Posterior reversible encephalopathy syndrome after liver transplantation in children: A rare complication related to calcineurin inhibitor effects

PRES is a neuroclinical and radiological syndrome that results from treatment with calcineurin inhibitor immunosuppressives. Severe hypertension is commonly present, but some patients may be normotensive. We report herein two children who received liver transplants, as treatment for biliary atresia in the first case and for Alagille`s syndrome in the second one. In the early postoperative, both patients presented hypertension and seizures. In both cases, the image findings suggested the diagnosis of PRES. The CT scan showed alterations in the posterior area of the brain, and brain MRI demonstrated parietal and occipital areas of high signal intensity. Both children were treated by switching the immunosuppressive regimen and controlling arterial blood pressure. They displayed full recuperation without any neurologic sequelae. Probably, the pathophysiology of PRES results from sparse sympathetic innervation of the vertebrobasilar circulation, which is responsible for supplying blood to the posterior areas of the brain. In conclusion, all liver-transplanted children who present with neurological symptoms PRES should be considered in the differential diagnosis, although this is a rare complication. As treatment, we recommend rigorous control of arterial blood pressure and switching the immunosuppressive regimen.

Living Related Donor Liver Transplantation in Children

Objective. The objective of this study was to report our experience with pediatric orthotopic liver transplantation (OLT) with living related donors. Methods. We performed a retrospective chart analysis of 121 living related donor liver transplantations (LRDLT) from June 1998 to June 2010. Results. Indications were biliary atresia (BA; n = 81), primary sclerosing cholangitis (n = 5), alpha-1 antitrypsin deficiency (n = 4); cholestasis (n = 9), fulminant hepatic failure (n = 8), autoimmune hepatitis (n = 2), Alagille syndrome (n = 4), hepatoblastoma (n = 3), tyrosinemia (n = 2), and congenital hepatic fibrosis (n = 3). The age of the recipients ranged from 7-174 months (median, 22) and the weights ranged from 6-58 kg (median, 10). Forty-nine children (40.5%) weighed <= 10 kg. The grafts included the left lateral segment (n = 108), the left lobe (n = 12), and the right lobe (n = 1). The donors included 71 mothers, 45 fathers, 2 uncles, 1 grandmother, 1 grandfather, and 1 sister with a median age of 29 years (range, 16-53 ys) and a median weight of 68 kg (range, 47-106). Sixteen patients (12.9%) required retransplantation, most commonly due to hepatic artery thrombosis (HAT; n = 13; 10.7%). The other complications were biliary stenosis (n = 25; 20.6%), portal vein thrombosis (PVT; n = 11; 9.1%), portal vein stenosis (n = 5; 4.1%), hepatic vein stenosis (n = 6; 4.9%), and lymphoproliferative disorders (n = 8; 6.6%). The ultimate survival rate of recipients was 90.3% after 1 year and 75.8% after 3 years. Causes of early death within 1 month were HAT (n = 6), PVT (n = 2), severe graft dysfunction (n = 1), sepsis (n = 1), and intraoperative death in children with acute liver failure (n = 2). Causes of late deaths included lymphoproliferative disease (n = 3), chronic rejection (n = 2), biliary complications (n = 3), and recurrent disease (n = 3; hepatoblastoma and primary sclerosing cholangitis). Conclusions. Despite the heightened possibility of complications (mainly vascular), LRDLT represented a good alternative to transplantation from cadaveric donors in pediatric populations. It was associated with a high survival ratio.

Multiple Clinical Presentations of Lymphoproliferative Disorders in Pediatric Liver Transplant Recipients: A Single-Center Experience

Posttransplantation lymphoproliferative disorder (PTLD) is a serious complication following solid organ transplantation that has been linked to Epstein-Barr virus (EBV) infection. The aim of this article was to describe a single-center experience with the multiplicity of clinical presentations of PTLD. Among 350 liver transplantations performed in 303 children, 13 survivor children displayed a histological diagnosis of PTLD (13/242 survivors; 5.4%). The age at diagnosis ranged from 12 to 258 months (median, 47), and the time from transplantation ranged from 1 to 84 months (median, 13). Ten of these children (76.9%) were EBV-naive prior to transplantation. Fever was present in all cases. The clinical signs at presentation were anemia (92.3%), diarrhea and vomiting (69.2%), recurrent upper airway infections (38.4%), Waldeyer ring lymphoid tissue hypertrophy (23.0%), abdominal mass lesions (30.7%), massive cervical and mediastinal adenopathy (15.3%), or gastrointestinal and respiratory symptoms (30.7%). One child developed fulminant hepatic allograft failure secondary to graft involvement by PTLD. Polymorphic PTLD was diagnosed in 6 patients; 7 had the diagnosis of lymphoma. Treatment consisted of stopping immunosuppression as well as starting intravenous gancyclovir and anti-CD20 monoclonal antibody therapy. The mortality rate was 53.8%. The clinical presentation of PTLD varied from fever of unknown origin to fulminant hepatic failure. The other symptoms that may be linked to the diagnosis of PTLD are pancytopenia, tonsil and adenoid hypertrophy, cervical or mediastinal lymph node enlargement, as well as abdominal masses. Despite numerous advances, the optimal treatment approach for PTLD is not completely known and the mortality rate is still high.

The use of the Family Management Style Framework to evaluate the family management of liver transplantation in adolescence

Objective: To understand the family management experience of liver transplantation during adolescence based on the Family Management Style Framework(FMSF). Method: This is a case study that used the FMSF as theoretical framework and the hybrid model of thematic analysis as methodological reference. The case presented is from an adolescent’s family that lives in Salvador, Bahia. The data were collected through interviews with the mother and the patient charts analysis. Results: The results shows that the family defines the transplantation as threatening and there are divergence between mother and daughter related to the teen’s capabilities perception. Facing those discrepancies, the family assumes a protective posture by believing that the teen cannot take care of herself alone. The perceived consequences reflect how much the uncertainty permeates the family environment. Conclusion: It is concluded that the use of a model to evaluate the management can help professionals to direct and plan specific interventions.



Evaluating non-adherence to immunosuppressant medications in pediatric liver transplant recipients.

Non-adherence with recommended immunosuppressant medications is common post-pediatric liver transplant and is the most important reason for organ rejection in long-term survivors. However, there is currently no validated, standard method to measure adherence, with a well-defined threshold, making it extremely difficult to evaluate interventions to improve adherence. Previous studies have suggested that the degree of fluctuation of medication blood levels over time can provide an idea about how regularly the medication is being taken. The present study, conducted at UCLA medical center, sought to identify a specific threshold value of the s.d. of individual tacrolimus blood levels in pediatric liver transplant recipients which would be associated with rejection episodes in these patients. A threshold of 3.0 has been identified in other studies, and was supported by the analysis of retrospective data from 96 subjects. However, further analysis found that a s.d. of 2.5 appeared to have a better fit with the data. These findings suggest the utility of monitoring the s.d. of routine tacrolimus blood levels in pediatric liver transplant recipients for detecting non-adherence to immunosuppressant medication prior to clinical rejection, allowing earlier interventions.

Opinion of hepatic transplant waiting list patients regarding split liver transplantation

Background. Split liver transplantation (SLT) increases organ supply for hepatic transplantation. Long-term patient survival and complication rates seem to be equivalent between orthotopic liver transplantation (OLT) and SLT. There are controversies among transplant physicians due to an ethical dilemma between benefiting individual needs or those of society. Barshes and Goss (Am J Transplant 5:2047, 2005) demonstrated that the majority of adult liver transplant candidates are favorable to SLT. The aim of our study was to evaluate the opinions of patients at a Brazilian university hospital regarding SLT.Materials and Methods. A questionnaire with 14 questions was applied to 50 patients included in a hepatic transplant waiting list regarding SLT.Results. The overall attitudes of 66% of the participants were classified as utilitarian, 31% were classified as self-preserving, and 3% were undecided. Ninety-one percent of patients would be willing to share even if their expected survival after SLT was shorter than that with OLT. For 77% of patients, children must have priority over adults. However, 83% were unaware of the donors for pediatric transplantations.Conclusions. SLT is a consistent solution for organ demand despite controversies among transplant physicians. The present study demonstrated that most patients were favorable to SLT. In conclusion, attitudes toward graft sharing are not barriers to SLT.

Racial disparities in patient survival after liver transplantation in the United States

Background. Racial disparities in healthcare span such areas as access, outcomes after procedures, and patient satisfaction. Previous work suggested that minorities experience less healthcare and worse survival rates. In adult orthotopic liver transplantation (OLT) mixed results have been reported, with some showing African-American recipients having poor survival compared to Caucasians, and others finding no such discrepancy. ^ Purpose. This study’s purpose was to analyze the most recent United Network for Organ Sharing (UNOS) data, both before and after the implementation of the Model for End-Stage Liver Disease (MELD)/Pediatric End-Stage Liver Disease (PELD) scoring system, to determine if minority racial groups still experience poor outcomes after OLT. ^ Methods. The UNOS dataset for 1992-2001 (Era I) and 2002-2007 (Era II) was used. Patient survival rates for each Era and for adult and pediatric recipients were analyzed with adjustment. A separate multivariate analysis was performed on African-American adult patients in Era II in order to identify unique predictors for poor patient survival. ^ Results. The overall study included 66,118 OLT recipients. The majority were Caucasian (78%), followed by Hispanics (13%) and African-Americans (9%). Hispanic and African-American adults were more likely to be female, have Hepatitis C, to be in the intensive care unit (ICU) or ventilated at time of OLT, to have a MELD score ≥23, to have a lower education level, and to have public insurance when compared to Caucasian adults (all p-values < 0.05). Hispanic and African-American pediatric recipients were more likely have public insurance and less likely to receive a living donor OLT than were Caucasian pediatric OLT recipients (p <0.05). There was no difference in the likelihood of having a PELD score ≥21 among racial groups (p >0.40). African-American adults in Era I and Era II had worse patient survival rates than both Caucasians and Hispanic (pair-wise p-values <0.05). This same disparity was seen for pediatric recipients in Era I, but not in Era II. Multivariate analysis of African-American recipients revealed no unique predictors of patient death. ^ Conclusions. African-American race is still a predictor of poor outcome after adult OLT, even after adjustment for multiple clinical, demographic, and liver disease severity variables. Although African-American and Hispanic subgroups share many characteristics previously thought to increase risk of post-OLT death, only African-American patients have poor survival rates when compared to Caucasians. ^

Bradycardia in the Early Postoperative Period of Liver Transplantation in Children

The aim of this investigation was to describe the occurrence of bradycardia during the early postoperative period of liver transplantation in children. We retrospectively analyzed a cohort of 79 children with end-stage liver diseases who underwent liver transplantation. All children experienced >= 1 episode of a cardiac rate below the 2nd percentile of a 1-hour minimum duration, which was considered to be bradycardia. Patients <24 months were compared with older ones. The overall incidence of bradycardia was 37% (n = 31), including 25 patients who displayed bradycardia until postoperative day 3. In all cases, the electrocardiogram was normal, showing sinus rhythm. A comparison of the groups demonstrated an increased incidence of bradycardia among patients <24 months of age (P = .03). In all patients, there were no hemodynamic consequences; the cardiac rate returned to normal uneventfully. The explanations for bradycardia could not be applied to these patients because none of them had any volume change or electrolyte disturbances; liver function tests were not seriously altered. The mechanisms of this postoperative complications are unclear.

Splanchnic non-hepatic hemodynamics and metabolism during liver transplantation

Background/Aims: The aim of this study is to compare the splanchnic non-hepatic hemodynamics and the metabolic changes during orthotopic liver transplantation between the conventional with bypass and the piggyback methods. Methodology: A prospective, consecutive series of 59 primary transplants were analyzed. Oxygen consumption, glucose, potassium, and lactate metabolism were quantitatively estimated from blood samples from the radial artery and portal vein, collected up to 120 minutes after graft reperfusion. Mean arterial pressure, portal venous pressure, portal venous blood flow, and splanchnic vascular resistance were also measured or calculated at postreperfusion collection times. Results: There was a greater increase in portal venous blood flow (p=0.05) and lower splanchnic vascular resistance (p=0.04) in the piggyback group. Mean arterial pressure and portal venous pressure were similar for both groups. Oxygen, glucose and potassium consumption were higher in the piggyback group, but none of the metabolic parameters differed significantly between groups. Conclusions: In conclusion, the study detected a higher portal venous blood flow and a lower and splanchnic vascular resistance associated with the piggyback technique. After graft reperfusion, no difference in the splanchnic non-hepatic metabolic parameters was observed between the conventional with bypass and the piggyback methods of orthotopic liver transplantation.

Liver transplantation and quality of life: relevance of a specific liver disease questionnaire

Aim: A positive effect of liver transplantation on health-related quality of life (HRQOL) has been well documented in previous studies using generic instruments. Our aim was to re-evaluate different aspects of HRQOL before and after liver transplantation with a relatively new questionnaire the `liver disease quality of life` (LDQOL). Methods: The LDQOL and the Short Form 36 (SF-36) questionnaires were applied to ambulatory patients, either in the transplant list (n=65) or after 6 months to 5 years of liver transplant (n=61). The aetiology of cirrhosis, comorbidities, model for end-stage liver disease (MELD) Child-Pugh scores and recurrence of liver disease after liver transplantation were analysed using the Mann-Whitney and Kruskall-Wallis tests. Results: In patients awaiting liver transplantation, MELD scores >= 15 and Child-Pugh class C showed statistically significant worse HRQOL, using both the SF-36 and the LDQOL questionnaires. HRQOL in pretransplant patients was found to be significantly worse in those with cirrhosis owing to hepatitis C (n=30) when compared with other aetiologies (n=35) in 2/7 domains of the SF-36 and in 7/12 domains of the LDQOL. Significant deterioration of HRQOL after recurrence of hepatitis C post-transplant was detected with the LDQOL questionnaire although not demonstrated with the SF-36. The statistically significant differences were in the LDQOL domains: symptoms of liver disease, concentration, memory and health distress. Conclusions: The LDQOL, a specific instrument for measuring HRQOL, has shown a greater accuracy in relation to liver symptoms and could demonstrate, with better reliability, impairments before and after liver transplantation.

Inflammatory Cytokines during Liver Transplantation: Prospective Randomized Trial Comparing Conventional and Piggyback Techniques

Background/Aims: Cytokines have a significant role in the response to injury following liver transplantation, but the origin and course of such molecules are not completely known. The aim of this study was to evaluate the production and liver metabolism of the inflammatory cytokines interleukin (IL)-1 beta, IL-6, IL-8, interferon (IFN)-Y and tumor necrosis factor (TNF)-alpha in orthotopic liver transplantation (OLT), comparing the conventional and the piggyback methods. Methodology: We performed a study of 30 patients who underwent elective OLT and were randomized for the conventional or piggyback techniques at the beginning of the operation. The amount of cytokines and their hepatic metabolism were calculated based on plasma concentrations and vascular blood flow at 2, 5, 10, 15, 30, 60, 90, and 120 minutes after revascularization. Results: The amount of IL-1 beta in portal blood was higher in patients who underwent surgery using the conventional technique (estimate interest = 63,783.9 +/- 16,586.1 pg/min, versus 11,979.6 +/- 16,585.7 pg/min in the piggyback group, p=0.035). There were no significant differences between the two operative`s methods for IL-6, IL-8, IFN-Y and TNF-alpha production. The hepatic metabolism of cytokines was not different between groups. Although all the curves showed higher amounts of cytokines with the conventional technique, these were not statistically significant. Conclusion: The study shows the similarity between the two techniques concerning the stimuli for the production of inflammatory molecules.

Peripheral blood chimerism following human liver transplantation

The aim of this study was to prospectively investigate the peak levels and kinetics of donor leucocyte chimerism in human recipients following liver transplantation, The peak levels of chimerism mere observed within the first 48 hours following transplantation and ranged from 0.15% to 20% of total peripheral blood mononuclear cells, In all but one patient, who developed graft versus host disease, there was an early peak level of chimerism that declined over time such that donor leukocytes mere only intermittently detectable after 3 to 4 weeks. In 8 patients who had no episodes of graft rejection, the peak level of donor leukocyte chimerism ranged from 1.3% to 20% (mean +/- SEM; 5.5% +/- 2.1%). In 3 patients who were treated for episodes of acute graft rejection during the first four postoperative weeks, the peak level of donor leukocyte chimerism ranged from 0.15% to 0.2% (0.18 +/- 0.02, P = .012), The results demonstrate a marked variation in the total number of donor leukocytes detectable in the peripheral blood early after liver transplantation and also, that lower levels of chimerism may be associated with lower rates of initial graft acceptance and a higher incidence of acute rejection.

Long-Term Results of Percutaneous Bilioenteric Anastomotic Stricture Treatment in Liver-Transplanted Children

The purpose of this study was to evaluate the mid- and long-term results of percutaneous transhepatic cholangiography (PTC) and biliary drainage in children with isolated bilioenteric anastomotic stenosis (BAS) after pediatric liver transplantation. Sixty-four children underwent PTC from March 1993 to May 2008. Nineteen cholangiograms were normal; 10 showed intrahepatic biliary stenosis and BAS, and 35 showed isolated BAS. Cadaveric grafts were used in 19 and living donor grafts in 16 patients. Four patients received a whole liver, and 31 patients received a left lobe or left lateral segment. Roux-en-Y hepaticojejunostomy was performed in all patients. Indication for PTC was based on clinical, laboratory, and histopathologic findings. In patients with isolated BAS, dilation and biliary catheter placement, with changes every 2 months, were performed. Patients were separated into 4 groups according to number of treatment sessions required. The drainage catheter was removed if cholangiogram showed no significant residual stenosis and normal biliary emptying time after a minimum of 6 months. The relationship between risk factors (recipient`s weight < 10 kg, previous exposure to Cytomegalovirus, donor-recipient sex and weight relations, autoimmune disease as indication for transplantion, previous Kasai`s surgery, use of reduced liver grafts, chronic or acute rejection occurrence) and treatment was evaluated. Before PTC, fever was observed in 46%, biliary dilation in 23%, increased bilirubin in 57%, and increased gamma-glutamyltransferase (GGT) in 100% of patients. In the group with BAS, 24 of 35 (69%) patients had histopathologic findings of cholestasis as did 9 of 19 (47%) patients in the group with normal PTC. Of the 35 patients, 23 (65.7%) needed 1 (group I), 7 needed 2 (group II), 4 needed 3 (group III), and 1 needed 4 treatment sessions (group IV). The best results were observed after 1 treatment session, and the mean duration of catheter placement and replacement was 10 months. The primary patency rate was 61.2%, and the recurrence rate was 34.3% (group I). Seven patients (7 of 35; 20%) had their stricture treated with a second treatment session (group II). The average drainage time in group II was 24 months. During a period > 20 months, 4 patients (4 of 35; 11.4%) required 1 additional treatment session (group III), and 1 patient (1 of 35; 2.9%) had a catheter placed at the end of the study period (group IV). Drainage time in group I was significantly shorter than those in groups II, III, and IV (p < 0.05). There was no statistically significant relation between therapeutic response and the selected risk factors (p > 0.05). The majority of complications, such as catheter displacement and leakage, were classified as minor; however, 2 patients (5.7%) with hemobilia were noted. Complications increased according to the need for reintervention. In conclusion, balloon dilation and percutaneous drainage placement is safe and effective, and it has long-term patency for children with BAS after liver transplantation. Because of prolonged treatment time, reintervention may be necessary, thereby increasing the complication rate. Balloon dilation and percutaneous drainage placement should be considered as the first treatment option because of its minimally invasive nature.

Leprosy in transplant recipients: report of a case after liver transplantation and review of the literature

P>Leprosy still is an important public health problem in several parts of the world including Brazil. Unlike the diseases caused by other mycobacteria, the incidence and clinical presentation of leprosy seems little affected in immunosuppressed patients. We report the first case, to our knowledge, of a liver transplant patient who developed multi-bacillary leprosy. The patient presented with papules and infiltrated plaques with loss of sensation suggestive of leprosy 3.5 years after living-related liver transplantation for autoimmune hepatitis. A skin biopsy showing non-caseating macrophagic granulomas, neuritis, and intact acid-fast bacilli on Fite-Faraco stain, confirmed the diagnosis of borderline lepromatous leprosy. The donor of the liver did not show any evidence of leprosy. During follow-up, the patient presented 2 episodes of upgrading leprosy type I reactions, 1 mild before leprosy treatment, and 1 moderate 3 months after receiving standard multi-drug treatment (rifampicin, clofazimine, and dapsone). These reactions were accompanied by increase in liver function tests, especially of canalicular enzymes. This reaction occurred despite the patient`s triple immunosuppression regimen. The moderate reaction was successfully treated with further immunosuppression (prednisone, 0.5 mg/kg). Currently, the patient is asymptomatic, off leprosy medication, with routine liver transplant follow-up. The dilemmas in diagnosis and management of such a case are discussed and the literature on leprosy in transplant recipients is reviewed.

Potential Effect of Using ABO-Compatible Living-Donor Liver Transplantation

Liver transplantation increased 1.84-fold from 1988 to 2004. However, the number of patients on the waiting list for a liver increased 2.71-fold, from 553 to 1500. We used a mathematical equation to analyze the potential effect of using ABO-compatible living-donor liver transplantation (LDLT) on both our liver transplantation program and the waiting list. We calculated the prevalence distribution of blood groups (O, A, B, and AB) in the population and the probability of having a compatible parent or sibling for LDLT. The incidence of ABO compatibility in the overall population was as follows: A, 0.31; B, 0.133; O, 0.512; and AB, 0.04. The ABO compatibility for parent donors was blood group A, 0.174; B, 0.06; O, 0.152; and AB, 0.03; and for sibling donors was A, 0.121; B, 0.05; O, 0.354; and AB, 0.03. Use of LDLT can reduce the pressure on our liver transplantation waiting list by decreasing its size by at least 16.5% at 20 years after its introduction. Such a program could save an estimated 3600 lives over the same period.