Factors Predicting Ischemic-Type Biliary Lesions (ITBLs) After Liver Transplantation

Among biliary complications, ischemic-type biliary lesions (ITBLs) remain a major cause of morbidity in liver transplant recipients, significantly affecting the chance of survival of both patients and grafts. We retrospectively reviewed 10 years of prospectively collected donor and recipient data from April 2001 to April 2011. We evaluated the incidence of ITBL occurrence, exploring the possible predisposing factors, including donor and recipient data. Two hundred fifty-one grafts were harvested: 222 of them were transplanted at our institution, the remaining 29 (11.6%) discarded by our donor team as showing >40% macrovesicular steatosis. Mild-moderate (20%-40%) macrovesicular steatosis (P < .001) and cold ischemia time (P = .048) significantly increased the risk of ITBL, also as an independent risk factor after multivariate analysis.     

Steatosis of the Graft Is a Risk Factor for Posttransplantation Biliary Complications

Background

Despite recent advances in organ preservation, immunosuppression, and surgical techniques, the biliary tree is still considered the Achilles' heel of liver transplantation. The aim of this study was to retrospectively analyze the incidence of biliary complications and identify predisposing risk factors.

Methods

From January 2004 to December 2007, 117 consecutive deceased donor liver transplantations were retrospectively analyzed for the development of biliary complications by review of medical records. Patients were divided into group 1 with biliary complications (n = 43) and group 2 without biliary complications (n = 74).

Results

The overall biliary complication rate was 36.8%; leakage 6% and stricture 30.8%. Univariate analysis indicated that significant predictors of biliary complications were the time interval between portal and arterial reperfusion (P = .037) and macrovacuolar steatosis of the graft >25% (P = .004). A stepwise logistic regression model demonstrated that >25% macrosteatosis of the graft was the only independent risk factor predicting biliary complications after liver transplantation (odds ratio [OR] = 5.21; CI 95% [1.79-15.15]; P = .002). No differences were noted in patient or graft survival between the 2 groups.

Conclusion

Transplantation of a liver with >25% steatosis was a risk factor for the development of a biliary complication.     

Microvesicular Liver Graft Steatosis as a Risk Factor of Initial Poor Function in Relation to Suboptimal Donor Parameters

Objective

We sought to examine the role of microvesicular graft steatosis in relation to donor parameters.

Materials and Methods

We performed 269 consecutive orthotopic liver transplantations (OLT) between 2004 and 2006. Donor parameters of age, body mass index (BMI), intensive care unit (ICU) stay, hypotension, cardiac arrest, pressors, sodium concentration, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (GGT), bilirubin, and activated partial thromboplastin time (APTT), as well as the degree of microvesicular graft steatosis were collected into the study. The endpoint of the study was liver graft dysfunction (AST or ALT > 2500 IU/L or prothrombin index < 50% during the first 7 days after OLT).

Results

The risk of initial poor function (IPF) at day 7 posttransplantation was significantly related to hepatic microvesicular steatosis (odds ratio [OR] = 1.38 per 1 SD = 9.3%; P < .021). Accounting for the influence of the other donor factors produced little change in the numerical values of relative risk: from 1.22 (following exclusion of GGT) to 1.46 (after elimination of the influence of bilirubin concentration). A 50% increased risk of IPF was equivalent to 12% of the extent of steatosis.

Conclusion

Microvesicular steatosis is a risk factor for early hepatic dysfunction after OLT.     

Reversal of Graft Steatosis After Liver Transplantation: Prospective Study

Objective

To determine the risk factors for reversal of liver graft steatosis.

Patients and Methods

This prospective study included 70 patients (47 men and 23 women) who received steatotic liver grafts between July 2003 and February 2008. No grafts from prisoners were used in the study. Patients were divided into 3 groups according to degree of liver steatosis, as follows: mild (n = 29, group 1), moderate (n = 23, group 2), and severe (n = 18, group 3).

Results

The median (SD) degree of steatosis in liver grafts at transplantation was 15.7% (7.3%) in group 1, 26.3% (10.5%) in group 2, and 45.1% (8.3%) in group 3. Postoperative histologic analysis demonstrated dramatically decreased steatosis in all graft recipients.

Conclusion

Graft steatosis can be decreased substantially after liver transplantation. Factors for reversibility of steatosis include donor age, degree of macrovesicular steatosis, and cold ischemia time.     

Biological Changes After Liver Transplantation According to the Presence or Not of Graft Steatosis

Aim

To assess the consequences of graft steatosis on postoperative liver function as compared with normal liver grafts.

Patients and methods

From January 2005 to December 2007, liver transplant patients were prospectively included, excluding those who experienced arterial or biliary complications or presented acute rejection. All patients had a surgical biopsy after reperfusion. Patients were compared according to the rate of macrovacuolar steatosis: namely above or below 20%.

Results

Fifty-three patients were included: 10 in the steatosis group and 43 in the control group. No significant difference was observed in terms of morbidity, mortality, and primary non- or poor function. Nevertheless, biological changes after the procedure were significantly different during the first postoperative week. Prothrombin time, serum bilirubin, and transaminases were significantly increased among the steatosis group compared with the control group (P < .05).

Conclusion

This case-controlled study including a small number of patients, described postoperative biological changes among liver transplantations with steatosis in the graft.     

Intrahepatic Biliary Anatomy Derived From Right Graft Adult Live Donor Liver Transplantation

Objective

The successful management of the bile duct in right graft adult live donor liver transplantation requires knowledge of both its central (hilar) and distal (sectorial) anatomy. The purpose of this study was to provide a systematic classification of its branching patterns to enhance clinical decision-making.

Patients and Methods

We analyzed three-dimensional computed tomography (3-D CT) imaging reconstructions of 139 potential live liver donors evaluated at our institution between January 2003 and June 2007.

Results

Fifty-four (n = 54 or 38.8%) donor candidates had a normal (classic) hilar and sectorial right bile duct anatomy (type I). Seventy-eight (n = 78 or 56.1%) cases had either hilar or sectorial branching abnormalities (types II or III). Seven (n = 7 or 5.1%) livers had a mixed type (IV) of a rare and complex central and distal anatomy.

Conclusions

We believe that the classification proposed herein can aid in the better organization and categorization of the variants encountered within the right-sided intrahepatic biliary system.     

Chronic Immune-Mediated Reaction Syndrome as the Cause of Late Graft Mortality in Living-Donor Liver Transplantation for Primary Biliary Cirrhosis

Introduction

Few studies to date have investigated the causes of late graft mortality after living-donor liver transplantation (LDLT) for primary biliary cirrhosis (PBC).

Patients and Methods

Fifty-five LDLTs for PBC were retrospectively reviewed. Factors prognostic of graft survival after LDLT were investigated, and histologic findings in patients with late graft loss were assessed.

Results

The 1-, 5-, and 10-year cumulative graft survival rates were 85.1%, 82.5%, and 66.9%, respectively. Multivariate Cox regression analysis found that male donor and ≥4 HLA mismatches were independently associated with poor graft survival. Among the 13 grafts lost, 5 were lost >1 year after LDLT, including 1 each due to chronic rejection, veno-occlusive disease, and obliterative portal venopathy, and 2 to other causes. Pathologic reviews of the serial biopsy specimens and explanted grafts from these 5 patients, with graft rejections from “chronic immune-mediated reaction syndrome,” showed reciprocal changes over time. No patient died of recurrent PBC.

Conclusions

Male donor and ≥4 HLA mismatches were independent factors associated with poor graft survival. Late graft mortality after LDLT for PBC in some patients was due to chronic immune-mediated reaction syndrome, including chronic rejection, veno-occlusive disease, and obliterative portal venopathy, but not to recurrent PBC.     

Risk Factors Related to Early Biliary Complications After Liver Transplantation: a Single-Center Analysis

BackgroundThe aim of this study was to evaluate the risk factors of early biliary complications (EBC) after liver transplantation (LT) and seek effective treatments based on our single-center experience.MethodsA total of 124 adult patients were divided into a non-EBC group and EBC group. EBC usually accounts for biliary leakage, biliary stricture, biliary stones, sphincter of Oddi dysfunction, and transient jaundice within 3 months after LT. Statistical analysis including logistic regression was performed to determine EBC risk factors. All procedures complied with the Helsinki Congress and the Declaration of Istanbul.ResultsNon-EBC (n = 95) and EBC (n = 29) were finally compared, which had no difference in their general characteristics. EBC occurred in 29 patients (26.92%): 1 biliary hemorrhage (3.45%), 7 biliary leakage (24.13%), and 16 biliary stricture (55.18%), and 5 others (17.24%). Of all EBC patients, endoscopic retrograde cholangiopancreatography (68.96%) was higher used to deal with complications than conservative treatment (10.35%), percutaneous transhepatic cholangial drainage (17.24%), and surgical treatment (3.45%). On univariate analyses, risk factors for EBC were bilirubin (P = .014), warm ischemia time (WIT) (P = .020), second WIT (P = .042), and operative time (OT) (P = .033). On multivariate analysis, independent risk factors for BC were WIT (P = .011) and OT (P = .049).ConclusionsThe presence of WIT and OT were the independent risk factors for the development of EBC. In addition, we also confirmed that endoscopic retrograde cholangiopancreatography was beneficial and safe in the management of EBC after LT.     

Biliary Internal Stents and Biliary Complications in Adult Liver Transplantation

BackgroundBiliary complications in liver transplantation (LT) can cause significant morbidity or even lead to a potential graft loss and patient mortality. Oftentimes biliary internal stents (ISs) are used at the time of LT to lower the risk for or prevent these biliary complications; however, their efficacy and outcomes remain controversial.MethodsA retrospective cohort study was conducted on all of the adult patients who underwent a deceased-donor LT (DDLT) with an end-to-end choledococholedocostomy. An IS was placed across the biliary anastomosis, passing through the ampulla. We compared the demographic profiles and various outcomes between the 2 groups (no-IS group vs IS group) and examined risk factors associated with anastomotic biliary complications.ResultsThe study comprised 350 patients in the no-IS group and 132 patients in the IS group. Anastomotic biliary fistula (ABF) occurred in 5 (1.4%) and 1 (0.8%) patients in the no-IS group and the IS group, respectively (P = .55). Anastomotic biliary stricture (ABS) occurred in 53 (15.1%) and 18 (13.6%) patients, respectively (P = .68). No significant difference was found in the overall biliary complications between the 2 groups (P = .33). In multivariate logistic regression analysis, acute rejection was the only risk factor for ABS (P = .02). One biliary complication–induced mortality occurred in the no-IS group in which the patient died of an ABF-induced hepatic artery pseudoaneurysm rupture.ConclusionThe use of biliary ISs in DDLT did not reduce the overall risk for biliary complications, but more research is needed to draw definite conclusions.     

External Biliary Fistula in Orthotopic Liver Transplantation

During orthotopic liver transplantation (OLT), various situations may occur in which biliary reconstruction is neither technically feasible nor recommended. One bridge to a delayed anastomosis can be an external biliary fistula (EBF). This procedure allows the surgeon to execute hemostatic maneuvers, such as abdominal packing; therefore, biliary reconstruction can be subsequently performed in a bloodless operative field without edematous tissues. EBF can be made by placing in the donor biliary tract a cannula that is fixed to the bile duct using 2-0 silk ties and secured outside the abdominal wall. The biliary anastomosis will be performed within 2 days after the OLT. The aim of this study was to examine the safety of EBF in terms of the incidence of biliary complications compared with a direct anastomosis. Among 1634 adult OLTs performed in 17 years in our center, 1322 were carried out with termino-terminal hepaticocholedochostomy (HC-TT); two with side-to-side hepaticocholedochostomy; 208 with hepaticojejunostomy (HJ); 31 with EBF and delayed HC-TT, and 71 with EBF and delayed HJ. Biliary complication rates in the EBF group were 24.5%, including 23.9% in the delayed HJ and 25.8% in the delayed HC-TT. Biliary complication incidence among all OLTs was 24.6% (P = NS). No complications related to the procedure were observed. Therefore, EBF is a safe technique without a higher biliary complication rate. It may be useful when a direct biliary anastomosis is dangerous.     

Hepatic Hilar and Sectorial Vascular and Biliary Anatomy in Right Graft Adult Live Liver Donor Transplantation

Introduction

The aim of this study was to analyze vascular and biliary variants at the hilar and sectorial level in right graft adult living donor liver transplantation.

Methods

From January 2003 to June 2007, 139 consecutive live liver donors underwent three-dimensional computed tomography (3-D CT) reconstructions and virtual 3-D liver partitioning. We evaluated the portal (PV), arterial (HA), and biliary (BD) anatomy.

Results

The hilar and sectorial biliary/vascular anatomy was predominantly normal (70%-85% and 67%-78%, respectively). BD and HA showed an equal incidence (30%) of hilar anomalies. BD and PV had a nearly identical incidence of sectorial abnormalities (64.7% and 66.2%, respectively). The most frequent “single” anomaly was seen centrally in HA (21%) and distally in BD (18%). A “double” anomaly involved BD/HA (7.2%) in the hilum, and HA/PV and BD/PV (6.5% each) sectorially. A “triple” anomaly involving all systems was found at the hilum in 1.4% of cases, and at the sectorial level in 9.4% of instances. Simultanous central and distal abnormalities were rare. In this study, 13.7% of all donor candidates showed normal hilar and sectorial anatomy involving all 3 systems. A simultaneous central and distal “triple” abnormality was not encountered. A combination of “triple” hilar anomaly with “triple” sectorial normality was observed in 2 cases (1.4%). A central “triple” normality associated with a distal “triple” abnormality occurred in 7 livers (5%).

Conclusions

Our data showed a variety of “horizontal” (hilar or sectorial) and “vertical” (hilar and sectorial) vascular and biliary branching patterns, providing comprehensive assistance for surgical decision-making prior to right graft hepatectomy.     

Biliary Complications After Pediatric Liver Transplantation

ObjectivesAfter liver transplantation, biliary complications are more prevalent in pediatric patients, with reported rates varying between 15% and 30%.MethodsWe retrospectively analyzed biliary complications observed in 84 pediatric liver transplantation patients between July 2006 and September 2012. Biliary reconstruction was accomplished via a duct-to-duct anastomosis in 5 (83.3%) of the 6 patients receiving whole liver grafts and in 44 (56.4%) of the 78 patients who received a segmental live donor graft. For the remaining 34 patients with living donor and 1 patient with whole liver graft, Roux-en-Y hepaticojejunostomy was the preferred method.ResultsPost-transplantation biliary complications were encountered in 26 patients (30.1%). The biliary complication rate was 38% in 49 duct-to-duct anastomosis, whereas it was 20% in the hepaticojejunostomy group consisting of 35 recipients. Thirteen of the 18 biliary leaks were from duct-to-duct anastomoses and the remaining 5 were from the hepaticojejunostomies and 6 of the 8 biliary strictures were observed in recipients with duct-to-duct anastomosis. In 19 of the 26 patients, the biliary complications were successfully treated with interventional radiologic procedures and 1 was treated with stent placement during endoscopic retrograde cholangiopancreatography.ConclusionsPercutaneous interventional procedures are valuable, effective, and life-saving therapeutic alternatives for the treatment of bile leaks and strictures after pediatric liver transplantations.     

Living Donor Liver Transplantation with Left Liver Graft

Small-for-size syndrome in LDLT is associated with graft exposure to excessive portal perfusion. Prevention of graft overperfusion in LDLT can be achieved through intraoperative modulation of portal graft inflow. We report a successful LDLT utilising the left lobe with a GV/SLV of only 20%. A 43 year-old patient underwent to LDLT at our institution. During the anhepatic phase a porto-systemic shunt utilizing an interposition vein graft anastomosed between the right portal branch and the right hepatic vein was performed. After graft reperfusion splenectomy was also performed. Portal vein pressure, portal vein flow and hepatic artery flow were recorded. A decrease of portal vein pressure and flow was achieved, and the shunt was left in place. The recipient post-operative course was characterized by good graft function. Small-for-size syndrome by graft overperfusion can be successfully prevented by utilizing inflow modulation of the transplanted graft. This strategy can permit the use of left lobe in adult-to-adult living donor liver transplantation.     

Early Graft Dysfunction After Liver Transplantation

Liver transplantation has become the treatment of choice for fulminant hepatic failure and end-stage liver diseases. Several factors have been described to be predictors of graft function. Since early graft dysfunction dramatically influences graft and patient outcomes after liver transplantation, prevention of this event is mandatory. Donor-, procurement-, operative- and recipient-related factors influence the development of graft dysfunction. We have presented herein a review of the impact of these factors on graft dysfunction.     

Graft Loss After Pediatric Liver Transplantation

OBJECTIVE: To describe the epidemiology and causes of graft loss after pediatric liver transplantation and to identify risk factors. SUMMARY BACKGROUND DATA: Graft failure after transplantation remains an important problem. It results in patient death or retransplantation, resulting in lower survival rates. METHODS: A series of 157 transplantations in 120 children was analyzed. Graft loss was categorized as early (within 1 month) and late (after 1 month). Risk factors were identified by analyzing recipient, donor, and transplantation variables. RESULTS: Kaplan-Meier 1-month and 1-, 3-, and 5-year patient survival rates were 85%, 82%, 77%, and 71%, respectively. Graft survival rates were 71%, 64%, 59%, and 53%, respectively. Seventy-one of 157 grafts (45%) were lost: 18 (25%) by death of patients with functioning grafts and 53 (75%) by graft-related complications. Forty-five grafts (63%) were lost early after transplantation. Main causes of early loss were vascular complications, primary nonfunction, and patient death. Main cause of late graft loss was fibrosis/cirrhosis, mainly as a result of biliary complications or unknown causes. Child-Pugh score, anhepatic phase, and urgent transplantation were risk factors for early loss. Donor age, donor/recipient weight ratio, blood loss, and technical-variant liver grafts were risk factors for late loss. CONCLUSIONS: To prevent graft loss after pediatric liver transplantation, potential recipients should be referred early so they can be transplanted in an earlier phase of their disease. Technical-variant liver grafts are risk factors for graft survival. The logistics of the operation need to be optimized to minimize the length of the anhepatic phase.     

The Impact of Hepatitis C and Biliary Complications on Patient and Graft Survival Following Liver Transplantation

Recurrent hepatitis C (HCV) and biliary complications (BC) are major causes of post liver transplant morbidity and mortality. The impact of these complications may be additive or synergistic. We performed a retrospective cohort study to analyze the effects of HCV and BC on all patients transplanted at two institutions over 6 years. BC was defined by imaging findings in the setting of abnormal liver function tests that required intervention. The primary outcomes were graft and patient survival over a mean 3.4 years. 709 patients (619 deceased, 90 living donor) were included, 337 with HCV and 372 without. BC was diagnosed more frequently in patients with HCV, 26% versus 18% (p = 0.008). One-year and overall patient and graft survival were significantly lower in patients with HCV, but BC impacted only 1-year graft survival. The combination of BC and HCV had no additional impact on survival or fibrosis rates on 1-year protocol biopsies. Multivariate analysis revealed HCV (HR 2.1) and HCC (HR 1.9) to be independent predictors of mortality. Since BC are diagnosed more frequently in HCV patients and only affect early graft loss, it is likely that recurrent HCV rather than BC accounts for the majority of adverse graft outcomes.     

Risk Factors for and Clinical Course of Non-Anastomotic Biliary Strictures After Liver Transplantation

Non-anastomotic biliary stricture (NAS) formation is a major complication of liver transplantation. We prospectively determined the time to development of responsiveness to treatment, and clinical outcomes following NAS formation. In addition, an extensive analysis of the association of recipient, donor, and clinical variables with NAS formation was performed. A total of 749 consecutive patients was studied in a prospective, protocol-based fashion. Seventy-two patients (9.6%) developed NAS at a mean of 23.6 +/- 34.2 weeks post-transplantation. Non-anastomotic biliary stricture formation resolved in only 6% of affected patients. Although patient survival was not affected, retransplantation and graft loss rates were significantly greater in recipients who developed NAS. In contrast to previous reports, a pretransplant diagnosis of HCV was associated with a low frequency of NAS formation. The incidence of NAS was independently associated with pretransplant diagnoses of PSC and autoimmune hepatitis. Hepatic artery thrombosis, and prolonged warm and cold ischemia times were also independent risk factors for NAS formation. We conclude that NAS developed in approximately 10% of primary liver transplant recipients. A pretransplant diagnosis of autoimmune hepatitis has been identified as a novel independent risk factor for NAS formation. Development of NAS significantly attenuates graft but not patient survival.