title: Biliary complications in liver transplantation: Impact of anastomotic technique and ischemic time on short- and long-term outcome.
abstract: OBJECTIVE
  To elucidate the impact of various donor recipient and transplant factors on the development of biliary complications after liver transplantation.
  
  
  METHODS
  We retrospectively reviewed 200 patients of our newly established liver transplantation (LT) program, who received full size liver graft. Biliary reconstruction was performed by side-to-side (SS), end-to-end (EE) anastomosis or hepeaticojejunostomy (HJ). Biliary complications (BC), anastomotic stenosis, bile leak, papillary stenosis, biliary drain complication, ischemic type biliary lesion (ITBL) were evaluated by studying patient records, corresponding radiologic imaging and reports of interventional procedures [e.g., endoscopic retrograde cholangiopancreatography (ERCP)]. Laboratory results included alanine aminotransferase (ALT), gammaglutamyltransferase and direct/indirect bilirubin with focus on the first and fifth postoperative day, six weeks after LT. The routinely employed external bile drain was examined by a routine cholangiography on the fifth postoperative day and six weeks after transplantation as a standard procedure, but also whenever clinically indicated. If necessary, interventional (e.g., ERCP) or surgical therapy was performed. In case of biliary complication, patients were selected, assigned to different complication-groups and subsequently reviewed in detail. To evaluate the patients outcome, we focussed on appearance of postoperative/post-interventional cholangitis, need for rehospitalisation, retransplantation, ITBL or death caused by BC.
  
  
  RESULTS
  A total of 200 patients [age: 56 (19-72), alcoholic cirrhosis: n = 64 (32%), hepatocellular carcinoma: n = 40 (20%), acute liver failure: n = 23 (11.5%), cryptogenic cirrhosis: n = 22 (11%), hepatitis B virus /hepatitis C virus cirrhosis: n = 13 (6.5%), primary sclerosing cholangitis: n = 13 (6.5%), others: n = 25 (12.5%) were included. The median follow-up was 27 mo until June 2015. The overall biliary complication rate was 37.5% (n = 75) with anastomotic strictures (AS): n = 38 (19%), bile leak (BL): n = 12 (6%), biliary drain complication: n = 12 (6%); papillary stenosis (PS): n = 7 (3.5%), ITBL: n = 6 (3%). Clinically relevant were only 19% (n = 38). We established a comprehensive classification for AS with four grades according to clinical relevance. The reconstruction techniques [SS: n = 164, EE: n = 18, HJ: n = 18] showed no significant impact on the development of BCs in general (all n < 0.05), whereas in the HJ group significantly less AS were found (P = 0.031). The length of donor intensive care unit stay over 6 d had a significant influence on BC development (P = 0.007, HR = 2.85; 95%CI: 1.33-6.08) in the binary logistic regression model, whereas other reviewed variables had not [warm ischemic time > 45 min (P = 0.543), cold ischemic time > 10 h (P = 0.114), ALT init > 1500 U/L (P = 0.631), bilirubin init > 5 mg/dL (P = 0.595), donor age > 65 (P = 0.244), donor sex (P = 0.068), rescue organ (P = 0.971)]. 13% (n = 10) of BCs had no therapeutic consequences, 36% (n = 27) resulted in repeated lab control, 40% (n = 30) received ERCP and 11% (n = 8) surgical therapy. Fifteen (7.5%) patients developed cholangitis [AS (n = 6), ITBL (n = 5), PS (n = 3), biliary lesion BL (n = 1)]. One patient developed ITBL twelve months after LT and subsequently needed retransplantation. Rehospitalisation rate was 10.5 % (n= 21) [AS (n = 11), ITBL (n = 5), PS (n = 3), BL (n = 1)] with intervention or reinterventional therapy as main reasons. Retransplantation was performed in 5 (2.5%) patients [ITBL (n = 1), acute liver injury (ALI) by organ rejection (n = 3), ALI by occlusion of hepatic artery (n = 1)]. In total 21 (10.5%) patients died within the follow-up period. Out of these, one patient with AS developed severe fatal chologenic sepsis after ERCP.
  
  
  CONCLUSIONS
  In our data biliary reconstruction technique and ischemic times seem to have little impact on the development of BCs.
authors.affiliation: Stefan Kienlein, Wenzel Schoening, Anne Andert, Ulf Peter Neumann, Maximilian Schmeding, Department of General, Visceral and Transplantation Surgery, University Hospital Aachen, 52074 Aachen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kienlein
authors.affiliation: Stefan Kienlein, Wenzel Schoening, Anne Andert, Ulf Peter Neumann, Maximilian Schmeding, Department of General, Visceral and Transplantation Surgery, University Hospital Aachen, 52074 Aachen, Germany.
authors.forename: Wenzel
authors.initials: W
authors.lastname: Schoening
authors.affiliation: Stefan Kienlein, Wenzel Schoening, Anne Andert, Ulf Peter Neumann, Maximilian Schmeding, Department of General, Visceral and Transplantation Surgery, University Hospital Aachen, 52074 Aachen, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Andert
authors.affiliation: Stefan Kienlein, Wenzel Schoening, Anne Andert, Ulf Peter Neumann, Maximilian Schmeding, Department of General, Visceral and Transplantation Surgery, University Hospital Aachen, 52074 Aachen, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Kroy
authors.affiliation: Stefan Kienlein, Wenzel Schoening, Anne Andert, Ulf Peter Neumann, Maximilian Schmeding, Department of General, Visceral and Transplantation Surgery, University Hospital Aachen, 52074 Aachen, Germany.
authors.forename: Ulf Peter
authors.initials: UP
authors.lastname: Neumann
authors.affiliation: Stefan Kienlein, Wenzel Schoening, Anne Andert, Ulf Peter Neumann, Maximilian Schmeding, Department of General, Visceral and Transplantation Surgery, University Hospital Aachen, 52074 Aachen, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Schmeding
keywords: Anastomotic stenosis; Bile leak; Biliary complications; Biliary drain complications; Ischemic time; Ischemic type biliary lesion; Liver transplantation; Non-anastomotic strictures