Colestasis intrahepática del embarazo: forma de presentación temprana y relación con la infección por el virus de la hepatitis C: reporte de casos / Intrahepatic cholestasis of pregnancy: early presentation and relationship with infection by the hepatitis C virus: case reports / Colestase intra-hepática da gravidez: forma de apresentação precoce e sua relação com a infecção por vírus da hepatite C: relato de casos

Se describe los casos de tres pacientes a quien se les realiza diagnóstico de colestasis intrahepática del embarazo (CIE) de aparición temprana. En dos de ellos el diagnóstico se relacionó con infección por el virus de la hepatitis C (VHC). Reconocer que esta enfermedad puede presentarse de manera temprana en el embarazo y su relación con la infección por el VHC es fundamental para hacer un diagnóstico oportuno de ambas enfermedades y tomar las conductas terapéuticas adecuadas, mejorando así el pronóstico materno y fetal.

It is of great importance to acknowledge that this disease can occur early in pregnancy and that its relationship with HCV infection is a key point for a prompt diagnosis, allowing taking timely appropriate therapeutic decisions, aimed at improving the fetal prognosis.

Descrevemos os casos de três pacientes com diagnóstico de colestase intra-hepática da gravidez de início precoce. Em dois deles o diagnóstico estava relacionado à infecção pelo vírus da hepatite C (VHC). Reconhecer que esta doença pode se manifestar precocemente na gravidez e sua relação com a infecção pelo VHC é fundamental para fazer um diagnóstico oportuno de ambas as doenças e assumir condutas terapêuticas adequadas, melhorando assim o prognóstico materno e fetal.

Variante "no clásica" o "atípica" del síndrome de Stauffer en paciente con carcinoma renal de células claras: reporte de caso / "Non-classical" or "atypical" variant of Stauffer syndrome in a patient with clear cell renal carcinoma: a case report

La manifestación paraneoplásica conocida como síndrome de Stauffer tiene una presentación atípica, caracterizada por ictericia y colestasis intrahepática. Presentamos el caso de un paciente de 53 años de edad, con antecedente de una masa renal derecha en plan de resección quirúrgica programada, con cuadro de evolución de dolor abdominal en hipocondrio derecho e ictericia. A su ingreso se documentó hepatoesplenomegalia, elevación de bilirrubinas a expensas de la directa, y de fosfatasa alcalina junto con elevación de transaminasas. Se descartaron causas obstructivas a nivel de vía biliar intra y extrahepática. No se documentaron metástasis o lesiones focales a nivel de parénquima, ni lesiones de etiología vascular que explicaran el cuadro. También se descartó hepatitis B, C e infección por VIH, por lo cual se consideró un probable síndrome de Stauffer. Fue llevado a nefrectomía intrahospitalaria, con posterior diagnóstico patológico compatible con carcinoma de células claras. Luego del procedimiento se normalizó la bioquímica hepática y se corrigió la ictericia. Es importante reconocer que la afectación hepática en el contexto de neoplasias, no es solo atribuida a metástasis a distancia, sino también a la existencia de síndromes paraneoplásicos como condicionantes.

The paraneoplastic manifestation known as Stauffer syndrome has an atypical presentation, characterized by jaundice and intrahepatic cholestasis. We present the case of a 53-year-old patient, with a history of a right renal mass with a planned surgical resection, who developed abdominal pain in the right upper quadrant and jaundice. Upon admission, hepatosplenomegaly, elevated bilirubin, at the expense of direct bilirubin, alkaline phosphatase and elevated transaminases were documented. Intra- and extrahepatic bile ducts obstruction were ruled out. There were no documented metastases or focal lesions at the level of the parenchyma, or lesions of vascular etiology that could explain the condition. Hepatitis B, C and HIV infection were also ruled out, and a probable Stauffer syndrome was considered. In-hospital nephrectomy was performed, with subsequent pathology compatible with clear cell carcinoma. After the procedure, liver biochemistry was normalized and jaundice was corrected. It is important to recognize that liver involvement in the context of neoplasms is not only attributed to distant metastases but to the existence of paraneoplastic syndromes as determining factors.

Hepatotoxicidade induzida por azatioprina em portadora da síndrome de Vogt-Koyanagi-Harada / Azathioprine-induced hepatotoxicity in a Vogt-Koyanagi-Harada syndrome patient

Este relato teve como objetivo apresentar um caso de hepatotoxicidade colestática induzida por azatioprina em portadora da síndrome de Vogt-Koyanagi-Harada. À admissão, apresentava icterícia +3/+4, acolia fecal e colúria, além de aumento de marcadores hepáticos, sendo compatível com síndrome colestática, cuja etiologia foi confirmada após exclusão de outras causas possíveis e retirada da azatioprina. A paciente evoluiu, após 1 semana de retirada do fármaco, com diurese livre de coloração menos escura e evacuação presente, sem acolia. Além disso, houve melhora nos exames que precederam a alta hospitalar

This report aimed at presenting a case of azathioprine-induced cholestatic hepatotoxicity in a patient with Vogt-Koyanagi-Harada syndrome. On admission, she presented with jaundice +3/+4, acholic feces, and choluria, as well as increased hepatic markers, all consistent with cholestatic syndrome, the etiology of which was confirmed after other possible causes were ruled out and azathioprine was discontinued. After 1 week of the drug discontinuation, the patient progressed with free diuresis of lighter color and defecation, with no acholia. In addition, tests performed before discharge were improved.

Consenso de hiperbilirrubinemia del primer trimestre de la vida / Consensus on hyperbilirubinemia of the first trimester of life

La presencia de ictericia en la etapa neonatal puede responder a diversas causas, desde situaciones fisiológicas hasta enfermedades graves. En los neonatos de término que persisten ictéricos más allá de los 14 días de vida, debe determinarse si la hiperbilirrubinemia es no conjugada o conjugada para establecer, a la brevedad, el plan de estudios etiológicos y la terapéutica correspondiente. La hiperbilirrubinemia conjugada (colestasis) refleja una disfunción hepática en la mayoría de los casos, cuyas consecuencias son alteraciones del flujo biliar secundarias a anormalidades estructurales o moleculares del hígado y/o del tracto biliar.Durante la última década, los nuevos estudios moleculares revolucionaron el abordaje de los pacientes colestáticos, lo que permitió el diagnóstico de diversas entidades genéticas. La etiología de la hiperbilirrubinemia del primer trimestre debe determinarse con urgencia, ya que, en muchos casos, el tratamiento instituido de modo precoz puede modificar sustancialmente la evolución de la enfermedad o salvar la vida del paciente.

Neonatal jaundice may be due to different causes, ranging from physiological conditions to severe diseases. In term neonates with persistent jaundice beyond 14 days of life, it should be determined whether hyperbilirubinemia is unconjugated or conjugated, in order to study the etiology and start early treatment. In the majority of cases, conjugated hyperbilirubinemia (cholestasis) is a sign of liver dysfunction possibly associated with alterations in the bile flow secondary to structural or molecular abnormalities of the liver and/or the biliary tract. Over the past decade, new molecular studies have revolutionized the approach of cholestatic patients, leading to the identification of different genetic entities. It is important to determine the etilogy of neonatal hyperbilirubinemia since in many cases early treatment will substantially improve morbidity and mortality.

Severe cholestatic syndrome secondary to Graves' disease

This paper reports a case of severe cholestasis as an atypical manifestation of Graves' disease. It discusses the pathophysiology, the diagnosis and the investigation of this complication of hyperthyroidism as well as the impact of this finding on the therapeutic options for managing the disease. (AU)

Identification of Matrix Metalloproteinase-2 and 9 as Biomarker of Intrahepatic Cholestasis of Pregnancy

ABSTRACT Intrahepatic cholestasis of pregnancy (ICP) is a severe liver disease uniquely occurring during pregnancy. In this study we aimed to identify novel biomarker for the diagnosis of ICP in Chinese population. 50 healthy pregnant women, 50 mild ICP patients and 48 severe ICP patients were enrolled for this study. Liver function tests, including serum total bilirubin, direct bilirubin, alanine transaminase, aspartate aminotransferase and cholyglycine, were performed in all participants. After an overnight fast serum levels of total bile acids (TBA), matrix metalloproteinase (MMP)-2 and MMP-9 were measured, and their correlation with liver function tests were analyzed. The observed increase in serum TBA in ICP patients was not statistically significant which made it unreliable for diagnosis of ICP in Chinese population. On the other hand, both MMP-2 and MMP-9 serum levels exhibited a progressive and significant elevation in mild and severe ICP patients compared with healthy pregnant women, which also positively correlated with liver function tests. Serum levels of both MMP-2 and MMP-9 could be reliably used as laboratory abnormalities for accurate diagnosis and sensitive grading of ICP in Chinese population.

Living Donor Liver Transplantation for an Infant with Osteogenesis Imperfecta and Intrahepatic Cholestasis: Report of a Case

Osteogenesis imperfecta (OI) is a group of genetic disorders characterized by bone fragility and connective tissue manifestations. We report a successful liver transplantation (LT) in an 8-month-old boy with OI and cholestatic biliary cirrhosis. After 4 cycles of intravenous pamidronate, LT was performed under intravenous anesthesia using a left lateral section from his mother without mechanical retractors. The operation time was 420 min and estimated blood loss was 520 mL requiring one unit of RBC transfusion. He was discharged without surgical complications. Therefore, LT should be considered for patients with end stage liver disease and OI under organic multidisciplinary cooperation.

Neumonía por Mycoplasma pneumoniae complicada con pancreatitis y hepatitis aguda: a propósito de un caso / Mycoplasma pneumoniae pneumonia complicated with acute pancreatitis and hepatitis: a case study

La infección por Mycoplasma pneumoniae (M pneumoniae) puede producir manifestaciones pulmonares y extrapulmonares a nivel cardiológico, dermatológico, neurológico, hematológico, musculoesquelético y gastrointestinal (vómitos, diarrea, hiporexia, dolor abdominal, hepatomegalia, hepatitis aguda, colecistitis alitiásica, y pancreatitis aguda). Presentamos un caso de infección aguda por M pneumoniae que se manifestó con neumonía, pancreatitis aguda y hepatitis colestásica. Paciente masculino de 15 años, con clínica de neumonía y dolor abdominal con elevación de pruebas hepáticas, amilasa y lipasa, y cambios sugestivos de pancreatitis aguda por ultrasonido abdominal y tomografía de abdomen y pelvis con doble contraste. El paciente evolucionó satisfactoriamente con el tratamiento indicado. Es importante considerar la posibilidad de infección por M. pneumoniae en pacientes con cuadros infecciosos respiratorios y manifestaciones digestivas sobre todo elevación de amilasa y enzimas hepáticas. Se describe el primer caso en nuestro país de pancreatitis y hepatitis asociada con infección por M. pneumoniae y el segundo en la literatura internacional

Mycoplasma pneumoniae (M pneumoniae) infection can cause pulmonary and extrapulmonary manifestations such as: cardiac, dermatological, neurological, hematological, musculoskeletal and gastrointestinal (vomiting, diarrhea, decreased appetite, abdominal pain, hepatomegaly, acute hepatitis, acalculous cholecystitis and acute pancreatitis). We report the case of a 15 years old male with pneumonia, abdominal pain, elevated liver tests with hyperamylasemia, elevated lipase, and changes suggestive of acute pancreatitis on abdominal ultrasound and double contrast CT scan of the abdomen and pelvis. The patient did well with the indicated treatment. It’s important to consider M pneumoniae infection in patients with respiratory disease and digestive manifestations including elevated liver tests and hyperamylasemia. To our knowledge this is the first case reported in our country of M pneumonia associated with pancreatitis and hepatitis and the second one in the literature

Nutrición enteral en hepatopatías crónicas en niños y adolescentes / Enteral nutrition in chronic liver disease in children and adolescents

La desnutrición que se observa en enfermedades hepáticas crónicas en niños se asocia a un aumento de requerimientos por gasto calórico elevado. La historia clínica incluye un recordatorio de alimentación, evaluación clínica, antropometría. Los niños con colestasis deben recibir una dieta hipercalórica. Es fundamental garantizar el aporte calórico calculado completo y la alimentación enteral. Se debe garantizar un crecimiento adecuado en un niño en lista de espera para trasplante. Los niños con enfermedades metabólicas requieren el uso de fórmulas comerciales especiales.

Malnutrition seen in chronic liver disease in children is associated with increased requirements for high caloric expenditure. The medical history includes a reminder of food, clinical evaluation, anthropometry. Children with cholestasis should receive a high calorie diet. It is essential to ensure complete and estimated calorie enteral feeding. It must ensure adequate growth in a child on the waiting list for transplantation. Children with metabolic diseases require the use of special comercial formulations.

Hepatitis colestásica por Mycoplasma pneumoniae sin compromiso pulmonar: caso clínico y revisión de la literatura / Cholestatic hepatitis due to mycoplasma pneumoniae without lung involvement: case report and review

El compromiso hepático es una rara manifestación de la infección por Mycoplasma pneumoniae. Casos de hepatitis colestásica sin compromiso pulmonar han sido descritos en niños con infección por M. pneumoniae, pero en adultos sólo unos pocos casos han sido reportados. En este artículo, presentamos el caso de un hombre de 21 años que consultó por un cuadro de fiebre, ictericia y dolor epigástrico asociado con alteración de los exámenes de laboratorio hepático. Los estudios serológicos de M. penumoniae fueron positivos para IgM e IgG. Los síntomas y exámenes de laboratorio mejoraron completamente luego del tratamiento con claritromicina y ácido ursodeoxicólico.

Liver dysfunction is an unusual manifestation of Mycoplasma pneumoniae infection. Cases of cholestatic hepatitis without pulmonary involvement have been described in children with M. pneumoniae infection,but only a few cases have been reported in adults. In this article, we report the case of a 21-year-old man who presented fever, jaundice and epigastric pain associated with altered liver function tests. Serological tests for M. pneumoniae were positive for IgG and IgM. Clinical symptoms and laboratory tests resolved completely after treatment with clarithromycin and ursodeoxicolic acid. A review of reported cases of liver involvement in M. pneumoniae infection is presented.

Hepatic amyloidosis presenting as intrahepatic cholestasis and portal hypertension: case series and review of literature

Liver involvement in systemic amyloidosis is not uncommon; however, presentation with jaundice is rare. It is considered a preterminal sign. We present four cases of primary AL amyloidosis with severe intrahepatic cholestasis, two of whom presenting also with features of portal hypertension with oesophageal varices. Histopathology revealed diffuse hepatic amyloid deposits in the lobules, portal tracts and sinusoidal space. Review of literature reveals that hepatic amyloidosis presenting with cholestasis and portal hypertension is unusual and portends a poor prognosis

Colestasia intrahepática familiar progresiva tipo 3: presentación de casos clínicos y actualización de tema / Type 3 familial intrahepatic cholestasis: clinical cases and update

Abstract: Familial Intrahepatic Cholestasis (FIC) includes a heterogeneous group of recessive autosomic alterations characterized by hepatocellular cholestasis secondary to the interruption of the normal process of synthesis of bilis. Objective: A description of FIC in 3 of 5 children of an index family. Clinical case: a 5 y.o. child with hepatosplenomegaly increased serum hepatic enzymes and biliary acids. Abdominal echography showed alterations compatible with hepatic fibrosis. Biopsy showed bridge fibrosis, duct proliferation, minimal chronic cholestasis. These findings were compatible with a phenotype FIC-3 with elevate levels of Gamma-glutamyl transferase. A mutation of MDR3 gene is responsible for the absence of biliary phospholipids, allowing a detergent effect of biliary acids upon the duct epithelium, developing cholangitis, fibrosis and later cirrhosis. Among four brothers, the mutation was found in two twin sisters. Three affected brothers were treated with ursodeoxicolic acid, 30 mg/Kg. Excellent results were obtained in the twin girls not in the index boy. The clinical expression of this illness is variable, and an elevation of aminotransferase must call attention to this possibility. Early diagnostic and treatment could avoid the development of hepatic damage and cirrhosis.

La Colestasia Intrahepática Familiar Progresiva (CIFP) comprende un grupo heterogéneo de alteraciones autosómicas recesiva caracterizadas por una colestasia hepatocelular secundaria a una interrupción del proceso normal de síntesis de la bilis. Objetivo: Describir la presentación de CIFP en 3 de 5 hijos de una familia estudiada. Caso clínico: Paciente de 5 a±os de edad (caso 1), que presenta una hepatoesplenomegalia, aumento de enzimas hepáticas y de ácidos biliares en suero. La ecotomografía abdominal describe alteraciones compatibles con fibrosis hepática. La biopsia reveló fibrosis en puente, proliferación ductular y colestasia crónica mínima. Estos hallazgos fueron compatibles con el fenotipo de una CIFP-3 con niveles elevados de Gamaglutamiltransferasa (GGT). Una mutación del gen MDR3 es responsable de la ausencia de fosfolípidos en la bilis, lo que permite la acción detergente de los ácidos biliares sobre el epitelio de los conductos desencadenando una colangitis, fibrosis y luego cirrosis. De los cuatro hermanos del caso 1 se detectó la enfermedad en 2 hermanas gemelas (casos 2 y 3). Estos tres niños afectados fueron tratados con ácido ursodeoxicólico 30 mg/kilo/peso, logrando excelentes resultados en las gemelas pero no en el caso 1. Conclusión: Se presenta a 3 hermanos con el fenotipo de CIFP. La expresión clínica de esta enfermedad puede ser variable y de manifestación tardía, la elevación de las aminotransferasas debe considerar esta patología en el diagnóstico diferencial de las numerosas causas que dan origen a un aumento de estas enzimas. Sólo el diagnóstico y tratamiento precoz puede evitar la evolución a un daño hepático irreversible como es la cirrosis.

Colestasis genéticas / Genetic cholestasis

Los avances en genética molecular han cambiado nuestro abordaje de los pacientes con colestasis intrahepática. La identificación de mutaciones enciertos genes nos permite hoy arribar al diagnóstico genético de varias formas de colestasis, agrupadas previamente como colestasis intrahepáticafamiliar progresiva. Las tres formas descriptas:tipos 1, 2 y 3, son el resultado de mutaciones en los genes ATP8B1, ABCB11 y ABCB4. Hallazgosclínicos, bioquímicos e histológicos nos orientan en el diagnóstico. El tratamiento tiene como objetivosaliviar los síntomas y mejorar la calidadde vida. Los errores congénitos en la síntesis de ácidos biliares representan un subgupo de las colestasis familiares. El tratamiento de reemplazo con ácido ursodesoxicólico y ácido cólico evitanla progresión de la lesión hepática.

Calculose intra-hepática: desafio diagnóstico como causa de colestase: relato de caso / Íntra-hepatic gallstones: a diagnostic challenge as etiology of cholestasis: a case report

A colestase pode resultar de diversas etiologias e pode se constituir em importante problema diagnóstico na prática médica. Os exames laboratoriais são inespecíficos e não determinam a causa da colestase. O quadro clínico pode ser amplamente variável, podendo não revelar qualquer sintoma em algumas ocasiões, e, em outras, apresentar quadro toxêmico compatível com a síndrome colangio-hepatite ou a colangite piogênica. Na avaliação diagnóstica realizada por exames radiológicos de imagem, vários métodos podem ser utilizados com essa finalidade: ultrassonografia (US) e tomografia computadorizada de abdômen (TC), ressonância nuclear magnética com colangiografia (CRMN), colangiopancreatografia por via endoscópica retrógrada (CPRE), colangiografia por via transparieto-hepática (CTPH) ou por dreno biliar e, ainda, métodos complementares, como a colangioscopia e ultrassonografia intraoperatórias. Relata-se caso de calculose intra-hepática (ClH), diagnosticada por CRMN de repetição, em paciente assintomática e anictérica, que, após realização de vários métodos de imagem não elucidativos da causa de colestase, evoluiu com presença persistente de elevação dos níveis de enzimas canaliculares, desde o pós-operatório imediato até dois anos após a realização de colecistectomia.

A Case of Idiopathic Adulthood Ductopenia

Idiopathic adulthood ductopenia (IAD) is a chronic cholestatic liver disease of unknown etiology characterized by adult onset, an absence of autoantibodies, inflammatory bowel disease, and a loss of interlobular bile ducts. In the present report, a case fulfilling the IAD criteria is described. A 19-year-old man was admitted to the hospital for persistent elevation of transaminases and alkaline phosphatase without clinical symptoms. Viral hepatitis markers and autoantibodies were absent. The patient had a normal extrahepatic biliary tree and had no evidence of inflammatory bowel disease. A liver biopsy specimen showed absence of interlobular bile ducts from 58% of the portal tracts. He was diagnosed with IAD and was treated with ursodeoxycholic acid.

Colestase intra-hepática benigna recorrente / Benign recurrent intrahepatic cholestasis

A colestase intra-hepática recorrente benigna é uma doença rara, caracterizada por episódios autolimitados e recorrentes de icterícia e prurido de duração variável, na ausência de obstrução extra-hepática ou outras causas de colestase, tendo prognóstico clínico favorável. O objetivo deste artigo é mostrar um caso de síndrome colestática em uma paciente jovem do sexo feminino com história de icterícia e prurido no período gestacional, sendo atribuída inicialmente à colestase intra-hepática gestacional com interrupção prematura da gravidez; a recorrência dos sintomas numa fase tardia do puerpério redirecionou-nos a outro diagnóstico etiológico. Neste episódio foi realizada uma investigação criteriosa, para a exclusão de outras causas de colestase (AU)

Benign recurrent intrahepatic cholestasis is a rare disorder, characterized by selflimited and recurrent episodes of jaundice and pruritus with variable duration, in the absence of extrahepatic obstruction or other causes of cholestasis, having a favorable clinical prognosis. The objective of this article is to show a case of cholestatic syndrome in a young female patient with a history of jaundice and pruritus in the pregnancy period, which was first attributed to an intrahepatic cholestasis of pregnancy with premature interruption of pregnancy, but the recurrence of symptoms in a late puerperal stage redirected us to a different etiologic diagnosis. In this episode a judicious investigation was carried out for excluding other causes of cholestasis (AU)