Emerging Disease: A Case Series of post-COVID-19 Cholangiopathy

Introduction: Post-COVID-19 cholangiopathy is a novel condition characterized by biliary tract sclerosis and elevated alkaline phosphatase levels in critically ill patients. This case series aims to describe the experience of a Latin American reference hospital in managing this condition. Methods: This case series includes patients with confirmed coronavirus disease 2019 (COVID-19) who exhibited subsequent elevation of alkaline phosphatase levels exceeding three times the normal value. The patients also had documented bile duct abnormalities observed through cholangioresonance or endoscopic retrograde cholangiopancreatography (ERCP). The clinical presentation, imaging findings, complications, and treatment approaches are described. Results: Eight patients (56.5 ± 9.2 years old, 62.5% male) were included in the study. All patients had previously experienced severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pneumonia and required mechanical ventilation. Four patients (50%) received sedoanalgesia with ketamine, and all eight patients (100%) received propofol. All patients developed infections, such as cholangitis or liver abscesses, caused by gram-negative bacteria. The peak alkaline phosphatase level during follow-up averaged 1646.12 ± 611.3. Imaging findings revealed intrahepatic (100%) and extrahepatic (87.5%) bile duct dilation. In 75% of cases, bile molds with a black appearance were extracted. Seven patients experienced recurrent cholangitis, and three patients were referred for pre-liver transplant consultation. Conclusions: Post-COVID-19 cholangiopathy is characterized by severe cholestasis, intra- and extrahepatic bile duct dilation, formation of bile molds, and recurrent cholangitis. In our study, a possible association between sepsis caused by gram-negative bacteria and the use of sedative medications is hypothesized. Further studies are necessary to establish the most appropriate management strategies for these patients, as they currently face unfavorable long-term morbidity and mortality outcomes.

Introducción: la colangiopatía pos-COVID-19 es una entidad nueva caracterizada por esclerosis del tracto biliar y elevación de fosfatasa alcalina en el paciente críticamente enfermo. Esta serie de casos describe la experiencia de un hospital de referencia en Latinoamérica. Métodos: serie de casos que incluye a pacientes con enfermedad por coronavirus de 2019 (COVID-19) confirmada y elevación posterior de fosfatasa alcalina > 3 veces del valor normal, asociados a anormalidades en las vías biliares documentada por colangiorresonancia o colangiopancreatografía retrógrada endoscópica (CPRE). Se describe la presentación clínica, hallazgos imagenológicos, complicaciones y tratamiento. Resultados: se incluyeron a 8 pacientes (56,5 ± 9,2 años, 62,5% hombres). Todos presentaron neumonía por coronavirus del síndrome respiratorio agudo grave de tipo 2 (SARS-CoV-2) previo a desarrollo de colangiopatía, y requirieron ventilación mecánica. Cuatro pacientes (50%) recibieron sedoanalgesia con ketamina y ocho (100%) con propofol. Todos presentaron infecciones (colangitis/abscesos hepáticos) por bacterias gramnegativas. El nivel pico de fosfatasa alcalina durante el seguimiento fue en promedio 1646,12 ± 611,3. Los hallazgos imagenológicos incluyeron dilatación de la vía biliar intrahepática (100%) y extrahepática (87,5%). En el 75% se extrajo el molde biliar de apariencia negra. Siete pacientes presentaron recurrencia de colangitis y tres pacientes fueron referidos a consulta de pretrasplante hepático. Conclusiones: la colangiopatía pos-COVID-19 está caracterizada por colestasis grave con dilatación de la vía biliar intra- y extrahepática, formación de moldes biliares y colangitis recurrente. En nuestro estudio se plantea como hipótesis una posible relación con sepsis por bacterias gramnegativas y uso de medicamentos sedativos. Se requieren nuevos estudios para establecer el manejo más adecuado para estos pacientes, que hasta el momento presentan una morbimortalidad desfavorable a largo plazo.

Immunoglobulin G4-related sclerosing cholangitis

Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory condition of which IgG4-related sclerosing cholangitis (IgG4-SC) is the biliary manifestation. In this review, we provide an overview of IgG4-RD, with a focus on the biliary manifestations. In particular, we describe the important differential diagnoses of IgG4-SC, namely, primary sclerosing cholangitis and cholangiocarcinoma, outline diagnostic criteria for IgG4-SC, provide insight into possible pathophysiological mechanisms underlying the disease and discuss short and long-term management options of this recently described disease.

Validez diagnóstica de la endosonografía biliopancreática en el diagnóstico de colangitis aguda secundaria a obstrucción biliar / Diagnostic Validity of Biliopancreatic Endosonography in the Diagnosis of Acute Cholangitis Secondary to Biliary Obstruction

Resumen El diagnóstico de las colangiopatías obstructivas por endosonografía biliopancreática (EUS, por sus siglas en inglés) se ha estudiado en profundidad, y existe un extenso reconocimiento de su papel para el diagnóstico de coledocolitiasis, tumores de la encrucijada biliopancreática y síndromes de compresión extrínseca de la vía biliar. La colangitis, la complicación más frecuente de la obstrucción biliar y responsable de gran parte de su morbimortalidad, no se ha relacionado en forma suficiente con los hallazgos endosonográficos. Nuestro estudio buscó definir la validez diagnóstica de la endosonografía en los pacientes con colangitis aguda con el fin de limitar la morbimortalidad del retraso diagnóstico. Se realizó un estudio descriptivo, analizando las historias clínicas de pacientes sometidos a endosonografía biliopancreática, por ictericia obstructiva de cualquier etiología, y quienes posteriormente fueron llevados a colangiopancreatografía retrógrada endoscópica (CPRE) para manejo de obstrucción biliar. Comparamos los hallazgos endosonográficos compatibles con colangitis aguda (engrosamiento de la vía biliar de 1,5 mm o más, presencia de halo pericolangítico de al menos 1,5 cm de longitud y presencia de contenido de ecogenicidad mixta en el interior de la vía biliar) con el drenaje purulento durante la CPRE. Se encontró una alta frecuencia de estos hallazgos en los pacientes con colangitis, y el engrosamiento de las paredes de la vía biliar fue el más común, en el 92,6% de los casos, seguido por la presencia de halo pericolangítico en el 59,3% de los casos y contenido ductal en el 66,7% de los casos. Igualmente, se encontró asociación ascendente de las frecuencias con grado de severidad de la colangitis. Resulta recomendable realizar estudios con un mayor poder estadístico que permitan validar nuestros resultados para una futura inclusión de la EUS en el algoritmo diagnóstico de las guías de práctica clínica en colangitis aguda.

Abstract Diagnosis of obstructive cholangiopathy with biliopancreatic endosonography (BUS) has been extensively studied, and its role in the diagnosis of choledocholithiasis, biliopancreatic junction tumors and extrinsic biliary compression syndromes is widely recognized. Endosonographic diagnosis of cholangitis, a more frequent complication of biliary obstruction which is responsible for much of its morbidity and mortality, has not been sufficiently studied. Our study's objective is to define the diagnostic validity of endosonography for patients with acute cholangitis in order to limit morbidity and mortality due to diagnostic delay. This is a descriptive study that analyzes clinical histories of patients who underwent biliopancreatic endosonography because of obstructive jaundice of any etiology and who later underwent endoscopic retrograde cholangiopancreatography (ERCP) to manage biliary obstruction. We compared endosonographic findings compatible with acute cholangitis: thickening of the bile duct of 1.5 mm or more, periportal halo sign of at least 1.5 cm in length, mixed echogenicity of bile duct content, and purulent drainage during ERCP. Patients with cholangitis most frequently presented thickened gallbladders (92.6% of cases) periportal halo signs (59.3% of cases) and mixed echogenicity of bile duct content (66.7% of cases). We also found an ascending association of frequencies with the degree of severity of cholangitis. Studies with greater statistical power are needed for validation of our results and for future inclusion of EUS in the diagnostic algorithm for clinical practice guidelines in cases of acute cholangitis.

Biology of Cholangiocytes: From Bench to Bedside

Cholangiocytes, the lining epithelial cells in bile ducts, are an important subset of liver cells. They are activated by endogenous and exogenous stimuli and are involved in the modification of bile volume and composition. They are also involved in damaging and repairing the liver. Cholangiocytes have many functions including bile production. They are also involved in transport processes that regulate the volume and composition of bile. Cholangiocytes undergo proliferation and cell death under a variety of conditions. Cholangiocytes have functional and morphological heterogenecity. The immunobiology of cholangiocytes is important, particularly for understanding biliary disease. Secretion of different proinflammatory mediators, cytokines, and chemokines suggests the major role that cholangiocytes play in inflammatory reactions. Furthermore, paracrine secretion of growth factors and peptides mediates extensive cross-talk with other liver cells, including hepatocytes, stellate cells, stem cells, subepithelial myofibroblasts, endothelial cells, and inflammatory cells. Cholangiopathy refers to a category of chronic liver diseases whose primary disease target is the cholangiocyte. Cholangiopathy usually results in end-stage liver disease requiring liver transplant. We summarize the biology of cholangiocytes and redefine the concept of cholangiopathy. We also discuss the recent progress that has been made in understanding the pathogenesis of cholangiopathy and how such progress has influenced therapy.

Hypereosinophilic Syndrome Presenting as Eosinophilic Cholangiopathy and Cystitis / 대한췌담도학회지

Eosinophilic cholangiopathy is a rare disease characterized by dense transmural eosinophilic infiltration of the gallbladder and bile duct. It's clinical and laboratory manifestations are not different from those of other causes of cholangiopathy, and the diagnosis is usually made based on pathologic findings after cholecystectomy. Moreover, the occurrence of eosinophilic cystitis accompanied by cholangiopathy is extremely rare. We report a rare case of hypereosinophilic syndrome manifested as eosinophilic cholangiopathy accompanied with eosinophilic cystitis, for the first time in Korea, in a 49-year-old woman who presented with persistent right upper quadrant pain. After performing imaging study to validate the diagnosis of acute acalculous cholecystitis and cholangitis, an urgent cholecystectomy was performed. Pathologic examination of the excised gallbladder was consistent with eosinophilic cholecystitis. The patient underwent bladder biopsy because there was persistant irritative voiding symptoms combined with constant mild peripheral eosinophilia even after cholecystectomy, and the pathologic findings revealed eosinophilic cystitis. Symptoms and peripheral eosinophilia were improved after steroid therapy for an indicated period.

IgG4-Associated Cholangitis Can Mimic Hilar Cholangiocarcinoma

IgG4-associated cholangitis can mimic hilar cholangiocarcinoma. Previously reported patients with IgG4-associated cholangitis mimicking cholangiocarcinoma had elevated serum IgG4 levels and long-segment biliary strictures. However, in the absence of other diagnostic criteria for malignancy, IgG4-associated cholangitis should remain a consideration among patients with normal serum IgG4 and a hilar mass suspicious for cholangiocarcinoma. The presence of a hilar mass and a malignant-appearing biliary stricture in two patients with normal serum IgG4 prompted further evaluation and subsequent concomitant liver and bile duct resection and reconstruction. The diagnosis of IgG4-associated cholangitis was established during the pathologic evaluation of the resected specimens. IgG4-associated cholangitis is a known imitator of hilar cholangiocarcinoma and should be considered in the differential diagnosis even among serologically IgG4-negative patients with a hilar mass prior to operative resection.

Portal cholangiopathy: case report / Colangiopatia portal: relato de caso

The present report describes the case of a child that after blunt abdominal trauma presented with portal thrombosis followed by progressive splenomegaly and jaundice. Ultrasonography and percutaneous cholangiography revealed biliary dilatation secondary to choledochal stenosis caused by dilated peribiliary veins, characterizing a case of portal biliopathy. The present case report is aimed at presenting an uncommon cause of this condition.

Relata-se o caso de uma criança que após trauma abdominal fechado apresentou trombose portal, seguida por esplenomegalia progressiva e icterícia. Os achados da ultrassonografia e da colangiografia percutânea mostraram dilatação de vias biliares secundária à constrição do colédoco por veias pericoledocianas dilatadas, configurando caso de colangiopatia portal. O objetivo deste relato é a apresentação de causa incomum desta condição.

Imbalance between proliferation and apoptosis of cholangiocytes and its relation to cholangiopathies / 国际外科学杂志

Cholangiocytes are the epithelial cells that line the intrahepatic biliary tree and also the target of cholangiopathies. Despite the heterogeneous etiology ,most of cholangiopathies share the common pathological process which is the imbalance between proliferation and apoptosis of cholangiocytes. The article is a review about the characteristics and mechanism of proliferation and apoptosis of cholangiocytes and their relationship to cholangiopathies.

The Biology of the Cholangiocytes / 한양의대학술지

The biliary system is comprised of intrahepatic bile ducts, extrahepatic bile ducts, and the gallbladder. Bile is transported in the biliary ductal system. The length of the biliary ductal system in humans is about 2 kilometers. A layer of epithelial cells lines this extensive network. In general, cholangiocytes is defined as the epithelial cells that line the intrahepatic bile ducts. The extrahepatic ductal epithelial cells and gallbladder epithelial cells share many features of cholangiocytes. The primary cell target of biliary disorders is the biliary epithelium. Cholangiocytes have many functions, not limited to bile production. Cholangiocytes are involved in transport processes that regulate the volume and composition of bile. Cholangiocytes undergo proliferation and cell death under a variety of conditions. Cholangiocytes have functional and morphological heterogenecity - not all cholangiocytes are the same functionally and morphologically. The immunobiology of the cholangiocyte is important, particulary to the understanding of biliary disease. Secretion of different pro-inflammatory mediators, cytokines, and chemokines indicates a major role of cholangiocytes in the inflammatory reaction. Furthermore, paracrine secretion of growth factors and peptides mediates an extensive cross-talk with other liver cells, including hepatocytes, stellate, and endothelial and inflammatory cells.

A Case of Overlap Syndrome with Auoimmune Hepatitis and Cholangiopathy in a Child / 대한소아소화기영양학회지

Although autoimmune liver diseases are common in Western countries, only sporadic cases have been reported in Korean children. Autoimmune hepatitis, primary biliary cirrhosis, autoimmune cholangiopathy and primary sclerosing cholangitis are major classes of liver diseases currently considered autoimmune. The overlap syndrome has features associated with both autoimmune hepatitis and other liver diseases. We treated a case of the overlap syndrome that included auoimmune hepatitis and cholangiopathy in a 12 year-old boy. Considering that these entities, autoimmune liver diseases or overlap syndromes, are potentially treatable diseases in children, a high index of suspicion is needed for the appropriate diagnosis.