Paul M. J. G. Peeters

Anastomotic biliary strictures after liver transplantation: Causes and consequences

We retrospectively studied the prevalence, presentation, results of treatment, and graft and patient survival of grafts developing an anastomotic biliary stricture (AS) in 531 adult liver transplantations performed between 1979 and 2003. Clinical and laboratory information was obtained from the hospital files, and radiological studies were re‐evaluated. Twenty‐one possible risk factors for the development of AS (variables of donor, recipient, surgical procedure, and postoperative course) were analyzed in a univariate and stepwise multivariate model. Forty‐seven grafts showed an anastomotic stricture: 42 in duct‐to‐duct anastomoses, and 5 in hepaticojejunal Roux‐en‐Y anastomoses. The cumulative risk of AS after 1, 5, and 10 years was 6.6%, 10.6%, and 12.3% respectively. Postoperative bile leakage (P = 0.001), a female donor/male recipient combination (P = 0.010), and the era of transplantation (P = 0.006) were independent risk factors for the development of an AS. In 47% of cases, additional (radiologically minor) nonanastomotic strictures were diagnosed. All patients were successfully treated by 1 or more treatment modalities. As primary treatment, endoscopic retrograde cholangiopancreaticography (ERCP) was successful in 24 of 36 (67%) cases and percutaneous transhepatic cholangiodrainage in 4 of 11 (36%). In the end 15 patients (32%) were operated, all with long‐term success. AS presenting more than 6 months after transplantation needed more episodes of stenting by ERCP, and more stents per episode compared to those presenting within 6 months and recurred more often. Graft and patient survival were not impaired by AS. Liver Transpl 12:726–735, 2006.

Ultrasound and cholangiography for the diagnosis of biliary complications after orthotopic liver transplantation: A comparative study

The ability of ultrasound to detect biliary obstruction, bile leakage and generalized ductal changes after orthotopic liver transplantation (OLT) was compared to cholangiography. Cholangiography was considered to be the gold standard. Adequate opacification of the biliary tree was achieved in 139 cholangiograms. Biliary obstruction, intermediate or large bile leakage, and generalized ductal changes were diagnosed with cholangiography in 15% (21/139), 14% (20/139), and 16% (22/139), respectively. Normal ultrasound findings could not exclude biliary stricture, generalized ductal changes, or bile leakage, and fluid collections were not correlated with bile leakage. Abnormal ultrasound findings were highly predictive of the cholangiographic diagnosis of biliary obstruction or generalized ductal changes (specificity of 98% and 100%, respectively). An irregular appearance of the bile ducts and increased periductal echogenicity proved to be characteristic features for generalized ductal changes.

The Clinical Relevance of the Anhepatic Phase During Liver Transplantation

This study assesses the relation between the anhepatic phase duration and the outcome after liver transplantation. Of 645 patients who underwent transplantation between 1994 and 2006, 194 were recipients of consecutive adult primary piggyback liver transplants using heart‐beating donors. The anhepatic phase was defined as the time from the physical removal of the liver from the recipient to recirculation of the graft. Other noted study variables were the cold and warm ischemia times, donor and recipient age, donor and recipient body mass index, perioperative red blood cell (RBC) transfusion, indication for transplantation, and Model for End‐Stage Liver Disease score. The primary outcome parameter was graft dysfunction, which was defined as either primary nonfunction or initial poor function according to the Ploeg‐Maring criteria. The median anhepatic phase was 71 minutes (37–321 minutes). Graft dysfunction occurred in 27 patients (14%). Logistic regression analysis showed an anhepatic phase over 100 minutes [odds ratio (OR), 4.28], a recipient body mass index over 25 kg/m2 (OR, 3.21), and perioperative RBC transfusion (OR, 3.04) to be independently significant predictive factors for graft dysfunction. One‐year patient survival in patients with graft dysfunction was 67% versus 92% in patients without graft dysfunction (P < 0.001). A direct relation between the anhepatic phase duration and patient survival could, however, not be established. In conclusion, this study shows that liver transplant patients with an anhepatic phase over 100 minutes have a higher incidence of graft dysfunction. Patients with graft dysfunction have significantly worse 1‐year patient survival. Liver Transpl 15:1050–1055, 2009.

Surgical injuries of postmortem donor livers : Incidence and impact on outcome after adult liver transplantation

The exact frequency and clinical consequences of surgical hepatic injuries during organ procurement are unknown. We analyzed the incidence, risk factors, and clinical outcome of surgical injuries in 241 adult liver grafts. Hepatic injuries were categorized as parenchymal, vascular, or biliary. Outcome variables were bleeding complications, hepatic artery thrombosis (HAT), and graft survival. In 82 livers (34%), 96 injuries were detected. Most injuries were minor, but clinically relevant injuries were detected in 6.6% (16/241) of the livers. Fifty (21%) liver grafts had some degree of parenchymal or capsular injury, 40 (17%) had vascular injury, and 6 (2%) had an injury to the bile duct. Procurement region was the only risk factor significantly associated with surgical injury. The rate of hepatic artery injury was significantly higher in livers with aberrant arterial anatomy. Bleeding complications were found in 18% of patients who received livers with a parenchymal or capsular injury in contrast to 9% without parenchymal injury (P = 0.065). HAT was found in 23% of the patients who received a liver with arterial injury compared to 4% without arterial injury (P = 0.001). Overall graft survival rates were not significantly different for grafts with or without anatomical injury. In conclusion, surgical injuries of donor livers are an underestimated problem in liver transplantation and can be observed in about one‐third of all cases. Clinically relevant injuries are detected in 6.6% of all liver grafts. Arterial injuries are associated with an increased risk of HAT. Liver Transpl 12:1365‐1370, 2006.

Hepatic expression of ABC transporters G5 and G8 does not correlate with biliary cholesterol secretion in liver transplant patients

The adenosine triphosphate (ATP)‐binding cassette (ABC)‐transporters ABCG5 and ABCG8 have been shown to mediate hepatic and intestinal excretion of cholesterol. In various (genetically modified) murine models, a strong relationship was found between hepatic expression of ABCG5/ABCG8 and biliary cholesterol content. Our study aimed to relate levels of hepatic expression of ABCG5 and ABCG8 to biliary excretion of cholesterol in man. From 24 patients who had received a liver transplant, bile samples were collected daily after transplantation over a 2‐week period to determine biliary composition. Expression of ABCG5, ABCG8, MDR3, and BSEP was assessed by real‐time polymerase chain reaction (PCR) in liver biopsy specimens collected before and after transplantation. Levels of hepatic ABCG5, ABCG8, and MDR3 messenger RNA (mRNA) were strongly correlated. After transplantation, the biliary secretion rate of cholesterol continuously increased, coinciding with gradual increases in bile salt and phospholipid secretion. In contrast, hepatic levels of ABCG5 and ABCG8 mRNA remained unchanged. Surprisingly, no correlation was found between the hepatic expression of ABCG5 and ABCG8 and rates of biliary cholesterol secretion, normalized for biliary phospholipid secretion. As expected, the concentration of biliary phospholipids correlated well with MDR3 expression. In conclusion, the strong relationship between ABCG5 and ABCG8 gene expression is consistent with the coordinate regulation of both genes, and in line with heterodimerization of both proteins into a functional transporter. Hepatic ABCG5/ABCG8 expression, at least during the early phase after transplantation, is not directly related to biliary cholesterol secretion in humans. This finding suggests the existence of alternative pathways for the hepatobiliary transport of cholesterol that are not controlled by ABCG5/ABCG8. (HEPATOLOGY 2005;42:1166–1174.)

Analysis of differences in outcome of two European liver transplant centers

Authors analyzed the differences in the outcome of two European liver transplant centers differing in case volume and experience. The first was the Transplantation and Surgical Clinic, Semmelweis University, Budapest, Hungary (SEB) and the second the University Medical Center Groningen, Groningen, The Netherlands (UMCG). We investigated if such differences could be explained. The 1‐, 3‐ and 5‐year patient survival in the UMCG was 86%, 80%, and 77% compared with 65%, 56%, and 55% in SEB. Graft survival at the same time points was 79%, 71%, and 66% in the UMCG and 62%, 55%, and 53% in SEB. Significant differences were present regarding the donor and recipient age, diagnosis mix, disease severity and operation variables, per‐operative transfusion rate, vascular complications, postoperative infection rate, and need for renal replacement. To determine factors correlating with survival, a separate uni‐ and multivariate analysis was performed in each center individually, between study parameters and patient survival. In both centers, peri‐operative red blood cell (RBC) transfusion rate was a significant predictor for patient survival. The difference in blood loss can be explained by different operation techniques and shorter operation time in SEB, with consequently less time spent on hemostasis. It was jointly concluded that measures to reduce blood loss by adapting the operation technique might lead to improved survival and reduced morbidity.

Buccal vs. nasogastric tube administration of tacrolimus after pediatric liver transplantation

Abstract:  Tacrolimus is an important drug for immunosuppression after liver transplantation. Bioavailability of enterally administered tacrolimus is poor, and further reduced by gastric residuals or by enteral nutrition. Buccal administration might be an alternative route especially in children. Tacrolimus trough levels (TTLs) obtained after buccal administration of tacrolimus after liver transplantation have not been reported. The aim of this study was to determine whether buccal administration of tacrolimus is feasible and to compare TTLs after nasogastric tube (NGT) administration with buccal administration. TTLs after NGT or buccal administration during the first week after pediatric liver transplantation were analyzed from 28 cadaveric liver transplants in 23 pediatric recipients between June 2002 and March 2004. Each level was scored within, under or above the target range. Buccal administration was well tolerated in all patients. A total of 149 TTLs were obtained of which nine were excluded because of incomplete information on target levels. Overall 27% of TTLs was adequate. The percentage of levels under, within and above the target range were comparable in both groups (chi‐square test; p = 0.64). Both groups had a decrease in percentages within the target range on day 3 and 4 after liver transplantation with a subsequent rise. Buccal tacrolimus administration is feasible. Similar TTLs are achieved compared with NGT tacrolimus administration during the first week after pediatric liver transplantation.

Mortality of biliary atresia in children not undergoing liver transplantation in the Netherlands

de Vries W, de Langen ZJ, Aronson DC, Hulscher JBF, Peeters PMJG, Jansen‐Kalma P, Verkade HJ also on behalf of NeSBAR. Mortality of biliary atresia in children not undergoing liver transplantation in the Netherlands.
Pediatr Transplantation 2011: 15:176–183.

End-to-side caval anastomosis in adult piggyback liver transplantation.

Abstract:  No consensus exists regarding the optimal reconstruction of the cavo‐caval anastomosis in piggyback orthotopic liver transplantation (PB‐LT). The aim of this study was to analyze our experience with end‐to‐side (ES) cavo‐cavostomy. Outcome parameters were patient and graft survival and surgical complications. During the period 1995–2002 146 full‐size PB‐LT in 137 adult patients were performed with ES cavo‐cavostomy without the routine use of temporary portocaval shunt (TPCS). In 12 patients (8%) this technique was used for implantation of second or third grafts. Veno‐venous bypass was not used in any case and TPCS was performed only in eight patients (6%). One‐, three‐ and five‐yr patient and graft survival were 84%, 79% and 75%, and 81%, 74% and 69%, respectively. The median number of intraoperative transfusion of packed red blood cells (RBC) was 2.0 (range 0–33) and 30% of the patients (n = 43) did not require any RBC transfusion. Surgical complications of various types were observed after 49 LT (34%) and none of the complications was specifically related to the technique of ES cavo‐cavostomy. Our experience indicates that PB‐LT with ES cavo‐cavostomy is a safe procedure, can safely be performed without the routine use of a TPCS, has a very low risk of venous outflow obstruction and can also be used effectively during retransplantations.

The evolution of surgical techniques in clinical liver transplantation. A review

Abstract:  Currently, liver transplantation (LT) is an accepted method of treatment of end‐stage liver disease, metabolic diseases with their primary defect in the liver and unresectable primary liver tumors. Surgical techniques in LT have evolved considerably over the past 40 yr. The developments have led to a safer procedure for the recipient reflected by continuously improving survival figures after LT. Also the new techniques offer the possibility of tailoring the operation to the needs and condition of the recipient as in partial grafting or in different revascularization techniques, or in techniques of biliary reconstructions. In addition, the new techniques such as split LT, domino transplantation and living donor LT have brought about an increase in the available grafts. In this review the evolution of surgical techniques in LT over the past 40 yr and their contribution to the current results are discussed.