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.     

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.     

Metabolic Alkalosis After Orthotopic Liver Transplantation

To ascertain the etiology of metabolic alkalosis (MA) following orthotopic liver transplantation (OLT) the records of patients with 123 consecutive OLTs from 1995 to 2000 were reviewed. Metabolic alkalosis occurred in 51.2% of patients. Patients with MA had a larger fluid deficit (-3991 +/- 4324 vs. -1018 +/- 4863, p < 0.05), cumulative furosemide dose (406 +/- 356 vs. 243 +/- 189, p < 0.02), and citrate load from blood transfusions (9164 +/- 4870 vs. 7809 +/- 3967, p < 0.05). There was no difference in serum lactate concentration (3.15 +/- 1.63 vs. 3.11 +/- 1.91) in patients with and without MA. The duration of ICU stay was longer in patients with MA (14.9 +/- 15.3 vs. 5.3 +/- 3.9 days, p < 0.004). Treatment of severe MA in 19 (15.4%) patients consisted of 0.1 N hydrochloric acid and/or acetazolamide. Hypokalemia and hypomagnesemia occurred in 37.4% and 59.3% of patients, respectively. In conclusion, MA is a common post-OLT complication that is associated with a longer ICU stay. Diuretic-induced volume depletion, the citrate load from blood transfusions, hypokalemia, and hypomagnesemia contribute to the pathogenesis of MA in OLT.     

Prevalence of the Metabolic Syndrome in Kidney Transplantation

Objectives

We investigated the prevalence of the metabolic syndrome (MS) in kidney transplantation patients and assessed its development based on plasma adiponectin levels and the results of an oral glucose tolerance test (OGTT).

Methods

We performed a cross-sectional study of 94 recipients with stable graft function who underwent kidney transplantation between January 1999 and October 2008. The presence of MS was determined using National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria with body mass index (BMI) used in place of waist circumference. In addition, we measured plasma adiponectin level and performed a 75-g oral GTT.

Results

Fourteen (14.9 %) recipients suffered from MS for a mean period of 46.7 months (range, 1-106) after transplantation. BMI at the time of transplantation was significantly greater in the MS group (23.4 ± 3.24 vs 20.1 ± 2.50; P < .0001), whereas plasma adiponectin level was significantly lower (11.95 ± 5.13 vs 17.71 ± 8.47; P = .0158). The insulinogenic index values were similar, whereas the homeostatic model assessment of insulin resistance was greater in the MS group (2.598 ± 1.918 vs 1.340 ± 0.934; P = .0002).

Conclusion

The level of adiponectin, which was lower in kidney transplant recipients who developed MS, was negatively correlated with insulin sensitivity. We concluded that a low adiponectin level may correlate with the prevalence of MS in kidney transplantation in association with impaired insulin sensitivity.     

Acute Kidney Injury After Pediatric Liver Transplantation

BackgroundThe aim of the present study is to assess acute kidney injury (AKI) incidence according to the pRIFLE and AKIN criteria and to evaluate the risk factors for early developing AKI in postoperative intensive care unit after pediatric liver transplantation (LT).MaterialsAfter exclusion of retransplantations, 7 cadaveric and 44 living donors, totaling 51 pediatric LT patients that were performed between 2005 and 2017, were reviewed retrospectively. AKI was defined according to both pediatric RIFLE (Risk for renal dysfunction, Injury to the kidney, Failure of kidney function, Loss of kidney function, and End-stage renal disease) and Acute Kidney Injury Network (AKIN) criteria. Documented data were compared between AKI and non-AKI patients.ResultsAKI incidences were 17.6% by AKIN and 37.8% by pRIFLE criteria. AKIN-defined AKI group had statistically lower serum albumin level, higher serum sodium level, higher furosemide dose, and higher rate of red blood cell (RBC) transfusion than the non-AKI group (P = .02, P = .02, P = .01 and P = .04, respectively). AKI patients had significantly prolonged mechanical ventilation (P = .01) and hospital LOS (P = .02). The pRIFLE-defined AKI group had significantly lower serum albumin level, higher blood urea nitrogen (BUN) level, and higher ascites drained and also showed higher requirement for RBC and 20% human albumin transfusions than the non-AKI group (P = .02, P = .04, P: =.007, P = .02 and P = .05, respectively).ConclusionWe evaluated that hypoalbuminemia, high requirement for RBC and 20% human albumin transfusions, high serum sodium, high furosemide use, and high flow of ascites are risk factors for AKI and high BUN levels can be predictive for AKI in pediatric LT patients. The effect of AKI on outcome variables were prolonged mechanical ventilation and hospital LOS.     

Hepatopulmonary Syndrome: Morbidity and Survival After Liver Transplantation

Hepatopulmonary Syndrome (HPS) is a triad of liver disease, intrapulmonary vascular dilatation (IPVD), and arterial deoxygenation. Orthotopic liver transplantation (OLT) constitutes the only effective treatment; however, adverse outcomes have been reported. The aim of this study was to evaluate the early morbidity and short- and long-term survival after OLT for patients with and without HPS. We studied 59 transplant recipients divided into 2 groups: with HPS (HPS group n = 25) and without HPS (control group, n = 34) before the OLT. IPVD was diagnosed using transthoracic contrast-enhanced echocardiography. Arterial deoxygenation was defined as PA-a,O₂ ≥ 15 mm Hg. The HPS and control groups were homogeneous regarding age (P = .36; 43.8 ± 12.2 vs 46.9 ± 13.5), gender (P = .47), male/female ratio (68%:32% and 78%:22%, respectively), and severity of liver disease. The PaO₂ was significantly lower (74.9 ± 12.1 vs 93 ± 6.4 mm Hg; P < .001) and the PA-a,O₂ was significantly higher in the HPS group (30.3 ± 10.6 vs 11.0 ± 7.0; P < .001). The percentage of severe (n = 3) and very severe (n = 1) hypoxemia was 16%. There were no significant differences between HPS and control groups regarding short- (68% vs 77%; P = .27) and long-term survival (60% vs 64%; P = .67) as well as among patients with mild, moderate, severe, or very severe HPS and the control group (P = .53). Also, intensive care unit (ICU) stay (7.0 vs 5.5; P = .41), duration of mechanical ventilation (38.0 vs 27.5; P = .43), reintubation rate (32.0% vs 23.5%; P = .45), and early postoperative complications (P = .72) were not different. In conclusion, there were no significant differences regarding the outcomes of OLT for patients with versus without HPS related to early morbidity or short- and long-term survival.     

Iron Overload After Pediatric Liver Transplantation: A Case Report

Iron is an essential nutrient for living cells; however, an excessive accumulation of iron leads to organ damage and directly affects systemic immunity. Iron overload is clinically classified as hereditary or secondary. Most of secondary iron overload is caused by frequent blood transfusions because there is no active mechanism to excrete iron from the body. As recommended in various guidelines, chelation therapy is effective for reducing iron burden and improving organ function. There have been few reports on iron overload through blood transfusion during the perioperative period of liver transplantation. This report presents a case of iron overload due to repeated transfusions after pediatric liver transplantation managed by chelation therapy. The patient, an 11-month-old female with biliary atresia, underwent living donor liver transplantation. She revealed refractory anemia and required frequent blood transfusion. Both serum ferritin and transferrin saturation tended to increase after repeated transfusions, leading to secondary iron overload. Iron chelation therapy was started to prevent progression to organ failure and infection due to iron overload, and yielded a favorable outcome. It is crucial to consider the possibility of secondary iron overload and to achieve early detection and treatment to avoid progression to irreversible organ damage.     

Impact of Liver Ex Situ Transection on Pediatric Liver Transplantation

Ex situ hepatic transection (ESHT) has allowed transplantation of younger and smaller patients than whole liver grafts. Liver transection is a technical challenge due to the prolonged back table time, possible graft lesions, and increased surgical bleeding from the cut surface. We compare the outcomes of whole versus transected liver grafts in pediatric liver transplantation.

Methods

We retrospectively studied 41 pediatric patients who underwent 42 consecutive liver transplants (1 retransplant) from cadaveric donors. The study included all patients <18 years old who were transplanted at our institution from December 2001 to September 2009. Patients were distributed into 2 groups: whole organ (WO; n = 20) and transected liver grafts (TLG; n = 21). The ESHT grafts included 17 splits and 5 reduced size livers. We evaluated the age, weight, blood component transfusions, 1-year survival, laboratory tests at 2nd and 7th days postoperatively, surgical complications, reoperations, rejection episodes, cold ischemia time, biliary reconstruction type, and donor laboratory tests. Data were analyzed using Fisher and Student's t-tests.

Results

The mean age was 115 months (range, 7 months to 17.6 years) in the WO group and 43.3 months (range, 5 months to 16.25 years) in the TLG group (P = .0003). Mean weight was 19.8 kg (range, 5.8-67) and 9.7 Kg (range, 5.2-57) in the WO and TLG groups, respectively (P = .0079). Red blood cell transfusion was higher in the TLG group (P = .0479). Laboratory tests showed no difference between the 2 groups considering hepatic lesions or function markers. One-year patient survivals were 90% and 85.8% among the WO and LTG, respectively (P = .588). The overall 1-year survival rate was 88.8%.

Conclusion

ESHT allowed smaller and younger children to be transplanted. There was an increased necessity of red blood cell transfusions after hepatic transection. There was no impact on liver function or 1-year patient or graft survival after ESHT.     

Risk Factors of Cytomegalovirus Infection After Pediatric Liver Transplantation

PurposeCytomegalovirus (CMV) infection is known to be the most frequently viral infection among patients after liver transplantation. This is especially true in pediatric living-donor liver transplantation because the recipients have often not been infected with CMV and postoperative primary infection with CMV frequently occurs.Patients and MethodsOf 93 patients who underwent pediatric liver transplantation at our department, 33 patients (36.3%) were diagnosed with CMV infection using the antigenemia method (C7-HRP). Retrospective review and statistical analysis were conducted to confirm risk factors of post-transplantation CMV infection.ResultPositive lymphocytes were diagnosed between postoperative days 8 and 111 after transplantation. Ganciclovir or foscavir were administrated to 21 patients. The other 10 patients who had one positive lymphocyte were observed and the cell disappeared on follow-up examination. We did not observe any cases of positive lymphocytes with C7-HRP in patients who received a graft from a CMV antibody?negative donor. Independent predictors associated with CMV infection in the multivariable analysis were administration of OKT3 and grafts from CMV antibody?positive donors.ConclusionIn CMV infection after pediatric liver transplantation, cases with CMV antibody?positive donors and with OKT3 administration for acute rejection are considered high risk, and cases with CMV antibody?negative donors are considered low risk.     

Steroid-Free Immunosuppression After Liver Transplantation Does Not Increase the Risk of Graft Fibrosis

Background

Steroid-free immunosuppression after liver transplantation (OLT) is effective and safe in the short and mid terms. However, research has shown a higher risk for late fibrosis among pediatric liver transplant recipients who have steroids withdrawn. Our aim was to test this hypothesis in the adult population.

Patients and Methods

The study involved 27 adults, 14 of whom were on a regimen of cyclosporine, azathioprine, and steroid (group A) and 13 cyclosporine and azathioprine steroid-free immunosuppression (group B). The main end point of the study was liver graft histology in the late stage after OLT, with emphasis on the evolution of fibrosis, which was scored according to Ishak. The secondary end points were patient and graft survivals, liver and kidney functions, rejection rates, infections, and tumors, as well as the incidences of cardiovascular and metabolic complications.

Results

After a mean follow-up of 89.3 ± 21 months, the mean fibrosis scores did not differ between the 2 groups (2.2 ± 1.5 vs 1.9 ± 1.2; P = NS). One group A patient developed a severe acute rejection episode. The 7-year patient and graft survivals, as well as liver and kidney functions, incidence of infections, and cardiovascular and metabolic complications were comparable. Patients receiving steroids showed a trend toward an higher rate of de novo malignancies.

Conclusion

Steroid-free immunosuppression did not increase the risk of graft fibrosis in the long term.     

Fulminant Liver Failure After Vancomycin in a Sulfasalazine-Induced DRESS Syndrome: Fatal Recurrence After Liver Transplantation

DRESS syndrome (drug rash with eosinophilia and systemic symptoms) is a rare drug hypersensitivity reaction with a significant mortality. We describe a 60-year-old man with polyarthritis treated with sulfasalazine who developed DRESS and fulminant liver failure after additional vancomycin treatment. Liver histology revealed infiltration of granzymeB+ CD3+ lymphocytes in close proximity to apoptotic hepatocytes. After a superurgent liver transplantation and initial recovery, the patient developed recurrent generalized exanthema and eosinophilia, but only moderate hepatitis. Histology showed infiltration of FasL+ lymphocytes and eosinophils in the transplanted liver. Treatment with high-dose methylprednisolone was unsuccessful. Postmortem examination revealed extensive necrosis of the liver transplant. This case report illustrates that patients with DRESS may develop fulminant liver failure and that DRESS recurrence can recur in the transplanted liver. Histological and immunological investigations suggest an important role of granzymeB and FasL mediated cell death in DRESS associated hepatitis.     

Influence of Graft Type on Outcomes After Pediatric Liver Transplantation

We sought to determine which type of donor graft provides children and young adults with the best outcomes following liver transplantation. Using the US Scientific Registry of Transplant Recipients database, we identified 6467 recipients of first liver transplants during 1989-2000 aged < 30 years. We used Cox models to examine adjusted patient and graft outcomes by age (< 2, 2-10, 11-16, 17-29) and donor graft type (deceased donor full size (DD-F), split (DD-S), living donor (LD)]. For patients aged < 2, LD grafts had a significantly lower risk of graft failure than DD-S (RR = 0.49, p < 0.0001) and DD-F (RR = 0.70, p = 0.02) and lower mortality risk than DD-S (RR = 0.71, p = 0.08) during the first year post-transplant. In contrast, older children exhibited a higher risk of graft loss and a trend toward higher mortality associated with LD transplants. In young adults, DD-S transplants were associated with poor outcomes. Three-year follow up yielded similar graft survival results but no significant differences in mortality risk by graft type within age group. For recipients aged < 2, LD transplants provide superior graft survival than DD-F or DD-S and trend toward better patient survival than DD-S. Living donor is the preferred donor source in the most common pediatric age group (< 2 years) undergoing liver transplantation.     

Abdominal Compartment Syndrome Associated With Capillary Leak Syndrome After Liver Transplantation

Orthotopic liver transplantation was performed in a 49-year-old man with metastatic liver sarcoma. After surgery, both abdominal compartment syndrome (ACS) and capillary leak syndrome (CLS) developed. Exploratory laparotomy and colon exteriorization were performed. Five days later, a diagnosis of severe CLS was established, and hydroxyethyl starch was infused to prevent leakage of albumin. The patient gradually recovered over 3 weeks. Awareness of ACS and CLS is important to improve outcome because early diagnosis and immediate therapy are essential. Bladder pressure is a key factor in diagnosing ACS, and pressure of 35 mm Hg is an indication for decompressive laparotomy. During the early stage of CLS, hydroxyethyl starch but not albumin should be used to alleviate edema and hypoalbuminemia.     

Psychological Functioning, Nonadherence and Health Outcomes After Pediatric Liver Transplantation

The present study empirically assessed the relationships between adherence behaviors and HRQOL, parent and child psychological functioning and family functioning, and investigated the relationship between adherence behaviors and health outcomes in children who were within 5 years of their liver transplantation. Participants included 38 children (mean = 8.5 years, range 28 months to 16 years) and their parent/guardian(s). HRQOL and psychological functioning were examined using well-validated assessment measures. Measures of adherence included the rate of clinic attendance and standard deviations (SDs) of consecutive tacrolimus blood levels, which were collected and evaluated retrospectively. Measures of child health status included the frequency of hospital admissions, liver biopsies, episodes of rejection and graft function for the year prior to study participation. Results indicated that nonadherence was related to lower physical HRQOL, more limitations in social and school activities related to emotional and behavioral problems, parental emotional distress and decreased family cohesion. Nonadherence was also related to frequency and duration of hospitalizations, liver biopsies and rejection episodes. These results suggest that empirically based assessment of HRQOL, parenting stress and family functioning may help identify patients at risk for nonadherence, and may allow for the need-based delivery of appropriate clinical interventions.     

Prevention of the Osmotic Demyelination Syndrome After Liver Transplantation: A Multidisciplinary Perspective

The osmotic demyelination syndrome (ODS) is a serious neurologic condition that occurs in the setting of rapid correction of hyponatremia. It presents with protean manifestations, from encephalopathy to the “locked‐in” syndrome. ODS can complicate liver transplantation (LT), and its incidence may increase with the inclusion of serum sodium as a factor in the Mayo End‐Stage Liver Disease score. A comprehensive understanding of risk factors for the development of ODS in the setting of LT, along with recommendations to mitigate the risk of ODS, are necessary. The literature to date on ODS in the setting of LT was reviewed. Major risk factors for the development of ODS include severe pretransplant hyponatremia (serum sodium [SNa] < 125 mEq/L), the magnitude of change in SNa pre‐ versus posttransplant, higher positive intraoperative fluid balance, and the presence of postoperative hemorrhagic complications. Strategies to reduce the risk of ODS include correcting hyponatremia pretransplant via fluid restriction and/or ensuring an appropriate rate of increase from the preoperative SNa via close attention to fluid and electrolyte management both during and after surgery. Multidisciplinary management involving transplant hepatology, nephrology, neurology, surgery, and anesthesiology/critical care is key to performing LT safely in patients with hyponatremia.     

Living Donor Liver Transplantation for Pediatric Patients with Inheritable Metabolic Disorders

Forty-six pediatric patients who underwent living donor liver transplantation (LDLT) using parental liver grafts for inheritable metabolic disorders (IMD) were evaluated to determine the outcomes of the surgery, decisive factors for post-transplant patient survival and the impact of using donors who were heterozygous for the particular disorder. Disorders included Wilson disease (WD, n = 21), ornithine transcarbamylase deficiency (OTCD, n = 6), tyrosinemia type I (TTI, n = 6), glycogen storage disease (GSD, n = 4), propionic acidemia (PPA, n = 3), methylmalonic acidemia (MMA, n = 2), Crigler-Najjar syndrome type I (CNSI, n = 2), bile acid synthetic defect (BASD, n = 1) and erythropoietic protoporphyria (EPP, n = 1). The post-transplant cumulative patient survival rates were 86.8 and 81.2% at 1 and 5 years, respectively. Post-transplant patient survival and recovery of the growth retardation were significantly better in the liver-oriented diseases (WD, OTCD, TTI, CNSI and BASD) than in the non-liver-oriented diseases (GSD, PPA, MMA and EPP) and pre-transplant growth retardation disadvantageously affected post-transplant outcomes. Although 40 of 46 donors were considered heterozygous for each disorder, neither mortality nor morbidity related to the heterozygosis has been observed. LDLT using parental donors can be recommended as an effective treatment for pediatric patients with IMD. In the non-liver-oriented diseases, however, satisfactory outcomes were not obtained by hepatic replacement alone.