Gunawan T.A., Widiyanto G., Yuanita A., Mulyani N.S., Makhmudi A. Liver transplant score for prediction of biliary atresia patients’ survival following Kasai procedure. BMC Res. Notes. 2018;11:381. doi: 10.1186/s13104-018-3498-z.
    1. Lee J.Y., Lim L.T., Quak S.H., Prabhakaran K., Aw M. Cholangitis in children with biliary atresia: Health-care resource utilisation. J. Paediatr. Child Health. 2014;50:196–201. doi: 10.1111/jpc.12463.
    1. Chuang J.H., Lee S.Y., Shieh C.S., Chen W.J., Chang N.K. Reappraisal of the role of the bilioenteric conduit in the pathogenesis of postoperative cholangitis. Pediatr. Surg. Int. 2000;16:29–34. doi: 10.1007/s003830050008.
    1. Van Heurn L.W.E., Saing H., Tam P.K. Cholangitis after hepatic portoenterostomy for biliary atresia: A multivariate analysis of risk factors. J. Pediatr. 2003;142:566–571. doi: 10.1067/mpd.2003.195.
    1. Stagg H., Cameron B.H., Ahmed N., Butler A., Jimenez-Rivera C., Yanchar N.L., Martin S.R., Emil S., Anthopoulos G., Schreiber R.A., et al. Variability of diagnostic approach, surgical technique, and medical management for children with biliary atresia in Canada—Is it time for standardization? J. Pediatr. Surg. 2017;52:802–806. doi: 10.1016/j.jpedsurg.2017.01.041.
    1. Wada K., Takada T., Kawarada Y., Nimura Y., Miura F., Yoshida M., Mayumi T., Strasberg S., Pitt H.A., Gadacz T.R., et al. Diagnostic criteria and severity assessment of acute cholangitis: Tokyo Guidelines. J. Hepatobiliary Pancreat. Surg. 2007;14:52–58. doi: 10.1007/s00534-006-1156-7.
    1. Takada T., Strasberg S.M., Solomkin J.S., Pitt H.A., Gomi H., Yoshida M., Mayumi T., Miura F., Gouma D.J., Garden O.J., et al. TG13: Updated Tokyo Guidelines for the management of acute cholangitis and cholecystitis. J. Hepatobiliary Pancreat. Sci. 2013;20:1–7. doi: 10.1007/s00534-012-0566-y.
    1. Lai H.S., Chen W.J., Chen C.C., Hung W.T., Chang M.H. Long-term prognosis and factors affecting biliary atresia from experience over a 25 year period. Chang Gung. Med. J. 2006;29:234–239.
    1. Pang W.B., Zhang T.C., Chen Y.J., Peng C.H., Wang Z.M., Wu D.Y., Wang K. Ten-Year Experience in the Prevention of Post-Kasai Cholangitis. Surg. Infect. 2019;20:231–235. doi: 10.1089/sur.2018.047.
    1. Wong K.K., Fan A.H., Lan L.C., Lin S.C., Tam P.K. Effective antibiotic regime for postoperative acute cholangitis in biliary atresia—An evolving scene. J. Pediatr. Surg. 2004;39:1800–1802. doi: 10.1016/j.jpedsurg.2004.08.027.
    1. Petersen C., Harder D., Melter M., Becker T., Wasielewski R.V., Leonhardt J., Ure B.M. Postoperative high-dose steroids do not improve mid-term survival with native liver in biliary atresia. Am. J. Gastroenterol. 2008;103:712–719. doi: 10.1111/j.1572-0241.2007.01721.x.
    1. Graham B., Regehr G., Wright J.G. Delphi as a method to establish consensus for diagnostic criteria. J. Clin. Epidemiol. 2003;56:1150–1156. doi: 10.1016/S0895-4356(03)00211-7.
    1. Dalkey N.C. An experimental application of the Delphi method to the use of experts. Manag. Sci. 1963;9:458–467. doi: 10.1287/mnsc.9.3.458.
    1. Burns K.E., Duffett M., Kho M.E., Meade M.O., Adhikari N.K., Sinuff T., Cook D.J., Group A. A guide for the design and conduct of self-administered surveys of clinicians. CMAJ. 2008;179:245–252. doi: 10.1503/cmaj.080372.
    1. Lally K.P., Kanegaye J., Matsumura M., Rosenthal P., Sinatra F., Atkinson J.B. Perioperative factors affecting the outcome following repair of biliary atresia. Pediatrics. 1989;83:723–726. doi: 10.1542/peds.83.5.723.
    1. Meyers R.L., Book L.S., O’Gorman M.A., Jackson W.D., Black R.E., Johnson D.G., Matlak M.E. High-dose steroids, ursodeoxycholic acid, and chronic intravenous antibiotics improve bile flow after Kasai procedure in infants with biliary atresia. J. Pediatr. Surg. 2003;38:406–411. doi: 10.1053/jpsu.2003.50069.
    1. Kelly D.A., Davenport M. Current management of biliary atresia. Arch. Dis. Child. 2007;92:1132–1135. doi: 10.1136/adc.2006.101451.
    1. Stringer M.D., Davison S.M., Rajwal S.R., McClean P. Kasai portoenterostomy: 12-year experience with a novel adjuvant therapy regimen. J. Pediatr. Surg. 2007;42:1324–1328. doi: 10.1016/j.jpedsurg.2007.03.026.
    1. Vejchapipat P., Passakonnirin R., Sookpotarom P., Chittmittrapap S., Poovorawan Y. High-dose steroids do not improve early outcome in biliary atresia. J. Pediatr. Surg. 2007;42:2102–2105. doi: 10.1016/j.jpedsurg.2007.08.038.
    1. De Vries W., de Langen Z.J., Groen H., Scheenstra R., Peeters P.M., Hulscher J.B., Verkade H.J., Netherlands Study Group of Biliary Atresia and Registry (NeSBAR) Biliary atresia in the Netherlands: Outcome of patients diagnosed between 1987 and 2008. J. Pediatr. 2012;160:638–644.e2. doi: 10.1016/j.jpeds.2011.09.061.
    1. Wang B., Feng Q., Ye X., Zeng S. The experience and technique in laparoscopic portoenterostomy for biliary atresia. J. Laparoendosc. Adv. Surg. Tech. A. 2014;24:350–353. doi: 10.1089/lap.2013.0138.
    1. Tyraskis A., Davenport M. Steroids after the Kasai procedure for biliary atresia: The effect of age at Kasai portoenterostomy. Pediatr. Surg. Int. 2016;32:193–200. doi: 10.1007/s00383-015-3836-3.
    1. Webb N.L., Jiwane A., Ooi C.Y., Nightinghale S., Adams S.E., Krishnan U. Clinical significance of liver histology on outcomes in biliary atresia. J. Paediatr. Child Health. 2017;53:252–256. doi: 10.1111/jpc.13371.
    1. Lee W.S., Ong S.Y., Foo H.W., Wong S.Y., Kong C.X., Seah R.B., Ng R.T. Chronic liver disease is universal in children with biliary atresia living with native liver. World J. Gastroenterol. 2017;23:7776–7784. doi: 10.3748/wjg.v23.i43.7776.
    1. Parolini F., Boroni G., Milianti S., Tonegatti L., Armellini A., Garcia Magne M., Pedersini P., Torri F., Orizio P., Benvenuti S., et al. Biliary atresia: 20-40-year follow-up with native liver in an Italian centre. J. Pediatr. Surg. 2019;54:1440–1444. doi: 10.1016/j.jpedsurg.2018.10.060.
    1. Ramachandran P., Safwan M., Balaji M.S., Unny A.K., Akhtarkhavari A., Tamizhvanan V., Rela M. Early Cholangitis after Portoenterostomy in Children with Biliary Atresia. J. Indian Assoc. Pediatr. Surg. 2019;24:185–188. doi: 10.4103/jiaps.JIAPS_96_18.
    1. Baek S.H., Kang J.M., Ihn K., Han S.J., Koh H., Ahn J.G. The Epidemiology and Etiology of Cholangitis After Kasai Portoenterostomy in Patients With Biliary Atresia. J. Pediatr. Gastroenterol. Nutr. 2020;70:171–177. doi: 10.1097/MPG.0000000000002555.
    1. Chen G., Liu J., Huang Y., Wu Y., Lu X., Dong R., Shen Z., Sun S., Jiang J., Zheng S. Preventive effect of prophylactic intravenous antibiotics against cholangitis in biliary atresia: A randomized controlled trial. Pediatr. Surg. Int. 2021;37:1089–1097. doi: 10.1007/s00383-021-04916-z.
    1. Goh L., Phua K.B., Low Y., Chiang L.W., Yong C., Chiou F.K. Analysis of Cholangitis Rates with Extended Perioperative Antibiotics and Adjuvant Corticosteroids in Biliary Atresia. Pediatr. Gastroenterol. Hepatol. Nutr. 2021;24:366–376. doi: 10.5223/pghn.2021.24.4.366.
    1. Lien T.H., Bu L.N., Wu J.F., Chen H.L., Chen A.C., Lai M.W., Shih H.H., Lee I.H., Hsu H.Y., Ni Y.H., et al. Use of Lactobacillus casei rhamnosus to Prevent Cholangitis in Biliary Atresia After Kasai Operation. J. Pediatr. Gastroenterol. Nutr. 2015;60:654–658. doi: 10.1097/MPG.0000000000000676.
    1. Chiang L.W., Lee C.Y., Krishnaswamy G., Nah S.A., Kader A., Ong C., Low Y., Phua K.B. Seventeen years of Kasai portoenterostomy for biliary atresia in a single Southeast Asian paediatric centre. J. Paediatr. Child Health. 2017;53:412–415. doi: 10.1111/jpc.13379.
    1. Li Z., Ye Y., Wu Z., Wang B. Learning Curve Analysis of Laparoscopic Kasai Portoenterostomy. J. Laparoendosc. Adv. Surg. Tech. A. 2017;27:979–982. doi: 10.1089/lap.2016.0204.
    1. Calinescu A.M., Wilde J.C.H., Korff S., McLin V.A., Wildhaber B.E. Perioperative Complications after Kasai Hepatoportoenterostomy: Data from the Swiss National Biliary Atresia Registry. Eur. J. Pediatr. Surg. 2020;30:364–370. doi: 10.1055/s-0039-1692686.
    1. Chung P.H.Y., Chok K.S.H., Wong K.K.Y., Tam P.K.H., Lo C.M. Determining the optimal timing of liver transplant for pediatric patients after Kasai portoenterostomy based on disease severity scores. J. Pediatr. Surg. 2020;55:1892–1896. doi: 10.1016/j.jpedsurg.2019.10.016.
    1. Sifri C.D., Madoff L.C. Mandell, Douglas and Bennett’s Priciples and Practice of Infectious Diseases. 8th ed. WB Saunders; Philadelphia, PA, USA: 2015. Infections of the Liver and Biliary system (Liver abscess, cholangitis, cholecystitis)
    1. Kumagi T., Drenth J.P., Guttman O., Ng V., Lilly L., Therapondos G., Hiasa Y., Michitaka K., Onji M., Watanabe Y., et al. Biliary atresia and survival into adulthood without transplantation: A collaborative multicentre clinic review. Liver Int. 2012;32:510–518. doi: 10.1111/j.1478-3231.2011.02668.x.
    1. Kiriyama S., Takada T., Hwang T.L., Akazawa K., Miura F., Gomi H., Mori R., Endo I., Itoi T., Yokoe M., et al. Clinical application and verification of the TG13 diagnostic and severity grading criteria for acute cholangitis: An international multicenter observational study. J. Hepatobiliary Pancreat. Sci. 2017;24:329–337. doi: 10.1002/jhbp.458.
    1. Chung P.H.Y., Tam P.K.H., Wong K.K.Y. Does the identity of the bacteria matter in post-Kasai cholangitis? A comparison between simple and intractable cholangitis. J. Pediatr. Surg. 2018;53:2409–2411. doi: 10.1016/j.jpedsurg.2018.08.028.
    1. Sandy N.S., Hessel G., Bellomo-Brandao M.A. Major Complications of Pediatric Percutaneous Liver Biopsy Do Not Differ Among Physicians with Different Degrees of Training. Am. J. Gastroenterol. 2020;115:786–789. doi: 10.14309/ajg.0000000000000459.
    1. Luo Y., Zheng S. Current concept about postoperative cholangitis in biliary atresia. World J. Pediatr. 2008;4:14–19. doi: 10.1007/s12519-008-0003-0.
    1. Pakarinen M.P., Rintala R.J. Surgery of biliary atresia. Scand. J. Surg. 2011;100:49–53. doi: 10.1177/145749691110000109.
    1. Selvalingam S., Mahmud M.N., Thambidorai C.R., Zakaria Z., Mohan N., Isa, Sheila M. Jaundice clearance and cholangitis in the first year following portoenterostomy for biliary atresia. Med. J. Malays. 2002;57:92–96.
    1. Ogasawara Y., Yamataka A., Tsukamoto K., Okada Y., Lane G.J., Kobayashi H., Miyano T. The intussusception antireflux valve is ineffective for preventing cholangitis in biliary atresia: A prospective study. J. Pediatr. Surg. 2003;38:1826–1829. doi: 10.1016/j.jpedsurg.2003.08.025.
    1. Kobayashi H., Yamataka A., Koga H., Okazaki T., Tamura T., Urao M., Yanai T., Lane G.J., Miyano T. Optimum prednisolone usage in patients with biliary atresia postportoenterostomy. J. Pediatr. Surg. 2005;40:327–330. doi: 10.1016/j.jpedsurg.2004.10.017.
    1. Shinohara T., Muraji T., Tsugawa C., Nishijima E., Satoh S., Takamizawa S. Efficacy of urinary sulfated bile acids for diagnosis of bacterial cholangitis in biliary atresia. Pediatr. Surg. Int. 2005;21:701–704. doi: 10.1007/s00383-005-1493-7.
    1. Sanghai S.R., Shah I., Bhatnagar S., Murthy A. Incidence and prognostic factors associated with biliary atresia in western India. Ann. Hepatol. 2009;8:120–122. doi: 10.1016/S1665-2681(19)31789-2.
    1. Suzuki T., Hashimoto T., Kondo S., Sato Y., Hussein M.H. Evaluating patients’ outcome post-Kasai operation: A 19-year experience with modification of the hepatic portoenterostomy and applying a novel steroid therapy regimen. Pediatr. Surg. Int. 2010;26:825–830. doi: 10.1007/s00383-010-2637-y.
    1. Ng V.L., Haber B.H., Magee J.C., Miethke A., Murray K.F., Michail S., Karpen S.J., Kerkar N., Molleston J.P., Romero R., et al. Medical status of 219 children with biliary atresia surviving long-term with their native livers: Results from a North American multicenter consortium. J. Pediatr. 2014;165:539–546.e2. doi: 10.1016/j.jpeds.2014.05.038.
    1. Wada M., Nakamura H., Koga H., Miyano G., Lane G.J., Okazaki T., Urao M., Murakami H., Kasahara M., Sakamoto S., et al. Experience of treating biliary atresia with three types of portoenterostomy at a single institution: Extended, modified Kasai, and laparoscopic modified Kasai. Pediatr. Surg. Int. 2014;30:863–870. doi: 10.1007/s00383-014-3551-5.
    1. Qiao G., Li L., Cheng W., Zhang Z., Ge J., Wang C. Conditional probability of survival in patients with biliary atresia after Kasai portoenterostomy: A Chinese population-based study. J. Pediatr. Surg. 2015;50:1310–1315. doi: 10.1016/j.jpedsurg.2015.03.062.
    1. Kelay A., Davenport M. Long-term outlook in biliary atresia. Semin. Pediatr. Surg. 2017;26:295–300. doi: 10.1053/j.sempedsurg.2017.09.003.
    1. Jiang H., Gao P., Chen H., Zhong Z., Shu M., Zhang Z., She J., Liu J. The Prognostic Value of CD8(+) and CD45RO(+) T Cells Infiltration and Beclin1 Expression Levels for Early Postoperative Cholangitis of Biliary Atresia Patients after Kasai Operation. J. Korean Med. Sci. 2018;33:e198. doi: 10.3346/jkms.2018.33.e198.
    1. Nakajima H., Koga H., Okawada M., Nakamura H., Lane G.J., Yamataka A. Does time taken to achieve jaundice-clearance influence survival of the native liver in post-Kasai biliary atresia? World J. Pediatr. 2018;14:191–196. doi: 10.1007/s12519-018-0139-5.
    1. Xiao H., Huang R., Chen L., Diao M., Li L. The Application of a Shorter Loop in Kasai Portoenterostomy Reconstruction for Ohi Type III Biliary Atresia: A Prospective Randomized Controlled Trial. J. Surg. Res. 2018;232:492–496. doi: 10.1016/j.jss.2018.07.002.
    1. Ginstrom D.A., Hukkinen M., Kivisaari R., Pakarinen M.P. Biliary Atresia-associated Cholangitis: The Central Role and Effective Management of Bile Lakes. J. Pediatr. Gastroenterol. Nutr. 2019;68:488–494. doi: 10.1097/MPG.0000000000002243.
    1. Madadi-Sanjani O., Schukfeh N., Uecker M., Eckmann S., Dingemann J., Ure B.M., Petersen C., Kuebler J.F. The Intestinal Flora at Kasai Procedure in Children with Biliary Atresia Appears Not to Affect Postoperative Cholangitis. Eur. J. Pediatr. Surg. 2021;31:80–85. doi: 10.1055/s-0040-1715614.
    1. Chung P.H.Y., Chan E.K.W., Yeung F., Chan A.C.Y., Mou J.W.C., Lee K.H., Hung J.W.S., Leung M.W.Y., Tam P.K.H., Wong K.K.Y. Life long follow up and management strategies of patients living with native livers after Kasai portoenterostomy. Sci. Rep. 2021;11:11207. doi: 10.1038/s41598-021-90860-w.

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