Humberto Bohorquez

Thrombolytic protocol minimizes ischemic‐type biliary complications in liver transplantation from donation after circulatory death donors

Liver transplantation (LT) with donation after circulatory death (DCD) donors has been associated with a high rate of ischemic‐type biliary strictures (ITBSs) and inferior graft survival. To investigate the impact of an intraoperative tissue plasminogen activator (tPA) on outcomes following DCD LT, we conducted a retrospective analysis of DCD LT at the Toronto General Hospital (TGH) and the Ochsner Medical Center (OMC). Between 2009 and 2013, 85 DCD LTs were performed with an intraoperative tPA injection (n = 30 at TGH, n = 55 at OMC), and they were compared with 33 DCD LTs without a tPA. Donor and recipient characteristics were similar in the 2 groups. There was no significant difference in the intraoperative packed red blood cell transfusion requirement (3.2 ± 3.4 versus 3.1 ± 2.3 U, P = 0.74). Overall, biliary strictures occurred less commonly in the tPA‐treated group (16.5% versus 33.3%, P = 0.07) with a much lower rate of diffuse intrahepatic strictures (3.5% versus 21.2%, P = 0.005). After 1 and 3 years, the tPA group versus the non‐tPA group had superior patient survival (97.6% versus 87.0% and 92.7% versus 79.7%, P = 0.016) and graft survival (96.4% versus 69.7% and 90.2% versus 63.6%, P < 0.001). In conclusion, a tPA injection into the hepatic artery during DCD LT reduces ITBSs and improves graft and patient survival without increasing the risk for bleeding. Liver Transpl 21:321–328, 2015.

Early subclinical coronary artery calcification in young adults who were pediatric kidney transplant recipients

Coronary artery disease (CAD) is the leading cause of death in adults after successful kidney transplantation. Children who have undergone successful kidney transplantation are entering young adulthood; however, the prevalence and extent of CAD in this population is unknown. We conducted a pilot study in young adults with stable allograft function, who received kidney transplants as children to measure coronary artery calcification (CAC), a marker of coronary artery atherosclerosis and CAD. We evaluated 19 young adults after successful pediatric kidney transplantation for known CAD risk factors; these patients underwent noninvasive imaging with electron‐beam computed tomography (EBCT) for measurement of CAC. Prevalence and quantity of CAC were then compared to asymptomatic individuals from the community. All patients had multiple risk factors for CAD. Mean age at evaluation was 32 years (range: 21–48 years). CAC is uncommon in individuals in the community in this age range; however, nearly half of our patients had CAC detected with the quantity of CAC comparable to asymptomatic individuals from the community 10–40 years older. These data suggest young adults who received pediatric kidney transplants are at increased risk for developing early CAC and need close monitoring to detect early CAD so as to prevent premature cardiac morbidity and mortality.

Liver transplantation in hepatitis B core–negative recipients using livers from hepatitis B core–positive donors: A 13‐year experience

The use of livers from hepatitis B surface antigen–negative (HBsAg−)/hepatitis B core antibody–positive (HBcAb+) donors in liver transplantation (LT) for HBsAg−/HBcAb− recipients is still controversial because of a lack of standard antiviral prophylaxis and long‐term follow‐up. We present our 13‐year experience with the use of HBcAb+ donor livers in HBcAb− recipients. Patients received prophylaxis with hepatitis B immunoglobulin at the time of LT and then lamivudine daily. De novo hepatitis B virus (HBV) was defined as positive HBV DNA detection. Between January 1999 and December 2010, 1013 adult LT procedures were performed at our center. Sixty‐four HBsAg−/HBcAb− patients (6.3%) received an HBsAg−/HBcAb+ liver. All donor sera were negative for HBcAb immunoglobulin M and HBV DNA. The mean follow‐up was 48.8 ± 40.1 months (range = 1.2‐148.8). Both the patient survival rates and the graft survival rates were 92.2% and 69.2% at 1 and 5 years, respectively. No graft losses or deaths were related to de novo HBV. Nine of the 64 patients (14.1%) developed de novo HBV. The mean time from LT to de novo HBV was 21.4 ± 26.1 months (range = 10.8‐92.8 months). De novo HBV was successfully treated with adefovir or tenofovir. In conclusion, HBcAb+ allografts can be safely used in HBcAb− recipients without increased mortality or graft loss. Lifelong prophylaxis, continuous surveillance, and compliance are imperative for success. Should a de novo infection occur, our experience suggests that a variety of treatments can be employed to salvage the graft and obtain serum HBV DNA clearance. Liver Transpl 19:611–618, 2013.

Weighing the risk: Obesity and outcomes following liver transplantation.

Obesity is on the rise worldwide. As a result, unprecedented rates of patients are presenting with end stage liver disease in the setting of non-alcoholic fatty liver disease (NAFLD) and are requiring liver transplantation. There are significant concerns that the risk factors associated with obesity and the metabolic syndrome might have a detrimental effect on the long term outcomes following liver transplantation. In general, short term patient and graft outcomes for both obese and morbidly obese patients are comparable with that of non-obese patients, however, several studies report an increase in peri-operative morbidity and increased length of stay. Continued studies documenting the long-term outcomes from liver transplantation are needed to further examine the risk of recurrent disease (NAFLD) and also further define the role risk factors such cardiovascular disease might play long term. Effective weight reduction in the post liver transplant setting may mitigate the risks associated with the metabolic syndrome long-term.

Safety and Outcomes in 100 Consecutive Donation After Circulatory Death Liver Transplants Using a Protocol That Includes Thrombolytic Therapy

Donation after circulatory death (DCD) liver transplantation (LT) reportedly yields inferior survival and increased complication rates compared with donation after brain death (DBD). We compare 100 consecutive DCD LT using a protocol that includes thrombolytic therapy (late DCD group) to an historical DCD group (early DCD group n = 38) and a cohort of DBD LT recipients (DBD group n = 435). Late DCD LT recipients had better 1‐ and 3‐year graft survival rates than early DCD LT recipients (92% vs. 76.3%, p = 0.03 and 91.4% vs. 73.7%, p = 0.01). Late DCD graft survival rates were comparable to those of the DBD group (92% vs. 93.3%, p = 0.24 and 91.4% vs. 88.2%, p = 0.62). Re‐transplantation occurred in 18.4% versus 1% for the early and late DCD groups, respectively (p = 0.001). Patient survival was similar in all three groups. Ischemic‐type biliary lesions (ITBL) occurred in 5%, 3%, and 0.2% for early DCD, late DCD, and DBD groups, respectively, but unlike in the early DCD group, in the late DCD group ITBL was endoscopically managed and resolved in each case. Using a protocol that includes a thrombolytic therapy, DCD LT yielded patient and graft survival rates comparable to DBD LT.

Epsilon-Aminocaproic Acid Has No Association With Thromboembolic Complications, Renal Failure, or Mortality After Liver Transplantation.

OBJECTIVES To examine the role of epsilon-aminocaproic acid (EACA) administered after reperfusion of the donor liver in the incidences of thromboembolic events and acute kidney injury within 30 days after orthotopic liver transplantation. One-year survival rates between the EACA-treated and EACA-nontreated groups also were examined. DESIGN Retrospective, observational, cohort study design. SETTING Single-center, university hospital. PARTICIPANTS The study included 708 adult liver transplantations performed from 2008 to 2013. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS EACA administration was not associated with incidences of intracardiac thrombosis/pulmonary embolism (1.3%) or intraoperative death (0.6%). Logistic regression (n = 708) revealed 2 independent risk factors associated with myocardial ischemia (age and pre-transplant vasopressor use) and 8 risk factors associated with the need for post-transplant dialysis (age, female sex, redo orthotopic liver transplantation, preoperative sodium level, pre-transplant acute kidney injury or dialysis, platelet transfusion, and re-exploration within the first week after transplant); EACA was not identified as a risk factor for either outcome. One-year survival rates were similar between groups: 92% in EACA-treated group versus 93% in the EACA-nontreated group. CONCLUSIONS The antifibrinolytic, EACA, was not associated with an increased incidence of thromboembolic complications or postoperative acute kidney injury, and it did not alter 1-year survival after liver transplantation.

Thromboprophylaxis With Heparin During Orthotopic Liver Transplantation: Comparison of Hepcon HMS Plus and Anti-Xa Assays for Low-Range Heparin

OBJECTIVES The purpose of this study was to compare the agreement between two heparin assays, Hepcon HMS plus/Kaolin-ACT and Anti-Xa, and their predictive power in detecting circulating heparin levels post-reperfusion of the liver graft when compared with thromboelastogram (TEG) r time ratio in patients undergoing orthotopic liver transplantation (OLT). DESIGN Prospective, observational cohort study design. SETTING Single center, university hospital. PARTICIPANTS Thirty-eight consecutive adults who had undergone liver transplant. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Paired arterial blood samples were collected before surgical incision, 5 minutes after administration of an average dose of 2,054±771 units of intravenous unfractionated heparin before caval cross-clamping, 5 minutes after portal reperfusion, 5 minutes after hepatic artery reperfusion, and 1 hour after hepatic artery reperfusion. The observations that heparin assay measurements were within the predetermined limits of agreement, strongly suggested the two heparin assays (Hepcon HMS plus and Anti-Xa assay) are interchangeable during prophylactic heparin dose therapy during OLT. Post-reperfusion, receiver operating characteristic curve analysis revealed high accuracy in measuring circulating heparin levels with both Anti-Xa and Hepcon HMS assays when compared with the TEG r time ratio assay. CONCLUSIONS The point-of-care Hepcon HMS plus/Kaolin-ACT (activated clotting time) assay appeared to be a reliable alternative to the more expensive and laboratory-required Anti-Xa assay in monitoring the response to intravenous heparin in patients undergoing OLT.

Elevated Lung Shunt Fraction as a Prognostic Indicator for Disease Progression and Metastasis in Hepatocellular Carcinoma

PURPOSE To evaluate lung shunt fraction (LSF) as an early predictor for local disease progression or the development of metastatic disease. MATERIALS AND METHODS Retrospective analysis was performed on 52 patients with hepatocellular carcinoma who underwent preradioembolization assessment, including the calculation of LSF. Comparison of preprocedural and postprocedural surveillance imaging was performed. Mean patient age was 67 years (range, 50-88 y), with a mean surveillance of 245 days (range, 24-871 d). Statistical analysis was conducted to assess the relationship between LSF and local disease progression or development of new metastatic disease. RESULTS In patients in whom metastatic disease developed during routine surveillance, the mean LSF was almost double that in patients in whom no metastasis developed (18.3% vs 9.3%; P = .001). Patients with elevated LSFs were also more likely to show intrahepatic disease progression (15.6% vs 8.5%; P = .003). LSFs < 8% corresponded to negative predictive values of 74% for local disease progression and 95% for development of metastasis, signaling a better prognosis. Of pretreatment variables examined (age, sex, previous treatment with disease progression, lesion size, lesion number, LSF, α-fetoprotein level, and portal vein thrombus), only LSF was an independent predictor for new metastasis (odds ratio [OR] = 1.2; P = .01). LSF (OR = 1.2; P = .03) and progression after previous treatment (OR = 4.7; P = .04) were independent predictors for local progression. CONCLUSIONS As local disease progression and metastatic disease were more likely to occur in patients with elevated LSFs, LSF may be the most sensitive predictor for local disease progression and new metastatic disease.

Novel Biliary Reconstruction Techniques During Liver Transplantation

Biliary complications remain a significant problem following liver transplantation. Several surgical options can be used to deal with a significant size mismatch between the donor and recipient bile ducts during the biliary anastomosis. We compared biliary transposition to recipient biliary ductoplasty in cadaveric liver transplant. A total of 33 reconstructions were performed from January 1, 2005 to December 31, 2013. In the biliary transposition group (n=23), 5 reconstructions were performed using an internal stent (5 or 8 French pediatric feeding tube), and 18 were performed without. Of the 10 biliary ductoplasties, 2 were performed with a stent. All patients were managed with standard immunosuppression and ursodiol. Follow-up ranged from 2 months to 5 years. No patients in the biliary transposition group required reoperation; 1 patient had an internal stent removed for recurrent unexplained leukocytosis, and 2 patients required endoscopic retrograde cholangiography and stent placement for evidence of stricture. Three anastomotic leaks occurred in the biliary ductoplasty group, and 2 patients in the biliary ductoplasty group required reoperation for biliary complications. Our results indicate that biliary reconstruction can be performed with either biliary transposition or biliary ductoplasty. These techniques are particularly useful when a significant mismatch in diameter exists between the donor and recipient bile ducts.

Liver transplantation and the management of progressive familial intrahepatic cholestasis in children

Progressive familial intrahepatic cholestasis (PFIC) is a constellation of inherited disorders that result in the impairment of bile flow through the liver that predominantly affects children. The accumulation of bile results in progressive liver damage, and if left untreated leads to end stage liver disease and death. Patients often present with worsening jaundice and pruritis within the first few years of life. Many of these patients will progress to end stage liver disease and require liver transplantation. The role and timing of liver transplantation still remains debated especially in the management of PFIC1. In those patients who are appropriately selected, liver transplantation offers an excellent survival benefit. Appropriate timing and selection of patients for liver transplantation will be discussed, and the short and long term management of patients post liver transplantation will also be described.