FÍGADO GORDO NÃO-ALCOÓLICO ASSOCIADO A HIPOBETALIPOPROTEINEMIA: APRESENTAÇÃO DE TRÊS CASOS CLÍNICOS E DE UMA NOVA MUTAÇÃO NO GENE APOB

Background: Non-alcoholic fatty liver disease, the leading cause of chronic liver disease in children, is defined by hepatic fat infiltration >5% of hepatocytes, in the absence of excessive alcohol intake, evidence of viral, autoimmune or drug-induced liver disease. Conditions like rare genetic disorders must be considered in the differential diagnosis. Case Report: Two male brothers, and a non-related girl, all overweight, had liver steatosis. One of the brothers and the girl had elevated transaminases; all three presented with low total cholesterol, low density lipoproteins and very low density lipoproteins cholesterol levels, hypotriglyceridemia and low apolipoprotein B. A liver biopsy performed in the brother with citolysis confirmed steatohepatitis and the molecular study of apolipoprotein B gene showed a novel homozygous mutation (c.9353dup p.Asn3118Lysfs17). Patients with cytolysis lost weight, however liver steatosis persists. Conclusion: Fatty liver disease might be a consequence of hypobetalipoproteinemia. Evidence is scarce due to low number of reported cases

Neonatal Cholestasis Over Time: Changes in Epidemiology and Outcome in a Cohort of 154 Patients from a Portuguese Tertiary Center

Introduction: In the last two decades there have been advances in the diagnosis and management of neonatal cholestasis, which may have changed its epidemiology, diagnostic accuracy, outcomes, and survival. Our goal was to characterize these changes over time in our setting. Methods: Retrospective cohort study in a tertiary center, enrolling patients born between January 1985 and October 2019. The cohort was divided into two periods, before (A; n = 67) and after (B; n = 87) the year 2000; and in two groups, according to patient's outcome (favorable, unfavorable). Overall survival and survival with and without orthotopic liver transplant (OLT) were evaluated in the two periods (A and B) and in different subgroups of underlying entities. Results: We found that the age of cholestasis recognition decreased significantly from period A to period B [median 43 days and 22 days, respectively, (p < 0.001)]; the changes in epidemiology were relevant, with a significant decrease in alpha-1-antitrypsin deficiency (p < 0.001) and an increase in transient cholestasis (p = 0.004). A next-generation sequencing (NGS) panel available since mid-2017 was applied to 13 patients with contributory results in 7, but, so far, only in 2 patients led to conclusive diagnosis of underlying entities. The number of cases of idiopathic cholestasis did not vary significantly. Over time there was no significant change in the outcome (p = 0.116). Overall survival and survival without OLT had no significant improvement during the period of observation (in periods A and B, 86 vs. 88%, and 85 vs. 87%, respectively). However, in period B, with OLT we achieved the goal of 100% of survival rate. Conclusions: Our data suggest that transient cholestasis became a very important subset of neonatal cholestasis, requiring specific guidance. The NGS panels can provide important inputs on disease diagnosis but, if applied without strict criteria and expertise, they can open a Pandora's box due to misinterpretation. Despite all the advances in accurate diagnosis and timely management-including early recognition of cholestasis-the improvement in patient outcomes and survival were still not significant.This work was supported by Applied Molecular Biosciences Unit (UCIBIO), which was financed by national funds from FCT/MCTES (UID/MULTI/04378/2019)info:eu-repo/semantics/publishedVersio

Estilo de vida e adesão à terapêutica num grupo de pessoas portadoras de hipertensão arterial

The aim was to evaluate the lifestyle and adherence to therapy in a group of people with HTA, in a Personalized Health Care Unit. It is a quantitative, descriptive, and cross-sectional study. The sample is from 314 customers. An assessment protocol was used, with the following scales: Treatment Compliance Measure, Eating Habits Scale, Alcohol Use Disorders Identification Test, the Fagerström Nicotine Dependence Test and the International Physical Activity Questionnaire, short version. Results show that 88.2% of respondents adhere to the prescribed therapy. In terms of lifestyle, it appears that 96.2% of customers have adequate eating habits; 94.3% are unlikely to consume alcoholic beverages, 5.1% are smokers and 49.4% are “insufficiently active”. The results suggest the need to intervene in health promotion through a community program aimed at adherence to therapy and empowering the person to adopt a healthy lifestyle.Objetivou-se avaliar o estilo de vida e a adesão à terapêutica num grupo de pessoas portadoras de HTA, numa Unidade de Cuidados de Saúde Personalizados. É um estudo quantitativo, descritivo e transversal. A amostra é de 314 clientes. Utilizou-se um protocolo de avaliação, com as escalas: Medida de Adesão aos Tratamentos, Escala de Hábitos Alimentares, Alcohol Use Disorders Identification Test, o Teste de Fagerström de Dependência à Nicotina e o Questionário Internacional de Atividade Física versão curta. Resultados revelam que 88,2% dos inquiridos aderem à terapêutica prescrita. No estilo de vida, constata-se que 96,2% dos clientes têm hábitos alimentares adequados; 94,3% têm baixa probabilidade de consumir bebidas alcoólicas, 5,1% são fumadores e 49,4% são “insuficientemente ativos”. Os resultados sugerem a necessidade de intervir na promoção da saúde através de um programa comunitário que vise a adesão à terapêutica e capacite a pessoa na adoção de um estilo de vida saudável

Estilo de vida e adesão à terapêutica num grupo de pessoas portadoras de hipertensão arterial

The aim was to evaluate the lifestyle and adherence to therapy in a group of people with HTA, in a Personalized Health Care Unit. It is a quantitative, descriptive, and cross-sectional study. The sample is from 314 customers. An assessment protocol was used, with the following scales: Treatment Compliance Measure, Eating Habits Scale, Alcohol Use Disorders Identification Test, the Fagerström Nicotine Dependence Test and the International Physical Activity Questionnaire, short version. Results show that 88.2% of respondents adhere to the prescribed therapy. In terms of lifestyle, it appears that 96.2% of customers have adequate eating habits; 94.3% are unlikely to consume alcoholic beverages, 5.1% are smokers and 49.4% are “insufficiently active”. The results suggest the need to intervene in health promotion through a community program aimed at adherence to therapy and empowering the person to adopt a healthy lifestyle.Objetivou-se avaliar o estilo de vida e a adesão à terapêutica num grupo de pessoas portadoras de HTA, numa Unidade de Cuidados de Saúde Personalizados. É um estudo quantitativo, descritivo e transversal. A amostra é de 314 clientes. Utilizou-se um protocolo de avaliação, com as escalas: Medida de Adesão aos Tratamentos, Escala de Hábitos Alimentares, Alcohol Use Disorders Identification Test, o Teste de Fagerström de Dependência à Nicotina e o Questionário Internacional de Atividade Física versão curta. Resultados revelam que 88,2% dos inquiridos aderem à terapêutica prescrita. No estilo de vida, constata-se que 96,2% dos clientes têm hábitos alimentares adequados; 94,3% têm baixa probabilidade de consumir bebidas alcoólicas, 5,1% são fumadores e 49,4% são “insuficientemente ativos”. Os resultados sugerem a necessidade de intervir na promoção da saúde através de um programa comunitário que vise a adesão à terapêutica e capacite a pessoa na adoção de um estilo de vida saudável

A New Mutation Causing Progressive Familiar Intrahepatic Cholestasis Type 3 in Association with Autoimmune Hepatitis

Background: Some patients exhibit features of both autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC). Similarly, patients with progressive familial intrahepatic cholestasis type 3 (PFIC3) may share histological features with PSC. Case report: We report the case of a 22-year-old man who, since he was 5 years of age, has presented with pruritus, an approximately ninefold elevation of aminotransferases, and γ-glutamyl transferase levels ~10 times the upper limit. Initially he was diagnosed with an overlap syndrome of small duct PSC plus AIH. However, fluctuations in liver enzymes were observed over the following years. Analysis of the ABCB4 gene indicated the diagnosis of PFIC3, revealing a mutation not previously reported. Conclusion: With this case report we aim to describe a new mutation, raise awareness of this rare pathology and highlight the importance of genetic testing of the ABCB4 gene in patients with autoimmune liver disease (mainly small duct PSC) with incomplete response to immunosuppressive treatmen

Fatty Liver and Autoimmune Hepatitis: Two Forms of Liver Involvement in Lipodystrophies

Introduction: Lipodystrophies are a heterogeneous group of rare diseases (genetic or acquired) characterized by a partial or generalized deficit of adipose tissue, resulting in less energy storage capacity. They are associated with severe endocrine-metabolic complications with significant morbidity and mortality. In the pathogenesis of the acquired forms, immunological disorders may be involved. Case 1: A 13-year-old female was diagnosed with acquired generalized lipodystrophy and observed for suspicion of portal hypertension. She presented with generalized absence of adipose tissue, cervical and axillary acanthosis nigricans, and massive hepatosplenomegaly. Laboratory tests revealed AST 116 IU/L, ALT 238 IU/L, GGT 114 IU/L, HOMA-IR 28.2, triglycerides 491 mg/L, and leptin &#x3c; 0.05 ng/mL. Upper gastrointestinal endoscopy saw no signs of portal hypertension. Hepatic histology showed macrovesicular fatty infiltration (60% of hepatocytes) and advanced fibrosis/cirrhosis. Her clinical condition worsened progressively to diabetes requiring treatment with subcutaneous insulin and hepatopulmonary syndrome. Case 2: A 15-year-old female, diagnosed with acquired partial lipodystrophy, Parkinson syndrome, autoimmune thyroiditis, and autoimmune thrombocytopenia was observed for hypertransaminasemia since the age of 8 years. She had absence of subcutaneous adipose tissue in the upper and lower limbs and ataxia. Laboratory tests showed AST 461 IU/L, ALT 921 IU/L, GGT 145 IU/L, HOMA-IR 32.6, triglycerides 298 mg/dL, normal leptin levels, platelets 84,000/μL, IgG 1,894 mg/dL, positive anti-LKM and anti-LC-1. Hepatic histology was suggestive of autoimmune hepatitis, without steatosis. She progressed favorably under metformin and immunosuppressive treatment. Conclusion: Early recognition and adequate characterization of liver disease in lipodystrophies is essential for a correct treatment approach. In acquired generalized lipodystrophy, the severe endocrine-metabolic disorder, which leads to steatohepatitis with cirrhotic progression, may benefit from recombinant leptin treatment

Analysis of the UDP-glucuronosyltransferase gene in Portuguese patients with a clinical diagnosis of Gilbert and Crigler–Najjar syndromes

We describe the molecular study in a cohort of 120 Portuguese patients with the clinical diagnosis of Gilbert syndrome and in one with the diagnosis of Crigler–Najjar syndrome type II, as well as a prenatal diagnosis of Crigler–Najjar syndrome type I. Among the 120 unrelated patients with Gilbert syndrome, 110 were homozygous for the [TA]7 allele ([TA]7/[TA]7), and one patient was a compound heterozygote for two different insertions ([TA]7/[TA]8). The remaining 9 patients were heterozygous for the TA insertion ([TA]6/[TA]7). Additional studies in these 9 patients revealed heterozygosity for the c.674T>G, c.488_491dupACCT and c.923G>A mutations, in 1, 1 and 4 patients, respectively. The patient with Crigler–Najjar syndrome type II was a compound heterozygote for [TA]7 and the c.923G>A mutation. The undocumented polymorphisms c.-1126C>T and c.997-82T>C were also detected in the course of this study. Prenatal diagnosis in a family with a boy previously diagnosed as Crigler–Najjar syndrome type I and homozygosity for the c.923G>A mutation revealed that the fetus was unaffected. Homozygosity for the [TA] insertion was found to be the most frequent cause of GS in our population. Identification of further mutations in the UGT1A1 gene was also seen to contribute significantly towards diagnosis

Fatty Liver Caused by Glycogen Storage Disease Type IX: A Small Series of Cases in Children

Background: The prevalence of non-alcoholic fatty liver disease (NAFLD) affecting children and adolescents has increased dramatically in recent years. This increase is most probably related to the obesity pandemic and the high consumption of fructose. However, hepatic steatosis has some rare causes (e.g., some metabolic diseases) of which clinicians should be aware, particularly (but not only) when patients are non-obese or non-overweight. Differential diagnosis is notably important when pathologies have a specific treatment, such as for glycogenosis type IX (GSD-IX). Aims: To contribute to the knowledge on the differential diagnosis of NAFLD in paediatric age and to the clinical, biochemical, molecular, and histological characterisations of GSD-IX, a rare metabolic disorder. Methods: We performed a retrospective study of a small series of cases (n = 3) of GSD-IX diagnosed in the past 6 years, who were currently being followed up in the Units of Gastroenterology or Metabolic Diseases of the Paediatric Division of our hospital and whose clinical presentation was NAFLD in paediatric age. Results: Three male patients were diagnosed with NAFLD before 2 years of age, 2 with confirmed diagnosis before the age of 3 years (alanine aminotransferase [ALT], liver ultrasound, and molecular analysis) and 1 whose diagnosis was confirmed at 11 years (ALT, liver ultrasound, liver histology, and molecular analysis). None of the patients were obese or overweight, and the daily fructose consumption was unknown. The outcome was favourable in all 3 patients, with follow-up periods ranging from 2 to 6 years. Conclusion: The decision on how far the search for secondary causes of NAFLD should go can be difficult, and GSD-IX must be on the list of possible causes