Preeclampsia de presentación grave asociada a hígado graso agudo del embarazo / Severe preeclampsia associated with acute fatty liver of pregnancy / Pré-eclâmpsia grave associada a fígado gorduroso agudo da gravidez

La preeclampsia se puede asociar a una patología poco frecuente como es el hígado graso agudo del embarazo. Se reporta el caso clínico de una paciente de 35 años, tercigesta, cursando embarazo gemelar que presenta preeclampsia con elementos de gravedad, asociada a hígado graso agudo del embarazo. Se realiza diagnóstico y tratamiento precoz de ambas patologías, presentando buena evolución materno-fetal.

Preeclampsia can be associated with acute fatty liver of pregnancy, a rare disease. This report describes the case of a 35-year-old patient, gravida 3, pregnant with twins, who presented with severe pre-eclampsia associated with acute fatty liver of pregnancy. Early diagnosis and treatment of both pathologies was performed, resulting in good maternal-fetal evolution.

A pré-eclâmpsia pode estar associada a uma patologia rara, como o fígado gorduroso agudo da gravidez. Neste relato, apresentamos uma paciente de 35 anos, terciária, em gestação gemelar, apresentando pré-eclâmpsia grave, associada a esteatose hepática aguda na gestação. É realizado diagnóstico e tratamento precoces de ambas as patologias, apresentando boa evolução materno-fetal.

Hígado graso agudo del embarazo en una gestante peruana: a propósito de un caso / Acute fatty liver of pregnancy in a Peruvian pregnant woman: a case report

RESUMEN El hígado graso agudo del embarazo es una rara enfermedad de la gestación que se presenta con mayor preponderancia durante el tercer trimestre. Su etiología es desconocida, pero se evidencia un depósito micro vesicular de grasa a nivel del hepatocito. Tiene una mortalidad materno-fetal hasta un 20% debido a que el único tratamiento es terminar la gestación. Se reporta el caso de una gestante de 28 años de edad, con 36 semanas de embarazo, que acude con cuadro clínico de dolor abdominal asociado a malestar general, náuseas y vómitos. Los exámenes de laboratorio mostraron alteración del perfil hepático, falla renal y coagulopatía. La ecografía abdominal mostró infiltración hepática grasa. Se brindó manejo de soporte y regulación de trastornos hemodinámicos. El manejo final fue intervención de cesárea por emergencia debido a complicación de óbito fetal. La paciente fue dada de alta con mejoría de cuadro clínico y de las alteraciones de laboratorio.

ABSTRACT Acute fatty liver of pregnancy is a rare disease of pregnancy that occurs with greater preponderance during the third trimester. Its etiology is unknown, but there is evidence of a micro vesicular fat deposit in the hepatocyte. It has a maternal-fetal mortality up to 20% because the only treatment is to end gestation. We present a case of a 28-year-old pregnant woman, with 36 weeks of pregnancy, who had abdominal pain associated with general malaise, nausea and vomiting. Laboratory tests showed liver profile alteration, renal failure and coagulopathy. Abdominal ultrasound showed fatty liver infiltration. Support management and correction of hemodynamic disorders were provided. The final management was emergency caesarean section to avoid fetal death as a dreaded complication. The patient was discharged with improvement of clinical symptoms and laboratory alterations.

Actualización en el diagnóstico y manejo del daño hepático agudo grave en el embarazo / Causes and management of severe acute liver damage during pregnancy

Abnormalities in liver function tests appear in 3% of pregnancies. Severe acute liver damage can be an exclusive condition of pregnancy (dependent or independent of pre-eclampsia) or a concomitant disease. HELLP syndrome and acute fatty liver of pregnancy are the most severe liver diseases associated with pregnancy. Both appear during the third trimester and have a similar clinical presentation. Acute fatty liver may be associated with hypoglycemia and HELLP syndrome is closely linked with pre-eclampsia. Among concomitant conditions, fulminant acute hepatitis caused by medications or virus is the most severe disease. Its clinical presentation may be hyper-acute with neurological involvement and severe coagulation disorders. It has a high mortality and patients should be transplanted. Fulminant hepatic failure caused by acetaminophen overdose can be managed with n-acetyl cysteine. Because of the high fetal mortality rate, the gestational age at diagnosis is crucial.

Enfermedad de hígado graso no alcohólico: Un problema silente en la salud Costarricense / Non alcoholic fatty liver disease: A silent problem in Costa Rican health

La enfermedad de hígado graso no alcohólico es una condición que engloba el espectro de esteatosis hepática no alcohólica simple y esteatohepatitis no alcohólica. Esta entidad afecta de un 20 a 30% de la población adulta general en sociedades occidentales. Asimismo suele estar asociada a obesidad, síndrome metabólico, diabetes, entre otras patologías cada vez más frecuentes a nivel mundial. Recientemente se reporta una prevalencia alarmante de 72% en pacientes diabéticos tipo 2 en Costa Rica, los cuales representan un aproximado 10,5% de los costarricenses. Su alta prevalencia, clínica silente, asociación importante a riesgo cardiovascular y de complicaciones hepáticas serias, convierten esta entidad en un tema de suma relevancia para la salud pública...

Non-alcoholic fatty liver disease is a condition that encompasses the spectrum of simple hepatic steatosis and non-alcoholic steatohepatitis. This condition affects 20 to 30% of the general adult population in Western societies. Is often associated with obesity, metabolic syndrome, and diabetes among other frequent diseases nowadays. Recently it has been reported an alarming prevalence of 72% diabetic type 2 patients in Costa Rica, which are approximately 10,5% of the population in the country. Its high prevalence, silent clinical manifestations, important cardiovascular risk and serious liver complications association, turn this entity on a topic of great relevance to public health...

Hígado graso no alcohólico en pediatría / Pediatric nonalcoholic fatty liver

La obesidad es un síndrome o trastorno nutricional multifactorial complejo con causas genéticas, conductuales y ambientales, es la forma más común de malnutrición en los países desarrollados y en muchos en vías de desarrollo. El HGNA se define como una entidad anátomo-patológica con la acumulación macrovesicular de grasa (triglicéridos) superior al 5 por ciento de los hepatocitos. El espectro de esta enfermedad incluye la esteatosis simple, la esteatohepatitis no alcohólica, que puede acompañarse de varios grados de fibrosis, y en su etapa final la cirrosis. El objetivo de esta revisión resumir en forma monográfica los aspectos más esenciales de esta afección en pediatría para el uso de cualquier especialista médico...

Obesity is a complex multifactor nutritional syndrome or disease with genetic, behavioral and environmental causes, and it is also the most common form of malnutrition in developed and in many developing countries. The NAFL is defined as an anatomical-pathological disease showing over 5 percent macrovesicular accumulation of adiposity (triglycerides) in hepatocytes. The spectrum of this disease includes simple steatosis, non-alcoholic steatohepatitis that may be accompanied by several levels of fibrosis, and finally cirrhosis in the final stage. The objective of this review was to summarize in a monographic way the most essential aspects of this disease at pediatric ages so that this information may be used by any medical expert...

Hígado graso agudo del embarazo y síndrome HELLP: aspectos diagnósticos y terapéuticos / Acute fatty liver of pregnancy and HELLP syndrome: diagnostic and therapeutic aspects

HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count) and acute fatty liver of pregnancy (AFLP), cause liver dysfunction in the third trimester of pregnancy and determine risk of maternal and fetal mortality. Many maternal complications can occur, including acute renal failure and coagulopathy. Early diagnosis, prompt delivery and adequate supportive care are the key to a good outcome in most of the patients. In some cases, despite an appropriate conventional management, the disease may progress to multiple organ dysfunction, progressive liver insufficiency or severe hepatic complications (subcapsular hematoma, liver rupture), requiring adjunctive medical therapy, such as plasma exchange, surgery or liver transplantation.

El síndrome HELLP (hemolysis, elevated liver enzymes, and low platelet count) y el hígado graso agudo del embarazo (acute fatty liver of pregnancy -AFLP), son causa de disfunción hepática en el tercer trimestre del embarazo y condicionan riesgo de mortalidad materna fetal. Se pueden presentar diversas complicaciones como insuficiencia renal aguda y coagulopatía, entre otras. El diagnóstico oportuno, la interrupción del embarazo y un manejo de sostén adecuado permiten sacar adelante a la mayoría de las pacientes. En algunos casos, a pesar de un manejo convencional adecuado, la enfermedad puede evolucionar con disfunción multiorgánica, insuficiencia hepática progresiva o complicaciones hepáticas graves (hematoma subcapsular, rotura hepática), requiriendo de terapia médica adyuvante, como la plasmaféresis, cirugía o incluso trasplante hepático.

Effect of a probiotic and metformin on liver aminotransferases in non-alcoholic steatohepatitis: a double blind randomized clinical trial

Non-alcoholic steatohepatitis [NASH] is a clinicopathological entity that is being recognized more frequently in recent years. This study aimed to evaluate the effects of Metformin, with and without a probiotic supplement on liver aminotransferases in patients with NASH. Sixty four patients 18-75 years with NASH confirmed by biopsy and histological assessment were enrolled to study. Patients were randomized to one of the following treatments for 6 months: Group I, probiotic [Protexin two tablets per day] plus Metformin 500 mg two tablets per day [Met/Pro], or group II, Metformin 500 mg two tablets per day plus two placebo tablet [Met/P]. After 6 month alanine aminotransferase [ALT], aspartate aminotransferase, and ultrasound grading of NASH were assessed. In group I, serum alanine aminotransferase [ALT: 133.7 +/- 70 vs. 45.2 +/- 32.5; P < 0.00], and aspartate aminotransferase activity [AST: 123.1 +/- 72 vs. 44.2 +/- 33.9; P < 0.001], and ultrasound grading of NASH [P < 0.001] all decreased significantly by the end of the treatment period. In group II, while serum alanine aminotransferase [ALT] was not significantly reduced [118.4 +/- 67.9 vs. 112.5 +/- 68.7; P < 0.064], aspartate aminotransferase activity [AST: 125.3 +/- 71 vs. 113.4 +/- 71; P < 0.001], and ultrasound grading of NASH did fall significantly [P < 0.01]. Body mass index [BMI], fasting blood sugar [FBS], cholesterol, and triglyceride fell significantly in both groups. Probiotic combination with Metformin improves liver aminotransferases better than metformin alone in patients with NASH

Novedades en esteatohepatitis no alcohólica / Advances in non–alcoholic steatohepatitis

The non-alcoholic fatty liver disease is the most common cause of chronic liver disease in the western countries. A subset of patients with this problem may progress to cirrhosis and liver cancer. The development of nonalcoholic steatohepatitis (NASH) and fibrosis identifies patients with an increased risk of cirrhosis. Although the exact pathological mechanism is unknown. Several hypotheses suggest that the liver damage is multifactorial. Lipototoxicity, oxidative stress, and cytokines may each play a role in transition of steatosis into NASH. Despite a number of clinical trials on the treatment, there is still no approved therapy. The most important treatment for this disease is to motivate affected persons to adopt a healthier lifestyle. In this article, the recent overall evidence on pathogenesis, treatment and potential lines of future research of nonalcoholic fatty liver disease are reviewed.

La enfermedad hepática grasa no alcohólica es la causa más prevalente de enfermedad hepática crónica en el mundo occidental. Una parte de estos pacientes desarrollará cirrosis y hepatocarcinoma. Obesidad, diabetes mellitus II e insulino resistencia son los principales factores de riesgo. La presencia de esteatohepatitis y fibrosis se relaciona directamente con progresión a cirrosis y sus complicaciones. A pesar de los avances en el conocimiento sobre la enfermedad, su patogénesis aún no está dilucidada; la mayoría de las hipótesis apuntan a un daño multifactorial. Lipotoxicidad, estrés oxidativo, citoquinas inflamatorias y predisposición genética juegan un importante rol en la progresión de la enfermedad. Numerosos estudios se han efectuado para validar las opciones de tratamiento, sin embargo, están limitados por el número pequeño de pacientes enrolados, la corta duración y el seguimiento inadecuado. Se requieren ensayos randomizados, controlados y doble-ciego para evaluar la eficacia y seguridad de estas drogas. Como aún no existe una droga eficaz y segura para el tratamiento, nuestros esfuerzos deben dirigirse a modificar los estilos de vida, promoviendo la baja de peso y el aumento de la actividad física. En este artículo se revisan las novedades en el diagnóstico, patogénesis, tratamiento y futuras líneas de investigación.

effect of chronic intermittent hypoxia in the evolution of NASH

Obstructive sleep apnea [OSA] causes chronic intermittent hypoxia [CIH] during sleep. OSA is associated with nonalcoholic steatohepatitis [NASH] in obese individuals and may contribute to progression of nonalcoholic fatty liver disease [NAFLD] from steatosis to steatohepatitis. To assess the potential role of hypoxia in the development of NASH in obstructive sleep apnea patients. Nocturnal polysomnography was performed in 60 consecutive patients for clinical suspicion of OSA. We investigated fasting blood glucose, serum insulin, TNF-alpha, ABG and liver enzymes for 30 patients with nocturnal polysomnographic recording of OSA and for 15 patients without recording OSA used as controls. Liver biopsy was offered to 15 of 30 patients with elevated liver enzymes. Patients with OSA had significantly higher levels of insulin and were more insulin-resistant according to HOMA-IR than in controls. We found that the parameters which significantly correlated with AHI were elevated liver enzyme, BMI, ultrasound grading, TNF-alpha and HOMA-IR in patients group but did not find a similar correlation in controls. Liver biopsy showed steatosis with lobular necrosis or hepatocyte ballooning in the 15 patients, associated with fibrosis in 5 patients. Hypoxic stress of obstructive sleep apnea may be implicated in the evolution of insulin resistance and steatohepatitis in obese individuals

Non-alcoholic steatohepatitis: an update in pathophysiology, diagnosis and therapy

Non-alcoholic steatohepatitis [NASH], first described by Ludwig et al, in 1980, is a stage in the wide spectrum of non-alcoholic fatty liver diseases [NAFLDs] and one of the leading causes of chronic liver disease. Several scientists have tried to more distinctly discover and describe different aspects of NASH. In contrast with its counterpart in the NAFLDs-the NAFL-NASH consists of inflammation as well as necrosis in the liver tissue resulting in a poor outcome. NASH is also a known etiology for cryptogenic liver cirrhosis. Evidence suggests that cirrhosis developing due to NASH have a relatively worse outcome compared to that of hepatitis C-related cirrhosis. In this review article, we try to review and present all relevant articles about NASH

Tratamiento del hígado graso no alcohólico: ¿qué sabemos?: [revisión] / Treatment of non-alcoholic fatty liver disease: what do we know?: [review]

Non-alcoholic fatty liver disease (NAFLD) is now recognized as one the most common liver diseases worldwide and is emerging as a frequent cause of liver-related mortality thus representing a significant health burden around the world. NAFLD is a clinical-pathological disease that has become more relevant in the recent years, resulting in a vast corpus of scientific information. Major clinical issues in management of patients with NAFLD are recognition of subjects at risk of progression towards chronic liver disease including cirrhosis as well as medical treatment of the condition with both pharmacological and non-pharmacological strategies. This article reviews currently available evidence about NAFLD management.

El hígado graso no alcohólico (HGNA) es considerada en la actualidad como una de las enfermedades hepáticas más comunes a nivel mundial y emerge como una causa frecuente de mortalidad asociada a enfermedades hepáticas, así como un significativo impacto en los costos de salud alrededor del mundo. El HGNA es una entidad clínico-patológica que ha cobrado relevancia en los últimos años, dando origen a gran cantidad de información científica. Los aspectos clínicos más importantes del manejo de pacientes con HGNA son el reconocimiento de sujetos en riesgo de progresar a formas de enfermedad hepática más avanzadas, incluyendo la cirrosis así como el tratamiento medico de esta condición con medidas farmacológicas y no-farmacológicas. El presente articulo revisa la evidencia disponible acerca de los conceptos actuales sobre el manejo del hígado graso no alcohólico.

effect of weight reduction on ultrasonographic findings of non alcoholic fatty liver

Non-alcoholic fatty liver [NAFL] includes a spectrum of diseases ranging from simple hepatic steatosis to nonalcoholic steatohepatitis [NASH] and cirrhosis. NAFL is typically seen in association with obesity, diabetes and hypertriglyceridaemia. In order to seek the role of diet therapy in treatment of NAFL, we compared the ultrasonographic findings of patients with fatty liver disease before and after standard diet therapy. Twenty-three overweight or obese subjects with incidental fatty liver discovered during ultrasonography were included. Subjects underwent 3 months of diet therapy, and anthropometric data including weight, height, BMI, waist circumference, and hip circumference were measured. Ultrasonographic findings were graded from 0 to 3. Changes in ultrasonographic findings and anthropometric data were studied. After three months of dieting, the ultrasonographic grade of all patients decreased by one or two grades. Fifteen patients decreased one grade while 8 others decreased by 2 grades. We observed a significant correlation between the decrease in ultrasonographic grade and the decrease in weight and BMI. Our study indicates that standard diet therapy could be used as an effective treatment for NAFL patients

Hígado graso no alcohólico: una entidad relevante para el endocrinólogo / The relevance of non-alcoholic fatty liver for endocrinologists

Non-alcoholic fatty liver disease (NAFLD) is emerging as a leading cause of chronic liver disease worldwide. Although its pathophysiology is not completely understood, insulin resistance has been identified as a central event involved in both pathogenesis and progression of the disease. Due to its asymptomatic nature and its benign evolution in the majority of cases, awareness about the possibilityof progression of NAFLD among non-hepatologists is limited. Different studies indicate that non-alcoholic steatohepatitis, the inflammatory form of NAFLD, can progress to more advanced stages of chronic liver disease including cirrhosis in up to 25 percent of cases in a decade. Furthermore, recent data show that NAFLD is an important risk factor for developing cardiovascular events and diabetes. This article briefly reviews current concepts on NAFLD. As endocrinologists frequently face patients with insulin resistance, the identification of patients with NAFLD and the assessment of prognosis acquires significant clinical relevance.

Protective roles of adiponectin in obesity-related fatty liver diseases: mechanisms and therapeutic implications: [review] / Adiponectina e seu papel na proteção contra a doença hepática gordurosa na obesidade: mecanismos e implicações terapêuticas: [revisão]

Adiponectin is an insulin-sensitizing adipokine possessing multiple beneficial effects on obesity-related medical complications. This adipokine is secreted from adipocytes into the circulation as three oligomeric isoforms, including trimer, hexamer and the high molecular weight (HMW) oligomeric complex. Each oligomeric isoform of adiponectin possesses distinct biological properties and activates different signaling pathways in various target tissues. The hepato-protective activities have been demonstrated by many clinical and experimental studies. The decreased level of serum adiponectin represents an independent risk factor for nonalcoholic fatty liver disease (NAFLD) and liver dysfunctions in humans. In animals, elevation of circulating adiponectin by either pharmacological or genetic approaches leads to a significant alleviation of hepatomegaly, steatosis and necro-inflammation associated with various liver diseases. In adiponectin knockout mice, there is a pre-existing condition of hepatic steatosis and mitochondria dysfunction, which might contribute to the increased vulnerabilities of these mice to the secondary liver injuries induced by obesity and other conditions. This review aims to summarize recent advances on delination of the structural, molecular and cellular mechanisms underlying the hepato-protective properties of adiponectin.

A adiponectina é uma adipocitocina com ação insulino-sensibilizadora com múltiplos efeitos benéficos sobre as complicações clínicas da obesidade. Essa adipocitocina é secretada pelos adipócitos na circulação sistêmica em três isoformas oligoméricas, incluindo as formas em trímeros, hexâmeros e complexas de alto peso molecular (HMW). Cada forma oligomérica da adiponectina apresenta propriedades biológicas distintas e ativam diferentes vias de sinalização celular em diversos tecidos. Suas atividades hepatoprotetoras têm sido descritas em vários estudos clínicos e experimentais. Em humanos, os níveis reduzidos da adiponectina sérica, características da obesidade, representam um fator de risco independente para a doença hepática gordurosa não-alcoólica (NAFLD), incluindo variados graus de disfunções hepáticas. Em animais, a elevação dos níveis circulantes de adiponectina, por manipulações genéticas ou farmacológicas, conduz a uma atenuação da hepatomegalia, da esteatose e da necroinflamação usualmente associadas a várias doenças hepáticas. No animal sem o gene da adiponectina (knockout), existe uma condição preexistente de esteatose e disfunção mitocondrial que contribui para a vulnerabilidade desses animais aos processos de lesões teciduais hepáticos induzidos pela obesidade e outras condições. Esta revisão sumariza os recentes avanços na compreensão e caracterização dos mecanismos celulares, moleculares e estruturais das ações hepatoprotetoras da adiponectina.

Acute fatty liver of pregnancy [Incidence, pathogenesis, diagnosis, treatment and prognosis]

Acute fatty liver of pregnancy [AFLP] is a rare, potentially fatal complication that occurs in the third trimester or early postpartum period. It generally appears between weeks 30 and 38. Usually the APLF symptoms start one to two weeks before hospitalization with nausea, emesis, general uneasiness, jaundice, epigastric pain and other symptoms. A careful history and physical examination, in conjunction with compatible laboratory and imaging results, are often sufficient to make the diagnosis, and liver biopsy is rarely indicated. The maternal outcome has improved enormously during the last decade. Early diagnosis, pregnancy interuption and handling in special care or treating complications has lead to good materno-fetal results

Hígado graso: enfoque diagnóstico y terapéutico / Fatty liver. Diagnostic and therapeutic approach

El enfoque diagnóstico y terapéutico propuesto en esta revisión sobre hígado graso se hizo en función de las necesidades del médico práctico. Se planteó una disquisición teórica sobre el problema terminológico de este síndrome y se abordaron los mecanismos patogénicos comunes en las diferentes condiciones clínicas que predisponen a padecer este problema de salud que puede presentarse como una simple esteatosis hepática, pero también puede llegar a ser causa de una cirrosis hepática que conduzca al paciente a un transplante hepático. Se consideró la importancia de sopesar la suma de factores que predisponen a la enfermedad, los estudios imagenológicos y marcadores de riesgo de desarrollo de fibrosis antes de indicar la biopsia hepática. El tratamiento va dirigido a disminuir el flujo de ácidos grasos al hígado, proteger al hepatocito de mecanismos oxidativos, evitar tóxicos conocidos que dañen al hígado y tratar los factores condicionantes o asociados. Se propuso un algoritmo de atención y seguimiento de estos enfermos.

Hepatites / Hepatitis

É um estudo aprofundado das hepatites virais, em sua epidemiologia, clínica e no diagnóstico e tratamento das formas agudas e crônicas. As hepatites virais B e C são abordadas também em situações especiais, como no paciente renal crônico, no pós-transplante, nas co-infecções HIV-VHC, HIV-VHB e nas hepatites agudas com evolução para formas fulminantes. Questões relevantes e atuais sobre a esteatoepatite não-alcoólica, hepatites medicamentosas, hepatites alcoólica e auto-imune, que podem ter evolução para formas graves, com desenvolvimento de cirrose hepática, são relevantes nesta obra. Em capítulo especial é analisado o carcinoma hepatocelular, visto sua elevada frequência e relação com as hepatites virais (VHB e VHC).