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Cholestatic jaundice is a common presenting feature of hepatobiliary and/or metabolic dysfunction in the newborn and young infant. Timely detection of cholestasis, followed by rapid step-wise evaluation to determine the etiology, is crucial to identify those causes that are amenable to medical or surgical intervention and to optimize outcomes for all infants. In the past 2 decades, genetic etiologies have been elucidated for many cholestatic diseases, and next-generation sequencing, whole-exome sequencing, and whole-genome sequencing now allow for relatively rapid and cost-effective diagnosis of conditions not previously identifiable via standard blood tests and/or liver biopsy. Advances have also been made in our understanding of risk factors for parenteral nutrition-associated cholestasis/liver disease. New lipid emulsion formulations, coupled with preventive measures to decrease central line-associated bloodstream infections, have resulted in lower rates of cholestasis and liver disease in infants and children receiving long-term parental nutrition. Unfortunately, little progress has been made in determining the exact cause of biliary atresia. The median age at the time of the hepatoportoenterostomy procedure is still greater than 60 days; consequently, biliary atresia remains the primary indication for pediatric liver transplantation. Several emerging therapies may reduce the bile acid load to the liver and improve outcomes in some neonatal cholestatic disorders. The goal of this article is to review the etiologies, diagnostic algorithms, and current and future management strategies for infants with cholestasis.

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El cáncer de vesícula es la neoplasia maligna más frecuente del tracto biliar. Con un mal pronóstico, su enfoque terapéutico muchas veces se centra en el tratamiento paliativo debido a que los pacientes suelen recibir un diagnóstico en estadios avanzados de la neoplasia, en los cuales ya no son candidatos para tratamientos quirúrgicos curativos. Por esta razón se utilizan stents o drenajes vesiculares, a fin de reducir el principal síntoma que se presenta: la ictericia, con sus consecuencias, por obstrucción biliar maligna. Este artículo pretende hacer una revisión de la evidencia recolectada en los últimos 5 años (período 2016 - 2021) acerca de los diferentes abordajes mínimamente invasivos en el tratamiento paliativo del cáncer de vesícula, sus resultados clínicos, y las diferencias entre ellos.

Gallbladder cancer is the most common malignancy neoplasm of the bile ducts. With a poor prognosis, its therapeutic approach is often focused on palliative treatment because patients usually receive a diagnosis in advanced stages of the neoplasm, in which they are no longer candidates for curative surgical treatments. For this reason, stents or gallbladder drains are used in order to reduce the main symptom that occurs: jaundice, with its consequences, due to malignant biliary obstruction. This article aims to review the evidence collected in the last 5 years (period 2016 - 2021) about the different minimally invasive approaches in the palliative treatment of gallbladder cancer, their clinical results, and the differences between them.

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The most concerned issue in the context of drug/herb-induced chronic cholestasis is vanishing bile duct syndrome. The progressive destruction of intrahepatic bile ducts leading to ductopenia is usually not dose dependent, and has a delayed onset that should be suspected when abnormal serum cholestasis enzyme levels persist despite drug withdrawal. Immune-mediated cholangiocyte injury, direct cholangiocyte damage by drugs or their metabolites once in bile, and sustained exposure to toxic bile salts when biliary epithelium protective defenses are impaired are the main mechanisms of cholangiolar damage. Current therapeutic alternatives are scarce and have not shown consistent beneficial effects so far. This review will summarize the current literature on the main diagnostic tools of ductopenia and its histological features, and the differential diagnostic with other ductopenic diseases. In addition, pathomechanisms will be addressed, as well as the connection between them and the supportive and curative strategies for ductopenia management.

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PURPOSE: The aim of this study was to determine the effect of hyperbilirubinemia in the sensitivity of percutaneous transluminal forceps biopsy (PTFB) in patients with suspected malignant biliary stricture. MATERIALS AND METHODS: Ninety-three patients with suspicion of malignant biliary stricture underwent percutaneous transhepatic cholangiography followed by PTFB. Sensitivity, specificity and predictive values were analysed based on the presence or absence of hyperbilirubinemia, defined as total bilirubin equal to, or higher than 5 mg/dL. Variables included demographic and clinical features, laboratory, tumour type and localization, stricture length, therapeutic approach and histopathology. Additionally, major morbidity and mortality were assessed. RESULTS: The overall sensitivity, specificity, positive predictive value and accuracy of PTFB were 61.1%, 100%, 100%, and 62.4%, respectively. Hyperbilirubinemia affected 57% of patients at the time of PTFB. There were 35 (37%) false negative results, none of them related to tumour type or localization, stricture length, or previous biliary intervention (i.e. PBBD (percutaneous biliary balloon dilatation), ERCP (endoscopic retrograde cholangiopancreatography)) (p > 0.05). However, when bilirubin was < 5 mg/dL, false negative results decreased globally (p = 0.024) and sensitivity increased significantly for intrahepatic and hilar localization, as well as for colorectal metastasis, gallbladder carcinoma, and pancreatic carcinoma. No major morbidity occurred. CONCLUSION: The sensitivity of percutaneous transluminal biopsy for diagnosis of malignant stricture may significantly increase if samples are obtained in the absence of hyperbilirubinemia, without adding morbidity to the procedure. LEVEL OF EVIDENCE: Level 3, Case- Control studies.

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Bile secretion by hepatocytes is an osmotic process. The output of bile salts and other organic anions (e.g. glutathione), through the bile salt transporter BSEP/ABCB11 and the organic anion transporter MRP2/ABCC2, respectively, are considered to be the major osmotic driving forces for water secretion into bile canaliculi mainly via aquaporin-8 (AQP8) channels. The down-regulated canalicular expression of these key solute transporters and AQP8 would be a primary event in the establishment of hepatocellular cholestasis. Recent studies in animal models of hepatocellular cholestasis show that the hepatic delivery of AdhAQP1, an adenovector encoding for the archetypical water channel human aquaporin-1 (hAQP1), improves bile secretion and restores to normal the elevated serum bile salt levels. AdhAQP1-transduced hepatocytes show that the canalicularly-expressed hAQP1 not only enhances osmotic membrane water permeability but also induces the transport activities of BSEP/ABCB11 and MRP2/ABCC2 by redistribution in canalicular cholesterol-rich microdomains likely through interactions with the cholesterol-binding protein caveolin-1. Thus, the hepatic gene transfer of hAQP1 improves the bile secretory failure in hepatocellular cholestasis by increasing both biliary output and choleretic efficiency of key osmotic solutes, such as, bile salts and glutathione. The study of hepatocyte aquaporins has provided new insights into the mechanisms of bile formation and cholestasis, and may lead to innovative treatments for cholestatic liver diseases.

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RESUMEN Introducción: las enfermedades del eje pancreático/biliar son una consecuencia en la morbimortalidad del aparato digestivo, y es la causa en ocasiones de una obstrucción biliar. La colangiopancreatografía retrógrada endoscópica es un método preciso para el diagnóstico de la obstrucción biliar, y se asocia con una elevada tasa de sensibilidad y especificidad. Materiales y métodos: se realizó un estudio observacional descriptivo de corte transversal, con el objetivo de valorar el comportamiento de la colangiopancreatografía retrógrada endoscópica como medio diagnóstico y terapéutico en una muestra de 90 pacientes con dictamen presuntivo de íctero obstructivo. Resultados: predominaron las féminas en el grupo de edad superior a los 50 años. La coluria, la acolia y el íctero como representativos de una enfermedad obstructiva de las vías biliares, fueron las manifestaciones más frecuentes, corroboradas por el estudio endoscópico, donde la litiasis coledociana fue la principal causa de íctero. Conclusión: la esfinterotomía endoscópica fue el proceder terapéutico de elección, y la pancreatitis aguda postintervención fue la complicación más frecuente (AU).

ABSTRACT Introduction: the diseases of the pancreatic-biliary axis are a consequence in the digestive tract morbidity-mortality, and sometimes they are the cause of a biliary obstruction. The endoscopic retrograde cholangiopancreatography is a precise method for diagnosing the biliary obstruction, and is associated to high rates of sensitivity and specificity. Materials and methods: a cross-sectional, descriptive, observational study was carried out with the aim of assessing the behavior of endoscopic retrograde cholangiopancreatography as a therapeutic and diagnostic mean in a sample of 90 patients with presumptive report of obstructive jaundice. Results: women aged more than 50 years predominated. Choluria, acholia and jaundice, as representative of the biliary ducts obstructive disease, were the most frequent manifestations, corroborated by the endoscopic study, where choledocal lithiasis was the main cause of jaundice. Conclusions: endoscopic sphincterotomy was the elective therapeutic procedure, and post-intervention acute pancreatitis was the most frequent complication (AU).

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OBJECTIVE: To compare the aspartate aminotransferase to platelet ratio index, liver transplantation, and mortality rates between children with intestinal failure-associated liver disease who received fish oil lipid emulsion (FOLE) or soybean oil intravenous lipid emulsion (SOLE). STUDY DESIGN: In this multicenter integrated analysis, FOLE recipients (1 g/kg/d) (n = 189) were compared with historical controls administered SOLE (≤3 g/kg/d) (n = 73). RESULTS: Compared with SOLE, FOLE recipients had a higher direct bilirubin level at baseline (5.8 mg/dL vs 3.0 mg/dL; P < .0001). Among FOLE recipients, 65% experienced cholestasis resolution vs 16% of SOLE recipients (P < .0001). The aspartate aminotransferase to platelet ratio index scores improved in FOLE recipients (1.235 vs 0.810 and 0.758, P < .02) but worsened in SOLE recipients (0.540 vs 2.564 and 2.098; P ≤ .0003) when baseline scores were compared with cholestasis resolution and end of study, respectively. Liver transplantation was reduced in FOLE vs SOLE (4% vs 12%; P = .0245). The probability of liver transplantation in relation to baseline direct or conjugated bilirubin (DB) was lower in FOLE vs SOLE recipients (1% vs 9% at DB of 2 mg/dL; 8% vs 35% at DB of 12.87 mg/dL; P = .0022 for both). Death rates were similar (FOLE vs SOLE: 10% vs 14% at DB of 2 mg/dL; 17% vs 23% at a DB of 12.87 mg/dL; P = .36 for both). CONCLUSIONS: FOLE recipients experienced a higher rate of cholestasis resolution, lower aspartate aminotransferase to platelet ratio index, and fewer liver transplants compared with SOLE. This study demonstrates that FOLE may be the preferred parenteral lipid emulsion in children with intestinal failure-associated liver disease when DB reaches 2 mg/dL. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00910104 and NCT00738101.

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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.

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.

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Multidrug resistance-associated protein 2 (MRP2/ABCC2), a hepatocyte canalicular transporter involved in bile secretion, is downregulated in cholestasis triggered by lipopolysaccharide. The human aquaporin-1 (hAQP1) adenovirus-mediated gene transfer to liver improves cholestasis by incompletely defined mechanisms. Here we found that hAQP1 did not affect MRP2/ABCC2 expression, but significantly increased its transport activity assessed in situ with endogenous and exogenous substrates, likely by a hAQP1-induced increase in canalicular membrane cholesterol amount. Our results suggest that hAQP1-induced MRP2/ABCC2 activation contributes to the cholestasis improvement.

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