Gastrointestinal and Hepatic Involvement in Primary Sjögren's Syndrome: Case Report and Literature Review

Sjögren's syndrome is a systemic autoimmune disease characterized by dry eyes and mouth due to the involvement of exocrine glands. However, it can manifest with GI symptoms that cover a broad spectrum from esophageal and intestinal dysmotility, achalasia, hypochlorhydria, and chronic atrophic gastritis to pancreatic enzyme deficiency, biliary dysfunction, and liver cirrhosis, which varies in its clinical manifestations and is often associated with erroneous approaches. This article reviews the GI manifestations of Sjögren's syndrome. It presents the case of a woman in her eighth decade of life with this syndrome. She showed asymptomatic hepatobiliary disease, documented abnormalities in liver profile tests, and a subsequent diagnosis of primary sclerosing cholangitis, for which she received initial treatment with ursodeoxycholic acid. During her condition, the patient has had three episodes of cholangitis, requiring endoscopic retrograde cholangiopancreatography with no findings of stones, with scant biliary sludge and discharge of purulent bile precipitated by her underlying liver disease. The association between Sjögren's syndrome and primary sclerosing cholangitis is rare and calls for special consideration.

El síndrome de Sjögren es una enfermedad autoinmune sistémica que se caracteriza por la sequedad ocular y bucal debido a la afección de glándulas exocrinas; sin embargo, puede manifestarse con síntomas gastrointestinales que abarcan un espectro amplio desde la dismotilidad esofágica e intestinal, acalasia, hipoclorhidria y gastritis crónica atrófica hasta enzimodeficiencia pancreática, disfunción biliar y cirrosis hepática, que tiene variación en sus manifestaciones clínicas y se asocia con abordajes erróneos en muchas ocasiones. En este artículo se hace una revisión acerca de las manifestaciones gastrointestinales de síndrome de Sjögren y se presenta el caso de una mujer en la octava década de la vida con este síndrome, que cursa con enfermedad hepatobiliar asintomática, documentación de alteración en pruebas de perfil hepático y diagnóstico ulterior de colangitis esclerosante primaria, por lo que recibió un tratamiento inicial con ácido ursodesoxicólico. Durante el curso de su enfermedad ha presentado 3 episodios de colangitis, con requerimiento de colangiopancreatografía retrógrada endoscópica sin hallazgos de cálculos, con escaso barro biliar y salida de bilis purulenta, precipitada por su enfermedad hepática de base. La asociación entre el síndrome de Sjögren y la colangitis esclerosante primaria es infrecuente y justifica una consideración especial.

Carcinoma de vías biliares intrahepáticas: análisis de defunciones según sexo, grupo etario y regiones en Chile entre 2017-2021 / Intrahepatic bile duct carcinoma: analysis of deaths according to sex, age group, and regions in Chile between 2017-2021

Introducción: el colangiocarcinoma intrahepático es un cáncer agresivo de células epiteliales de los conductos biliares intrahepáticos y su desarrollo se asocia a inflamación crónica del árbol biliar. En Chile, su epidemiología es limitada y el presente estudio tiene por objetivo describir su tasa de mortalidad. Métodos: se realizó un estudio descriptivo observacional transversal y ecológico de las defunciones por carcinoma de vías biliares en Chile durante 2017 y 2021 según sexo, grupo etario y región de residencia. Resultados: la tasa de mortalidad nacional de personas mayores a 20 años durante el periodo estudiado fue de 1,56 por cada 100.000 habitantes. La tasa de mortalidad más alta del sexo masculino se observó en 2020, siendo de 2,61. La mayor mortalidad se encontró en personas mayores a 80 años en el sexo masculino con una tasa de 24,38. A nivel regional, en Magallanes se observó la mayor tasa de mortalidad con 5,66, mientras que Tarapacá presentó la menor tasa con un valor de 0,96. Finalmente, el índice de Swaroop fue igual o mayor al 92% en todas las regiones del país. Conclusión: la mayor mortalidad por colangiocarcinoma intrahepático se presenta en personas de edad avanzada y de sexo masculino. Interesantemente la mayor mortalidad por esta causa se concentra en la zona sur de Chile. Dada la magnitud del problema que representa esta enfermedad en la salud pública nacional es que futuros estudios son necesarios para establecer medidas de prevención y/o tratamiento de esta enfermedad.

Introduction: intrahepatic cholangiocarcinoma is an aggressive cancer of epithelial cells of the intrahepatic bile ducts, and its deve-lopment is associated with chronic inflammation of the biliary tree. In Chile, its epidemiology is limited, and the present study aims to describe its mortality rate. Methods: a descriptive, cross-sectional, observational, and ecological study of deaths from bile duct carcinoma in Chile between 2017 and 2021 was performed according to sex, age group, and region of residence. Results: the national mortality rate of people over 20 years old during the study period was 1.56 per 100,000 inhabitants. The highest mortality rate for the male sex was observed in 2020, with a value of 2.61. In turn, the highest mortality rate was found in people over 80 years old in the male sex, with a rate value of 24.38. On a regional level, Magallanes had the highest mortality rate, with a rate value of 5.66, while Tarapacá had the lowest rate, with a value of 0.96. Finally, Swaroop's index was equal to or greater than 92% in all regions of the country. Conclusion: the highest mortality from intrahepatic cholangiocarcinoma occurs in older people and males. Interestingly, the highest mortality from this cause is concentrated in the southern zone of Chile. Given the magnitude of the problem that this disease represents for national public health, future studies are necessary to establish both prevention measures and treatments

Drug-induced bile duct injury: progress and challenges / 中华肝脏病杂志

Drug-induced bile duct injury is a specific kind of drug-induced liver injury that has two main pathological types, namely ductopenia, or vanishing bile duct syndrome, and secondary sclerosing cholangitis. However, in recent years, the reports of new drugs that cause bile duct injury have been constantly increasing, and these drugs have different clinicopathological features and a novel pathogenesis. Therefore, this paper summarizes and analyzes the progress and challenges in the etiology, pathogenesis, diagnosis and treatment, and other aspects of drug-induced bile duct injury.

Highlights of the EASL clinical practice guidelines on sclerosing cholangitis versus the latest Chinese guideline / 临床肝胆病杂志

In 2022, the European Association for the Study of the Liver issued Clinical practice guidelines on sclerosing cholangitis. With reference to the 2017 edition of Role of endoscopy in primary sclerosing cholangitis: European Society of Gastrointestinal Endoscopy (ESGE) and European Association for the Study of the Liver (EASL) Clinical Guideline (2017) and in comparison to the corresponding contents in Guidelines on the diagnosis and management of primary sclerosing cholangitis (2021) issued by Chinese Society of Hepatology, Chinese Medical Association, in 2021, this article summarizes the updates in diagnosis, treatment, monitoring, and management of special populations and analyzes the basis for updated recommendations and their guiding significance in optimizing the clinical management of primary sclerosing cholangitis (PSC). The comparative analysis shows that the new version of the guidelines is similar to the Chinese guidelines in terms of diagnosis, treatment, and follow-up, and it is worth learning from the technical details such as the recommended dose of ursodeoxycholic acid and long-term follow-up plan. Since PSC is a chronic refractory disease, the drugs recommended by current guidelines cannot delay or reverse disease progression, and there is still a lack of consensus statements on immunotherapy and screening protocols for end-stage complications, which might be the directions for further research.

Excerpt from the 2022 American Association for the Study of Liver Diseases clinical practice guideline: management of primary sclerosing cholangitis and cholangiocarcinoma / 中华肝脏病杂志

What are the new contents of the guideline since 2010?A.Patients with primary and non-primary sclerosing cholangitis (PSC) are included in these guidelines for the diagnosis and management of cholangiocarcinoma.B.Define "related stricture" as any biliary or hepatic duct stricture accompanied by the signs or symptoms of obstructive cholestasis and/or bacterial cholangitis.C.Patients who have had an inconclusive report from MRI and cholangiopancreatography should be reexamined by high-quality MRI/cholangiopancreatography for diagnostic purposes. Endoscopic retrograde cholangiopancreatography should be avoided for the diagnosis of PSC.D. Patients with PSC and unknown inflammatory bowel disease (IBD) should undergo diagnostic colonoscopic histological sampling, with follow-up examination every five years until IBD is detected.E. PSC patients with IBD should begin colon cancer monitoring at 15 years of age.F. Individual incidence rates should be interpreted with caution when using the new clinical risk tool for PSC for risk stratification.G. All patients with PSC should be considered for clinical trials; however, if ursodeoxycholic acid (13-23 mg/kg/day) is well tolerated and after 12 months of treatment, alkaline phosphatase (γ- Glutamyltransferase in children) and/or symptoms are significantly improved, it can be considered to continue to be used.H. Endoscopic retrograde cholangiopancreatography with cholangiocytology brushing and fluorescence in situ hybridization analysis should be performed on all patients suspected of having hilar or distal cholangiocarcinoma.I.Patients with PSC and recurrent cholangitis are now included in the new unified network organ sharing policy for the end-stage liver disease model standard.J. Liver transplantation is recommended after neoadjuvant therapy for patients with unresectable hilar cholangiocarcinoma with diameter < 3 cm or combined with PSC and no intrahepatic (extrahepatic) metastases.

Manifestaciones hepatobiliares asociadas a la enfermedad inflamatoria intestinal / Hepatobiliary manifestations associated with inflammatory bowel disease

La enfermedad inflamatoria intestinal (EII) engloba dos entidades, la enfermedad de Crohn (EC) y la colitis ulcerativa (CU), las cuales son enfermedades inmunomediadas, crónicas y recurrentes que, aunque afectan al intestino, pueden ir acompañadas de manifestaciones extraintestinales de tipo hepatobiliar en el 5 % de los casos. Entre ellas, las más frecuentes son la enfermedad por hígado graso no alcohólico (EHGNA), la colelitiasis, la colangitis esclerosante primaria (CEP), la colangitis relacionada con IgG4, la hepatitis autoinmune (HAI), el síndrome de superposición HAI/CEP, así como la lesión hepática inducida por fármacos (DILI); y otras menos frecuentes como la colangitis biliar primaria (CBP), la trombosis de la vena porta, los abscesos hepáticos, la hepatitis granulomatosa, las hepatitis B y C, la reactivación de la hepatitis B por terapia inmunosupresora, y la amiloidosis. Estas manifestaciones hepatobiliares cursan con una fisiopatología similar o inclusive la misma de la EII, en la que participan el sistema inmune innato y adaptativo, alteración de la microbiota (disbiosis), permeabilidad intestinal, factores de riesgo genéticos (comunes para EII y manifestaciones hepatobiliares) y desencadenantes ambientales. La primera manifestación de un trastorno hepatobiliar es la alteración del perfil de función hepática, por lo que el abordaje diagnóstico se debe dirigir a evaluar y monitorizar las enzimas hepáticas y su asociación a algún patrón diferencial de alteración hepatocelular o colestásico, con el fin de tomar decisiones oportunas con respecto a la suspensión, indicación o modificación de algún medicamento, o cualquier otro abordaje que impida o retrase la evolución de la enfermedad hepatobiliar, y al mismo tiempo garantice el control de la EII, mejorando potencialmente el pronóstico de estos pacientes.

Inflammatory bowel disease (IBD) encompasses two entities, Crohn's disease (CD) and ulcerative colitis (UC), which are chronic, recurrent, immune-mediated inflammatory diseases that, although affect the gut, may be accompanied by extraintestinal hepatobiliary manifestations in 5% of the cases. Among them, the most frequent are non-alcoholic fatty liver disease (NAFLD), cholelithiasis, primary sclerosing cholangitis (PSC), IgG4-related cholangitis, autoimmune hepatitis (AIH), AIH/PSC overlap syndrome, as well as drug-induced liver injury (DILI); and other less frequent such as primary biliary cholangitis (PBC), portal vein thrombosis, liver abscesses, granulomatous hepatitis, hepatitis B and C, reactivation of hepatitis B due to different drugs, and amyloidosis. These hepatobiliary manifestations present with a pathophysiology similar or even the same as that of IBD, where several factors participate, including the innate and adaptive immune system, an interaction with the components of the microbiota, leaky gut, genetic risk factors (common for both IBD and hepatobiliary manifestations) and environmental triggers. The first manifestation of a hepatobiliary disorder is the alteration of the liver profile; therefore, the diagnostic approach should be aimed at evaluating and monitoring liver enzymes and their association with some differential pattern of hepatocellular or cholestatic changes, in order to make appropriate decisions regarding the suspension or modification of any medication, or any other approach that prevents or delays the evolution of hepatobiliary disease, and at the same time guarantees control of IBD, improving the prognosis of these patients.

Clinical research advances in mesenchymal stem cells for the treatment of autoimmune liver diseases / 临床肝胆病杂志

Due to limited options and modalities for the etiological treatment of autoimmune liver diseases, it is urgent to seek new therapeutic methods for liver autoimmune diseases. As the most common source of cells for stem cell therapy, mesenchymal stem cells (MSCs) play an important role in regulating innate and adaptive immune responses and have been widely used in clinical trials for the treatment of autoimmune diseases and inflammatory diseases. Recent experimental and clinical studies have shown that MSCs and MSC-EVs can inhibit the activation and proliferation of a variety of liver proinflammatory cells (such as Th1, Th17, and M1 macrophages), regulate the differentiation of different subsets of T and B cells, reduce the secretion of proinflammatory cytokines, and promote the proliferation of anti-inflammatory cells, thereby playing an immunoregulatory role. This article reviews the clinical trials of MSCs and MSC-EVs in the treatment of autoimmune liver diseases and their mechanism in regulating immune function and promoting hepatocyte regeneration and briefly describes the potential application and limitations of MSCs and MSC-EVs in clinical practice.

Role of T lymphocytes in primary sclerosing cholangitis / 临床肝胆病杂志

Primary sclerosing cholangitis （PSC） is an immune-mediated chronic cholestatic liver disease and can progress to end-stage liver diseases such as liver cirrhosis and liver failure， and there are still no effective treatment methods at present. Studies have found that T lymphocytes are closely associated with the development and progression of PSC. This article reviews the role of T lymphocytes in PSC， so as to provide new ideas for research on the pathogenesis of PSC and the clinical diagnosis and treatment of PSC.

Association between primary sclerosing cholangitis and the risk of colorectal cancer: A two-sample Mendelian randomization study / 临床肝胆病杂志

Objective To investigate the association between primary sclerosing cholangitis (PSC) and colorectal cancer (CRC) by using two-sample Mendelian randomization (TSMR). Methods The single nucleotide polymorphism (SNP) data associated with PSC and CRC were obtained from Finland Biobank and UK Biobank, respectively. A secondary data analysis was performed for all pooled data based on genome-wide association studies to select the genetic loci closely associated with PSC as instrumental variables, and TSMR was conducted by seven methods, i.e., Egger regression in Mendelian randomization, weighted median, inverse variance weighted (IVW) random effects model, maximum likelihood, linear weighted median, IVW radial method, and IVW fixed effects model. Odds ratio (OR) value was used to evaluate the causal relationship between PSC and the risk of CRC. Results There was a positive causal relationship between gene predicted PSC and CRC, and with the IVW fixed effects model as an example, genetically determined patients with PSC could increase the risk of CRC ( OR =1.002 243, 95% confidence interval: 1.001 319-1.003 167). TSMR results showed no heterogeneity ( P =0.87) or horizontal pleiotropy ( P =0.95). The three instrumental variables selected for PSC were strong instrumental variables ( F =11.86). Conclusion TSMR shows the genetic evidence for the association between PSC and the risk of CRC. Regardless of the presence or absence of inflammatory bowel disease, active enteroscopy screening among patients with PSC may help with the early identification and timely intervention of CRC.

Autoimmune hepatitis � primary biliary cirrhosis and overlap syndrome: A case report

Important immune-mediated liver illnesses include autoimmunity hepatitis (AIH) and primary biliary cirrhosis. Typically, they are distinguished based on histological, biochemical, serological, and clinical parameters. Diagnostic criteria for many conditions are typically met by patients with autoimmune liver disease. The diagnosis of AIH/primary sclerosing cholangitis overlap is based on a mix of biochemistry, autoantibody profile, cholangiogram, and liver histology; there are no universally accepted criteria for this. The patient can remain asymptomatic or present with pruritis and jaundice. Diagnosis is through liver biopsy showing bile duct destruction and proliferation. The treatment is by high-dose ursodeoxycholic acid.

A Case of Overlapping Autoimmune Sclerosing Cholangitis and Autoimmune Hemolytic Anemia

This case study revolves around a 14-year old female patient, who was otherwise healthy and normal, but brought to the hospital for her condition. The patient presented with complaints of fever, sore throat, severe abdominal pain, and generalized body aches for the last two days. She appeared to be lethargic and weak. Her condition had made her fatigued and a yellowish tinge of the face and sclera was obvious, pointing towards a likely case of jaundice. Upon abdominal examination, the patient also had hepatomegaly and splenomegaly present, and the muscles appeared to be tender as well. The child was admitted to the hospital, where her lab investigations revealed that she was anemic. Other investigations revealed that her liver enzymes and bilirubin levels were significantly elevated. Her DAT was positive and there was a presence of high eosinophilia. However, her Hepatitis A, B, and C screening came out to be negative. She was kept as a suspected case of Autoimmune Hemolytic Anemia as it appeared to be themost probable diagnosis, given her condition, but following a biopsy she was also confirmed as a case of Autoimmune Sclerosing Cholangitis.Once the diagnosis was confirmed, the child was treated accordingly. This was a unique case because it involved a significant overlap in the presence of two diseases. Both of the diseases, although similar in appearance, could have caused great havoc if they were not separately diagnosed and treated accordingly. This case study deals with such an overlapping case that was brought to the hospital. With a myriad of confusing symptoms, it was obvious that the diagnosis could have been misdiagnosed or incorrectly diagnosed. However, the lab reports and examinations that were carried out smartly helped in excluding the other diagnoses which would have obviously lead to confusions and also in starting the wrong treatment. This case study deals with the examination, laboratory protocols, along with the association of symptoms, all of which help in reaching towards the final diagnosis in a timely manner and thus, helped treat the patient effectively. The case study also highlights how both of these diseases present in a patient of the younger population, and how they need to be managed effectively and efficiently to ensure that there are no complications that might alter the already deteriorating state of the patient.

Guidelines on the diagnosis and management of primary sclerosing cholangitis (2021) / 中华肝脏病杂志

In 2015, the first Chinese consensus on the diagnosis and management of primary sclerosing cholangitis was issued. In the past years, more data have emerged from the literature. Herein, the Autoimmune Liver Disease Group of the Chinese Society of Hepatology organized an expert group to review the evidence and updated the recommendations to formulate the guidelines. There are 21 recommendations on PSC clinical practice. To facilitate the differentiation between PSC and IgG4-related sclerosing cholangitis, 10 recommendations on IgG4-SC are also attached. These guidelines aim to provide a working reference for the management of PSC and IgG4-SC.

Características epidemiológicas y clínicas de pacientes con cirrosis hepática

RESUMEN Introducción: La cirrosis hepática constituye la etapa final de muchas enfermedades del hígado. Objetivo: Determinar las características epidemiológicas y clínicas de pacientes con cirrosis hepática. Métodos: Se realizó una investigación descriptiva, retrospectiva, con datos de archivo, de 57 pacientes cirróticos. Se excluyeron aquellos con datos insuficientes en la historia clínica. Las variables analizadas fueron: edad, sexo, etiología, modo de diagnóstico, comorbilidades, manifestaciones endoscópicas de la hipertensión portal, complicaciones, estadios de la enfermedad según D'Amico y clasificación de Child-Pugh. Para el análisis de los resultados se emplearon técnicas de la estadística descriptiva. Resultados: Hubo 19 pacientes (33,3 %) en el grupo de edad entre 60 y 69 años; 31 (54,4 %) mujeres y 26 (45,6 %) hombres. El virus de la hepatitis C fue encontrado en 21 pacientes (36,8 %). El 96,4 % de los enfermos se diagnosticaron mediante ecografía abdominal; 12 (21,1 %) presentaron ascitis y 38 (66,6 %) manifestaciones endoscópicas de hipertensión portal. En estadio 4 de D'Amico estaban 20 (35 %) enfermos y 26 (45,6 %) en estadio de Child-Pugh A; 24 (42,1 %) en Child-Pugh B y 7 (12,3 %) en Child-Pugh C. Conclusiones: La cirrosis hepática predomina en la séptima década de la vida, en el sexo femenino. Prevalece el ultrasonido abdominal como modo de diagnóstico. Las causas más frecuentes son el virus de hepatitis C y el alcoholismo. La ascitis es la complicación que más se presenta. La mayoría de los pacientes muestran signos de hipertensión portal. Predominan las formas no compensadas de la enfermedad.

ABSTRACT Introduction: Liver cirrhosis is the end stage of many liver diseases. Objective: To determine the epidemiological and clinical characteristics of patients with liver cirrhosis. Results: There were 19 patients (33.3%) in the age group between 60 and 69 years; 31 (54,4 %) women and 26 (45,6 %) men. Hepatitis C virus was found in 21 patients (36,8 %). 96,4 % of the patients were diagnosed by abdominal ultrasound; 12 (21,1 %) presented ascites and 38 (66,6 %) endoscopic manifestations of portal hypertension. In D'Amico stage 4 there were 20 (35 %) patients and 26 (45,6 %) in Child-Pugh A stage; 24 (42,1 %) in Child-Pugh B and 7 (12,3 %) in Child-Pugh C. Conclusions: Liver cirrhosis predominates in the seventh decade of life, in females. Abdominal ultrasound prevails as a diagnostic mode. The most common causes are hepatitis C virus and alcoholism. Ascites is the most common complication. Most patients present with signs of portal hypertension. Uncompensated forms of the disease predominate.

Colelitíase sintomática como apresentação de colangite esclerosante primária na infância - série de casos e revisão de literatura / Symptomatic cholelithiasis as the presentation of pediatric primary sclerosing cholangitis - case series and literature review

ABSTRACT BACKGROUND: Primary sclerosing cholangitis (PSC) is a rare hepatobiliary disorder, whose etiology remains not fully elucidated. Given how rare PSC is in childhood, until the recent publication of a multicenter international collaboration, even data on its characteristics and natural history were scarce. Symptomatic cholelithiasis has not been previously reported as the presentation of PSC. OBJECTIVE: The aim of this study was the diagnosis of PSC following the initial unusual presentation with symptomatic cholelithiasis, that followed an atypical clinical course that could not be explained by cholelithiasis alone. A literature review was also conducted. METHODS: We conducted a retrospective chart review of three patients, who were diagnosed and/or followed at the Clinics Hospital, University of Campinas - Sao Paulo/ Brazil, between 2014 and 2020. Data analyzed included gender, age of presentation, past medical history, imaging findings, laboratory results, endoscopic evaluation, response to medical therapy and follow-up. RESULTS: Age at time of presentation with cholelithiasis varied from 10 to 12 years. In two of the cases reported, a more subacute onset of symptoms preceded the episode of cholelithiasis. Two patients were managed with cholecystectomy, not followed by any surgical complications, one patient was managed conservatively. Percutaneous liver biopsy was performed in all three cases, showing histological findings compatible with PSC. Associated inflammatory bowel disease (IBD) was not seen in any of the patients. The patients have been followed for a mean time of 3.4 years. CONCLUSION: PSC and cholelithiasis are both rare in the pediatric population. This study reports on symptomatic cholelithiasis as a presentation of PSC and raises the importance of suspecting an underlying hepatobiliary disorder in children with cholelithiasis without any known predisposing factors and/or that follow an atypical clinical course for cholelithiasis alone.

RESUMO CONTEXTO: A colangite esclerosante primária (CEP) é uma doença hepatobiliar rara, cuja etiologia ainda não está totalmente elucidada. Dada a raridade do CEP na infância, até a recente publicação de uma colaboração multicêntrica internacional, mesmo dados sobre suas características e história natural eram escassos. A colelitíase sintomática não foi relatada anteriormente como a apresentação inicial de CEP na infância. OBJETIVO: O objetivo deste estudo foi o diagnóstico de CEP após a apresentação inicial incomum com colelitíase sintomática, que seguiu um curso clínico atípico que não poderia ser explicado apenas pela colelitíase. Também foi realizada uma revisão da literatura. MÉTODOS: Foi realizada uma revisão retrospectiva dos prontuários de três pacientes, que foram diagnosticados e/ou acompanhados no Hospital das Clínicas da Universidade Estadual de Campinas - São Paulo / Brasil, entre 2014 e 2020. Os dados analisados incluíram sexo, idade de apresentação, história médica pregressa, achados de imagem, resultados laboratoriais, avaliação endoscópica, resposta à terapia médica e acompanhamento. RESULTADOS: A idade no momento da apresentação da colelitíase variou de 10 a 12 anos. Em dois dos casos relatados, um início mais subagudo dos sintomas precedeu o episódio de colelitíase. Dois pacientes foram tratados com colecistectomia, não seguida de qualquer complicação cirúrgica, e um paciente foi tratado de forma conservadora. Biópsia hepática percutânea foi realizada em todos os três casos, mostrando achados histológicos compatíveis com CEP. Doença inflamatória intestinal associada não foi observada em nenhum dos pacientes. Os pacientes foram acompanhados por um tempo médio de 3,4 anos. CONCLUSÃO: CEP e colelitíase são raras na população pediátrica. Este estudo relata a colelitíase sintomática como uma apresentação de CEP e levanta a importância da suspeita de doença hepatobiliar subjacente em crianças com colelitíase sem quaisquer fatores predisponentes conhecidos e/ou que seguem um curso clínico atípico.

Enfermedad de Crohn con compromiso extenso y manifestaciones extradigestivas inusuales: a propósito de un caso / Crohn's disease with extensive involvement and rare extraintestinal manifestations: A case report

Resumen La enfermedad de Crohn (EC) es considerada una entidad inmunológicamente mediada que compromete el tracto digestivo. Su compromiso suele ser transmural y puede afectar cualquier parte del tubo digestivo, desde la cavidad oral hasta el ano. Aunque se sabe que su extensión es variable, es poco habitual ver un compromiso extenso y multiorgánico. Se presenta el caso de un paciente joven, quien debutó con síntomas pulmonares asociados con la EC y años más tarde se presentaron los síntomas digestivos y de la vía biliar. El tratamiento se basó en la terapia con anticuerpos contra el factor de necrosis tumoral alfa (TNF-α), con lo cual se obtuvo una respuesta clínica satisfactoria. La relevancia clínica de este caso es la forma de presentación clínica tan florida, tanto por el compromiso gastrointestinal extenso como por las manifestaciones extradigestivas tan infrecuentes.

Abstract Crohn's disease (CD) is considered an immunologically mediated entity that involves the digestive tract. It is characterized by transmural inflammation and can affect any part of the digestive tract, from the oral cavity to the anus. Although it is recognized that its severity varies, extensive and multiple organ failure is unusual. We present the case of a young patient, who initially presented with pulmonary symptoms associated with CD. Years later, digestive and bile duct symptoms appeared. Treatment was based on anti-tumor necrosis factor-alpha antibody therapy, resulting in a satisfactory clinical response. The clinical relevance of this case is its full-blown presentation, which includes extensive gastrointestinal involvement and rare extraintestinal manifestations.

Colangitis esclerosante primaria / Primary sclerosing cholangitis

La colangitis esclerosante primaria (CEP) se define por la inflamación, fibrosis y estenosis de los conductos biliares intra o extrahepáticos que no pueden ser explicadas por otras causas. La prevalencia de CEP está estimada entre 0 a 16,2 por 100.000 habitantes, mientras que la incidencia está entre 0 y 1,3 casos por cada 100.000 personas por año. Las causas siguen siendo difíciles de dilucidar y en muchos casos se establece como de origen idiopático. Sin embargo, se han propuesto factores genéticos, ambientales e isquémicos asociados, además de un componente autoinmune. Existe además una fuerte asociación entre la enfermedad inflamatoria intestinal y la CEP. Los síntomas suelen ser inespecíficos, 50% de los pacientes son asintomáticos, presentando únicamente alteración en el perfil hepático de patrón colestásico, con predominio de elevación de la fosfatasa alcalina. La ictericia es un signo de mal pronóstico que con frecuencia se asocia a colangiocarcinoma. La confirmación diagnóstica se hace por colangiopancreatografía retrógrada endoscópica (CPRE) e imágenes por resonancia magnética. Aún no existe un tratamiento establecido, y en la mayoría de los casos coexiste con otras patologías. El tratamiento es multimodal con fármacos, terapia endoscópica y trasplante hepático.

Primary sclerosing cholangitis (PSC) is defined by inflammation, fibrosis, and stenosis of the intra or extrahepatic bile ducts that cannot be explained by other causes. The prevalence of PSC is estimated between 0 to 16.2 per 100,000 inhabitants, while the incidence is between 0 and 1.3 cases per 100,000 persons-year. The causes remain elusive and, in many cases, it is established as idiopathic in origin. However, genetic, environmental and ischemic factors have been proposed in addition to an autoimmune component. There is also a strong association between inflammatory bowel disease and PSC. Symptoms are usually nonspecific, 50% of the patients are asymptomatic, presenting only an alteration in the liver profile with a cholestatic pattern, and predominance of elevated alkaline phosphatase. Jaundice is a poor prognostic sign and is frequently associated with cholangiocarcinoma. Diagnostic confirmation is made by endoscopic retrograde cholangiopancreatography and magnetic resonance imaging. There is still no established treatment, and in most cases, the disease coexists with other pathologies. Treatment is multimodal with drugs, endoscopic therapy and liver transplantation.

Hepatopatías autoinmunes. Hallazgos clínicos y de laboratorio en pacientes de un hospital de referencia nacional / Autoimmune liver diseases. Clinical and laboratory findings in patients in a national reference hospital

Introducción. Las enfermedades autoinmunes del hígado son un grupo de patologías caracterizadas por una respuesta autoinmune contra los hepatocitos y/o el epitelio biliar. Sus manifestaciones clínicas son variadas, con alteraciones en las pruebas de función hepática y presencia de autoanticuerpos. Metodología. Estudio observacional descriptivo con 101 pacientes atendidos en el Hospital Universitario de La Samaritana de Bogotá D.C., entre enero a diciembre de 2019, con los diagnósticos de hepatitis autoinmune, colangitis biliar primaria, colangitis esclerosante primaria y síndrome de sobreposición. Se evaluaron los parámetros clínicos y de laboratorio, con el fin de caracterizar su frecuencia en estas patologías, debido a la importancia de un diagnóstico precoz. Resultados. Se encontraron 54 casos de hepatitis autoinmune, 19 casos de colangitis biliar primaria, 4 casos de colangitis esclerosante primaria y 24 casos de síndrome de sobreposición. El 81% fueron mujeres y la edad promedio fue de 55 años. El 39% de los pacientes tenían cirrosis. En general, los resultados se ajustaron a lo descrito internacionalmente, como es el predominio en mujeres y la comorbilidad autoinmune. Conclusión. Los hallazgos indican que cualquier alteración del perfil bioquímico hepático debe ser considerado, y se debe descartar la presencia de hepatopatías autoinmunes para diagnosticarlas de manera precoz, evitando que lleguen a cirrosis y sus complicaciones, con la necesidad de un trasplante hepático como única alternativa terapéutica.

Introduction. Autoimmune liver diseases are a group of pathologies characterized by an autoimmune response against hepatocytes and/or the biliary epithelium. Their clinical manifestations are varied, with alterations in liver function tests and the presence of autoantibodies. Methodology. Descriptive study with 101 patients who attended at the Hospital Universitario de La Samaritana in Bogota D.C., between January and December 2019, with the diagnoses of autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis and overlap syndrome. Clinical and laboratory parameters were evaluated in order to characterize their frequency in these pathologies, due to the importance of an early diagnosis. Results. There were 54 cases of autoimmune hepatitis, 19 cases of primary biliary cholangitis, 4 cases of primary sclerosing cholangitis, and 24 cases of overlap syndrome. Of all patients, 81% were women, the average age was 55 years, and 39% had cirrhosis. In general, the findings were consistent with what has been described worldwide, such as a higher prevalence in women and autoimmune comorbidity. Conclusion. The findings indicate that any alteration in the liver biochemical profile should be considered to rule out an autoimmune liver disease for an early diagnosis, avoiding the possibility of cirrhosis and its complications, with the need for a liver transplant as the only therapeutic alternative.

Pairing analysis of clinical prognosis between liver transplantation with autoimmune liver disease and viral hepatitis cirrhosis / 器官移植

Objective To analyze the difference and influential factors of clinical prognosis between liver transplantation with autoimmune liver disease (AILD) and viral hepatitis cirrhosis. Methods Clinical data of 75 recipients undergoing liver transplantation from January 2002 to January 2017 were retrospectively analyzed. All recipients were divided into the AILD group (n=25) and viral hepatitis cirrhosis group (n=50). The intraoperative conditions of the recipients were observed including warm ischemia time, cold ischemia time, operation time, anhepatic phase and blood transfusion volume. Postoperative complications were observed including severe acute kidney injury (AKI), infection, acute rejection, biliary tract-related complications, vascular-related complications and post transplantation diabetes mellitus (PTDM). The follow-up status were monitored after discharge. The prognostic factors of liver transplant recipients were analyzed. Results The warm ischemia time, cold ischemia time, operation time and anhepatic phase did not significantly differ between two groups (all P > 0.05). In the AILD group, the incidence of postoperative acute rejection was remarkably higher, whereas the incidence of postoperative severe AKI was significantly lower than those in the viral hepatitis cirrhosis group (both P < 0.05). The postoperative 1-, 3- and 5-year survival rates in the AILD group was 92%, 87%, and 87%, which did not significantly differ from 88%, 88% and 88% in the viral hepatitis cirrhosis group (all P > 0.05). Univariate analysis showed that age, model for end-stage liver disease (MELD) score, severe AKI, infection and biliary tract-related complications were the influencing factors of clinical prognosis of the recipients (all P < 0.05). Conclusions The overall survival prognosis does not significantly differ between the AILD and viral hepatitis cirrhosis groups. Age, MELD score, severe AKI, infection and biliary tract-related complications are the risk factors affecting the clinical prognosis of liver transplantation recipients.

Role of gut microbiota in chronic liver disease and its potential therapeutic strategies / 中国药理学通报

An increasing number of studies have shown that intestinal microbes play an important role in maintaining liver homeostasis. The liver is closely linked to the intestine through the portal vein, and the transfer of intestinal microbcs, and their metabolites to the liver can affect the normal physiological function of the liver. Willi the deepening of research on intestinal microbes in recent years, a large number of studies have found that intestinal microbes play an important role in the development of chronic liver diseases. and more and more studies have shown that the regulation of intestinal microbes may be a potential therapeutic target for chronic liver diseases. This article summarizes the role of intestinal microbes in the development of chronic liver diseases and its related mechanisms in recent years, aiming to provide a reference for the prevention and treat-ment of chronic liver diseases.

Polimorfismos do gene HLA-DRB1 em pacientes pediátricos com hepatite autoimune tipo 1 e hepatite autoimune associada à colangite autoimune / Hla-drb1 gene polymorphisms in pediatric patients with type 1 autoimmune hepatitis and type 1 autoimmune hepatitis overlap syndrome with autoimmune cholangitis

ABSTRACT BACKGROUND: Autoimmune hepatitis (AIH) is a rare chronic inflammatory liver disease associated with a loss of immunological tolerance to self-antigens. Susceptibility to AIH is partially determined by the presence of genes related to human leukocyte antigen (HLA), mainly allelic variants of DRB1. OBJECTIVE: The purpose of this study was to investigate the frequencies of the polymorphisms in HLA-DRB1 gene in children and adolescents with type 1 AIH and type 1 AIH overlap syndrome with autoimmune cholangitis (overlap syndrome, OS) in comparison to healthy sex and age-matched individuals (control group). METHODS: This is a cross-sectional study of 25 pediatric patients diagnosed with type 1 AIH and 18 with OS. Fifty-seven healthy individuals were included as controls. The polymorphisms of the HLA-DRB1 gene were evaluated by PCR and included HLA-DRB1*03, HLA-DRB1*04, HLA-DRB1*07, and HLA-DRB1*13. RESULTS: Our results showed that the presence of the allele HLA-DRB1*13 increased the chance of autoimmune cholangitis (OR=3.96, CI 1.07 to 14.61, P=0.04). The HLA-DRB1*04 and HLA- DRB1*07 have no association with the AIH and autoimmune cholangitis in a young sample. CONCLUSION: This work demonstrates an association of the main polymorphisms in the HLA-DRB1 gene to AIH with or without cholangitis in a Brazilian sample.

RESUMO CONTEXTO: Hepatite autoimune (HAI) é uma doença hepática inflamatória crônica, rara, associada à perda da tolerância imunológica aos auto-antígenos. A susceptibilidade à HAI é parcialmente determinada pela presença de genes relacionados ao antígeno leucocitário humano (HLA), principalmente variantes alélicas do DRB1. OBJETIVO: O objetivo deste estudo foi investigar a frequência de polimorfismos no gene HLA-DRB1 em crianças e adolescentes com HAI tipo 1 e HAI tipo 1 associada à colangite autoimune, em comparação com indivíduos saudáveis pareados por sexo e idade (grupo controle). MÉTODOS: Este é um estudo transversal de 25 pacientes pediátricos com diagnóstico de HAI tipo 1 e 18 com HAI associada à colangite autoimune. Cinquenta e sete indivíduos saudáveis foram incluídos como controles. Os polimorfismos do gene HLA-DRB1 foram avaliados por PCR e incluíram HLA-DRB1*03, HLA-DRB1*04, HLA-DRB1*07 e HLA-DRB1*13. RESULTADOS: Nossos resultados mostraram que a presença do alelo HLA-DRB1*13 aumentou a chance de colangite autoimune (OR=3,96; IC 1,07 a 14,61; P=0,04). O HLA-DRB1*04 e o HLA-DRB1*07 não apresentam associação com a HAI e colangite autoimune no grupo de pacientes mais jovens. CONCLUSÃO: Este trabalho demonstra uma associação dos principais polimorfismos no gene HLA-DRB1 à HAI com ou sem colangite na população brasileira.