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.

Clinical features of primary sclerosing cholangitis and inflammatory bowel disease / 中华内科杂志

Objective: To explore disease characteristics of primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) and compare the differences between PSC with and without IBD. Methods: Study design was cross sectional. Forty-two patients with PSC who were admitted from January 2000 to January 2021 were included. We analyzed their demographic characteristics, clinical manifestations, concomitant diseases, auxiliary examination, and treatment. Results: The 42 patients were 11-74(43±18) years of age at diagnosis. The concordance rate of PSC with IBD was 33.3%, and the age at PSC with IBD diagnosis was 12-63(42±17) years. PSC patients with IBD had higher incidences of diarrhea and lower incidences of jaundice and fatigue than in those without IBD (all P<0.05). Alanine aminotransferase, total bilirubin, direct bilirubin, total bile acid and carbohydrate antigen 19-9 levels were higher in PSC patients without IBD than in those with IBD (all P<0.05). The positive rates for antinuclear antibodies and fecal occult blood were higher in PSC patients with IBD than in those without IBD (all P<0.05). Patients with PSC complicated with ulcerative colitis mainly experienced extensive colonic involvement. The proportion of 5-aminosalicylic acid and glucocorticoid application in PSC patients with IBD was significantly increased compared with that of PSC patients without IBD (P=0.025). Conclusions: The concordance rate of PSC with IBD is lower at Peking Union Medical College Hospital than in Western countries. Colonoscopy screening may benefit PSC patients with diarrhea or fecal occult blood-positive for early detection and diagnosis of IBD.

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.

Urgent liver retransplantation due to transmission of intrahepatic cholangiocarcinoma by donor: the first report in the literature / Retransplante de fígado urgente devido à transmissão de colangiocarcinoma intra-hepático pelo doador: o primeiro relato da literatura

ABSTRACT BACKGROUND: Liver transplantation represents the best therapeutic modality in end-stage chronic liver disease, severe acute hepatitis, and selected cases of liver tumors. AIMS: To describe a double retransplant in a male patient diagnosed with Crohn's disease and complicated with primary sclerosing cholangitis, severe portal hypertension, and cholangiocarcinoma diagnosed in the transplanted liver. METHODS: A 48-year-old male patient diagnosed with Crohn's disease 25 years ago, complicated with primary sclerosing cholangitis and severe portal hypertension. He underwent a liver transplantation in 2018 due to secondary biliary cirrhosis. In 2021, a primary sclerosing cholangitis recurrence was diagnosed and a liver retransplantation was indicated. Recipient's hepatectomy was very difficult by reason of complex portal vein thrombosis requiring extensive thromboendovenectomy. Intraoperative ultrasound with liver doppler evaluation was performed. Two suspicious nodules were incidentally diagnosed in the donor's liver and immediately removed for anatomopathological evaluation. RESULTS: After pathological confirmation of carcinoma, probable cholangiocarcinoma, at frozen section, the patient was re-listed as national priority and a new liver transplantation was performed within 24 hours. The patient was discharged after 2 weeks. CONCLUSIONS: The screening for neoplasms in donated organs should be part of our strict daily diagnostic arsenal. Moreover, we argue that, for the benefit of an adequate diagnosis and the feasibility of a safer procedure, the adoption of imaging tests routine for the liver donor is essential, allowing a reduction of the costs and some potential risks of liver transplant procedure.

RESUMO RACIONAL: O transplante de fígado representa a melhor modalidade terapêutica na doença hepática crônica terminal, hepatite aguda grave e casos selecionados de tumores hepáticos. OBJETIVOS: Descrever um retransplante duplo em paciente do sexo masculino, diagnosticado com doença de Crohn e complicado com colangite esclerosante primária, hipertensão portal grave e colangiocarcinoma diagnosticado no fígado transplantado. MÉTODOS: Paciente do sexo masculino, 48 anos, diagnosticado com doença de Crohn há 25 anos e complicado com colangite esclerosante primária e hipertensão portal grave. Foi submetido a um transplante de fígado em 2018 devido a cirrose biliar secundária. Em 2021, foi diagnosticada recidiva de colangite esclerosante primária e indicado retransplante hepático. A hepatectomia do receptor foi de alta complexidade devido à trombose complexa da veia porta, exigindo extensa tromboendovenectomia. Foi realizada ultrassonografia intraoperatória com doppler hepático. Dois nódulos suspeitos foram diagnosticados incidentalmente no fígado do doador e imediatamente removidos para avaliação anatomopatológica. RESULTADOS: Após confirmação patológica de carcinoma, provável colangiocarcinoma, pela congelação, o paciente foi relistado como prioridade nacional, e novo transplante hepático foi realizado em 24 horas. O paciente teve alta após 2 semanas. CONCLUSÕES: O rastreamento de neoplasias em órgãos doados deve fazer parte de nosso estrito arsenal diagnóstico diário. Além disso, defendemos que, em benefício de um diagnóstico correto e da viabilidade de um procedimento mais seguro, a adoção de uma rotina de exames de imagem é essencial em doadores hepáticos, permitindo a redução dos custos e alguns riscos potenciais do procedimento de transplante hepático.

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.

Hiperbilirrubinemia: visión del patólogo / Hyperbilirubinemia: pathologist's view

Los niveles de bilirrubina sérica normal en el adulto varían entre 0,3 mg/dL y 1,2 mg/dL, y su valor está determinado por la tasa de captación hepática, conjugación y excreción. La ictericia se hace evidente cuando los niveles de bilirrubina sérica se elevan por encima de 2,5 mg/dL a 3 mg/dL, siendo un indicador de enfermedad subyacente. La bilis es producida por los hepatocitos y fluye desde los canalículos, canales de Hering, conductos biliares intrahepáticos, conductos hepáticos derechos e izquierdos hasta llegar al duodeno. A nivel histopatológico, cualquier entidad que lleve a la acumulación intrahepática de bilis por disfunción hepatocelular u obstrucción biliar genera colestasis, que se observa en la biopsia hepática como la acumulación de tapones de color marrón verdoso de pigmento biliar en los hepatocitos, y secundariamente se observan los canalículos dilatados. Las causas de colestasis intrahepática son diversas e incluyen enfermedades como colangitis biliar primaria, colangitis esclerosante primaria, hepatitis autoinmune, hepatitis virales y toxicidad medicamentosa. Esta revisión tiene como objetivo analizar algunos tipos de hiperbilirrubinemia, resaltando sus características histopatológicas.

Normal serum bilirubin levels in adults range from 0.3 mg/dL to 1.2 mg/dL, and its value is determined by the rate of hepatic uptake, conjugation, and excretion. Jaundice becomes apparent when serum bilirubin levels rise above 2.5 mg/dL to 3.5 mg/dL and is an indicator of underlying disease. Bile is produced by hepatocytes and flows from the canaliculi, Hering's canals, intrahepatic bile ducts, and right and left hepatic ducts to the duodenum. Pathologically, any condition that leadsto intrahepatic accumulation of bile due to hepatocellular dysfunction or biliary obstruction, generates cholestasis, which is observed in liver biopsy as the accumulation of greenish-brown deposits of bile pigment in hepatocytes, with dilated canaliculi. The causes of intrahepatic cholestasis are diverse and include diseases such as primary biliary cholangitis and primary sclerosing cholangitis, autoimmune hepatitis, viral hepatitis, and drug toxicity. This review aims to analyze some types of hyperbilirubinemia, highlighting their histopathological characteristics.

Colangitis esclerosante asociada a infección severa por SARS-CoV-2 / Sclerosing cholangitis associated with severe infection by SARS-CoV-2

La colangitis esclerosante secundaria es una enfermedad poco prevalente, de etiología multifactorial y con una fisiopatología progresiva, caracterizada por obstrucción biliar y fibrosis. Entre las múltiples causas se destacan las siguientes: inmunomediada por IgG4, isquémica, infecciosa y relacionada a medicamentos. En el contexto de la pandemia por SARS-CoV-2, se han reportado algunas series de casos que determinan una asociación entre estas dos entidades. Se presenta el caso de una mujer en la octava década de la vida con infección por SARS-CoV-2 grave, que cursó con ictericia progresiva, perfil hepático con patrón colestásico, y hallazgos imagenológicos de colangitis esclerosante con vía biliar desestructurada de manera difusa, microcálculos y barro biliar. Se diagnosticó colangitis esclerosante secundaria a SARS-CoV-2 y se dio manejo con ácido ursodesoxicólico.

Secondary sclerosing cholangitis is a rare disease of multifactorial etiology with a progressive pathophysiology, characterized by biliary obstruction and fibrosis. Multiple causes include: IgG4-immunemediated, ischemic, infectious and drug-induced. In the context of the SARS-CoV-2 pandemic, some case series have been reported that determine an association between these two entities. We present the case of a woman in her eighth decade with severe SARS-CoV-2 infection that presented with progressive jaundice, liver profile with cholestatic pattern, and imaging findings of sclerosing cholangitis with obliterated bile ducts, microlithiasis and biliary sludge. Sclerosing cholangitis secondary to SARS-CoV-2 was diagnosed and the patient was treated with ursodeoxycholic acid.

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.

Antineutrophil cytoplasmic antibody profiles differ according to type of primary sclerosing cholangitis and autoimmune hepatitis

OBJECTIVES: To determine the frequency of the antineutrophil cytoplasmic antibodies (ANCA), antiproteinase-3 and antimyeloperoxidase, in primary sclerosing cholangitis (PSC) with or without inflammatory bowel disease (IBD+ or IBD-) and in different types of autoimmune hepatitis (AIH). Additionally, to verify the agreement between ANCA patterns by indirect immunofluorescence and their antigenic specificities by ELISA. METHODS: For this study, 249 patients were enrolled (42 PSC/IBD+; 33 PSC/IBD-; 31 AIH type-1; 30 AIH type-2; 31 AIH type-3; 52 primary biliary cirrhosis; 30 healthy controls) whose serum samples were tested for ANCA autoantibodies. RESULTS: There were fewer female subjects in the PSC/IBD- group (p=0.034). Atypical perinuclear-ANCA was detected more frequently in PSC/IBD+ patients than in PSC/IBD- patients (p=0.005), and was significantly more frequent in type-1 (p<0.001) and type-3 AIH (p=0.012) than in type-2 AIH. Proteinase-3-ANCA was detected in 25 samples (only one with cytoplasmic-ANCA pattern), and more frequently in PSC/IBD+ than in PSC/IBD- patients (p=0.025). Myeloperoxidase-ANCA was identified in eight samples (none with the perinuclear-ANCA pattern). Among the 62 reactive samples for atypical perinuclear-ANCA, 13 had antigenic specific reactions for proteinase-3 and myeloperoxidase. CONCLUSIONS: PSC/IBD+ differed from PSC/IBD- in terms of sex and proteinase 3-ANCA and atypical perinuclear-ANCA reactivity, the latter of which was more frequently detected in type-1 and type-3 AIH than in type-2 AIH. There was no agreement between ANCA patterns and antigenic specificities in IBD and autoimmune liver diseases, which reinforces the need for proteinase-3 and myeloperoxidase antibody testing.

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.

Colangitis esclerosante primaria. Una revisión narrativa / Primary Sclerosing Cholangitis. A narrative review

RESUMEN La colangitis esclerosante primaria (CEP) es una patología hepática crónica y rara que se caracteriza por la inflamación y fibrosis de los conductos biliares, cuya evolución puede llevar a la cirrosis, hipertensión portal y enfermedad hepática en etapa terminal. Su etiología es desconocida, pero se ha relacionado con factores genéticos y autoinflamatorios. Además, tiene una relación muy estrecha con la enfermedad inflamatoria intestinal (EII). Su presentación clínica es muy inespecífica, sus principales síntomas son el prurito y la fatiga. La prueba estándar para su diagnóstico es la colangiopancreatografía por resonancia magnética (CPRM), donde se observa un aspecto anular ocasionado por estenosis multifocales cortas con segmentos alternos normales o dilatados. Actualmente, no existe ningún tratamiento farmacológico que logre prolongar la supervivencia sin un trasplante de hígado en la CEP. Sólo se puede hacer tratamiento sintomático, especialmente del prurito. El único manejo curativo con el que se cuenta hoy en día es el trasplante hepático, aunque existe un riesgo de recurrencia de la enfermedad. Es muy importante la vigilancia de los trastornos inflamatorios intestinales, la malignidad y la enfermedad metabólica ósea en estos pacientes. Se ha visto que algunos factores, como el diagnóstico temprano, son de buen pronóstico para la enfermedad.

SUMMARY Primary sclerosing cholangitis (PSC) is a rare, chronic liver pathology characterized by inflammation and fibrosis of the bile ducts, whose evolution can lead to cirrhosis, portal hypertension and end-stage liver disease. Its etiology is unknown, but it has been related to genetic and autoinflammatory factors. In addition, it has a very close relationship with inflammatory bowel disease. Its clinical presentation is nonspecific, the main symptoms are pruritus and fatigue. The standard test for diagnosis is magnetic resonance cholangiopancreatography (MRCP), where an annular aspect is observed caused by short multifocal stenoses with alternating normal or dilated segments. Currently, there is no pharmacological treatment that can prolong the survival without liver transplantation in PSC. Symptomatic treatment is warranted, especially for pruritus. The only curative treatment that is currently available is liver transplantation, although there is a risk of recurrence of the disease. The monitoring of intestinal inflammatory disorders (IID), malignancy and metabolic bone disease in these patients is very important. It has been seen that some factors, such as early diagnosis, are good prognosis for the disease.

Type 1 autoimmune pancreatitis: relapse with liver abscess / Pancreatite autoimune tipo 1: recidiva com abscesso hepático

ABSTRACT: Type 1 autoimmune pancreatitis is a cause of chronic pancreatitis related to the systemic disease known as IgG4-related Sclerosing Disease. Case report: We report the case of a 64-year-old male patient who presented recurrentepigastric pain radiating to the back, associated with jaundice, xerostomia, nausea, and vomiting, since 2014, diagnosed two years later with an unresectable pancreatic adenocarcinoma. The diagnosis was questioned after a few follow-up months without clinical deterioration when it was suggested the possibility of type 1 autoimmune pancreatitis in its pseudotumoral form. The patient was then treated with glucocorticoids, obtaining significantclinical improvement. After two years of follow-up, he returned asymptomatic with images suggestive of sclerosingcholangitis and a large liver abscess. Importance of the issue: The present case denotes the difficulty found in this diagnosis due to clinical and radiological resemblances with pancreatic adenocarcinoma. Besides that, it presents a seldom described disease complication, the liver abscess. (AU)

RESUMO: A pancreatite autoimune tipo 1 é uma causa de pancreatite crônica relacionada à doença sistêmica conhecida como Doença Esclerosante relacionada à IgG4. Relato do caso: Relatamos o caso de um paciente do sexo masculino,64 anos, que apresentou quadros recorrentes de dor epigástrica com irradiação para as costas, associada com icterícia, xerostomia, náuseas e vômitos desde 2014, diagnosticado após 2 anos com adenocarcinoma pancreático irressecável. O diagnóstico foi questionado após alguns meses de acompanhamento sem deterioração clínica, quando aventaram a possibilidade de forma pseudotumoral da pancreatite autoimune tipo 1. Realizou tratamento com glicocorticoides, obtendo melhora clínica importante. Após dois anos de acompanhamento, retorna assintomático com imagens sugestivas de colangite esclerosante e volumoso abscesso hepático. Importância do problema: O presente caso denota uma dificuldade encontrada no diagnóstico dessa entidade devido a semelhanças clínico-radiológicas com o adenocarcinoma pancreático. Além disso, apresenta uma complicação pouco descrita da doença, o abscesso hepático. (AU)

Detection of Autoantibodies Against Nucleoporin p62 in Sera of Patients With Primary Biliary Cholangitis

BACKGROUND: Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by specific autoantibodies. We evaluated the prevalence of autoantibodies against nucleoporin p62 (anti-p62) in PBC patients' sera to determine whether it can be a marker for PBC, in comparison with other immunological and biochemical parameters. We validated the performance of our in-house ELISA technique. METHODS: Serum samples were collected from 135 PBC patients. Thirty patients with primary sclerosing cholangitis (PSC) and 30 with autoimmune hepatitis (AIH) were included as pathological controls, and 40 healthy blood donors served as healthy controls. The presence of anti-p62 was determined by an in-house ELISA using a recombinant protein. We calculated the sensitivity, specificity, positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratio (LR+ and LR−) of our in-house ELISA for diagnosing PBC based on anti-p62. Findings were correlated with biochemical data and survival. RESULTS: Anti-p62 was detected in 32 PBC patients (23.7%). Specificity and PPV of anti-p62 for PBC were 99% and 97%, respectively. The difference between proportions of anti-p62-positive patients and controls was 0.23 (95% confidence interval [CI]: 0.03–0.40; P < 0.0001); LR+ and LR− were 23.7 and 0.77, respectively. The presence of anti-p62 was associated with higher levels of bilirubin and alkaline phosphatase (P < 0.001). The odds ratio for survival was 2.44 (95% CI: 0.87–6.87; P=0.091). CONCLUSIONS: Anti-p62 may be regarded as a significant serological marker of PBC.

IgG4-Related Sclerosing Cholangitis and Primary Sclerosing Cholangitis

Sclerosing cholangitis (SC) is defined as a condition with progressive stenosis and destruction of the bile ducts due to diffuse inflammation and fibrosis and currently includes three categories: primary sclerosing cholangitis (PSC), secondary cholangitis, and IgG4-related sclerosing cholangitis (IgG4-SC). SC categories share similar clinical features, such as cholestasis. Patients with SC present with cholestatic symptoms, including jaundice and pruritus, and blood tests reveal elevation of cholestatic enzymes. Cholangiography, endoscopic or magnetic, is inevitably required for making a diagnosis. Although the presentation of IgG4-SC and PSC are similar, the comorbidities, treatment response, and outcomes differ significantly, and therefore, it is strongly advisable to be familiar with these two diseases to make a correct diagnosis. Differentiation of cholangiocarcinoma from IgG4-SC and PSC is also extremely important. In this review, the clinical characteristics, comorbidities, treatment and outcomes of IgG4-SC and PSC will be outlined based on experience mainly from Japan.

Secondary Sclerosing Cholangitis in Critically Ill Patients / 대한소화기학회지

No abstract available.

Hepatobiliary Manifestation of Inflammatory Bowel Disease / 대한소화기병학회잡지

The hepatobiliary system is one of the most common sites of extraintestinal manifestation in patients with inflammatory bowel disease (IBD). The progression of IBD can lead to a primary hepatobiliary manifestation and can occur secondary to multiple drugs or accompanying viral infections. Primary sclerosing cholangitis is the representative hepatobiliary manifestation of IBD, particularly in ulcerative colitis. Although most agents used in the treatment of IBD are potentially hepatotoxic, the risk of serious hepatitis or liver failure is low. The prevalence of HBV and HCV in IBD is similar to the general population, but the clinical concern is HBV reactivation associated with immunosuppressive therapy. Patients undergoing cytotoxic chemotherapy or immunosuppressive therapy with a moderate to high risk of HBV reactivation require prophylactic antiviral therapy. On the other hand, HCV has little risk of reactivation. Patients with IBD are more likely to have nonalcoholic fatty liver disease than the general population and tend to occur at younger ages. IBD and cholelithiasis are closely related, especially in Crohn's disease.

Hepatobiliary Manifestation of Inflammatory Bowel Disease / 대한소화기학회지

The hepatobiliary system is one of the most common sites of extraintestinal manifestation in patients with inflammatory bowel disease (IBD). The progression of IBD can lead to a primary hepatobiliary manifestation and can occur secondary to multiple drugs or accompanying viral infections. Primary sclerosing cholangitis is the representative hepatobiliary manifestation of IBD, particularly in ulcerative colitis. Although most agents used in the treatment of IBD are potentially hepatotoxic, the risk of serious hepatitis or liver failure is low. The prevalence of HBV and HCV in IBD is similar to the general population, but the clinical concern is HBV reactivation associated with immunosuppressive therapy. Patients undergoing cytotoxic chemotherapy or immunosuppressive therapy with a moderate to high risk of HBV reactivation require prophylactic antiviral therapy. On the other hand, HCV has little risk of reactivation. Patients with IBD are more likely to have nonalcoholic fatty liver disease than the general population and tend to occur at younger ages. IBD and cholelithiasis are closely related, especially in Crohn's disease.

Statin Exposure Is Not Associated with Reduced Prevalence of Colorectal Neoplasia in Patients with Inflammatory Bowel Disease

BACKGROUND/AIMS: Statins have been postulated to lower the risk of colorectal neoplasia. No studies have examined any possible chemopreventive effect of statins in patients with inflammatory bowel disease (IBD) undergoing colorectal cancer (CRC) surveillance. This study examined the association of statin exposure with dysplasia and CRC in patients with IBD undergoing dysplasia surveillance colonoscopies. METHODS: A cohort of patients with IBD undergoing colonoscopic surveillance for dysplasia and CRC at a single academic medical center were studied. The inclusion criteria were IBD involving the colon for 8 years (or any colitis duration if associated with primary sclerosing cholangitis [PSC]) and at least two colonoscopic surveillance exams. The exclusion criteria were CRC or high-grade dysplasia (HGD) prior to or at enrollment, prior colectomy, or limited ( < 30%) colonic disease. The primary outcome was the frequency of dysplasia and/or CRC in statin-exposed versus nonexposed patients. RESULTS: A total of 642 patients met the inclusion criteria (57 statin-exposed and 585 nonexposed). The statin-exposed group had a longer IBD duration, longer follow-up period, and more colonoscopies but lower inflammatory scores, less frequent PSC and less use of thiopurines and biologics. There were no differences in low-grade dysplasia, HGD, or CRC development during the follow-up period between the statin-exposed and nonexposed groups (21.1%, 5.3%, 1.8% vs 19.2%, 2.9%, 2.9%, respectively). Propensity score analysis did not alter the overall findings. CONCLUSIONS: In IBD patients undergoing surveillance colonoscopies, statin use was not associated with reduced dysplasia or CRC rates. The role of statins as chemopreventive agents in IBD remains controversial.