Acute Fatty Liver Disease Research Articles

Gene expression profiling in livers of mice after acute inhibition of β-oxidation

Inborn errors of mitochondrial β-oxidation cause ectopic fat accumulation, particularly in the liver. Fatty liver is associated with insulin resistance and predisposes to hepatic fibrosis. The factors underlying the pathophysiological consequences of hepatic fat accumulation have remained poorly defined. Gene expression profiling in a model of acute fatty liver disease induced by blocking long-chain fatty acid β-oxidation was performed to study the early effects of steatosis on the transcriptome. Tetradecylglycidic acid (TDGA) was used to irreversibly inhibit carnitine palmitoyltransferase 1, a key enzyme in the control of mitochondrial β-oxidation. TDGA treatment induced massive microvesicular hepatic steatosis within a 12-h time frame in male C57BL6/J mice. Increased hepatic long-chain acyl-CoA content, particularly of C16:0, C16:1 and C18:1, was associated with profound effects on the transcriptome as revealed by unbiased gene expression profiling and quantitative real-time PCR. The results indicate drastic changes in the expression of genes encoding proteins involved in lipid, carbohydrate, and amino acid metabolism. Pathway analysis identified transcription factors and coregulators such as hepatocyte nuclear factor 4 (HNF4), peroxisome proliferator-activated receptor-α (PPAR-α), and PPAR gamma coactivator 1α (PGC-1α ) as key players in these metabolic adaptations. Apoptotic and profibrotic responses were also affected. Surprisingly, a strong reduction in the expression of genes involved in hepatic bile salt metabolism and transport was observed. Therefore, this transcriptome analysis opens new avenues for research.

Acute Fatty Liver Disease after Suprasellar Tumor Resection

Acute Fatty Liver Disease after Suprasellar Tumor Resection

MATERNAL ACUTE FATTY LIVER OF PREGNANCY AND THE ASSOCIATED RISK FOR LONG-CHAIN 3-HYDROXYACYL-COENZYME A DEHYDROGENASE (LCHAD) DEFICIENCY IN INFANTS

Acute fatty liver disease of pregnancy has been recognized as a clinical problem since the 1980s. In the past 8 years, the association of this disease with a genetic inborn error of metabolism in the infant has been recognized. Women who are heterozygous for this disorder are usually asymptomatic until the capacity of their livers to metabolize free fatty acids (FFA) is overwhelmed by a homozygous fetus. The inborn error of metabolism, long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency, may not be immediately recognizable in the infant. Symptoms in the infant are often triggered by an increased long-chain fatty acid load in the diet, or by illness that results in breakdown of endogenous fat. The following case study reviews the clinical pathophysiology of this perinatal health problem and highlights the priorities for the care of infants born to mothers with acute fatty liver disease of pregnancy.

Morte materna em hospital terciário do Rio Grande do Sul - Brasil: um estudo de 20 anos

OBJETIVO: analisar os casos de morte materna ocorridos no Hospital de Clínicas de Porto Alegre (HCPA), hospital universitário de referência para gestação de alto risco no Rio Grande do Sul. MÉTODOS: realizamos estudo retrospectivo analisando os prontuários médicos das mulheres entre 10 e 49 anos que morreram no HCPA no período de 1980 a 1999. Foram analisadas apenas as mortes relacionadas a gestação e puerpério (até 365 dias após o término da gestação), independente do tipo e duração da gestação. As causas foram separadas em causas obstétricas diretas, obstétricas indiretas e causas não obstétricas. RESULTADOS: entre as causas obstétricas diretas (61,7%), destacaram-se a hipertensão arterial (18,5%), a infecção pós-cesariana (16%) e o aborto séptico (12,3%). Dentre as causas obstétricas indiretas (23,5%), as mais prevalentes foram a cardiopatia (8,6%), o fígado gorduroso agudo (3,5%) e o lúpus eritematoso sistêmico (2,5%). Dentre as causas não obstétricas (15,0%), destacam-se as neoplasias malignas (7,4%) e a AIDS (3,7%). CONCLUSÕES: a prevalência das principais causas de morte materna não sofreu modificação nas últimas duas décadas, sendo que a principal causa continua sendo a hipertensão arterial. Também, há número significativo de mortes relacionadas à cesariana (relacionadas ao procedimento) e às infecções. Podemos concluir que a prevalência de causas obstétricas diretas aponta para a baixa capacidade de prevenção de morte materna no nosso sistema de saúde.

HIV Screening by the Tri-Service Surgical Specialties

A 32-year-old HIV-positive black female underwent 70 days of intensive care after she developed acute fatty liver disease of pregnancy. During her hospitalization, multiple invasive procedures were performed on this patient and many residents, staff, nurses, and technicians were exposed to her body secretions. The patient was identified as HIV positive on a routine screen and denied any risk factors for AIDS. This case served as a catalyst to assess current screening efforts in the military for HIV. A questionnaire was distributed to OB/GYN, general surgery, and urology programs throughout the Army, Navy, and Air Force and the results are presented and discussed.