Bacteriobilia and fungibilia are associated with outcome in patients with endoscopic treatment of biliary complications after liver transplantation

Background and study aims: To determine the importance of bacteriobilia and fungibilia in patients with endoscopic treatment of biliary complications after orthotopic liver transplantation (OLT).

Patients and methods: In a prospective study at a tertiary center, 213 patients underwent 857 endoscopic retrograde cholangiographies (ERCs) after OLT. Findings at first ERC were: anastomotic stricture in 24.4 %, nonanastomotic stricture in 18.3 %, leakage in 11.3 %, and gallstones in 4.7 %.

Results: Bile samples from first ERC showed Gram-positive bacterial isolates in 102/180 (57 %) and Gram-negative in 44/180 (24 %). Main species were Enterococcus spp. (40 %; 72/180) and Escherichia coli (10 %; 18 /180). Enteric bacteria (present in 47 %) and Candida spp. (present in 18 %) were both associated with clinical signs of cholangitis, but not with laboratory signs of inflammation. Multiresistant strains (present in12 % of samples) showed no association with clinical or laboratory parameters. Detection of microbiological isolates was independent of endoscopic findings and treatment. In patients with successful endoscopic intervention, the actuarial survival free of retransplantation was significantly lower in those with detection of enteric bacteria, being 51.8 months (95 % confidence interval [CI] 42.9 – 60.6) vs. 62.9 months (95 %CI 59.1 – 66.7); P = 0.025). Fungibilia was associated with significantly lower actuarial retransplantation-free survival, independently of successful endoscopic treatment (mean 35.1 months [95 %CI 23.5 – 46.7] vs. 53.1 months [(95 %CI 48.0 – 58.2]; P = 0.019).

Conclusions: Bacteriobilia and fungibilia can frequently be detected by routine microbiological sampling in patients after OLT. Regular bile sampling is recommended since the presence of difficult-to-treat multiresistant strains is unpredictable. Survival is affected by this altered biliary microbiological environment after OLT.

^* Both authors contributed equally.

• References

• 1 Stratta RJ, Wood RP, Langnas AN et al. Diagnosis and treatment of biliary tract complications after orthotopic liver transplantation. Surgery 1989; 106: 675-83 ; discussion 683–684
• 2 Greif F, Bronsther OL, Van Thiel DH et al. The incidence, timing, and management of biliary tract complications after orthotopic liver transplantation. Ann Surg 1994; 219: 40-45
• 3 Rerknimitr R, Sherman S, Fogel EL et al. Biliary tract complications after orthotopic liver transplantation with choledochocholedochostomy anastomosis: endoscopic findings and results of therapy. Gastrointest Endosc 2002; 55: 224-231
• 4 Pfau PR, Kochman ML, Lewis JD et al. Endoscopic management of postoperative biliary complications in orthotopic liver transplantation. Gastrointest Endosc 2000; 52: 55-63
• 5 Thuluvath PJ, Pfau PR, Kimmey MB et al. Biliary complications after liver transplantation: the role of endoscopy. Endoscopy 2005; 37: 857-863
• 6 Boey JH, Way LW. Acute cholangitis. Ann Surg 1980; 191: 264-270
• 7 van Erpecum KJ. Gallstone disease. Complications of bile-duct stones: Acute cholangitis and pancreatitis. Best Pract Res Clin Gastroenterol 2006; 20: 1139-1152
• 8 Verdonk RC, Buis CI, van der Jagt EJ et al. Nonanastomotic biliary strictures after liver transplantation, part 2: Management, outcome, and risk factors for disease progression. Liver Transpl 2007; 13: 725-732
• 9 Shah JN, Haigh WG, Lee SP et al. Biliary casts after orthotopic liver transplantation: clinical factors, treatment, biochemical analysis. Am J Gastroenterol 2003; 98: 1861-1867
• 10 Wada K, Takada T, Kawarada Y et al. Diagnostic criteria and severity assessment of acute cholangitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg 2007; 14: 52-58
• 11 Lai EC, Mok FP, Tan ES et al. Endoscopic biliary drainage for severe acute cholangitis. N Engl J Med 1992; 326: 1582-1586
• 12 Deviere J, Motte S, Dumonceau JM et al. Septicemia after endoscopic retrograde cholangiopancreatography. Endoscopy 1990; 22: 72-75
• 13 Lee JG. Diagnosis and management of acute cholangitis. Nat Rev Gastroenterol Hepatol 2009; 6: 533-541
• 14 Nomura T, Shirai Y, Hatakeyama K. Enterococcal bactibilia in patients with malignant biliary obstruction. Dig Dis Sci 2000; 45: 2183-2186
• 15 Rosch T, Triptrap A, Born P et al. Bacteriobilia in percutaneous transhepatic biliary drainage: occurrence over time and clinical sequelae. A prospective observational study. Scand J Gastroenterol 2003; 38: 1162-1168
• 16 Bjornsson ES, Kilander AF, Olsson RG. Bile duct bacterial isolates in primary sclerosing cholangitis and certain other forms of cholestasis –ve a study of bile cultures from ERCP. Hepatogastroenterology 2000; 47: 1504-1508
• 17 Rudolph G, Gotthardt D, Klöters-Plachky P et al. Influence of dominant bile duct stenoses and biliary infections on outcome in primary sclerosing cholangitis. J Hepatol 2009; 51: 149-155
• 18 Negm AA, Schott A, Vonberg RP et al. Routine bile collection for microbiological analysis during cholangiography and its impact on the management of cholangitis. Gastrointest Endosc 2010; 72: 284-291 Epub 2010 Jun 11
• 19 Millonig G, Buratti T, Graziadei IW et al. Bactobilia after liver transplantation: frequency and antibiotic susceptibility. Liver Transpl 2006; 12: 747-753
• 20 Petersen BT, Chennat J, Cohen J et al. Multisociety guideline on reprocessing flexible gastrointestinal endoscopes: 2011. Gastrointest Endosc 2011; 73: 1075-1084
• 21 Rerknimitr R, Fogel EL, Kalayci C et al. Microbiology of bile in patients with cholangitis or cholestasis with and without plastic biliary endoprosthesis. Gastrointest Endosc 2002; 56: 885-889
• 22 Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med 2007; 357: 2601-2614
• 23 Ehrenstein BP, Salamon L, Linde HJ et al. Clinical determinants for the recovery of fungal and mezlocillin-resistant pathogens from bile specimens. Clin Infect Dis 2002; 34: 902-908
• 24 Lenz P, Conrad B, Kucharzik T et al. Prevalence, associations, and trends of biliary-tract candidiasis: a prospective observational study. Gastrointest Endosc 2009; 70: 480-487
• 25 Reid GE, Grim SA, Sankary H et al. Early intra-abdominal infections associated with orthotopic liver transplantation. Transplantation 2009; 87: 1706-1711
• 26 Jethwa P, Breuning E, Bhati C et al. The microbiological impact of pre-operative biliary drainage on patients undergoing hepato-biliary-pancreatic (HPB) surgery. Aliment Pharmacol Ther 2007; 25: 1175-1180
• 27 Werner G, Fleige C, Ewert B et al. High-level ciprofloxacin resistance among hospital-adapted Enterococcus faecium (CC17). Int J Antimicrob Agents 2009;
• 28 Buis CI, Geuken E, Visser DS et al. Altered bile composition after liver transplantation is associated with the development of nonanastomotic biliary strictures. J Hepatol 2009; 50: 69-79
• 29 Gotthardt D, Runz H, Keitel V et al. A mutation in the canalicular phospholipid transporter gene, ABCB4, is associated with cholestasis, ductopenia, and cirrhosis in adults. Hepatology 2008; 48: 1157-1166
• 30 Gotthardt D, Stiehl A. Endoscopic retrograde cholangiopancreatography in diagnosis and treatment of primary sclerosing cholangitis. Clin Liver Dis 2010; 14: 349-358
• 31 Gotthardt DN, Rudolph G, Kloters-Plachky P et al. Endoscopic dilation of dominant stenoses in primary sclerosing cholangitis: outcome after long-term treatment. Gastrointest Endosc 2010; 71: 527-534
• 32 Kulaksiz H, Weiss KH, Gotthardt D et al. Is stenting necessary after balloon dilation of post-transplantation biliary strictures? Results of a prospective comparative study. Endoscopy 2008; 40: 746-751
• 33 Sauer P, Chahoud F, Gotthardt D et al. Temporary placement of fully covered self-expandable metal stents in biliary complications after liver transplantation. Endoscopy 2012; 44: 536-538
• 34 Balderramo D, Navasa M, Cardenas A. Current management of biliary complications after liver transplantation: emphasis on endoscopic therapy. Gastroenterol Hepatol 2011; 34: 107-115