Severity of Ascites Is Associated with Increased Mortality in Patients with Cirrhosis Secondary to Biliary Atresia.

BACKGROUND: Very few prior studies have investigated the presence of ascites as a prognostic factor in children with cirrhosis. To the best of our knowledge, there are no prior studies evaluating the relationship between severity of ascites and patient survival in children with biliary atresia and cirrhosis. AIMS: To evaluate the association between severity of ascites and survival of children with cirrhosis and biliary atresia. METHODS: All children with cirrhosis secondary to biliary atresia evaluated at our institution from 2000 to 2014 were included in this study. Patients were classified into four groups: NA = no ascites; A1 = grade 1 ascites; A2 = grade 2 ascites; and A3 = grade 3 ascites. The primary endpoint of the study was mortality within the first year after patient inclusion. Ninety-day mortality was also evaluated. Prognostic factors related to both endpoints also were studied. RESULTS: One-year patient survival for NA was 97.1%, versus 80.8% for A1, versus 52% for A2, versus 13.6 for A3 (p < 0.001). The presence of ascites increased mortality by 17 times. In the multivariate analysis, clinically detectable ascites (HR 3.14, 95% CI 1.14-8.60, p = 0.026), lower sodium (HR 1.15, 95% CI 1.04-1.27, p = 0.006), higher bilirubin (HR 1.06, 95% CI 1.00-1.12, p = 0.023), and higher PELD score (HR 1.05, 95% CI 1.02-1.08, p = 0.001) were all associated with decreased survival. Lower serum sodium (HR 1.20, 95% CI 1.09-1.32, p < 0.001) and higher PELD score (HR 1.03, 95% CI 1.001-1.063, p = 0.043) were associated with increased 90-day mortality. CONCLUSIONS: Clinically detectable ascites is associated with decreased 1-year survival of children with biliary atresia. These patients should be treated with caution and prioritized for liver transplantation.

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.

NR3C1 rs6198 Variant May Be Involved in the Relationship of Graves' Disease with Stressful Events.

Although stressful events are known to trigger Graves' disease (GD), the mechanisms involved in this process are not well understood. The NR3C1 gene, encoding for the glucocorticoid receptor (GR), presents single nucleotide polymorphisms (SNPs) that are associated with stress-related diseases. To investigate the relationship between NR3C1 SNPs, GD susceptibility, and clinical features, we studied 792 individuals, including 384 patients, among which 209 presented with Graves' orbitopathy (GO), and 408 paired healthy controls. Stressful life events were evaluated in a subset of 59 patients and 66 controls using the IES-R self-report questionnaire. SNPs rs104893913, rs104893909, and rs104893911 appeared at low frequencies and presented similar profiles in patients and controls. However, variant forms of rs6198 were rarer in GD patients, suggesting a protective effect. Stressful events were more common in patients than controls, and were reported to have clearly occurred immediately before the onset of GD symptoms in 23 cases. However, no association was found between these events and rs6198 genotypes or GD/GO characteristics. We suggest that the NR3C1 rs6198 polymorphism may be an important protective factor against GD, but its relationship with stressful events needs further investigation.

T3 as predictor of mortality in any cause non-critically ill patients.

BACKGROUND: Low T3 syndrome refers to a set of thyroid hormone metabolism alterations present in the disease state. A correlation between low T3 and poor clinical outcomes in the intensive care unit is more established. Nonetheless, studies on non-critically ill patients are few and controversial. OBJECTIVE: To evaluate the prevalence and predictive value of low T3 levels on 30-day and 6-month mortality in non-critically ill patients. Secondary outcomes evaluated the length of hospital stay, overall mortality, and hospital readmission. DESIGN: Prospective cohort study. METHODS: A total of 345 consecutive patients from the Internal Medicine ward of a tertiary hospital in southern Brazil were included and followed from October 2018 to April 2019 (6 months). Levels of total serum T3 were measured weekly, from admission to discharge, and correlated with 30-day and 6-month mortality. RESULTS: Prevalence of low T3 was 36.6%. Low T3 levels were associated with higher 30-day hospital mortality (15.1% vs 4.1%, P < 0.001) and higher 6-month overall mortality (31.7% vs 13.2%, P < 0.001). Total serum T3 at admission was an independent predictor of 30-day hospital mortality. CONCLUSION: Low T3 levels are a prevalent condition among non-critically ill patients, and this condition is associated with poor clinical outcomes in this population. Total serum T3 levels, alone or in association with other predictive scores, were demonstrated to be an easy and valuable tool for risk stratification and should be further employed in this setting.

The first episode of spontaneous bacterial peritonitis is a threat event in children with end-stage liver disease.

OBJECTIVE: Studies on native liver survival (NLS) after the first episode of spontaneous bacterial peritonitis (SBP) are rare. Our objective was to evaluate NLS in children up to 1 year after SBP. METHODS: A historical cohort study of 18 children followed after the first episode of SBP was conducted. NLS, in-hospital mortality, causes of death, and rate of multidrug-resistant organisms were reported. RESULTS: Biliary atresia was the most prevalent diagnosis (72.2%); all were Child-Pugh C, and the median age was 1.0 year. The probability of NLS was 77.8, 27.8, and 11.1% at 1, 3 and 6 months, respectively. At 9 months, no child had the native liver. In-hospital mortality was 38.9%, and the main causes of death were septic shock and acute-on-chronic liver failure. Escherichia coli was the predominant organism cultured. Multidrug-resistant organisms were not detected. The cumulative probability of NLS was 77.8% at 1 month, 27.8% at 3 months, and 11.1% at 6 months. At 9-month follow-up, none of children had their native liver. Ascites PMN count cell more than 1000 cells/mm, positive ascites culture, and prolonged international normalized ratio reached a significant value as predictive factors of NLS and were selected for multivariate analysis. We did not identify independent predictors of survival. CONCLUSION: Development of SBP was a late event in children and had a high effect on NLS.

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)