Mechanism of gut-microbiota-liver axis in the pathogenesis of intestinal failure-associated liver disease / 中华胃肠外科杂志

Intestinal failure (IF) is defined as the critical reduction of functional intestines below the minimum needed to absorb nutrients and fluids, so that intravenous supplementation with parenteral nutrition (PN) is required to maintain health and/or growth. Although the benefits are evident, patients receiving PN can suffer from serious cholestasis due to lack of enteral feeding and small intestinal bacterial overgrowth (SIBO). One such complication that may arise is intestinal failure-associated liver disease (IFALD). Evidences from recent studies suggest that alterations in the intestinal microbiota, as well as intraluminal bile acid driven signaling, may play a critical role in both hepatic and intestinal injury. Since Marshall first proposed the concept of the gut-liver axis in 1998, the role of gut-liver axis disorders in the development of IFALD has received considerable attention. The conversation between gut and liver is the key to maintain liver metabolism and intestinal homeostasis, which influences each other and is reciprocal causation. However, as a "forgotten organ" , intestinal microbiota on the pathogenesis of IFALD has not been well reflected. As such, we propose, for the first time, the concept of gut-microbiota-liver axis to emphasize the importance of intestinal microbiota in the interaction of gut-liver axis. Analysis and research on gut-microbiota-liver axis will be of great significance for understanding the pathogenesis of IFALD and improving the prevention and treatment measures.

Manifestaciones gastrointestinales y hepáticas de COVID-19 en niños / Gastrointestinal and hepatic manifestations of COVID-19 in children

Resumen: SARS-CoV-2 es un virus de alta estabilidad ambiental. Es principalmente un patógeno respiratorio que también afecta el tracto gastrointestinal. El receptor ACE2 es el principal receptor de SARS- CoV-2, hay evidencia de su elevada presencia en intestino, colon y colangiocitos; igualmente se en cuentra expresado en hepatocitos pero en menor proporción. SARS-CoV-2 tiene un tropismo gas trointestinal que explica los síntomas digestivos y la diseminación viral en deposiciones. Las caracte rísticas de SARS-CoV-2 incluyen a la proteína S (Spike o Espícula) que se une de forma muy estable al receptor ACE2. La infección por SARS-CoV-2 produce disbiosis y alteraciones en el eje pulmón- intestino. A nivel intestinal y hepático produce una respuesta Linfocitos T evidente y una respuesta de citocinas que producirían daño intestinal inflamatorio. Las manifestaciones a nivel intestinal en orden de frecuencia son pérdida de apetito, diarrea, náuseas, vómitos y dolor abdominal. Éste último podría ser un marcador de gravedad. En niños la diarrea es habitualmente leve y autolimitada. A nivel hepático la hipertransaminasemia ocurre en 40-60% de los pacientes graves. SARS-CoV-2 puede per manecer en deposiciones un tiempo más prolongado que en secreciones respiratorias, este hallazgo influiría en la diseminación de enfermedad. En esta revisión se destaca la importancia de efectuar un reconocimiento precoz de las manifestaciones gastrointestinales y hepáticas, aumentar el índice de sospecha, efectuar un diagnóstico oportuno y reconocer eventuales complicaciones de la enferme dad. La potencial transmisión fecal oral puede influir en la diseminación de enfermedad. Reconocer este hallazgo es importante para definir aislamiento.

Abstract: SARS-CoV-2 is a high environmental stable virus. It is predominantly a respiratory pathogen that also affects the gastrointestinal tract. The ACE 2 receptor is the main receptor of SARS-CoV-2, with evidence of its high presence in the intestine, colon and cholangiocytes, and, in smaller proportion, in hepatocytes. SARS-CoV-2 has a gastrointestinal tropism that explains digestive symptoms and viral spread in stools. The characteristics of this virus include the S (Spike) protein that binds very stably to the ACE-2 receptor and, at the same time, SARS-CoV-2 produces dysbiosis and alterations in the gut-lung axis. It produces a clear T-cell response and a cytokines storm in the intestine and liver that would produce inflammatory bowel damage. Intestinal manifestations by order of frequency are loss of appetite, diarrhea, nausea and vomiting, and abdominal pain, where the latter could be a severity marker. In children, diarrhea is the most frequent symptom, usually mild and self-limiting. In the liver, hypertransaminasemia occurs in severe patients ranging from 40 to 60%. SARS-CoV-2 can re main in stools longer than in respiratory secretions, which would influence the spread of disease. This article highlights the importance of an early diagnosis of gastrointestinal and hepatic manifestations, increase the index of suspicion, make a timely diagnosis, and recognize eventual complications of the disease. The potential oral-fecal route of transmission may influence the disease spread. Recognizing this finding is important to define isolation.

Distúrbios ácido-base nas doenças hepáticas / Acid-base disorders in liver diseases

O objetivo deste artigo foi abordar as controvérsias científicas acerca dos distúrbios ácido-base nas doenças hepáticas. Nos estágios avançados da doença hepática, os distúrbios ácido-base atuam de forma complexa, comprometendo a qualidade de vida do paciente e desafiando o manejo clínico. A literatura apresenta a alcalose respiratória como uma das principais alterações, porém há uma longa discussão sobre o mecanismo fisiopatológico; em especial, citam-se a hipóxia, a hipocapnia e o nível de progesterona. Nas desordens metabólicas, com destaque para a acidose, os estudos apontam principalmente o lactato, os unmeasured ions ou íons não medidos e as alterações hidroeletrolíticas, mas cada componente desse sobressai-se dependendo da fase da doença estudada, compensada ou descompensada. As controvérsias dos distúrbios ácido-base nas doenças hepáticas devem-se ora à complexidade da fisiopatologia da própria doença, ora à necessidade de mais estudos esclarecedores.

The aim of this study is to address the scientific controversy about acid-base disorders in liver diseases. In the end stage of liver diseases, the acid-base disorder has a complex performance, impairing the patient's quality of life and challenging the clinic management. Although the literature shows respiratory alkalosis as one of the main alterations, there is a long discussion about the pathophysiological mechanism, specially regarding hypoxia, hypocapnia, and progesterone level. In metabolic disorders, especially acidosis, the studies mainly indicate the lactate, unmeasured ions, and hydroelectrolytic alterations, but, depending on the disease phase, either compensated or decompensated, each element has a particular action. The controversy about acid-base disorders in liver diseases is associated with the complexity of this condition, as well as with the necessity of more specialized research.

Impacto del COVID-19 en las enfermedades hepáticas y la salud pública en el Perú / Impact of COVID-19 on liver disease and the public health in Peru

RESUMEN La pandemia declarada por la OMS originada por el COVID-19 (enfermedad infecciosa originada por el virus SARS-CoV2), desde su aparición en Wuhan, China en diciembre 2019; esta diseminándose rápidamente y de manera inesperada por todo el mundo originando millones de casos y miles de muertes, afectando más de 120 países y desde el 06 marzo 2020 al Perú, distribuyéndose rápidamente por todo el país, originando crisis y colapso del sistema de servicios de salud, especialmente de las atenciones en emergencia, hospitalizaciones y unidades de cuidados intensivos abarrotadas; sin tener aún un tratamiento específico ni la posibilidad de una vacuna a corto plazo. Se sabe actualmente que COVID-19, es una enfermedad sistémica que puede afectar múltiples órganos y tejidos y que puede ser fatal. El objetivo de esta revisión es mostrar lo descrito en los recientes estudios publicados a nivel mundial incluido nuestro país, que han reportado sus manifestaciones clínicas, esbozando posibles mecanismos de disfunción hepática relacionados a COVID-19 y sus repercusiones, en especial sobre el aparato digestivo; analizando y discutiendo el potencial impacto sobre ellas y las enfermedades del hígado, enunciando las recomendaciones de expertos y organizaciones científicas respecto a medidas de prevención, control y manejo, además de esbozar algunas estrategias de salud pública en nuestro país para la adecuada atención de estos pacientes en tiempos de crisis generalizada.

ABSTRACT The pandemic of COVID-19 (an infectious disease caused by the SARS-CoV2 virus), declared as such by the WHO, is spreading since its appearance in Wuhan (China) in December 2019, rapidly and unexpectedly throughout the world, causing millions of cases and thousands of deaths and has affected more than 120 countries. It was officially acknowledged in Peru on March 6th, 2020, and has spread rapidly throughout the country, causing first the crisis and then the collapse of the healthcare system, especially emergency care, admissions, and overcrowded intensive care units, not having a specific treatment or the foreseeable possibility of a short-term vaccine. COVID-19 is currently known for being a systemic disease that can affect multiple organs and tissues and can be fatal. The goal of this review is to present what has been described in recent studies, published worldwide and including our country, that have reported clinical manifestations, outlining possible mechanisms of liver dysfunction related to COVID-19 and its repercussions, especially on the digestive system. These studies analyze and discuss the potential impact on liver diseases, offering recommendations of experts and scientific organizations regarding prevention, control and management measures, outlining also some public health strategies in our country for the proper care of COVID-19 patients in times of widespread crisis.

Glucogenosis hepática: a propósito de un caso / Hepatic glycogenosis: a case report

RESUMEN Las glucogenosis abarcan un rango de enfermedades que se caracterizan por el almacenamiento o utilización anormal del glucógeno, siendo los órganos más afectados el músculo y/o el hígado. La hepatomegalia puede ser un signo clínico que guie al diagnóstico. Describimos a un paciente de 15 años de edad con hepatomegalia, hipertransaminasemia y retraso del crecimiento, a quien se le diagnosticó glucogenosis por biopsia hepática.

ABSTRACT The glycogen storage diseases contain a range of diseases that are characterized by the abnormal storage or utilization of glycogen, the organs most affected being muscle and / or liver. Hepatomegaly may be a clinical sign that could guide to the diagnosis. We describe a 15-year-old patient with hepatomegaly, hypertransaminasemia and growth retardation. He was diagnosed with a glycogen storage disease by liver biopsy.

Enfermedad granulomatosa hepática / Hepatic granulomatous disease

Resumen Los granulomas son lesiones circunscritas compuestas principalmente por células mononucleares que surgen en respuesta a estímulos antigénicos pobremente degradables. Se encuentran en 2 a 15 % de las biopsias hepáticas; su hallazgo puede significar desde un fenómeno incidental, hasta la manifestación de una enfermedad sistémica de origen infeccioso, autoinmune o neoplásico. El cuadro clínico suele apuntar a la patología subyacente, sin embargo, la lista de condiciones asociadas es amplia y difiere con base en los antecedentes epidemiológicos y a las características basales del paciente. El elemento de mayor utilidad para su estudio es la historia clínica exhaustiva, con énfasis en viajes recientes, exposición de riesgo y consumo de fármacos o alimentos crudos o exóticos. El análisis histopatológico detallado puede auxiliar en la identificación de la etiología, por ejemplo, la presencia de granulomas epitelioides con necrosis caseosa indica tuberculosis y su ausencia, sarcoidosis; la abundancia de eosinófilos es señal de reacciones farmacológicas o infecciones parasitarias; la presencia de cuerpos extraños puede ser la causa de la enfermedad granulomatosa hepática. En este artículo describimos los aspectos clínico-patológicos básicos de esta enfermedad y proveemos un breve resumen de las etiologías más comunes, principalmente en la región de Latinoamérica.

Abstract Granulomas are circumscribed lesions mainly composed of mononuclear cells that arise in response to poorly degradable antigenic stimuli. They are found in 2-15 % of liver biopsies and the meaning of their finding can range from an incidental phenomenon to the manifestation of a systemic disease of infectious, autoimmune or neoplastic origin. Clinical presentation usually points at the underlying pathology; however, the list of associated conditions is extensive, and differs based on patient epidemiological history and baseline characteristics. The most useful element for their study is a thorough medical history, with an emphasis on recent trips, exposures and consumption of drugs or raw or exotic foods. Detailed histopathological analysis may help identify the etiology. For example, the presence of epithelioid granulomas with caseous necrosis indicates tuberculosis and, its absence, sarcoidosis; eosinophil abundance can be associated with drug reactions or parasitic infections; and the presence of foreign bodies can be the cause of granulomatous liver disease (GLD). In this article, we describe the basic clinical-pathological aspects of GLD, and provide a brief summary of the most common etiologies, with an emphasis on the Latin-American region.

Splenic ischemic preconditioning attenuates oxidative stress induced by hepatic ischemia-reperfusion in rats

Abstract Purpose: To evaluate the effects of splenic ischemic preconditioning (sIPC) on oxidative stress induced by hepatic ischemia-reperfusion in rats. Methods: Fifteen male Wistar rats were equally divided into 3 groups: SHAM, IRI and sIPC. Animals from IRI group were subjected to 45 minutes of partial liver ischemia (70%). In the sIPC group, splenic artery was clamped in 2 cycles of 5 min of ischemia and 5 min of reperfusion (20 min total) prior to hepatic ischemia. SHAM group underwent the same surgical procedures as in the remaining groups, but no liver ischemia or sIPC were induced. After 1h, hepatic and splenic tissue samples were harvested for TBARS, CAT, GPx and GSH-Rd measurement. Results: sIPC treatment significantly decreased both hepatic and splenic levels of TBARS when compared to IRI group (p<0.01). Furthermore, the hepatic and splenic activities of CAT, GPx and GSH- Rd were significantly higher in sIPC group than in IRI group. Conclusion: sIPC was able to attenuate hepatic and splenic IRI-induced oxidative stress.

Coagulación en daño hepático crónico / Coagulation in chronic liver disease

Cirrhotic patients frequently exhibit abnormal coagulation tests such as prothrombin time (PT) and activated partial thromboplastin time (APTT) due to impairment in hepatic synthesis of coagulation factors. Due to these abnormalities and also to the numerous bleeding episodes that characterize advanced or decompensated liver cirrhosis, these patients were traditionally considered as “anticoagulated”. More recently, this paradigm has been challenged due to the increased occurrence of thrombotic complications among this population. This can only be understood when analyzed under the prism of the cellular theory of coagulation, which describes the complex interactions between endothelial, platelets and inflammatory cells that determine the status of coagulation, anticoagulation and fibrinolysis. The liver participates actively in this process contributing to the maintenance of a dynamic equilibrium in healthy patients. During liver failure there is evidence of impairment of synthesis of factors involved in the coagulation process, but also in anticoagulation and fibrinolysis. However, stable cirrhotic patients tend to maintain a delicate dynamic equilibrium. This equilibrium can be altered in acute decompensations leading to hemorrhagic or thrombotic complications.

Los pacientes con cirrosis presentan disminución en la producción de factores de coagulación de síntesis hepática, esto determina alteración del tiempo de protrombina (TP) y tiempo de tromboplastina parcial activada (TTPa). Esta característica, junto con los episodios de sangrado, que se presentan frecuentemente en pacientes descompensados y en etapa avanzada de la enfermedad, significó que por muchos años se considerara a los pacientes con daño hepático crónico como “anticoagulados”. En los últimos años este paradigma ha sido desafiado por estudios que muestran una mayor frecuencia de trombosis en esta población. Este fenómeno se comprende mejor con la teoría celular de la coagulación que integra a la ecuación las membranas celulares, especialmente de endotelio, plaquetas y células inflamatorias, y que permite visualizar las complejas interacciones entre factores coagulantes, anticoagulantes y fibrinolisis. El hígado participa en forma activa en este proceso que determina un amplio equilibrio dinámico en individuos sanos. El daño hepático claramente altera la coagulación, sin embargo, la evidencia actual demuestra que en la mayoría de los pacientes se produce un delicado rebalance hemostático, que determina una coagulación efectiva. Si este frágil equilibrio se altera, se produce un desbalance que puede generar un estado hemorrágico o trombótico.

Intoxicação por Enterolobium contortisiliquum em bovinos na região Nordeste do Brasil / Poisoning by Enterolobium contortisiliquum in cattle in Northeastern Brazil

Descreve-se um surto de fotossensibilização causada por favas de Enterolobium contortisiliquum em bovinos no Estado de Pernambuco, Nordeste do Brasil. Os sinais clínicos observados foram hiporexia, prostração, perda de peso, edema generalizado, dermatite e icterícia. Havia anemia e atividades séricas de AST, LDH e GGT elevadas. A concentração sérica de ureia encontrava-se levemente aumentada e creatinina, proteínas séricas e albumina estavam em níveis normais. Na necropsia, o fígado estava aumentado de tamanho e difusamente alaranjado e os rins estavam aumentados de volume e apresentavam estriações esbranquiçadas irregulares entremeadas por áreas escuras na superfície subcapsular. Histologicamente, observou-se na pele, dermatite ulcerativa. No fígado havia vacuolização e necrose de hepatócitos da região centrolobular e ocasionalmente necrose individual de hepatócitos em outras regiões. O rim apresentava nefrose tubular tóxica. O diagnóstico diferencial da intoxicação por E. contortisiliquum na região semiárida deve incluir as intoxicações por Brachiaria spp, Panicum dichotomiflorum e Froelichia humboldtiana, que também causam fotossensibilização...

An outbreak of photosensitization caused by Enterolobium contortisiliquum pods is reported in cattle in the state of Pernambuco, semiarid region of Northeastern Brazil. The clinical signs included decreased appetite, prostration, weight loss, subcutaneous edema, dermatitis and jaundice. The animals presented mild anemia, elevated serum activities of AST, LDH and GGT, and increased serum concentrations of urea. Serum concentrations of creatinine, total proteins and albumin were within normal ranges. At necropsy, the liver was increased in size and diffusely orange. The subcapsular surface of the kidneys showed irregular whitish striations interspersed with dark areas. Histologically, the skin showed dermatitis, and the liver had centrolobular vacuolation and necrosis of hepatocytes and occasionally single cell necrosis. Tubular toxic nephrosis was also observed. The poisoning by E. contortisiliquum should be differentiate from photosensitation caused by other plants including Brachiaria spp., Panicum dichotomiflorum and Froelichia humboldtiana...

Alterações angiográficas e pressóricas determinadas pela esplenectomia e ligadura da veia gástrica esquerda em portadores de esquistossomose mansônica / Angiografic and pressoric changes determined by splenectomy with left gastric vein ligature in mansoni schistosomiasis

RACIONAL: Na esquistossomose mansônica na forma hepatoesplênica ocorre fibrose hepática difusa que associada à congestão venosa do sistema porta resulta em hepatoesplenomegalia. Pode produzir hemorragia digestiva alta por rotura das varizes de esôfago e do estômago ou lesões pépticas da mucosa gastroduodenal. OBJETIVO: Estudar os efeitos da esplenectomia e ligadura da veia gástrica esquerda sobre a hemodinâmica portohepática. MÉTODO: Vinte e três portadores de esquistossomose mansônica na forma hepatoesplênica foram estudados prospectivamente, antes e cerca de duas semanas após a operação, através de estudos angiográficos dos diâmetros da artéria hepática comum e própria, artéria esplênica, artéria mesentérica superior, veia porta, veia mesentérica superior e veia gástrica esquerda. Foram aferidas as pressões da veia cava inferior, venosa central, da veia hepática livre, da veia hepática ocluída e sinusoidal. RESULTADOS: A ligadura da veia gástrica esquerda determinou acréscimo significante nas seguintes variáveis: diâmetros da artéria hepática comum e própria; diâmetro da veia mesentérica superior; o acréscimo não foi significante nas seguintes medidas: pressão venosa central e diâmetro da artéria mesentérica superior. Ela promoveu decréscimo não significante nas variáveis: pressão da veia cava inferior; pressão da veia hepática livre; pressão da veia hepática ocluída; pressão sinusoidal; diâmetro da veia porta. CONCLUSÃO: A ligadura da veia gástrica esquerda, na maioria dos casos, não determina alterações hemodinâmicas significantes do sistema porta capazes de quebrar o equilíbrio hemodinâmico funcional, que caracteriza a esquistossomose mansônica na forma hepatoesplênica.

BACKGROUND: In hepatosplenic schistosomiasis occurs diffuse hepatic fibrosis associated with venous congestion of the portal system resulting in hepatosplenomegaly. It can produce digestive hemorrhage caused by rupture of esophageal and stomach varices or peptic gastroduodenal mucosal lesions. AIM: To study the effects of splenectomy and ligature of the left gastric vein on portohepatic hemodynamics. METHOD: Twenty-three patients with hepatosplenic schistosomiasis mansoni were studied before and about two weeks after operation through angiographic diameter of the common and proper hepatic artery, splenic artery, superior mesenteric artery, portal vein, superior mesenteric vein and left gastric vein. The pressures of the inferior vena cava and central venous pressure, free hepatic vein, the hepatic sinusoidal and occluded vein were measured. RESULTS: The splenectomy and ligature of the left gastric vein determined low morbidity and null mortality. It determined significant addition to the following variables: diameters of the common and proper hepatic artery; diameter of the superior mesenteric vein. It determined non significant increase on the following measurements: right atrial pressure and diameter of the superior mesenteric artery. It determined non significant decrease to the following variables: inferior vena cava pressure; free hepatic vein pressure; occluded hepatic vein pressure; sinusoidal pressure, diameter of the portal vein. CONCLUSION: Splenectomy and ligature of the left gastric vein do not determine portal hemodynamic changes capable of breaking the functional hemodinamic balance that characterizes the hepatosplenic mansoni schistosomiasis.

ComparaþÒo da forþa do aperto de mÒo com parÔmetros antropométricos e subjetivos na avaliaþÒo nutricional de hepatopatas / [Comparison of strength of the handshake with anthropometric and subjective parameters at the patients’ nutritional assessment with liver diseas].

OBJECTIVE: We aimed to assess the nutritional status of patients with chronic liver disease by evaluating the strength of grip of non-dominant hand (SGNDH), correlating it with other methods and analyzing their contribution to this assessment. METHODS: This study was conducted with patients having chronic chronic disease at the outpatient hepatology service of the Instituto de Medicina Integral Professor Fernando Figueira--IMIP, Recife-PE, from February to October 2010. Clinical and demographic variables were collected. The evaluation was performed according to anthropometric, subjective and functional parameters. RESULTS: There were evaluated 49 individuals and 65.3

of them were men. The mean age was 51.3 years and individuals over 60 year predominated. The patients presented non-alcoholic liver disease in 61.2

of cases, MELD < or = 10 in 67.3

, some gastroenteropathy in 67.4

, jaundice in 66.7

and ascites in 63

. The global average SGNDH was higher among men with higher prevalence of malnutrition by arm muscle area (AMA), followed by arm muscle circumference (AMC) and SGNDH, and lower prevalence by body mass index (BMI) and adapted subjective global assessment (SGA). There were not statistically significant differences between the prevalence of malnutrition by SGNDH and arm circumference (AC), triceps skinfold (TS), AMC, AMA and Mendenhall score. The diagnosis of malnutrition by SGND was higher among men and 100

among elderly (P < 0.05). There was strong correlation between SGNDH and AMC, regular between SGNDU and height, and weak between SGDNH and AC (P < 0.05). CONCLUSIONS: It is noted that the SGNDH showed similar contribution than AMA and AMC and higher than BMI and adapted SGA. The strong correlation between SGNDH and AMC indicates a major relationship with muscle reserves. Thus, more studies are needed to clarify the application of SGNDH in this nutritional assessment. We point out that an association of different methods is necessary.

Avaliação dos marcadores clínicos e inflamatórios da doença hepática gordurosa não alcoólica em mulheres na pós-menopausa com síndrome metabólica / Evalution of clinical and inflammatory markers in non alcoholic fatty liver disease in post menopausal women with methabolic syndrome

Avaliar marcadores clínicos e inflamatórios na doença hepática gordurosa não alcoólica (DHGNA) em mulheres na pós-menopausa com síndrome metabólica (SM). Estudo transversal, comparativo, envolvendo 180 mulheres na pósmenopausa (idade ≥45 anos e amenorréia ≥ 12 meses) acompanhada no Ambulatório de Climatério do Centro de Especialidades Médicas do Hospital Santa Casa de Belo Horizonte/Minas Gerais, de janeiro de 2011 a agosto de 2012. Os critérios de não inclusão foram: doença hepática (hepatites B e C, doença colestática, insuficiência hepática e tumor); uso de drogas que afetam o metabolismo hepático; etilistas; antecedente de HIV ou câncer; e obesidade mórbida. Foi diagnosticada SM na presença de três ou mais critérios: circunferência da cintura (CC) > 88cm; triglicerídeos (TG) ≥ 150mg/dL; HDL < 50mg/dL; pressão arterial ≥ 130/85mmHg; glicemia ≥ 100mg/dL. A DHGNA foi diagnosticada por meio da ultrassonografia abdominal. As participantes foram divididas em três grupos de acordo com a presença ou ausência de SM e/ou DHGNA: SM isolada (n=53); SM+DHGNA (n=67); sem SM ou DHGNA (controle, n=60). Foram realizadas avaliações clínicas, antropométricas e bioquímicas. O perfil inflamatório incluiu dosagens de adiponectina, interleucina-6 (IL-6) e fator de necrose tumoral alfa (TNF-α). Para análise estatística foram empregados os testes de Tukey, ANOVA, Qui-Quadrado, Correlação de Pearson e regressão logística (odds ratio-OR). As mulheres com SM+DHGNA mostraram-se obesas e com maior CC quando comparadas as mulheres com SM e controle (p<0.05). Assim como, apresentaram valores médios de glicemia e insulina superiores aos demais grupos, com resistência à insulina (RI) (p<0.05)...

To assess clinical and inflammatory markers in non-alcoholic fatty liver disease (NAFLD) in postmenopausal women with metabolic syndrome (MetS). In this cross-sectional study, 180 women (age ≥45 years and amenorrhea ≥ 12 months) followed the Belo Horizonte Specialty Clinic from January 2011 to August 2012, were included. Exclusion criteria were: liver disease (hepatitis B and C, cholestatic disease, liver insufficiency and tumor); use of drugs that affect the liver metabolism; alcoholics; HIV or cancer history; and morbid obesity. MetS was diagnosed as the presence of at least three components: waist circumference (WC) > 88 cm, triglycerides (TG) ≥ 150mg/dL, HDL <50mg/dL; blood pressure (BP) ≥ 130/85mmHg; glucose ≥ 100mg/dL. NAFLD was diagnosed by abdominal ultrasound. The participants were divided into three groups according to the presence or absence of MetS and/or NAFLD: MetS alone (n=53); MetS+NAFLD (n=67); or without NAFLD or MetS (controls, n=60). Clinic, anthropometric, and biochemical variables were measured. Inflammatory profile included adiponectin, interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α). Statistical analysis employed the ANOVA, Tukey test, Chi-square test, Pearson correlation, and logistic regression (odds ratio, OR). Women with MetS + NAFLD showed obesity, greater WC, higher glucose and insulin levels, with insulin resistance (IR) when compared to MetS alone and controls (p <0.05). Elevated values of IL-6 and TNF-α were observed as well as decreased adiponectin among women with MetS alone or MetS+NAFLD when compared to controls (p <0.05)...

Clinical Effects of Bile Aspiration Just before Contrast Injection during Endoscopic Retrograde Cholangiopancreatography / 대한소화기학회지

BACKGROUND/AIMS: This study was designed to determine whether bile aspiration before contrast injection cholangiogram prevent of post-ERCP cholangitis, liver function worsening, cholecystitis and pancreatitis. METHODS: One hundred and two patients in the bile aspiration group before contrast injection from December 1, 2008 to December 30, 2009 and 115 patients in the conventional control group from January 1, 2010 to June 30, 2010 were analyzed. The incidence of post-ERCP cholangitis, liver function worsening, cholecystitis, pancreatitis, and hyperamylasemia only were compared between these two groups. RESULTS: In the 102 patients with the bile aspiration group, post-ERCP cholangitis in 3 patients (2.9%), liver function worsening in 4 patients (3.9%), cholecystitis and pancreatitis in none, and hyperamylasemia only in 6 patients (5.8%) occurred. In the 115 patients with control group, post-ERCP cholangitis in 1 patient (0.4%), liver function worsening in 9 patients (7.8%), cholecystitis in none, pancreatitis in 3 patients (2.6%), hyperamylasemia only in 10 patients (8.6%) developed. The two groups did not significantly differ in terms of the incidence of post-ERCP cholangitis, liver function worsening, pancreatitis, and hyperamylasemia only (p>0.05). CONCLUSIONS: Initially bile juice aspiration just before contrast injection into the bile duct rarely prevented post-ERCP cholangitis, liver function worsening, and pancreatitis in patients with the extrahepatic bile duct obstruction.

Neonatal cholestasis in congenital pituitary hormone deficiency and isolated hypocortisolism: characterization of liver dysfunction and follow-up / Colestase neonatal na deficiência congênita de hormônio hipofisário e hipocortisolismo isolado: caracterização da disfunção hepática e acompanhamento

INTRODUCTION: Neonatal cholestasis due to endocrine diseases is infrequent and poorly reco-gnized. Referral to the pediatric endocrinologist is delayed. OBJECTIVE: We characterized cholestasis in infants with congenital pituitary hormone deficiencies (CPHD), and its resolution after hormone replacement therapy (HRT). SUBJECTS AND METHODS: Sixteen patients (12 males) were included; eleven with CPHD, and five with isolated central hypocortisolism. RESULTS: Onset of cholestasis occurred at a median age of 18 days of life (range 2-120). Ten and nine patients had elevated transaminases and γGT, respectively. Referral to the endocrinologist occurred at 32 days (range 1 - 72). Remission of cholestasis occurred at a median age of 65 days, whereas liver enzymes occurred at 90 days. In our cohort isolated, hypocortisolism was a transient disorder. CONCLUSION: Cholestasis due to hormonal deficiencies completely resolved upon introduction of HRT. Isolated hypocortisolism may be a transient cause of cholestasis that needs to be re-evaluated after remission of cholestasis.

INTRODUÇÃO: A colestase neonatal causada por doenças endócrinas é pouco frequente e reconhecida. Existe um atraso no encaminhamento dos pacientes a um endocrinologista pediátrico. OBJETIVO: Caracterizamos a colestase em recém-nascidos com deficiências congênitas de hormônio hipofisário (DCHH) e sua resolução após a terapia de reposição hormonal (TRH). SUJEITOS E MÉTODOS: Dezesseis pacientes (12 do sexo masculino) foram incluídos; sete com DCHH, e cinco com hipocortisolismo central isolado. RESULTADOS: O início da colestase ocorreu aos 18 dias de vida (variação 2-120). Dez e nove pacientes apresentaram elevação das transaminases e γGT, respectivamente. A consulta com um endocrinologista aconteceu aos 32 dias (variação 1-72). A remissão da colestase ocorreu em uma idade mediana de 65 dias, enquanto a remissão das enzimas hepáticas aconteceu aos 90 dias. Na coorte isolada, o hipocortisolismo foi uma desordem transitória. CONCLUSÃO: A colestase causada por deficiências hormonais foi completamente resolvida após a introdução da TRH. O hipocortisolismo pode ser uma causa transitória da colestase e precisa ser reavaliado após a remissão da colestase.

Insuficiência hepática aguda grave: diagnóstico e tratamento / Severe acute liver failure: diagnosis and treatment

A insuficiência hepática aguda grave (IHAG), embora seja uma entidade pouco frequente, possui letalidade que varia de 50% a 90 %, acometendo indivíduos, previamente hígidos, no que se concerne à função hepática. E caracterizada pela instalação súbita de perda das características fisiológicas dos hepatócitos, que costuma evoluir rapidamente, e está implicada no aparecimento da encefalopatia hepática, icterícia, hipoglicemia, alteracões da coagulação e insuficiência renal. A etiologia possui alta variabilidade geográfica. No Reino Unido e na América do Norte, a causa mais frequente é a intoxicação por paracetamol; no restante dos países predominam as hepatites virais, sobretudo a hepatite pelo vírus B. O tratamento da IHAG é feito em regime deUnidade de Terapia Intensiva, tendo no transplante hepático a modalidade terapêutica com melhores resultados. Considerando o comportamento agressivo e prognóstico reservado da IHAG, o cuidado a estes pacientes deve englobar a combinação da velha arte do cuidar hipocrático com a utilização dos recursos tecnológicos que a Medicina atual pode oferecer.

The severe acute liver failure (SALF), although a rare entity, whose mortality ranges from 50% to 90%, affects previously healthy individuals, in relation to liver function. It is characterized by a sudden loss of physiological characteristics of hepatocytes, which often change rapidly, and is implicated in the onset of hepatic encephalopathy, hypoglycemia, jaundice, changes in coagulation and renal failure. The etiology has high geographic variability. ln the UK and North America, the most frequent cause is paracetamol poisoning; in the remaining countries, the predominance is viral hepatitis, particularly by hepatitis B virus. Treatment of SALF is done on an intensive care unit and liver transplant is the treatment modality with better results. Considering the aggressive behavior and reserved prognosis of SALF, care to these patients should include a combination of the old Hippocratic art of care with the use of technological resources that current Medicine offers.

Viral hepatitis infection and insulin resistance: a review of the pathophysiological mechanisms / Hepatitis virales y resistencia a la insulina: revisión de los mecanismos fisiopatológicos

Viral hepatitis is a common cause of morbidity in Mexico. Insulin resistance (IR) is related to the liver damage caused by some viral infections, especially chronic infections. Chronic viral infection is an important risk factor for the development of type 2 diabetes mellitus, disease that is currently among the 10 main causes of morbidity and the most common cause of mortality. Although several studies have reported an association between IR and hepatitis B virus or hepatitis C virus (HCV) infection, the pathophysiology has been studied thoroughly only for the association between IR and HCV infection. It is thought that HCV infection causes direct damage through the action of the core proteins, which induces an inflammatory state characterized by secretion of proinflammatory cytokines that interfere with normal insulin signaling and disturb glucose, lipid and protein metabolism. This review summarizes the mechanisms by which viral infection is thought to induce IR.

Las hepatitis virales son una causa común de morbilidad en México. La resistencia a la insulina (RI) ha sido relacionada con el daño hepático causado por infecciones virales crónicas, haciendo de ellas un factor de riesgo para el desarrollo de diabetes mellitus tipo 2, problema de salud que se encuentra entre las primeras 10 causas de morbilidad y es la primera de mortalidad. Aunque varios estudios han reportado una asociación entre la RI y la infección con virus de la hepatitis B y virus de la hepatitis C, sólo con el último se ha estudiado su fisiopatología. Se ha sugerido que produce daño directo a través de proteínas de su núcleo e induce un estado inflamatorio que interfiere con la señalización normal de insulina, resultando en una alteración del metabolismo de glucosa, lípidos y proteínas. Esta revisión resume los mecanismos por los que se sugiere que estas infecciones inducen RI.

Curso de atualização em emergências médicas: aula 18: insuficiência hepatica aguda / Course of updating in medical emergencies: class 18: acute hepatic failure

A insuficiência hepática aguda (IHA) é uma síndrome clínica extremamente grave, de diagnóstico precoce difícil, evolução rápida e alta mortalidade. Nesta revisão buscamos reunir as informações mais atuais sobre classificação, etiologia, diagnóstico e tratamento, discutindo as diversas controvérsias sobre o tema. O diagnóstico da IHA é difícil e engloba o quadro clínico e laboratorial de hepatite aguda (grave), tempo de protrombina alargado, com qualquer alteração do sensório, além de pesquisa cuidadosa na história do paciente, incluindo o uso de medicações ou ervas e presença de diagnóstico prévio de hepatopatia. O diagnóstico etiólogico inclui infecções virais, medicamentos e toxinas, causas cardíacas e vasculares, metabólicas, além da hepatite autoimune, doenças de Wilson e neoplasias. O tratamento da IHA é dado em duas etapas, sendo a primeira constituída pelas medidas de suporte, prevenção e tratamento das complicações, que devem ser oferecidas a todos os pacientes, e a segunda pelas medidas específicas, que serão direcionadas dependendo da etiologia. O transplante hepático é a única terapia definitiva para os pacientes que não conseguem o restabelimento da função hepática.

Acute hepatic failure (AHF) is one extremely serious clinical syndrome of difficult pre-emptive diagnosis, rapid evolution and high mortality. In this review we summarized the current information regarding its classification, etiology, diagnosis and treatment, and discussed the controversies about the issue. The diagnosis of the AHF is difficult and includes laboratorial and clinical findings of severe acute hepatitis, increased prothrombin time and presence of hepatic encephalopathy. It is necessary that a careful history of the patient be obtained especially with respect to utilization of medications, herbs as well as the presence of previous diagnosis of liver disease. The possible etiologies include viral infections, cardiac and vascular affections, medications and toxins, metabolic causes, auto-immune hepatitis, Wilson's disease and neoplasm. The treatment of AHF requires support measures, prevention and treatment of complications that must be offered all patients and specific measures which should be offered according to the etiology of AHF. Liver transplant is the only definitive therapy for patients who do not recover the hepatic function.

Avaliação semiquantitativa ecocardiográfica de dilatações vasculares intrapulmonares em candidatos a transplante hepático: correlação com avaliação de shunt e parâmetros funcionais pulmonares / Semiquantitative echocardiographic evaluation of intrapulmonary vascular dilatations: correlation with evaluation of shunt levels and pulmonary function parameters

OBJETIVO: Verificar a relação entre a avaliação semiquantitativa de dilatações vasculares intrapulmonares (DVIP) e a avaliação quantitativa de shunt, e descrever achados clínicos e funcionais pulmonares em uma amostra de hepatopatas com DVIP. MÉTODOS: Pacientes com ecocardiografia transtorácica (ETT) positiva para DVIP foram submetidos à avaliação clínica e de função pulmonar assim como à quantificação de shunt intrapulmonar (cintilografia com macroagregados de albumina marcados com tecnécio-99m e por gasometria com oxigênio a 100 por cento). RESULTADOS: Foram estudados 28 pacientes cirróticos (média de idade, 47,5 anos; 60,7 por cento dos casos classificados como Child-Pugh B). Uma escala de 4 pontos, em ordem ascendente, foi utilizada para medir a intensidade das DVIP, classificada de 1 a 4, respectivamente, em 13 (46,4 por cento), 9 (32,1 por cento), 2 (7,1 por cento) e 4 (14,3 por cento) dos pacientes. A amostra foi dividida em grupo baixa intensidade (escores 1 e 2) e grupo alta intensidade (escores 3 e 4). A média de shunt por cintilografia foi 14,9 por cento na amostra total, sendo menor no grupo baixa intensidade (11,7 por cento vs. 26,3 por cento; p = 0,01). O grupo alta intensidade teve maiores valores de shunt através de gasometria (8,3 por cento vs. 16,3 por cento; p < 0.001). A PaO2 média foi inferior no grupo alta intensidade. A intensidade de DVIP e a DLCO correlacionaram-se de forma inversa (r = -0,406, p = 0,01). CONCLUSÕES: A ETT é um método útil e seguro para avaliação da gravidade das DVIP em pacientes com hepatopatia. A classificação ecocardiográfica da intensidade das DVIP se correlacionou com valores de shunt intrapulmonar obtidos pelos métodos quantitativos avaliados, bem como com anormalidades nas trocas gasosas pulmonares.

OBJECTIVE: To correlate semiquantitative evaluation of intrapulmonary vascular dilatations (IPVD) with quantitative evaluation of shunt levels, as well as to describe clinical and pulmonary function findings in a sample of liver disease patients with IPVD. METHODS: Patients presenting transthoracic echocardiography (TTE) positivity for IPVD underwent clinical evaluation, pulmonary function tests and pulmonary shunt quantification (scintigraphy with technetium-99m-labeled albumin macroaggregates and blood gas analysis after pure oxygen breathing). RESULTS: A total of 28 liver cirrhosis patients were studied (mean age, 47.5 years; 60.7 percent were Child-Pugh class B). A 4-point, ascending scale was used as a measure of IPVD intensity, which was scored as 1, 2, 3 and 4, respectively, in 13 (46.4 percent), 9 (32.1 percent), 2 (7.1 percent) and 4 (14.3 percent) of the patients. Patients were divided into a low-intensity group (scores 1 and 2) and a high-intensity group (scores 3 and 4). The mean shunt assessed using scintigraphy was 14.9 percent in the sample as a whole and was lower in the low-intensity group (11.7 percent vs. 26.3 percent; p = 0.01). The mean shunt by blood gas analysis was higher in the high-intensity group (8.3 percent vs. 16.3 percent; p < 0.001). Mean PaO2 was lower in the high-intensity group. There was a negative correlation between DLCO and IPVD severity (r = -0.406, p = 0.01). CONCLUSIONS: TTE is a safe, useful tool for assessing IPVD severity in liver disease patients. The IPVD intensity assessed using TTE correlated with the intrapulmonary shunt values obtained through the quantitative methods evaluated, as well as with pulmonary gas exchange abnormalities.