orthotopic liver transplantation ( olt ) remains the gold standard for treatment of end - stage liver disease ( esld ) despite advances in medical treatment and management of complications .
implantation includes reestablishment of three critical structures : the portal vein , the hepatic artery , and the biliary duct in a sequential fashion .
most often , hepatic artery reperfusion ( harp ) occurs after portal vein reperfusion ( pvrp ) and establishes the blood supply to the bile duct epithelium .
postoperative biliary complications may be attributable to hepatic artery thrombosis or stenosis , technical reasons , ischemia - reperfusion injury , and immunological injury .
these complications can be early , those occurring less than 30 days after olt , or late , those occurring after 30 days .
biliary complications secondary to long warm ischemia times , independent of vascular compromise , have been reported in the literature specifically in recipients who received livers from donation after cardiac death ( dcd ) donors [ 36 ] .
ischemic cholangiopathy has been described in 950% of dcd recipients with subsequent increased risk for graft loss , retransplantation , and death [ 3 , 6 ] . although the pvrp - harp interval and its effect on biliary complications have been studied before , this study aimed to identify the specific pvrp - harp time interval that is a  cut off  or safe to perform the arterial anastomosis leading to lower postoperative biliary strictures in olt .
we hypothesized that a longer time interval for harp may result in increased biliary strictures .
we retrospectively reviewed all patients who underwent olt from january 2007 to december 2009 through the organ transplant tracking record after study approval from the institutional review board .
we obtained information on all patients transplanted including demographics , reasons for transplantation , laboratory values pretransplant , operative reports with reperfusion times , and postoperative records to detect biliary strictures .
patients were included in the study if they were 18 years old , had survived the initial olt and 3 months postoperatively , and had data for pvrp and harp .
patients receiving allografts from dcd donors , pediatrics patients , retransplantations , split liver transplants , and cases in which arterial complications occurred before biliary strictures were excluded .
independent variables of interest included ; ( 1 ) demographics - age , gender ; ( 2 ) etiology of esld ; ( 3 ) meld ; ( 4 ) presence of hepatocellular carcinoma ( hcc ) ; ( 5 ) status ; and ( 6 ) year of olt . outcomes of interest were graft survival , average pvrp - harp time interval , and biliary strictures .
biliary strictures were detected via endoscopic retrograde cholangiopancreatography ( ercp ) with intervention ( i.e. , stent placement , etc . )
after they were suspected based on laboratory parameters ( increased bilirubin , alkaline phosphatase , and gamma - glutamyltransferase ) and/or ultrasound findings ( biliary ducts dilatation ) .
mild bile duct stenoses at the anastamosis detected on ercp not requiring intervention were excluded .
these patients were followed with routine monthly labs and ultrasound to ensure that they were excluded appropriately .
patients were followed for 6 months after - olt to see if they developed any biliary strictures .
aortic and portal flush ( through inferior mesenteric vein cannulation ) were used systematically with htk preservation solution ( 4 liters for systemic and 2 liters for portal circulation ) .
the biliary tract was flushed with cold saline through the gallbladder after the bile duct was divided .
rejection episodes were confirmed by liver biopsy and treated with steroid boluses or thymoglobulin based on individual cases .
biliary reconstruction type was choledochocholedochostomy performed in an end - to - end fashion with 5 - 0 pds running suture in all cases .
artery anastomoses were performed with 6 - 0 or 7 - 0 prolene running sutures in an end - to - end fashion between donor and recipient common hepatic arteries .
three different senior surgeons performed the total of the cases assisted by a junior surgeon .
two groups ( no biliary strictures versus biliary strictures ) were compared using the pearson 's chi - test , chi - square test , or the fisher 's exact test when appropriate .
one hundred sixty patients underwent olt from january 2007 to december 2009 . of these only 75 patients met all inclusion criteria to be included within the study .
there was no statistical significant difference between patients with and without biliary strictures in age , gender , etiology , hcc , mortality status ( alive or deceased ) , year of transplantation as well as the mean meld , graft survival , and pvrp - harp time interval .
however , patients with biliary strictures did have longer warm ( p = 0.06 ) and cold ischemia time ( p = 0.03 ) compared to those without biliary strictures ( table 1 ) .
the average pvrp - harp time was 50 minutes for 10 patients with biliary strictures .
most pvrp - harp time intervals were larger than 30 minutes ( only 1 patient had a pvrp - harp time interval less than 30 minutes ) ( figure 1 ) .
three categories of pvrp - harp time intervals were compared between patients with and without biliary strictures including 30 minutes , 48 minutes ( the average pvrp - harp time interval of all olt ) , and 1 hour ( table 2 ) .
nine of 10 ( 90% ) patients with biliary strictures had a pvrp - harp time interval > 30 minutes , as opposed to 50 of 65 ( 77% ) patients without biliary strictures .
the cold ischemia time was significantly different between the two groups ( p = 0.03 ) .
warm ischemia time is the duration the liver is removed from ice until it is reperfused with recipient blood . during warm ischemia time , the liver is susceptible to both ischemia and eventually reperfusion injury . although initial hypothermia halts metabolism , slow depletion of cellular energy stores occurs and rewarming at time of reimplantation causes an increase metabolic demands without oxygen and nutrients , leading to structural and functional cellular defects .
thus , due to this accelerated cellular damage during rewarming , a relatively short period of warm ischemia is more harmful to cells than a longer cold ischemia time .
one population in which the effect of warm ischemia has been widely studied is the dcd population .
the first reports of dcd organ procurement were published in 1995 by university of pittsburgh   and madison , wi .
dcd can be either uncontrolled or controlled [ 4 , 11 ] . in the former patients have unexpected cardiopulmonary arrest and/or unsuccessful resuscitation , and in the latter they undergo planned withdrawal of ventilatory and organ - perfusion support most often in the operating room [ 4 , 11 ] .
thus , dcd donors have higher incidence of biliary strictures and/or bile cast syndrome [ 5 , 6 , 11 , 13 , 14 ] as well as ischemic cholangiopathy , which has been reported in 950% of dcd recipients [ 4 , 6 , 1116 ] . with improvements in organ selection , retrieval , preservation , and implantation techniques , biliary complications have dramatically reduced since the 1970s . however
, biliary complications still occur 1030% of olt , resulting in death for 10% of patients [ 2 , 1723 ] .
the most common biliary complications are leaks and strictures , but sphincter of oddi dysfunction , hemobilia , and biliary obstruction from cystic duct mucocele , stones , sludge , or casts are also possible [ 17 , 24 , 25 ] . similar to other study findings , our biliary strictures were primary treated with ercp and stenting .
postintervention , our patients did well and likely have a long - term success rate of > 5070% [ 2631 ] .
this study examined the time interval between pvrp and harp to determine its effect on postoperative biliary strictures in dbd olt .
we found that the length of the interval between pvrp - harp did not impact the incidence of biliary strictures up to 6 months after olt .
moreover , none of our 10 patients with biliary strictures had ischemic cholangiopathy , which has been reported in up to 50% of dcd recipients [ 4 , 6 , 1116 ] .
this may be due to the physiological differences ( i.e. , longer warm ischemia ) in dcd versus dbd organ procurement .
animal models have indicated that dual vessel reperfusion ( both vein and artery reperfused at the same time ) has higher bile flow and biliary cholesterol than single reperfusion ( vein only ) , leading to better liver function in the former .
our study implies that at least in terms of biliary complication dual vessel reperfusion is not crucial . also , variation in timing of hepatic artery preparation ( i.e. , prior to implantation , after implantation and pvrp or a combination )
interestingly , almost all our patients with a biliary stricture had a pvrp - harp time above 30 minutes , although not statistically significant this may be clinically significant with 30 minutes being a critical time after which there is an increase in biliary stricture development . in our study , longer warm and cold ischemia time , especially the latter , were seen in patients with biliary strictures .
these findings are consistent with other studies in dcd olt , where cold and warm ischemia time were risk factors for predicting postoperative biliary complications .
we attempted to determine in this study whether other time - sensitive factors ( i.e. , pvrp - harp time interval ) impact the development of biliary strictures .
first , of all the possible olt patients available for this study , 160 , only 75 were met the inclusion criteria .
a significant number of these patients were excluded because they lacked pvrp and harp data values , or the values were not recorded correctly .
secondly , our small sample size prevented the study from having enough power to find any statistical significance in our results .
finally , the cause of biliary strictures in our subjects could be multifactorial , and the retrospective nature of this study further prevents us from drawing any temporal conclusions of causality or generalizing our results to other liver transplant populations . despite these limitations ,
this study does give us insight with regard to timing of hepatic artery reperfusion and olt outcomes .
the length of the time interval for harp after pvrp did not appear to affect the development of biliary strictures .
on the other hand , the cold ischemia time did appear to be significant , in accordance with the previous literature [ 7 , 33 ] .
although no statistically significant difference in pvrp - harp time was found between the groups with and without biliary strictures , it is possible to suggest a potential critical time of 30 minutes based on the observation that 9 out of 10 biliary strictures occurred when the pvrp - harp interval was greater than that time .
larger prospective randomized studies with longer follow - up time are needed to determine if the pvrp - harp time interval impacts postoperative biliary strictures development .
 during orthotopic liver transplantation ( olt ) , biliary tract perfusion occurs with hepatic artery reperfusion ( harp ) , commonly performed after the portal vein reperfusion ( pvrp ) . 
 we examined whether the average time interval between pvrp and harp impacted on postoperative biliary strictures occurrence . 
 patients undergoing olt from 2007 to 2009 were included if they were 18 years old , had survived 3 months postoperatively , and had data for pvrp and harp . 
 patients receiving allografts from dcd donors were excluded . 
 patients were followed for 6 months post - olt . 
 seventy - five patients met the study inclusion criteria . 
 of these , 10 patients had a biliary stricture . 
 there was no statistical difference between those with and without biliary stricture in age , gender , etiology , meld score , graft survival , and time interval between pvrp and harp . 
 ninety percent of patients with biliary stricture had a pvrp - harp time interval > 30 minutes , as opposed to 77% of patients without biliary stricture . 
 however , this was not statistically significant . 
 the cold ischemia time was significantly different between the two groups . 
 time interval for harp after pvrp did not appear to affect the development of biliary strictures . 
 however , 30 minutes may be suggested as a critical time after which there is an increase in biliary stricture occurrence . 
1. Introduction
2. Methods
3. Results
4. Discussion
5. Conclusion