Impact of COVID-19 Infection on Children and Adolescents after Liver Transplantation in a Latin American Reference Center.

Background: The COVID-19 infection has received the attention of the scientific community due to its respiratory manifestations and association with evolution to severe acute respiratory syndrome (SARS-CoV-2). There are few studies characterizing SARS-CoV-2 in pediatric immunocompromised patients, such as liver transplanted patients. The aim of this study was to analyze the outcomes of the largest cohort of pediatric liver transplant recipients (PLTR) from a single center in Brazil who were infected with COVID-19 during the pandemic. Methods: Cross-sectional study. Primary outcomes: COVID-19 severity. The Cox regression method was used to determine independent predictors associated with the outcomes. Patients were divided into two groups according to the severity of COVID-19 disease: moderate−severe COVID and asymptomatic−mild COVID. Results: Patients categorized as having moderate−severe COVID-19 were younger (12.6 months vs. 82.1 months, p = 0.03), had a higher prevalence of transplantation from a deceased donor (50% vs. 4.3%, p = 0.02), and had a higher prevalence of COVID infection within 6 months after liver transplantation (LT) (75% vs. 5.7%, p = 0.002). The independent predictor of COVID-19 severity identified in the multivariate analysis was COVID-19 infection <6 months after LT (HR = 0.001, 95% CI = 0.001−0.67, p = 0.03). Conclusion: The time interval of less than 6 months between COVID-19 infection and LT was the only predictor of disease severity in pediatric patients who underwent liver transplantation.

Progressive Familial Intrahepatic Cholestasis Associated With USP53 Gene Mutation in a Brazilian Child.

ABSTRACT: A case of low-γ-glutamyltranspetidase cholestasis associated with ubiquitin-specific peptidase 53 (USP53) gene mutation in a Brazilian child is described. Transient jaundice and hypocholia started at the age of 10 days. Liver enzymes, total bilirubin, and total bile acids were elevated at presentation. During follow-up, he developed cholelithiasis treated with cholecystectomy, and an intracranial hemorrhage resolved with full recovery. At last, evaluation at the age of 18 months, he was not jaundiced and had normal liver tests, but experienced from moderate pruritus despite treatment with rifampicin and ursodeoxycholic acid. A genetic study revealed novel homozygous mutations c.1687_1688delinsC p.Ser563Profs∗25 in the USP53 gene. His parents carried the same heterozygous mutation in the USP53 gene.

Technical Choices in Pediatric Living Donor Liver Transplantation: The Path to Reduce Vascular Complications and Improve Survival.

Pediatric living donor liver transplantation (PLDLT) is a successful therapeutic option for children with chronic and acute liver disease. After early transplant results, many technical advancements were introduced in the field to reduce the rate of complications and improve survival. The aim of this study is to present the outcomes of 975 primary PLDLTs in 3 periods: initial practice (period 1, 29 patients, January 1995 to December 1999), second period (period 2, 331 patients, January 2000 to December 2009), and third period (period 3 [P3], 615 patients, January 2010 to September 2019). Among the technical refinements introduced in P3 are the use of hyperreduced left lateral segment grafts, abdominal wall prosthetic mesh closure, double hepatic artery anastomosis, and increased use of vascular grafts for portal vein reconstruction. The outcomes included significant reductions of hepatic artery thrombosis (HAT), early portal vein thrombosis (EPVT), and retransplantation, with better patient and graft survival in P3. Additional analyses showed that the factors independently associated with worse 90-day patient survival were HAT, EPVT, and increasing Pediatric End-Stage Liver Disease score. In conclusion, the introduction of technical refinements in P3, in addition to improvements in patient care, determined a reduction in EPVT, HAT, and retransplantation. Consequently, patient and graft survival rates increased in all time points studied.

Autoimmune hepatitis in 828 Brazilian children and adolescents: clinical and laboratory findings, histological profile, treatments, and outcomes / Hepatite autoimune em 828 crianças e adolescentes brasileiros: achados clínicos e laboratoriais, perfil histológico, tratamentos e resultados

Abstract Objective: This large study with a long-term follow-up aimed to evaluate the clinical presentation, laboratory findings, histological profile, treatments, and outcomes of children and adolescents with autoimmune hepatitis. Methods: The medical records of 828 children and adolescents with autoimmune hepatitis were reviewed. A questionnaire was used to collect anonymous data on clinical presentation, biochemical and histological findings, and treatments. Results: Of all patients, 89.6% had autoimmune hepatitis-1 and 10.4% had autoimmune hepatitis-2. The female sex was predominant in both groups. The median age at symptom onset was 111.5 (6; 210) and 53.5 (8; 165) months in the patients with autoimmune hepatitis 1 and autoimmune hepatitis-2, respectively. Acute clinical onset was observed in 56.1% and 58.8% and insidious symptoms in 43.9% and 41.2% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively. The risk of hepatic failure was 1.6-fold higher for autoimmune hepatitis-2. Fulminant hepatic failure occurred in 3.6% and 10.6% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively; the risk was 3.1-fold higher for autoimmune hepatitis-2. The gamma globulin and immunoglobulin G levels were significantly higher in autoimmune hepatitis-1, while the immunoglobulin A and C3 levels were lower in autoimmune hepatitis-2. Cirrhosis was observed in 22.4% of the patients; biochemical remission was achieved in 76.2%. The actuarial survival rate was 93.0%. A total of 4.6% underwent liver transplantation, and 6.9% died (autoimmune hepatitis-1: 7.5%; autoimmune hepatitis-2: 2.4%). Conclusions: In this large clinical series of Brazilian children and adolescents, autoimmune hepatitis-1 was more frequent, and patients with autoimmune hepatitis-2 exhibited higher disease remission rates with earlier response to treatment. Patients with autoimmune hepatitis-1 had a higher risk of death.

Resumo Objetivo: Este estudo com acompanhamento de longo prazo visou a avaliar o quadro clínico, os achados laboratoriais, o perfil histológico, os tratamentos e os resultados de crianças e adolescentes com hepatite autoimune. Métodos: Foram analisados os prontuários médicos de 828 crianças e adolescentes com HAI. Foi usado um questionário para coletar os dados anônimos sobre o quadro clínico, os achados bioquímicos e histológicos e os tratamentos. Resultados: De todos os pacientes, 89,6% tinham hepatite autoimune-1 e 10,4% hepatite autoimune-2. O sexo feminino foi predominante nos dois grupos. A idade média no início dos sintomas foi 111,5 (6; 210) e 53,5 (8; 165) meses nos pacientes com hepatite autoimune-1 e hepatite autoimune-2, respectivamente. Foi observado início clínico agudo em 56,1% e 58,8% e sintomas insidiosos em 43,9% e 41,2% dos pacientes com hepatite autoimune-1 e hepatite autoimune-2, respectivamente. A probabilidade de insuficiência hepática foi 1,6 vezes maior para hepatite autoimune-2; 3,6% e 10,6% dos pacientes com hepatite autoimune-1 e hepatite autoimune-2, respectivamente, apresentaram insuficiência hepática fulminante; o risco foi 3,1 vezes maior para hepatite autoimune-2. Os níveis de gamaglobulina e imunoglobulina G foram significativamente maiores nos pacientes com hepatite autoimune-1, ao passo que os níveis de imunoglobulina A e C3 foram menores em pacientes com hepatite autoimune-2; 22,4% dos pacientes apresentaram cirrose e a remissão bioquímica foi atingida em 76,2%. A taxa de sobrevida atuarial foi de 93,0%. Um total de 4,6% pacientes foram submetidos a transplante de fígado e 6,9% morreram (hepatite autoimune-1: 7,5%; hepatite autoimune-2: 2,4%). Conclusões: Nesta grande série clínica de crianças e adolescentes brasileiros, a hepatite autoimune-1 foi mais frequente e os pacientes com hepatite autoimune-2 mostraram maiores taxas de remissão da doença com respostas mais rápidas aos tratamentos. Os pacientes com hepatite autoimune-1 apresentaram maior risco de óbito.

Domino Liver Transplant in Maple Syrup Urine Disease: Technical Details of Cases in Which the First Surgery Involved a Living Donor.

BACKGROUND: Data describing the technical aspects of living donor (LD) domino liver transplantation (DLT) in maple syrup urine disease (MSUD) are limited. The largest published series includes only 3 cases. One great challenge of this procedure is to ensure adequate vascular stumps for the LD, the MSUD patient, and the recipient of the domino graft. Here, we describe our experience in 11 cases of LD-DLT in MSUD, highlighting the technical aspects of LD-DLT. METHODS: From September 2012 to September 2017, 11 patients with MSUD underwent LD liver transplantation at our institution, and MSUD livers were used as domino grafts in 11 children. RESULTS: (1) MSUD patients: 10 patients received a left lateral segment. The donor's left hepatic vein (HV) was anastomosed to the confluence of the recipient's 3 HVs. No vascular grafts (VG) were required for portal vein (PV) anastomosis. Single arterial anastomosis was performed with microsurgery in 10 of 11 patients. (2) MSUD graft recipients: In 8 cases, HV reconstruction was performed between the graft's HV confluence and the recipient's HV confluence, and in 3 cases, a vena cava triangulation was necessary; 6 MSUD grafts required HV venoplasty. No VG were needed for HV reconstruction. VG were used for PV reconstruction in 3 cases due to sclerotic PV. In 2 cases, double arterial anastomoses were performed in the MSUD liver. All patients remain alive and well. CONCLUSIONS: Living donor liver transplantation followed by DLT for MSUD is a complex procedure and demands technical refinement. Special attention must be paid to vascular reconstruction.

Autoimmune hepatitis in 828 Brazilian children and adolescents: clinical and laboratory findings, histological profile, treatments, and outcomes.

OBJECTIVE: This large study with a long-term follow-up aimed to evaluate the clinical presentation, laboratory findings, histological profile, treatments, and outcomes of children and adolescents with autoimmune hepatitis. METHODS: The medical records of 828 children and adolescents with autoimmune hepatitis were reviewed. A questionnaire was used to collect anonymous data on clinical presentation, biochemical and histological findings, and treatments. RESULTS: Of all patients, 89.6% had autoimmune hepatitis-1 and 10.4% had autoimmune hepatitis-2. The female sex was predominant in both groups. The median age at symptom onset was 111.5 (6; 210) and 53.5 (8; 165) months in the patients with autoimmune hepatitis 1 and autoimmune hepatitis-2, respectively. Acute clinical onset was observed in 56.1% and 58.8% and insidious symptoms in 43.9% and 41.2% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively. The risk of hepatic failure was 1.6-fold higher for autoimmune hepatitis-2. Fulminant hepatic failure occurred in 3.6% and 10.6% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively; the risk was 3.1-fold higher for autoimmune hepatitis-2. The gamma globulin and immunoglobulin G levels were significantly higher in autoimmune hepatitis-1, while the immunoglobulin A and C3 levels were lower in autoimmune hepatitis-2. Cirrhosis was observed in 22.4% of the patients; biochemical remission was achieved in 76.2%. The actuarial survival rate was 93.0%. A total of 4.6% underwent liver transplantation, and 6.9% died (autoimmune hepatitis-1: 7.5%; autoimmune hepatitis-2: 2.4%). CONCLUSIONS: In this large clinical series of Brazilian children and adolescents, autoimmune hepatitis-1 was more frequent, and patients with autoimmune hepatitis-2 exhibited higher disease remission rates with earlier response to treatment. Patients with autoimmune hepatitis-1 had a higher risk of death.

Twenty Years of Experience in Pediatric Living Donor Liver Transplantation: Focus on Hepatic Artery Reconstruction, Complications, and Outcomes.

BACKGROUND: Hepatic artery thrombosis (HAT) increases morbidity and mortality after liver transplantation (LT). The identification of risk factors for HAT may aid transplant teams in the development of strategies aimed at reducing HAT. This article describes the risk factors for HAT and outcomes after LT. METHODS: This report describes a retrospective study (1995 to 2015) of primary pediatric living donor LT (LDLT). Pretransplant and technical variables were included in the study. Binary logistic regression was used for data analysis. RESULTS: This study included 656 primary LDLT. The median age, body weight, and pediatric end-stage liver disease score at the time of transplant were 13 months, 8.4 kg and 15, respectively. Twenty-one (3.2%) patients developed HAT. Intraoperative HAT (odds ratio, 62.63; 95% confidence interval, 12.64-310.19; P < 0.001) and the use of liver grafts with a graft-to-recipient weight ratio less than 1.1% (odds ratio, 24.46; 95% confidence interval, 4.55-131.56; P < 0.001) retained statistical significance in the multivariate model. Patient and graft survivals were significantly worse in cases with HAT. The overtime trend analysis revealed a decrease in the incidence of HAT (P = 0.008) and an increase in the use of 2-arterial anastomosis (P < 0.001). CONCLUSIONS: A graft-to-recipient weight ratio of 1.1% or less and intraoperative HAT were independently associated with HAT. Trend analysis further revealed a significant reduction in the incidence of HAT over time, as well as the increased use of 2 hepatic arteries for anastomosis during graft implantation. The double artery anastomosis may represent an extra protection to pediatric recipients undergoing LDLT.

Degos disease - malignant atrophic papulosis or cutaneointestinal lethal syndrome: rarity of the disease.

BACKGROUND: Degos disease is a very rare syndrome with a rare type of multisystem vasculopathy of unknown cause that affects the skin, gastrointestinal tract, and central nervous system. Other organs such as the kidneys, lungs, pleura, liver, heart, and eyes, can also be involved. OBJECTIVE: To highlight the incidence of Degos disease with regard to age and sex, discuss the necessity of its accurate and early diagnosis, and demonstrate the most current techniques for its diagnosis; to discuss whether early therapeutic intervention can impact patient prognosis; and to present a literature review about this disease. DESIGN: With a retrospective, observational, nonrandomized trial, we described the evolution of the different forms of Degos disease and referenced the literature. DATA SOURCES: Research on rare documented cases in the literature, including two cases of potentially lethal form of the disease involving the skin and gastrointestinal system and, possibly, the lungs, kidneys, and central nervous system. A case of the benign form of the disease involving the skin was observed by the authors. MAIN OUTCOME MEASURES: Differences between outcomes in patients with the cutaneointestinal form and skin-only form of the disease. There was one fatal outcome. We reviewed possible new approaches to diagnosis and treatment. RESULTS: The study demonstrated the rapid evolution of the aggressive and malignant form of the disease. It also described newly accessible Phase I diagnostic tools being currently researched as well as new therapeutic approaches. LIMITATION: The rarity of the disease, with only eleven cases throughout the literature. CONCLUSION: The gastrointestinal form of Degos disease can be lethal. Its vascular etiology has finally been confirmed; however, new and more accurate early diagnostic modalities need to be developed. There are new therapeutic possibilities, but the studies of them are still in the early stages and have not yet shown the full effectiveness of these new therapies.

Chronic hepatitis E virus infection in a pediatric female liver transplant recipient.

We describe a case of chronic hepatitis E virus (HEV) infection in a 13-year-old female liver transplant recipient with recurrent increased aminotransferase levels and acute cellular rejection. This finding demonstrates that chronic HEV infection can occur and should be further investigated in immunocompromised patients in Latin America.

Analysis of factors associated with portal vein thrombosis in pediatric living donor liver transplant recipients.

The technique of vascular reconstruction plays a major role in the outcome of living donor liver transplantation (LDLT). An increased use of vascular grafts (VGs) as replacements for sclerotic portal veins has become a standard technique for our group. The aim of this study was to analyze the factors associated with portal vein thrombosis (PVT) in pediatric LDLT. We performed a retrospective analysis of 486 primary pediatric LDLT procedures performed between October 1995 and May 2013. VGs used for portal reconstruction included living donor inferior mesenteric veins, living donor ovarian veins, recipient internal jugular veins, deceased donor iliac arteries, and deceased donor iliac veins. Thirty-four patients (7.0%) developed PVT. The incidence of PVT dropped from 10.1% to 2%; the overall utilization of VGs increased from 3.5% to 37.1%. In a multivariate analysis, only the use of VGs remained an independent risk factor for the occurrence of PVT (hazard ratio = 7.2, 95% confidence interval = 2.8-18.7, P < 0.001). There was no difference in survival rates between patients with PVT and patients without PVT. No patient with PVT underwent retransplantation. In conclusion, the use of VGs was independently associated with the development of PVT. Over time, there was a reduction in the incidence of early PVT in this cohort, and there was a trend toward a reduction in total PVT. The occurrence of isolated PVT in this study was not associated with decreased patient or graft survival.

HCC prevalence and histopathological findings in liver explants of patients with hereditary tyrosinemia type 1.

BACKGROUND: Untreated tyrosinemia type 1 (HT1) is manifested by liver failure associated with renal tubular dysfunction, growth failure, and rickets. The indication for liver transplantation (LT) is restricted to non-responders to 2-(2-nitro-4-trifluoromethylbenzoyl)-1, 3-cyclohexanedione (NTBC) treatment, patients not treated with NTBC or for patients with HCC. The aim of this study is to report on a series of NTBC naive HT1 patients submitted to LT along with the prevalence of HCC in their liver explants. PROCEDURE: This is a retrospective study of 16 children with HT1 who underwent liver transplantation between January 1993 and December 2012. CLINICAL FEATURES: liver failure in 12 (75%), growth failure in 4 (25%), rickets in 5 (31.2%), hypertrophic cardiomyopathy in three (18.7%), and renal tubulopathy in seven patients (43.7%). Median AFP level was 64,335 ng/ml. Abdominal CT scans showed multiple nodules in most patients. Histopathology of the explants showed cirrhosis in all patients and HCC in 12 (75%), 3 with microvascular invasion. The majority of the tumors were well differentiated. Patient survival rate was 86% at a median follow-up of 6.6 years. All survivors were tumor-free with no adjuvant chemotherapy. CONCLUSION: In countries where neonatal screening programs are not effective and NTBC treatment is not widely available, LT still plays an important role in the treatment of children with HT1. An early indication in patients who present with multinodular livers can also serve to treat an otherwise underdiagnosed HCC condition.

Diagnosis and management of biliary complications in pediatric living donor liver transplant recipients.

The incidence of biliary complications (BCs) after living donor liver transplantation (LDLT) can reach 40%. Published data on the pediatric population are limited, and treatment protocols vary. Our aim was to describe the clinical scenario for BCs and treatment approaches after LDLT. Between October 1995 and December 2012, 489 pediatric LDLT procedures were performed. BCs developed in 71 patients (14.5%). Biliary strictures (BSs) developed in 45 (9.2%) patients, and bile leaks (BLs) developed in 33 patients (6.7%). The BL diagnosis was clinical in all cases, and 69.7% of the patients underwent surgery. Nearly half of the BS cases had clinical features or suggestive ultrasound findings. Liver biopsy findings suggested BSs in 51.7%. Percutaneous transhepatic cholangiography was performed in 95.6% of the BS patients. The success rate was 77% [mean number of percutaneous biliary interventions (PBIs) = 3.9 ± 1.98, median drainage time = 8 months]. In conclusion, BL patients can be managed with conservative therapy, even though most of these patients will ultimately be treated with surgery. Diagnosing a BS requires a high degree of clinical suspicion because the available resources for its identification can fail in up to 50% of cases. A higher number of PBIs and the use of a drainage catheter for a longer time may be required to achieve better results with this technique.

Ascites and serum sodium are markers of increased waiting list mortality in children with chronic liver failure.

UNLABELLED: Ascites is the most common complication of cirrhosis and in adults it is associated with 50% mortality at 5 years if patients do not receive a liver transplant. The occurrence of hyponatremia in these patients has been associated with increased mortality on the waiting list. The importance of serum sodium levels and the presence of ascites in the pediatric setting remain to be clarified. A retrospective analysis of pediatric patients with cirrhosis on the transplant list was carried out between October 2000 and February 2012. The primary objective of this study was to evaluate the association of pretransplant variables with mortality within 90 days following the inclusion of patients on the waiting list. In all, 522 patients were included in the study; 345 (66%) patients were under 1 year of age; 208 (40%) of the children presented ascites. A multivariate Cox proportional hazards analysis was conducted and total bilirubin (P < 0.001, hazard ratio [HR] = 2.09, 95% confidence interval [CI] = 1.35-3.21), international normalized ratio (INR) (P < 0.001, HR = 9.83, 95% CI = 4.51-21.45), serum sodium levels (P = 0.03, HR = 0.96, 95% CI = 0.92-0.99), ascites (P = 0.001, HR = 2.59, 95% CI = 1.44-4.64), and categorized age (0-1 versus ≥ 1 year old) (P = 0.025, HR = 2.33, 95% CI = 1.11-4.86) were independently associated with risk of death in 90 days. Malnutrition (Z score height/age, weight/age) and serum albumin (pediatric endstage liver disease [PELD] formula) were not included in the final model. CONCLUSION: The presence of ascites and serum sodium levels are important variables associated with decreased patient survival while candidates wait for a liver graft. Multicenter studies are necessary to validate these findings in order to improve current allocation policies based on the PELD score.

Liver transplantation after stage II palliation for hypoplastic left heart syndrome.

The association of biliary atresia (BA) with congenital heart diseases has been extensively described, and there are a number of reports on the outcomes of patients in this group who undergo liver transplantation (LT). The intraoperative management and the timing of LT for patients with end-stage liver disease are matters of debate, especially when complex heart diseases are involved. This report describes the outcome after LT for a pediatric recipient with BA and hypoplastic left heart syndrome. The patient underwent Norwood-Sano and Glenn procedures for heart palliation before LT. He was cyanotic, was severely malnourished, and had complications secondary to chronic liver failure. At the time of transplantation, the child was 16 months old and weighed 5175 g. Despite the critical clinical scenario and the long hospitalization period, there were no cardiac, vascular, or biliary complications after LT. At the age of 48 months, the patient was awaiting the final cardiac repair. In conclusion, the presence of complex cardiac malformations may not be a contraindication to LT. An experienced surgical team and a multidisciplinary approach are key to a successful outcome.

Four hundred thirty consecutive pediatric living donor liver transplants: variables associated with posttransplant patient and graft survival.

The availability of living donors allows transplant teams to indicate living donor liver transplantation (LDLT) early in the course of liver disease before the occurrence of life-threatening complications. Late referral to transplant centers is still a problem and can compromise the success of the procedure. The aim of this study was to examine the perioperative factors associated with patient and graft survival for 430 consecutive pediatric LDLT procedures at Sirio-Libanes Hospital/A. C. Camargo Hospital (São Paulo, Brazil) between October 1995 and April 2011. The studied pretransplant variables included the following: recipient age and body weight, Pediatric End-Stage Liver Disease score, z score for height/age, bilirubin, albumin, international normalized ratio, hemoglobin, sodium, presence of ascites, and previous surgery. The analyzed technical aspects included the graft-to-recipient weight ratio and the use of vascular grafts for portal vein reconstruction. In addition, the occurrence of hepatic artery thrombosis (HAT), portal vein thrombosis (PVT), and biliary complications was also analyzed. The liver grafts included 348 left lateral segments, 5 monosegments, 51 left lobes, and 9 right lobes. In a univariate analysis, an age < 12 months, a low body weight (≤10 kg), malnutrition, hyperbilirubinemia, and HAT were associated with decreased patient and graft survival after LDLT. In a multivariate analysis, a body weight ≤ 10 kg and HAT were significantly associated with decreased patient and graft survival. The use of vascular grafts significantly increased the occurrence of PVT. In conclusion, a low body weight (≤10 kg) and the occurrence of HAT independently determined worse patient and graft survival in this large cohort of pediatric LDLT patients.

Th2 signals induce epithelial injury in mice and are compatible with the biliary atresia phenotype.

Biliary atresia (BA) is a destructive cholangiopathy of childhood in which Th1 immunity has been mechanistically linked to the bile duct inflammation and obstruction that culminate in liver injury. Based on reports of decreased Th1 cytokines in some patients and the development of BA in mice lacking CD4+ T cells, we hypothesized that Th1-independent mechanisms can also activate effector cells and induce BA. Here, we tested this hypothesis using Stat1-/- mice, which lack the ability to mount Th1 immune responses. Infection of Stat1-/- mice with rhesus rotavirus type A (RRV) on postnatal day 1 induced a prominent Th2 response, duct epithelial injury and obstruction within 7 days, and atresia shortly thereafter. A high degree of phosphorylation of the Th2 transcription factor Stat6 was observed; however, concurrent inactivation of Stat1 and Stat6 in mice did not prevent BA after RRV infection. In contrast, depletion of macrophages or combined loss of Il13 and Stat1 reduced tissue infiltration by lymphocytes and myeloid cells, maintained epithelial integrity, and prevented duct obstruction. In concordance with our mouse model, humans at the time of BA diagnosis exhibited differential hepatic expression of Th2 genes and serum Th2 cytokines. These findings demonstrate compatibility between Th2 commitment and the pathogenesis of BA, and suggest that patient subgrouping in future clinical trials should account for differences in Th2 status.

Schistosoma mansoni infection in the liver graft: The impact on donor and recipient outcomes after transplantation.

The increasing number of transplants performed each year has led to the identification of unusual diseases in liver grafts from asymptomatic donors that were unrecognized before liver transplantation. Here we report our experience with patients who received liver grafts infected with schistosomiasis. From September 1991 to August 2010, 482 pediatric liver transplants were performed at A. C. Camargo Hospital/Sírio-Libanês Hospital (São Paulo, Brazil). For the identification of Schistosoma mansoni infections, pathology slides for the recipients were reviewed; these included postreperfusion and follow-up liver biopsy samples. We were able to identify 6 cases of schistosomiasis transmitted through infected grafts (5 of these grafts were from living donors). All living donors were confirmed to have normal liver chemistries, negative fecal tests for parasitic diseases, and normal abdominal ultrasound findings. Liver biopsy was not performed before transplantation. In all cases, features of schistosomiasis were absent in the liver explants. The living donors were treated with praziquantel and were taught to avoid risk factors for reinfection. No specific treatment for schistosomiasis was given to the recipients. There were no perioperative deaths, but 2 recipients died after living donor liver transplantation (LDLT) because of Kaposi's sarcoma and non-Hodgkin's lymphoma. In conclusion, using liver grafts infected with S. mansoni eggs did not compromise the results of LDLT in this pediatric cohort. Because of the parasite's life cycle and the therapeutic target of praziquantel, only donors should be treated for the infection. Three years of follow-up showed an uneventful recovery for the living donors.

Left lateral segmentectomy for pediatric live-donor liver transplantation: special attention to segment IV complications.

BACKGROUND: During left lateral segmentectomy for live-donor liver transplant, the vascular inflow to segment IV can be compromised. An area of ischemia can be seen intraoperatively and further segment IV resection may be needed to prevent necrosis and abscess formation. METHODS: From July 1995 to February 2007, 324 consecutive living donor liver transplantations were performed at Hospital A. C. Camargo and Hospital Sirio-Libanes, Sao Paulo, Brazil. Two hundred eleven left lateral segments were transplanted in this period. Data on 204 left lateral segments donors were available for this analysis. RESULTS: There were 108 female and 96 male donors. Median age was 29 years (range, 16-48 years). Median follow-up time was 2.2 years (range, 2 months-11.8 years). Median intensive care unit stay was 1 day (range, 1-3 days), and median hospital stay was 5 days (range, 4-47 days). Postoperative complications were encountered in 39 donors (19.1%). Partial segment IV resection on the course of the primary surgery due to parenchyma discoloration was required in 107 cases (52.5%). Ten patients (4.9%) developed segment IV necrosis or abscesses, although four of them had had segment IVB resection intraoperatively. Segment IV necrosis or abscess significantly increased hospital stay and the number of readmissions, from 5.5+/-3.5 days to 8.4+/-3.7 days (P=0.012) and from 6 of 194 (3%) to 5 of 10 (50%) (P=0.001), respectively. CONCLUSIONS: Middle hepatic segment abscess or necrosis was the most frequent complication after left lateral segmentectomy (4.9%). Objective intraoperative strategies need to be developed to evaluate middle hepatic segment ischemia to identify and treat patients at higher risk.

Diabetes mellitus-related autoantibodies in childhood autoimmune hepatitis.

OBJECTIVE: To determine the frequency and significance of diabetes mellitus (DM)-related autoantibodies in children with autoimmune hepatitis (AIH). RESEARCH DESIGN AND METHODS: Anti-islet cell antibodies (ICA), insulin autoantibodies (IAA), and anti-glutamic acid decarboxylase (GAD65) antibodies were assessed in 28 children (25 female) with AIH before and after 3-9 years of therapy with azathioprine and prednisone. RESULTS: There was biochemical and clinical remission of AIH activity in 76% of the children after 1 year of immunosuppressive therapy. Positive ICA and IAA were found in 60.7% and 18.5% of the patients, decreasing to 38.5% and 12% after 3-9 years of therapy. Anti-GAD autoantibodies were present in only one patient who had Graves' disease, high ICA titer, and developed type 1 DM after 3 years. After 3-9 years of follow up, all had normal fasting glycemia, glycosylated hemoglobin (HbA1c), and, with a single exception, normal responses to oral glucose tolerance testing. No increase in the frequencies of HLA antigens was observed in ICA- and IAA-positive patients compared to antibody-negative patients or a control population. The majority of the patients with HLA-DRB1*03 or DRB1*04, however, were positive for ICA (7/10), and three of them had IAA. The frequency of high risk HLA DQB1*0302 or DQB1*02 alleles was low and similar to control frequencies, indicating low-risk for DM despite the presence of DM-related autoimmunity markers. CONCLUSIONS: AIH in childhood is associated with high frequency of ICA and IAA, with less than expected rates of progression to DM. Immunosuppression reduced ICA and IAA frequency and titers.

Chronic active hepatitis associated with anti-liver-kidney microsome antibody type 1

Trata-se de uma criança do sexo feminino de 3 anos de idade, com quadro clínico de hepatite aguda, com icterícia, hepatoesplenomegalia, altos níveis de transaminase glutâmico-pirúvica e gamaglobulina. Foi encontrada a presença de altos níveis de anticorpos anti-microssomo fígado rim tipo 1(anti-LKM 1) pelo método de imunofluorescência e confirmado por Elisa e análise de Werstern Blot. A biopsia hepática mostrou hepatite crônica ativa, e a terapia imunossupressora foi iniciada imediatamente