Consecutive Liver and Bone Marrow Transplantation for Erythropoietic Protoporphyria: Case Report and Literature Review.

BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare inherited disease of heme biosynthesis resulting in the accumulation of protoporphyrin, characterized by liver failure in a minority of cases. Although liver transplant (LT) is the therapeutic strategy for advanced hepatic disease, it does not correct the primary defect, which leads to recurrence in liver graft. Thus, hematopoietic stem cell transplantation (HSCT) is an approach for treating EPP. METHODS: We aim to describe the first sequential LT and HSCT for EPP performed in Latin America, besides reviewing the present-day literature. RESULTS: The patient, a 13-year-old female with a history of photosensitivity, presented with symptoms of cholestatic and hepatopulmonary syndrome and was diagnosed with EPP. Liver biopsy demonstrated cirrhosis. She was submitted to a successful LT and showed improvement of respiratory symptoms. However, she had disease recurrence on the liver graft. She underwent a myeloablative HSCT using a matched unrelated donor, conditioning with BuCy (busulfan and cyclophosphamide), and GvHD (graft vs. host disease) prophylaxis with ATG (thymoglobulin), tacrolimus and methotrexate. Neutrophil engraftment occurred on D+18. She has presented mixed chimerism, but normalization of PP levels, being 300 days after HSCT, in good state of health and normal liver function. CONCLUSIONS: Consecutive LT and HSCT for EPP is a procedure that has been described in 10 cases in the literature and, even though these patients are a highly diversified population, studies have shown favorable results. This concept of treatment should be considered in patients with established liver disease.

Daily Vitamin D Supplementation Improves Vitamin D Deficiency in Patients With Chronic Liver Disease.

OBJECTIVE: The objective of this article is to evaluate the response to 6000 IU oral cholecalciferol (OC) treatment in children with chronic liver disease (CLD) and 25(OH)D deficiency. METHODS: This historical cohort included non-transplanted CLD patients younger than 18 years old, which were analyzed for serum 25(OH)D, liver function, bone metabolism, Child-Pugh classification, and anthropometry. Patients with 25(OH)D deficiency (defined as 25(OH)D < 20 ng/mL) who received 6000 IU/day of OC were analyzed pre- and post-intervention, and considered responders if 25(OH)D > 20 ng/mL after at least 60 days. We compared clinical and laboratory data from patients with and without 25(OH)D deficiency, responders and nonresponders. RESULTS: We studied 96 patients, of which 57.2% had biliary atresia. The prevalence of 25(OH)D deficiency was 67.7% (65/96). These patients were younger ( P < 0.001), had higher Child-Pugh scores ( P < 0.001), higher levels of total bilirubin (TB) ( P < 0.001), gamma-glutamyl transferase ( P < 0.001), and alkaline phosphatase ( P = 0.002), as well as lower levels of phosphorus ( P = 0.009) compared with patients without 25(OH)D deficiency. The median treatment length was 126 days (70-307 days). At the end of treatment, we observed a higher median of 25(OH)D ( P < 0.001), and lower median of parathyroid hormone (PTH) ( P = 0.023). Nine patients (29%) restored 25(OH)D to normal range; they had lower Child-Pugh score ( P = 0.001), lower TB levels ( P = 0.001), and higher level of phosphorus ( P = 0.003) after treatment. CONCLUSION: Despite an increase in 25(OH)D and decrease in PTH levels, 6000 IU/day of OC was not sufficient to restore 25(OH)D deficiency in most of the patients in this study.

HIF-1alpha-pathway activation in cholangiocytes of patients with biliary atresia: An immunohistochemical/molecular exploratory study.

BACKGROUND: Biliary atresia is a neonatal disease characterized by choledochal obstruction and progressive cholangiopathy requiring liver transplantation in most patients. Hypoxia-ischemia affecting the biliary epithelium may lead to biliary obstruction. We hypothesized that ischemic cholangiopathy involving disruption of the peribiliary vascular plexus could act as a triggering event in biliary atresia pathogenesis. METHODS: Liver and porta hepatis paraffin-embedded samples of patients with biliary atresia or intrahepatic neonatal cholestasis (controls) were immunohistochemically evaluated for HIF-1alpha-nuclear signals. Frozen histological samples were analyzed for gene expression in molecular profiles associated with hypoxia-ischemia. Prospective clinical-laboratory and histopathological data of biliary atresia patients and controls were reviewed. RESULTS: Immunohistochemical HIF-1alpha signals localized to cholangiocytes were detected exclusively in liver specimens from biliary atresia patients. In 37.5% of liver specimens, HIF-1alpha signals were observed in biliary structures involving progenitor cell niches and peribiliary vascular plexus. HIF-1alpha signals were also detected in biliary remnants of 81.8% of porta hepatis specimens. Increased gene expression of molecules linked to REDOX status, biliary proliferation, and angiogenesis was identified in biliary atresia liver specimens. In addition, there was a trend towards decreased GSR expression levels in the HIF-1alpha-positive group compared to the HIF-1alpha-negative group. CONCLUSION: Activation of the HIF-1alpha pathway may be associated with the pathogenesis of biliary atresia, and additional studies are necessary to confirm the significance of this finding. Ischemic cholangiopathy and REDOX status disturbance are putative explanations for HIF-1alpha activation. These findings may give rise to novel lines of clinical and therapeutic investigation in the BA field.

Hypervolemic hyponatremia and transplant-free survival in children with cirrhosis due to biliary atresia.

BACKGROUND: Biliary atresia is the number one cause of cirrhosis and liver transplantation in children. Hyponatremia is the most important electrolytic disturbance observed in decompensated cirrhosis. Studies of hyponatremia in cirrhotic children are scarce and those that exist have defined hyponatremia as serum sodium < 130 mEq/L lasting for at least 7 days. METHODS: We evaluated transplant-free survival (Kaplan-Meier) of children with cirrhosis due to biliary atresia and serum sodium < 130 mEq/L persisting for 1, 2-6, and ≥7 days. This was a single-center, historical cohort that included all patients aged ≤ 18 years on a liver transplantation waiting list. RESULTS: We studied 128 patients. The overall frequency of hyponatremia was 30.5% (39/128). Thirteen patients (10.2%) had hyponatremia when put on the list, and 20.3% developed it during follow-up. The Kaplan-Meier overall transplant-free survival rate was 83.3%. Patients with persistent hyponatremia for at least two days had the lowest transplant-free survival. Glomerular filtration rate (P = .00, RR = 0.96, IC 95% = 0.94-0.99), BMI/age Z-score (P = .02, RR = 0.59, IC 95% = 0.39-0.91), INR (P = .00, RR = 1.43, IC 95% = 1.17-1.74), and serum sodium (P = .04, RR = 0.91, IC 95% = 0.84-0.99) were independently associated with transplant-free survival. We did not observe any difference in mortality prediction after adding sodium to the original PELD score. CONCLUSIONS: We conclude that persistent hyponatremia lasting at least two days may herald poor prognosis for children with cirrhosis due to biliary atresia.

Noninvasive Methods of Predicting Large Esophageal Varices in Children With Intrahepatic Portal Hypertension.

OBJECTIVE: Esophageal variceal bleeding is a severe complication of portal hypertension. The standard diagnostic screening test and therapeutic procedure for esophageal varices (EV) is endoscopy, which is invasive in pediatric patients. This study aimed to evaluate the role of noninvasive parameters as predictors of large varices in children with intrahepatic portal hypertension. METHODS: Participants included in this cross-sectional study underwent a screening endoscopy. Variceal size, red marks, and portal gastropathy were assessed and rated. Patients were classified into two groups: Group 1 (G1) with small or no varices and Group 2 (G2) with large varices. The population consisted of 98 children with no history of gastrointestinal (GI) bleeding, with a mean age of 8.9 ±â€Š4.7 years. The main outcome evaluated was the presence of large varices. RESULTS: The first endoscopy session revealed the presence of large varices in 32 children. The best noninvasive predictors for large varices were platelets (Area under the ROC Curve [AUROC] 0.67; 95% CI 0.57-0.78), the Clinical Prediction Rule (CPR; AUROC 0.65; 95% CI 0.54-0.76), and risk score (AUROC 0.66; 95% CI 0.56-0.76). The logistic regression model showed that children with a CPR value under 114 were 8.59 times more likely to have large varices. Risk scores higher than -1.2 also increased the likelihood of large varices (OR 6.09; P = 0.014), as did a platelet count/spleen size z score lower than 25 (OR 3.99; P = 0.043). The combination of these three tests showed a high negative predictive value. CONCLUSIONS: The CPR, the risk score, and the platelet count/spleen size z score could be helpful in identifying cirrhotic children who may be eligible for endoscopy.

Variability index of tacrolimus serum levels in pediatric liver transplant recipients younger than 12 years: Non-adherence or risk of non-adherence?

MLVI has been used to assess adherence. To determine the MLVI in children <12 years of age at transplantation and to identify demographic correlates and consequences for the graft. This is a retrospective study of 50 outpatients (4.0 ± 3.5 years), at least 13-month post-liver transplantation. The outcomes evaluated were MLVI, ALT > 60 IU/L, ACR, death, and graft loss. We analyzed demographic and socioeconomic characteristics, indication for transplantation, and type of donor. Student's t test and the chi-square test were used. Statistical significance was set at P ≤ .05. Seventy-two percent were infants or preschoolers, 62% biliary atresia. Seventy-four percent of the mothers had middle-school education, and 54% of the families had an income ≤3632.4 US$/y. Twenty-two (44%) patients had a MLVI ≥ 2 SD; this was more prevalent in families with higher incomes (P = .045). ALT levels > 60 IU/L were more common in MLVI ≥ 2 SD group (P = .035). ACR episodes were similar between groups (P = 1.000). No patient died or lost the graft. MLVI ≥ 2 SD may be an indicator of the risk of medication non-adherence.

Neonatal Liver Failure and Congenital Cirrhosis due to Gestational Alloimmune Liver Disease: A Case Report and Literature Review.

Neonatal liver failure (NLF) is a major cause of neonatal morbidity and mortality, presenting as acute liver failure and/or congenital cirrhosis. Many affected patients show antenatal signs of fetal injury. There are several causes of NLF and early diagnosis is mandatory to elucidate the etiology and determine a specific treatment or the best management strategy. Gestational alloimmune liver disease associated with neonatal hemochromatosis (GALD-NH) is a rare but potentially treatable cause of NLF. It should be considered in any neonate with fetal signs of disease and postnatal signs of liver failure with no other identifiable causes. GALD-NH is often diagnosed late and patients are therefore referred late to specialized centers, delaying treatment. This case highlights the consequences of late diagnosis and treatment of GALD-NH and emphasizes the importance of a high grade of suspicion of this disease in order to refer the patient to a specialized center soon enough to perform the appropriate treatment.

Paracrine Effects of Bone Marrow Mononuclear Cells in Survival and Cytokine Expression after 90% Partial Hepatectomy.

Acute liver failure is a complex and fatal disease. Cell-based therapies are a promising alternative therapeutic approach for liver failure due to relatively simple technique and lower cost. The use of semipermeable microcapsules has become an interesting tool for evaluating paracrine effects in vivo. In this study, we aimed to assess the paracrine effects of bone marrow mononuclear cells (BMMC) encapsulated in sodium alginate to treat acute liver failure in an animal model of 90% partial hepatectomy (90% PH). Encapsulated BMMC were able to increase 10-day survival without enhancing liver regeneration markers. Gene expression of Il-6 and Il-10 in the remnant liver was markedly reduced at 6 h after 90% PH in animals receiving encapsulated BMMC compared to controls. This difference, however, was neither reflected by changes in the number of CD68+ cells nor by serum levels of IL6. On the other hand, treated animals presented increased caspase activity and gene expression in the liver. Taken together, these results suggest that BMMC regulate immune response and promote apoptosis in the liver after 90% PH by paracrine factors. These changes ultimately may be related to the higher survival observed in treated animals, suggesting that BMMC may be a promising alternative to treat acute liver failure.

Encapsulated platelets modulate kupffer cell activation and reduce oxidative stress in a model of acute liver failure.

Acute liver failure (ALF) is characterized by massive hepatocyte cell death. Kupffer cells (KC) are the first cells to be activated after liver injury. They secrete cytokines and produce reactive oxygen species, leading to apoptosis of hepatocytes. In a previous study, we showed that encapsulated platelets (PLTs) increase survival in a model of ALF. Here, we investigate how PLTs exert their beneficial effect. Wistar rats submitted to 90% hepatectomy were treated with PLTs encapsulated in sodium alginate or empty capsules. Animals were euthanized at 6, 12, 24, 48, and 72 hours after hepatectomy, and livers were collected to assess oxidative stress, caspase activity, and gene expression related to oxidative stress or liver function. The number of KCs in the remnant liver was evaluated. Interaction of encapsulated PLTs and KCs was investigated using a coculture system. PLTs increase superoxide dismutase and catalase activity and reduce lipid peroxidation. In addition, caspase 3 activity was reduced in animals receiving encapsulated PLTs at 48 and 72 hours. Gene expression of endothelial nitric oxide synthase and nuclear factor kappa B were elevated in the PLT group at each time point analyzed. Gene expression of albumin and factor V also increased in the PLT group. The number of KCs in the PLT group returned to normal levels at 12 hours but remained elevated in the control group until 72 hours. Finally, PLTs modulate interleukin (IL) 6 and IL10 expression in KCs after 24 hours of coculture. In conclusion, these results indicate that PLTs interact with KCs in this model and exert their beneficial effect through reduction of oxidative stress that results in healthier hepatocytes and decreased apoptosis. Liver Transplantation 22 1562-1572 2016 AASLD.

Encapsulated Whole Bone Marrow Cells Improve Survival in Wistar Rats after 90% Partial Hepatectomy.

Background and Aims. The use of bone marrow cells has been suggested as an alternative treatment for acute liver failure. In this study, we investigate the effect of encapsulated whole bone marrow cells in a liver failure model. Methods. Encapsulated cells or empty capsules were implanted in rats submitted to 90% partial hepatectomy. The survival rate was assessed. Another group was euthanized at 6, 12, 24, 48, and 72 hours after hepatectomy to study expression of cytokines and growth factors. Results. Whole bone marrow group showed a higher than 10 days survival rate compared to empty capsules group. Gene expression related to early phase of liver regeneration at 6 hours after hepatectomy was decreased in encapsulated cells group, whereas genes related to regeneration were increased at 12, 24, and 48 hours. Whole bone marrow group showed lower regeneration rate at 72 hours and higher expression and activity of caspase 3. In contrast, lysosomal-ß-glucuronidase activity was elevated in empty capsules group. Conclusions. The results show that encapsulated whole bone marrow cells reduce the expression of genes involved in liver regeneration and increase those responsible for ending hepatocyte division. In addition, these cells favor apoptotic cell death and decrease necrosis, thus increasing survival.

Avaliação nutricional em crianças e adolescentes com cirrose: estudo transversal de duas séries / Nutritional assessment in children and adolescents with cirrhosis: cross-sectional study of two series

Introdução: A cirrose caracteriza-se por uma alteração crônica do parênquima hepático que frequentemente leva à desnutrição em crianças e adolescentes. A intervenção nutricional deve ser feita precocemente, o que requer um cuidadoso acompanhamento desses pacientes. Objetivos: Comparar os resultados da avaliação nutricional de crianças e adolescentes cirróticos realizada em dois períodos de tempo distintos. Métodos: Foram utilizados bancos de dados oriundos de duas pesquisas conduzidas com pacientes pediátricos com cirrose. Após a aplicação de critérios de inclusão e exclusão, 67 crianças e adolescentes foram avaliados em duas séries com intervalo de aproximadamente uma década entre elas. As duas séries tiveram as variáveis antropométricas estatura para idade (E/I) e dobra cutânea tricipital para idade (DCT/I) avaliadas de acordo com os padrões da Organização Mundial de Saúde. A gravidade da doença foi avaliada pelos modelos Pediatric End-stage Liver Disease (PELD)/ Model for End-stage Liver Disease (MELD) e pelo escore Child-Pugh. O nível de significância foi estabelecido em 5%. Resultados: Os resultados da avaliação do estado nutricional dos pacientes nas duas séries não mostraram diferença estatisticamente significativa. Na série 1, 22,6% dos pacientes apresentaram desnutrição, e 27,8% na série 2 (p = 0,955). Conclusões: Podemos concluir que nas duas séries avaliadas, separadas por aproximadamente uma década, o percentual de desnutrição e a gravidade da cirrose se mantiveram estáveis (AU)

Introduction: Cirrhosis is characterized by a chronic alteration of the liver parenchyma that often leads to malnutrition in children and adolescents. Nutritional intervention should be performed early, requiring careful follow-up of these patients. Objectives: To compare the nutritional assessment of cirrhotic pediatric patients performed in two separate periods of time. Methods: This research used two different databases originated from studies conducted with pediatric patients with cirrhosis. After applying inclusion and exclusion criteria, 67 children and adolescents were assessed in two series of tests performed within a time range of approximately a decade. Both series had standard deviation score for height-for-age (SDS-H/A), standard deviation score for triceps skinfold-for-age and (SDS-TSF/A), calculated according to the standards established by the World Health Organization. Disease severity was evaluated by the Pediatric End-stage Liver Disease (PELD)/Model for End-stage Liver Disease (MELD) and by the Child-Pugh score. Results were considered significant at p < 0.05. Results: The present study did not find any statistically significant difference for the nutritional status of the researched subjects in any of the series. In the first series, 22.6% of patients were undernourished, compared to 27.8% in the second one (p = 0.955). Conclusions: We can conclude that in both series of tests conducted with an interval of about a decade from each other the percentage of malnutrition and the severity of cirrhosis remained stable (AU)

ERK 1/2 activation does not contribute to increased survival mediated by bone marrow cells after 90% partial hepatectomy in Wistar rats

We investigated the influence of bone marrow cells upon activation of ERK 1/2 in an animal model of 90% PH. Phosphorylated ERK 1/2 was evaluated by western blot. No differences were found between the groups. Thus, increased survival does not appear to be mediated by ERK 1/2 activation (AU)

Hypoxic-ischemic gene expression profile in the isolated variant of biliary atresia.

BACKGROUND: Biliary atresia (BA) includes a sclerosing cholangiopathy whose nature is not fully deciphered. Aiming to evaluate the role of an arteriopathy as an etiologic factor in BA, we investigated hypoxia and the correlated angiogenic response in livers from affected patients. METHODS: Gene expression of the molecular axis: hypoxia-inducible factor (HIF)1a, HIF2a and vascular endothelial growth factor A (VEGFA)/VEGFR1, VEGFR2. Liver biopsy specimens collected at exploratory laparotomy of age-matched patients with isolated, cytomegalovirus IgM-negative BA (n = 32) and intrahepatic cholestasis (IHC, n = 9) were evaluated. RESULTS: We observed higher HIF1a and HIF2a expression in BA than in IHC. Paradoxically, VEGFR2, the main target of VEGFA-induced angiogenesis, was underexpressed in BA, and VEGFA was decreased in most BA patients. Patients with the highest expression of HIFs and the lowest VEGFA and VEGFR2 were essentially the same, indicating hypoxia without the necessary angiogenesis. This group included most BA patients and, except for HIF2a, they were older and presented increased bilirubin serum levels. In the highest HIF2a/lowest VEGFR2 subsets, gene expression of the cytokeratin 19, marker of cholangiocyte phenotype, was decreased. CONCLUSION: This study suggests that hypoxia-ischemia is present in the livers of patients with BA, progresses over time and leads to a decreased cholangiocyte mass.

Serum proinflammatory cytokines and nutritional status in pediatric chronic liver disease.

AIM: To evaluate the nutritional status and its association with proinflammatory cytokines in children with chronic liver disease. METHODS: We performed a cross-sectional study with 43 children and adolescents, aged 0 to 17 years, diagnosed with chronic liver disease. All patients regularly attended the Pediatric Hepatology Unit and were under nutritional follow up. The exclusion criteria were fever from any etiology at the time of enrollment, inborn errors of the metabolism and any chronic illness. The severity of liver disease was assessed by Child-Pugh, Model for End-stage Liver Disease (MELD) and Pediatric End Stage Liver Disease (PELD) scores. Anthropometric parameters were height/age, body mass index/age and triceps skinfold/age according to World Health Organization standards. The cutoff points for nutritional status were risk of malnutrition (Z-score < -1.00) and malnutrition (Z-score < -2.00). Interleukin-1ß (IL-1ß), IL-6 and tumor necrosis factor-α levels were assessed by commercial ELISA kits. For multivariate analysis, linear regression was applied to assess the association between cytokine levels, disease severity and nutritional status. RESULTS: The median (25(th)-75(th) centile) age of the study population was 60 (17-116)-mo-old, and 53.5% were female. Biliary atresia was the main cause of chronic liver disease (72%). With respect to Child-Pugh score, cirrhotic patients were distributed as follows: 57.1% Child-Pugh A, a mild presentation of the disease, 34.3% Child-Pugh B, a moderate stage of cirrhosis and 8.6% Child-Pugh C, were considered severe cases. PELD and MELD scores were only above the cutoff point in 5 cases. IL-6 values ​​were increased in patients at nutritional risk (34.9%) compared with those who were well-nourished [7.12 (0.58-34.23) pg/mL vs 1.63 (0.53-3.43) pg/mL; P = 0.02], correlating inversely with triceps skinfold-for-age z-score (rs = -0.61; P < 0.001). IL-6 levels were associated with liver disease severity assessed by Child-Pugh score (P = 0.001). This association remained significant after adjusting for nutritional status in a linear regression model. CONCLUSION: High IL-6 levels were found in children with chronic liver disease at nutritional risk. Inflammatory activity may be related to nutritional status deterioration in these patients.

Programa de Transplante Hepático Infantil do Hospital de Clínicas de Porto Alegre: resultados dos doze primeiros transplantes hepáticos intervivos / Pediatric liver transplantation program: results of living liver transplantation

Introdução: O Hospital de Clínicas de Porto Alegre (HCPA) é pioneiro na realização de transplante hepático infantil (THI) no RS. A menor oferta de doadores falecidos tem estimulado a realização de transplante hepático (TxH) intervivos. Objetivo: Descrever os resultados do THI intervivos do programa THI-HCPA. Método: Estudo descritivo. Incluídos: receptores de TxH intervivos, 18 anos, ambos os sexos e respectivos doadores, voluntários, ambos os sexos. Excluídos: insufi ciência hepática aguda. Variáveis: receptores: características clínico-demográficas, antropométricas; sorologias para Citomegalovírus (CMV) e Epstein-Barr (EBV); incidência de complicações pós-operatórias, tempo de internação, sobrevida 12 meses; doadores: características clínico-demográficas, sobrevida 12 meses. Todas as cirurgias foram realizadas pelo mesmo cirurgião e os dados, coletados prospectivamente. Estudo aprovado pelo Comitê de Ética em Pesquisa do HCPA (13-0208). Resultados: Doze TxH intervivos incluídos. Idade dos receptores: mediana=2 anos (sexo feminino:7). Espera em lista: 141,4±10,3d. Indicação de TxH: 83,3% atresia biliar. IMC normal: 100%. Child- -Pugh: C:7/12(58%). PELD: mediana=11,9a. Pré-TxH:IgG+CMV (10); IgG+EBV(4); ascite (7); peritonite bacteriana espontânea (3), hiponatremia dilucional (7); encefalopatia hepática (2); varizes esofágicas (4); hemorragia digestiva alta (3). Idade dos doadores: 31,8±8,4a. Sexo feminino=50%; 92% aparentado. Pesos receptor/doador: 19,2±8,9%. Implante do segmento hepático lateral esquerdo: 100%. Tempo de isquemia total: 1,34±0,67h. Duração da cirurgia: 5,94±2,58h. Duração da internação (receptores): 30,6 ± 25,2d. Complicações receptores: vascular (4), biliar (3), steal syndrome (1), small for size (2), sepse (1). Reintervenções cirúrgicas: 5. Tempo de permanência em UTI: mediana=9d. Primo-infecção: CMV (1), EBV (3). Rejeição celular aguda (4). Sobrevida em 1 ano: 76,7%. Tempo de internação(doadores): 8,1±4,0 d. Complicações ao doador: dor pós-operatória (80%). Conclusão: Os nossos resultados se assemelham àqueles da literatura no que se refere à incidência de complicações. A cirurgia tem se mostrado segura para o doador (AU)

Introduction: Hospital de Clínicas de Porto Alegre (HCPA) is a pioneer in conducting child liver transplantation (CLT) in RS. The lower supply of deceased donors has stimulated living liver transplant (LTx). Aim: To describe the results of living CLT in the THI-HCPA program. Methods: A descriptive study that included: LTx recipients from living donor, ≤ 18 years old, both sexes and their donors, volunteers, both sexes; and excluded: acute liver failure. Variables: Receptors: clinical, demographic and anthropometric characteristics, serology for cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection, incidence of postoperative complications, length of stay, 12-month survival; Donors: demographic and clinical characteristics, 12-month survival. All surgeries were performed by the same surgeon and the data were collected prospectively. This study was approved by the Research Ethics Committee of the HCPA (13-0208). Results: Twelve LTx from living donors were included. Age of recipients: median = 2 years (female: 7). Waiting in list: 141.4 ± 10.3 d. Indication for liver transplantation: 83.3% biliary atresia. Normal BMI: 100%. Child-Pugh C:7/12 (58%). PELD: median = 11.9a. Pre-LTx: CMV+IgG (10), EBV+IgG (4), ascites (7), spontaneous bacterial peritonitis (3), dilutional hyponatremia (7), hepatic encephalopathy (2), esophageal varices (4), high gastrointestinal bleeding (3). Donor age: 31.8 ± 8.4. Female = 50%, 92% related. Receiver/giver weights: 19.2 ± 8.9%. Implantation of left lateral hepatic segment: 100%. Total ischemic time: 1.34 ± 0.67 h. Length of surgery: 5.94 ± 2.58 h. Duration of hospitalization (receivers): 30.6 ± 25.2 d. Complications in receptors: vascular (4), bile (3), steal syndrome (1), small for size (2), sepsis (1). Surgical re-interventions: 5. Time in ICU: median = 9d. Primary infection: CMV (1), EBV (3). Acute cellular rejection (4). 1-year survival: 76.7%. Length of hospital stay (donors): 8.1 ± 4.0d. Donor complications: postoperative pain (80%). Conclusion: The results resemble those of the literature regarding the incidence of complications. The surgery has been shown to be safe for the donor (AU)

Noninvasive methods for prediction of esophageal varices in pediatric patients with portal hypertension.

AIM: To evaluate clinical and laboratory parameters for prediction of bleeding from esophageal varices (EV) in children with portal hypertension. METHODS: Retrospective study of 103 children (mean age: 10.1 ± 7.7 years), 95.1% with intrahepatic portal hypertension. All patients had no history of bleeding and underwent esophagogastroduodenoscopy for EV screening. We recorded variceal size (F1, F2 and F3), red-color signs and portal gastropathy, according to the Japanese Research Society for Portal Hypertension classification. Patients were classified into two groups: with and without EV. Seven noninvasive markers were evaluated as potential predictors of EV: (1) platelet count; (2) spleen size z score, expressed as a standard deviation score relative to normal values for age; (3) platelet count to spleen size z score ratio; (4) platelets count to spleen size (cm) ratio; (5) the clinical prediction rule (CPR); (6) the aspartate aminotransferase to platelet ratio index (APRI); and (7) the risk score. RESULTS: Seventy-one children had EV on first endoscopy. On univariate analysis, spleen size, platelets, CPR, risk score, APRI, and platelet count to spleen size z score ratio showed significant associations. The best noninvasive predictors of EV were platelet count [area under the receiver operating characteristic curve (AUROC) 0.82; 95%CI: 0.73-0.91], platelet: spleen size z score (AUROC 0.78; 95%CI: 0.67-0.88), CPR (AUROC 0.77; 95%CI: 0.64-0.89), and risk score (AUROC 0.77; 95%CI: 0.66-0.88). A logistic regression model was applied with EV as the dependent variable and corrected by albumin, bilirubin and spleen size z score. Children with a CPR < 114 were 20.7-fold more likely to have EV compared to children with CPR > 114. A risk score > -1.2 increased the likelihood of EV (odds ratio 7.47; 95%CI: 2.06-26.99). CONCLUSION: Children with portal hypertension with a CPR below 114 and a risk score greater than -1.2 are more likely to have present EV. Therefore, these two tests can be helpful in selecting children for endoscopy.

The effects of anesthetic regimen in 90% hepatectomy in rats.

PURPOSE: To evaluate the influence of the anesthetic regimen on anesthetic recovery, survival, and blood glucose levels following a 90% partial hepatectomy in rats. METHODS: Thirty adult male Wistar rats were divided into two groups according to their anesthetic regimens: intraperitoneal ketamine and xylazine or inhaled isoflurane. In order to prevent hypoglycemia, glucose was administered intraperitoneally and glucose (20%) was added to the drinking water. RESULTS: Anesthetic recovery time was longer in the ketamine and xylazine group. The survival rate after 72 hours was lower (log rank=0.0001) in the ketamine and xylazine group (0.0%) than in the isoflurane group (26.7%). The blood glucose after six hours was lower (p=0.017) in the ketamine and xylazine group (63 ± 31.7 mg/dL) than in the isoflurane group (98 ± 21.2 mg/dL). The prolonged anesthesia recovery time associated with ketamine and xylazine decreased the survival rate and blood glucose levels after 90% hepatectomy. CONCLUSION: Isoflurane anesthesia reduced the recovery time and incidence of hypoglycemia and increased the survival rate in the early hours, providing a therapeutic window that is suitable for experimental studies.

The effects of anesthetic regimen in 90% hepatectomy in rats / Os efeitos do regime anestésico na hepatectomia de 90% em ratos

PURPOSE: To evaluate the influence of the anesthetic regimen on anesthetic recovery, survival, and blood glucose levels following a 90% partial hepatectomy in rats. METHODS: Thirty adult male Wistar rats were divided into two groups according to their anesthetic regimens: intraperitoneal ketamine and xylazine or inhaled isoflurane. In order to prevent hypoglycemia, glucose was administered intraperitoneally and glucose (20%) was added to the drinking water. RESULTS: Anesthetic recovery time was longer in the ketamine and xylazine group. The survival rate after 72 hours was lower (log rank=0.0001) in the ketamine and xylazine group (0.0%) than in the isoflurane group (26.7%). The blood glucose after six hours was lower (p=0.017) in the ketamine and xylazine group (63±31.7 mg/dL) than in the isoflurane group (98±21.2 mg/dL). The prolonged anesthesia recovery time associated with ketamine and xylazine decreased the survival rate and blood glucose levels after 90% hepatectomy. CONCLUSION: Isoflurane anesthesia reduced the recovery time and incidence of hypoglycemia and increased the survival rate in the early hours, providing a therapeutic window that is suitable for experimental studies.

OBJETIVO: Avaliar a influência do regime anestésico sobre a recuperação anestésica, a sobrevida em 72 horas e a glicemia após hepatectomia parcial de 90% em ratos. MÉTODOS: Trinta ratos Wistar machos adultos foram distribuídos em dois grupos conforme o regime anestésico: combinação de ketamina e xilazina intraperitoneal ou isoflurano inalatório. Para prevenção de hipoglicemia foi administrada glicose intraperitoneal e adicionado glicose (20%) na água de beber. RESULTADOS: A recuperação anestésica no grupo ketamina e xilazina foi mais prolongada. Durante primeira hora após hepatectomia, nenhum rato anestesiado com ketamina e xilazina despertou. Todos do grupo isoflurano estavam ativos minutos após final da cirurgia. A sobrevida em 72 horas foi menor (Log rank=0,0001) no grupo ketamina e xilazina (0,0%) que no grupo isoflurano (26,7%). Glicemia em 6 horas do grupo ketamina e xilazina (63±31,7 mg/dL) foi menor (p=0,017) que no grupo isoflurano (98 ±21,2 mg/dL). Prolongado tempo de recuperação anestésica com ketamina e xilazina diminuiu sobrevida e glicemia após hepatectomia 90%. CONCLUSÃO: Anestesia com isoflurano reduziu tempo de recuperação e hipoglicemia, além de aumentar a sobrevida nas primeiras horas, possibilitando uma janela terapêutica adequada para estudos experimentais.

Peritonite bacteriana espontânea: novas perspectivas / Spontaneuous bacterial peritonitis: new perspectives

A peritonite bacteriana espontânea (PBE) é uma das infecções mais frequentes no paciente cirrótico, estando associada à alta morbi-mortalidade. Descrita desde a metade dos anos de 1960, diretrizes recentemente publicadas apontam para o surgimento de novos conceitos relacionados à patogênese, ao diagnóstico e ao tratamento da PBE, motivo desta revisão. Dentre os principais aspectos discutidos destacam-se o conceito de translocação bacteriana patológica e a identificação de polimorfismos genéticos associados ao desenvolvimento da PBE, este último sugerindo a existência de um fator de risco adicional para a infecção. Os critérios diagnósticos e terapêuticos são revisados, sendo enfatizada a crescente ocorrência de resistência bacteriana naqueles pacientes que desenvolvem PBE nosocomial, situação na qual é sugerida uma abordagem terapêutica específica. Discute-se finalmente, as atuais indicações de profilaxia primária e secundária. Quando pertinente, serão também apresentados os aspectos relacionados à PBE que acomete o paciente pediátrico (AU)

Spontaneous bacterial peritonitis (SBP) is one of the most common infections in cirrhotic patients and is associated with high morbidity and mortality. Described since the mid-1960s, recently published guidelines point to the emergence of new concepts related to the pathogenesis, diagnosis and treatment of SBP, subject of this review. The main aspects discussed include the concept of pathological bacterial translocation and identification of genetic polymorphisms associated with the development of SBP, the latter suggesting the existence of an additional risk factor for infection. The diagnostic and therapeutic criteria are reviewed, with an emphasis on the increasing occurrence of bacterial resistance in patients who develop nosocomial SBP, in which case a specific therapeutic approach is suggested. Finally we discuss the current indications for primary and secondary prophylaxis. Where relevant, SBP-related aspects affecting the pediatric patient will also be presented (AU)

Risco nutricional e desnutrição em crianças e adolescentes com cirrose: o papel da avaliação nutricional / Nutritional risk and malnutrition in children and adolescents with cirrhosis: the role of nutritional assessment

Introdução: A desnutrição é um importante fator que interfere no prognóstico de crianças e adolescentes com cirrose. Este estudo tem como objetivo avaliar o estado nutricional e a adequação da ingesta alimentar de crianças e adolescente com cirrose. Métodos: Estudo transversal, realizado com 39 crianças e adolescentes cirróticos com idade entre 0-15 anos. A gravidade da doença hepática foi avaliada pelo critério de Child-Pugh e escores Pediatric End-Stage Liver Disease e/ou Model for End-Stage Liver Disease. A classificação do estado nutricional foi determinada de acordo com os padrões WHO (2009) e Frisancho (2008). A avaliação da ingesta alimentar foi realizada a partir de um registro alimentar de três dias. Resultados: As médias e desvios padrão dos escores z para os parâmetros Peso/Idade (P/I), Índice de Massa Corporal/Idade (IMC/I), Estatura/Idade (E/I), Circunferência do Braço/Idade (CB/I) e Dobra Cutânea Tricipital/Idade (DCT/I) foram respectivamente -0,53 (±1,17), 16,8 (±2,53), -1,22 (±1,20), -1,04 (±1,61) e -0,99 (±1,67), caracterizando cerca de 44% como desnutridos; sendo que 69% destes eram desnutridos graves (abaixo do escore-z -3,00). A ingesta alimentar média dos cirróticos (33/39), excluindo aqueles em aleitamento materno, dieta enteral e/ou restrição dietética, comparada com a RDI para idade foi de 112% (±36), sendo que a maioria 78,4% (26/33) apresentou uma ingesta maior ou igual a 80% da recomendação para a idade. Conclusão: A associação de parâmetros antropométricos, clínicos e dietéticos deve ser utilizada para que se possa chegar a um diagnóstico nutricional coerente e intervenção nutricional efetiva.

Introduction: Malnutrition is an important factor affecting the prognosis of children and teenagers with cirrhosis. This study aims to evaluate the nutritional status and adequacy of food intake by children and adolescents with cirrhosis. Methods: Cross-sectional study of 39 cirrhotic children and adolescents aged 0-15 years. The severity of liver disease was evaluated by Child-Pugh scores and Pediatric End-Stage Liver Disease and/or Model for End-Stage Liver Disease. The nutritional status was determined according to WHO standards (2009) and Frisancho (2008). The evaluation of food intake was made by recording food intake for three days. Results: The means and standard deviations of z scores for the parameters weight/age (W/A), body mass index/age (BMI/A), Height/Age (H/A), arm circumference/age (A /I), and triceps skinfold/Age (TS/A) were respectively -0.53 (± 1.17), 16.8 (± 2.53), -1.22 (± 1.20), -1.04 (± 1.61), and -0.99 (± 1.67), characterizing about 44% as malnourished, 69% of whom as severely malnourished (z-score <3.00). The mean dietary intake of cirrhotic patients (33/39), excluding those in breast-feeding, enteral feeding and/or dietary restriction, as compared with the RDI for age was 112% (± 36), most of which (78.4% , 26/33) with an intake > 80% as recommended for their age. Conclusion: A combination of anthropometric, clinical and dietary factors should be used so that a coherent nutritional diagnosis and effective nutritional intervention can be made.