Autoimmune Liver Disease Associated Uveitis: An Extrahepatic Manifestation or a Polyautoimmunity Phenomenon? Case Reports.

PURPOSE: To report two cases of non-granulomatous unilateral anterior uveitis in two female patients associated with autoimmune liver diseases (ALD), emphasizing the possibility of this rare coexistence as a polyautoimmunity phenomenon. CASE DESCRIPTIONS: Case 1: An 18-year-old female with a history of congenital renal hypoplasia and metabolic syndrome presented with anterior uveitis in OS and a history of jaundice, blood elevated hepatic enzymes, and cholangioresonance compatible with primary sclerosing cholangitis (PSC). Laboratory work-up for additional autoimmune and infective causes were within normal limits. Case 2: An 58-year-old female presented an episode of anterior uveitis in OD and a history of Sjögren syndrome diagnosed at the age of 53, primary biliary cholangitis (PBC), systemic sclerosis, Raynaud's phenomenon, bilateral sacroiliitis, and vitiligo, consistent with polyautoimmunity and multiple autoimmune syndrome. CONCLUSIONS: Uveitis rarely coexists with ALD. However, it is essential to recognize the possibility of polyautoimmunity in patients presenting with ophthalmic manifestations and a previous diagnosis of ALD, such as PSC or PBC.

Liver transplant in patients with primary sclerosing cholangitis: A retrospective cohort from Northeastern Brazil.

BACKGROUND: Primary sclerosing cholangitis (PSC) manifests within a broad ethnic and racial spectrum, reflecting different levels of access to health care. AIM: To evaluate the clinical profile, complications and survival rates of patients with PSC undergoing liver transplantation (LTx) at a Brazilian reference center. METHODS: All patients diagnosed with PSC before or after LTx were included. The medical records were reviewed for demographic and clinical variables, including outcomes and survival. The level of statistical significance was set at P < 0.05. RESULTS: Our cohort represented 1.6% (n = 34) of the 2113 patients receiving liver grafts at our service over the past two decades. Most were male (n = 19; 56%). The average age (40 ± 14 years) was similar for men and women (P = 0.347). The mean follow-up time from diagnosis to LTx was 68 mo. Most patients had the classic form of PSC. Three women had PSC/autoimmune hepatitis overlap syndrome, and one patient had small-duct PSC. Alkaline phosphatase levels at diagnosis and pre-LTx model for end-stage liver disease. scores were significantly higher in males. Inflammatory bowel research (IBD) was investigated by colonoscopy in 26/34 (76%) and was present in most cases (18/26; 69%). IBD was less common in women than in men (44.4% vs. 55.6%) (P = 0.692). Cholangiocarcinoma (CCA) was diagnosed in 2/34 (5.9%) patients by histopathology of the explant (survival: 3 years 6 mo, and 4 years 11 mo). Two patients had complications requiring a second LTx (one after 7 d due to hepatic artery thrombosis and one after 17 d due to primary graft dysfunction). Five patients (14.7%) developed biliary stricture. The overall median post-LTx survival was 66 mo. Most deaths occurred in the first year (infection n = 2, primary liver graft dysfunction n = 3, unknown cause n = 1). The 1-year and 5-year survival rates of this cohort were 82.3% and 70.6%, respectively, matching the mean overall survival rates of LTx patients at our center (87.1% and 69.43%, respectively) (P = 0.83). CONCLUSION: Survival after 1 and 5 years was similar to that of other LTx indications. The observed CCA survival rate suggests CCA may be an indication for LTx in selected cases.

Hypereosinophilic Syndrome Secondary to Ulcerative Colitis and Primary Sclerosing Cholangitis.

Hypereosinophilic syndrome (HES) is a rare condition characterized by hypereosinophilia in peripheral blood or tissue infiltrate and organ damage. HES has been associated with several diseases, including inflammatory bowel diseases (IBDs), especially ulcerative colitis (UC). In this report, we describe a case of a UC and primary sclerosing cholangitis patient who was diagnosed with HES and severe cardiovascular and neurological injury. During hospitalization, an extensive diagnostic workup was performed and secondary causes of hypereosinophilia were ruled out. The patient was treated with glucocorticoids and full anticoagulation with significant clinical improvement and a marked reduction in the eosinophil count. In the literature, hypereosinophilia in the IBD population has been related to the severity of the disease and worse prognosis. The high index of clinical suspicion and the accurate diagnosis of HES are essential to avoid delay in therapy and prevent complications.

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.

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.

Stent versus Balloon Dilation for the Treatment of Dominant Strictures in Primary Sclerosing Cholangitis: A Systematic Review and Meta-Analysis.

BACKGROUND/AIMS: The endoscopic management of primary sclerosing cholangitis (PSC)-associated dominant strictures remains challenging. This systematic review and meta-analysis aimed to compare balloon dilation and stent placement in the treatment of dominant strictures among PSC patients. METHODS: Literature searches on MEDLINE, EMBASE, Cochrane CENTRAL and Lilacs/Bireme were performed for studies published until December 2020. Measured outcomes included clinical efficacy, stricture recurrence, cumulative recurrencefree rate, transplant rate, 5-year survival rate, and adverse events (i.e., pancreatitis, cholangitis, bleeding, perforation and death). RESULTS: A total of 5 studies (n=467) were included. Based on pooled analyses, there were no differences in clinical efficacy (risk difference [RD], -0.13; 95% confidence interval [CI], -0.58 to 0.33; I2=93%) or transplant rates (RD, -0.09; 95% CI, -0.19 to 0.01; I2=0%); however, the risk of occurrence of adverse events was lower with balloon dilatation than with stent placement (RD,-0.34; 95% CI, -0.45 to -0.23; I2=61%). Among the types of adverse events reported, only the rates of cholangitis/bacteremia were significantly lower in balloon dilation patients (RD, -0.19; 95% CI, -0.25 to -0.13; I2=51%). CONCLUSION: Compared to balloon dilation, stent placement for dominant strictures in PSC appeared to have higher complication rates without significant differences in efficacy.

Sclerosing Cholangitis in Pediatric Inflammatory Bowel Disease: Early Diagnosis and Management Affect Clinical Outcome.

OBJECTIVE: To describe the characteristics and clinical course of children and young persons with inflammatory bowel disease (IBD) and sclerosing cholangitis (SC). STUDY DESIGN: Retrospective analysis of clinical characteristics, management, and outcome of two separate cohorts of children and young persons with IBD-SC managed in a tertiary pediatric gastroenterology center and in a tertiary pediatric hepatology center in the UK. RESULTS: Eighty-two pediatric patients (31% female) with IBD-SC and a mean age at diagnosis of 11.9 ± 2.8 years were followed up for a mean of 6.8 ± 3.3 years. The most common type of IBD was ulcerative colitis (55%), followed by unclassified IBD (30%) and Crohn's disease (15%). Autoimmune SC (ASC) was diagnosed in 72%, and small duct SC was diagnosed in 28%. Complication-free and native liver survival were 96% and 100%, respectively, at 5 years after diagnosis and 75% and 88%, respectively, at 10 years after diagnosis. Patients in the gastroenterology center, who were diagnosed with liver disease sooner after diagnosis of IBD compared with the hepatology center cohort (mean, 2.7 ± 6.1 months vs 9.3 ± 19.4 months; P = .03), did not develop liver-related complications during follow-up. CONCLUSIONS: Our data suggest that children with IBD-SC have better clinical outcomes than have been reported previously, particularly if diagnosed early. We recommend prompt assessment for SC, including liver biopsy and biliary imaging, when liver function abnormalities are detected in a children diagnosed with IBD.

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.

Primary sclerosing cholangitis and autoimmune hepatitis overlap syndrome associated with inflammatory bowel disease: A case report and systematic review.

BACKGROUND: A previously healthy 22-year-old woman presented with abdominal pain and jaundice. She had a reagent antinuclear factor (1:640, with a homogeneous nuclear pattern) and hypergammaglobulinemia (2.16 g/dL). Anti-smooth muscle, anti-mitochondrial and anti-liver-kidney microsomal antibody type 1 antibodies were negative. Magnetic resonance cholangiography showed a cirrhotic liver with multiple focal areas of strictures of the intrahepatic bile ducts, with associated dilations. Liver biopsy demonstrated periportal necroinflammatory activity, plasmocyte infiltration and advanced fibrosis. Colonoscopy showed ulcerative pancolitis and mild activity (Mayo score 1), with a spared rectum. Treatment with corticosteroids, azathioprine, ursodeoxycholic acid and mesalamine was initiated, with improvement in laboratory tests. The patient was referred for a liver transplantation evaluation. AIM: To report the case of a female patient with autoimmune hepatitis and primary sclerosing cholangitis (PSC) overlap syndrome associated with ulcerative colitis and to systematically review the available cases of autoimmune hepatitis and PSC overlap syndrome. METHODS: In accordance with preferred reporting items for systematic reviews and meta-analysis protocols guidelines, retrieval of studies was based on medical subject headings and health sciences descriptors, which were combined using Boolean operators. Searches were run on the electronic databases Scopus, Web of Science, MEDLINE (PubMed), Biblioteca Regional de Medicina, Latin American and Caribbean Health Sciences Literature, Cochrane Library for Systematic Reviews and Opengray.eu. Languages were restricted to English, Spanish and Portuguese. There was no date of publication restrictions. The reference lists of the studies retrieved were searched manually. RESULTS: The search strategy retrieved 3349 references. In the final analysis, 44 references were included, with a total of 109 cases reported. The most common clinical finding was jaundice and 43.5% of cases were associated with inflammatory bowel disease. Of these, 27.6% were cases of Crohn's disease, 68% of ulcerative colitis, and 6.4% of indeterminate colitis. Most patients were treated with steroids. All-cause mortality was 3.7%. CONCLUSION: PSC and autoimmune hepatitis overlap syndrome is generally associated with inflammatory bowel disease and has low mortality and good response to treatment.

Gut Microbiome of Children and Adolescents With Primary Sclerosing Cholangitis in Association With Ulcerative Colitis.

Few studies reported the relation of intestinal microbiome composition and diversity in pediatric patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). In this cross-sectional study, we selected patients younger than 19 years old from the pediatric gastroenterology and hepatology outpatient clinic of a tertiary hospital to describe the intestinal microbiome of pediatric patients with PSC associated or not to UC. Patients were divided in PSC, PSC+UC, and UC diagnosis. A stool sample was collected from each patient (n=30) and from a healthy relative/neighbor (n=23). The microbiome composition was assessed using MiSeq (Illumina) platform. Differences in microbial composition were found between PSC and PSC+UC groups. The relative abundance of Veillonella and Megasphaera genera were increased depending on patients' age at diagnosis. Veillonella was also increased in patients who were in an active status of the disease. Both genera were positively correlated to total bilirubin and gamma-glutamyl transferase. As a conclusion, the disease, the age and the disease activity status seem to influence the intestinal microbiome, highlighting the difference of intestinal microbiome profile for patients depending on age at diagnosis. We also showed an increase of Veillonella in patients with PSC and PSC+UC, and a positive correlation of dysbiosis and higher gamma-glutamyl transferase and total bilirubin in PSC+UC patients. Our findings are promising in the diagnosis, prognosis, and future therapeutic perspectives for PSC patients.

Multiple therapeutic targets in rare cholestatic liver diseases: Time to redefine treatment strategies.

Primary biliary cholangitis and primary sclerosing cholangitis are rare diseases affecting the bile ducts and the liver. The limited knowledge of their pathogenesis leads to limited therapeutic options. Nevertheless, the landscape of novel therapies for these cholangiopathies is now rapidly changing, providing new treatment opportunities for patients and clinicians involved in their care. The aim of this review is to summarize the evidence of novel molecules under investigation for primary biliary cholangitis and primary sclerosing cholangitis and to discuss how they can potentially change current treatment paradigms.

Inflammatory Bowel Disease in Children with Elevated Serum Gamma Glutamyltransferase Levels.

OBJECTIVE: To assess the characteristics of inflammatory bowel disease and disease prognosis among children with elevated gamma glutamyltransferase (GGT) and primary sclerosing cholangitis (PSC)-ulcerative colitis (UC). STUDY DESIGN: Our longitudinal, population-based cohort comprised all children and young adults diagnosed with UC in the Canadian province of Manitoba between 2011 and 2018. Diagnosis of PSC was confirmed based on a combination of cholestatic biochemical markers and cholangiographic features. The Fisher exact test with Bonferroni correction was used to examine the relationship between categorical variables. RESULTS: We enrolled 95 children with UC/Inflammatory bowel disease-unclassified with a median age at diagnosis of 14 years (IQR: 10.4-15.9 years) and 1399 person-years follow-up. Among them, 9 children developed PSC-UC, with an incidence rate of 6.43 new cases per 1000 person-years. In this cohort, 8 (72.7%) of 11 children with high baseline serum GGT levels developed PSC-UC in comparison with 1 (1.2%) of 84 children with normal serum GGT levels at baseline (P < .001). All children with high serum GGT levels at diagnosis had pancolitis in comparison with 63.9% of children with normal serum GGT levels (P = .01). Children with high serum GGT levels were more likely to be perinuclear neutrophil antibodies-positive than those with normal levels (90.9% vs 52.0%, P = .01). CONCLUSIONS: Our findings indicated that pediatric patients with UC and with even mild elevations of serum GGT levels, especially at baseline, might be predisposed to develop PSC.

Acoustic Radiation Force Impulse (ARFI) Elastography in Autoimmune and Cholestatic Liver Diseases.

INTRODUCTION: Acoustic Radiation Force Impulse (ARFI) elastography evaluates hepatic fibrosis non-invasively and has been mainly validated in viral hepatitis. Data on rare liver diseases such as autoimmune hepatitis (AIH), overlap syndrome, primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC) are sparse. MATERIAL AND METHODS: 85 patients (including 31 AIH, 26 PBC, 16 PSC and 3 PSC-and 9 PBC-AIH-overlap syndromes) were retrospectively analysed pointing at ARFI elastography of the liver and the correlation with histologic Ishak fibrosis score (F0-6). Results of shear wave velocities (m/s) were expressed as mean ± standard deviation. RESULTS: The mean shear wave velocity of all 85 patients showed 1.80 ± 0.84 m/s (0.74-3.98). The ARFI elastography values correlated with the degree of fibrosis in all patients overall and in patients with AIH, overlap syndrome and PSC, respectively. The subgroup of 26 patients with PBC (only with Ishak F > 3) revealed no correlation between ARFI and these early fibrosis stages (r = 0.019, p = 0.927). ARFI elastography correlated with bilirubin, AST, but not with patient age, body mass index or measurement depth. The cut-off of 2.04 m/s for detecting cirrhosis (Ishak F > 5) leads to a sensitivity of 90.0% and specificity of 74.7% (AUROC 87.2%). CONCLUSION: ARFI elastography can evaluate fibrosis in AIH, PSC and PSC-/PBC-AIH-overlap syndrome with good accuracy for the detection of hepatic cirrhosis. Shear wave velocities in PBC should be interpreted with caution in early stages of fibrosis.

Colangiocarcinoma en pacientes con colangitis esclerosante primaria / Cholangiocarcinoma in patients with primary sclerosing cholangitis

Resumen La colangitis esclerosante primaria (CEP) es una enfermedad inflamatoria poco común que afecta los conductos biliares, produciendo colestasis. Actualmente, el único tratamiento disponible es el manejo sintomático con ácido ursodesoxicólico y el trasplante hepático. Además de ser una etiología de cirrosis a largo plazo, en su historia natural tiene una asociación importante con el colangiocarcinoma (CCA), una neoplasia agresiva que es casi exclusiva de este grupo de pacientes, y hoy en día constituye su principal causa de muerte debido a que es de difícil diagnóstico y cuenta con opciones muy limitadas de tratamiento. En el presente artículo se exponen conceptos actuales sobre esta patología, enfatizando la importancia de realizar una adecuada tamización con pruebas diagnósticas efectivas (CA 19-9 y colangiorresonancia) que ayuden a diferenciar el CCA de procesos benignos y poder detectarlo en estadios tempranos donde la probabilidad de tratamiento curativo es mucho mayor.

Abstract Primary sclerosing cholangitis (PSC) is an uncommon inflammatory disease that affects the bile ducts to produce cholestasis. Currently, the only treatment available is management of symptoms with ursodeoxycholic acid and liver transplantation. In addition to its relation to long-term cirrhosis, its natural history has an important association with cholangiocarcinoma (CCA), an aggressive neoplasia which is almost exclusive to this group of patients. Today CCA is the main cause of death of these patients, primarily due to the difficultly of diagnosis and the very limited treatment options. This article discusses current ideas about this pathology and emphasizes the importance of appropriate screening with effective diagnostic tests (CA 19-9 and magnetic resonance cholangiopancreatography (MRC)) that help differentiate CCA from benign processes and can detect it in early stages when the probability of curative treatment is much greater.

The Changing Face of the Diagnosis of Chronic and Malignant Liver Diseases: Potential New Biomarkers.

The early diagnosis of primary sclerosing cholangitis, hepatocellular carcinoma, and cholangiocarcinoma is often challenging. In a recent study in 134 patients (Arbelaiz, Hepatology 2017; 66:1125-1143), it was reported that specific proteins found in serum extracellular vesicles of patients with primary sclerosing cholangitis, hepatocellular carcinoma,orcholangiocarcinomamay be useful as noninvasive diagnostic and prognostic tools. This current article critically appraises this study.

Endoscopic Management of Primary Sclerosing Cholangitis.

Primary sclerosing cholangitis (PSC) remains a rare but potentially devastating chronic, cholestatic liver disease. PSC causes obstruction of intra- and/or extra-hepatic bile ducts by inflammation and fibrosis, leading to biliary obstruction, cirrhosis and portal hypertension with all associated sequelae. The most dreaded consequence of PSC is cholangiocarcinoma, occurring in 10-20% of patients with PSC, and with population-based estimates of a 398-fold increased risk of cholangiocarcinoma in patients with PSC compared to the general population. We use the 4-D approach to endoscopic evaluation and management of PSC based on currently available evidence. After laboratory testing with liver chemistries and high-quality cross-sectional imaging with MRCP, the first D is Dominant stricture diagnosis and evaluation. Second, Dilation of strictures found during ERCP is performed using balloon dilation to as many segments as possible. Third, Dysplasia and cholangiocarcinoma diagnosis is performed by separated brushings for conventional cytology and fluorescence in situ hybridization (FISH), and consideration for direct cholangioscopy with SpyGlass™. Fourt and finally, Dosing of antibiotics is critical to prevent peri-procedural cholangitis. The aim of this review article is to explore endoscopic tools and techniques for the diagnosis and management of PSC and provide a practical approach for clinicians.

Patología del trasplante hepático, aspectos más relevantes del período postrasplante tardío / Most Relevant Pathology Issues in the Late Post Liver Transplant Period

La sobrevida de los pacientes postrasplante hepático supera el 90% al año y el 75% a los 5 años. Entender las causas de pérdida del injerto, o inclusive la muerte del paciente, es esencial para mejorar aún más los resultados a largo plazo. La evaluación de las biopsias hepáticas tiene un papel importante en la explicación y manejo de la disfunción del injerto de hígado, que ocurre después del primer año del trasplante. La interpretación de estas biopsias puede ser muy difícil, en especial por la alta incidencia de enfermedades recurrentes que pueden mostrar un cuadro clínico y unas características histopatológicas que semejan varias condiciones, especialmente cuando el rechazo agudo o crónico pueden sobreponerse a una patología ya existente o presentarse de manera simultánea y contribuir a la disfunción tardía del injerto, por lo que el análisis de la biopsia puede ayudar a determinar el componente principal de la lesión. Es indispensable la correlación clínico patológica, teniendo en cuenta la enfermedad original, el tipo de inmunosupresión, las pruebas de función hepática, las serologías virales, los autoanticuerpos y los hallazgos radiológicos. En este artículo comentaré las patologías más frecuentes y las que causan más problemas en su diagnóstico durante el período postrasplante tardío

One year survival rates of liver transplant patients exceed 90% while five year survival rates exceed 75%. Understanding the causes of graft losses and patient deaths is essential for further improvement of long-term results. Evaluation of liver biopsies has an important role in explaining liver graft dysfunction that occurs more than one year after transplantation, and thus is key for post-transplant patient management. The interpretation of these biopsies can be very difficult especially because of the high incidence of recurrent diseases that sometimes have clinical and histopathological features that resemble various other conditions. This is especially true for acute and chronic rejection which can overwhelm an existing condition and which can develop simultaneously with other conditions that contribute to late graft dysfunction. Analysis of the biopsy can help determine the main component of a lesion. Clinical findings must be correlated to pathological findings, and the correlation must take into account the original disease, the type of immunosuppression, liver function tests, viral serology, autoantibodies and radiological findings. In this article I will discuss the most common diseases and those that cause the most problems for diagnosis during the late post-transplant period

Asociación entre enfermedad de Crohn y colangitis esclerosante primaria en una niña de 10 años / Association between Crohn's disease and primary sclerosing cholangitis in a 10 year old girl

Niña de 10 años con diarrea, abdominalgia, pérdida de peso y febrícula de un mes y medio de evolución. Los hallazgos analíticos y ecográficos hicieron sospechar una enfermedad inflamatoria intestinal. La endoscopía y la histología mostraron hallazgos compatibles con la enfermedad de Crohn. Se inició un tratamiento con mesalazina y nutrición enteral exclusiva, y se anadieron corticoides, inmunosupresores y ácido ursodesoxicólico por la persistencia de colestasis e hipergammaglobulinemia. La colangiorresonancia y la biopsia hepática confirmaron el diagnóstico de colangitis esclerosante primaria concomitante. La asociación entre la enfermedad de Crohn y la colangitis esclerosante primaria es muy poco frecuente; predomina en varones de entre los 20 y los 40 años de edad; y presenta una gran variabilidad clínica. El diagnóstico de confirmación requiere la realización de una colangiorresonancia o colangiopancreatografía retrógrada endoscópica. El pronóstico es malo y no existe ningún tratamiento capaz de frenar la progresión de la enfermedad.

A 10 year old girl with diarrhea, abdominal pain, weight loss and fever of one month and a half of evolution. Analytical and sonographic findings raised the possibility of inflammatory bowel disease. Endoscopy and histology showed findings consistent with Crohn's disease. Treatment was initiated with mesalazine and exclusive enteral nutrition. Later corticosteroid treatment, immunosuppressive drugs and ursodeoxycholic acid were added due to cholestasis and persistent hypergammaglobulinemia. Magnetic resonance cholangiography and liver biopsy confirmed the diagnosis of concomitant primary sclerosing cholangitis. The association between Crohn's disease and primary sclerosing cholangitis is rare, predominantly in males between 20 and 40 years old and it presents a great clinical variability. The confirmation of the diagnosis requires magnetic resonance cholangiography or endoscopic retrograde cholangiopancreatography. The prognosis is poor and there is no treatment to slow the progression of the disease.