Síndrome de Alagille, reporte de un caso y revisión de la literatura / Alagille Syndrome, case study and literature review / Sindrome de Alagille, relato de caso e revisão de literatura

El síndrome de Alagille es una patología poco frecuente, de herencia autosómica dominante. Se caracteriza por la presencia de colestasis crónica progresiva ocasionada por hipoplasia de las vías biliares; anomalías vertebrales, oculares y cardíacas, y fenotipo facial particular. Entre sus diagnósticos diferenciales se incluyen las infecciones, enfermedades endocrinometabólicas, atresia biliar y causas idiopáticas. El pronóstico de este síndrome es variable y depende de la entidad de la afectación hepática y los defectos cardiovasculares. El abordaje terapéutico suele ser interdisciplinario e individualizado, enfocado en el control sintomático, prevención de la malnutrición y el déficit de vitaminas liposolubles. Se presenta el caso de un lactante de 2 meses en el que se estudiaron las causas más frecuentes de colestasis y se llegó al diagnóstico de síndrome de Alagille. Se describe su abordaje terapéutico y seguimiento.

Alagille syndrome is an inherited autosomal dominant rare disease. It is characterized by the presence of progressive chronic cholestasis caused by hypoplasia of the bile ducts; vertebral, ocular and cardiac anomalies, and particular facial phenotype. Its differential diagnoses include infections, endocrine-metabolic diseases, biliary atresia and idiopathic causes. The prognosis of this syndrome is variable and depends on the degree of liver involvement and cardiovascular defects. The therapeutic approach is usually interdisciplinary and customized, focused on symptomatic control, prevention of malnutrition and fat-soluble vitamin deficiency. We present the case of a 2-month-old infant in whom the most frequent causes of cholestasis were studied and to whom Alagille Syndrome was diagnosed. We hereby describe its therapeutic approach and follow-up.

A síndrome de Alagille é uma doença rara, hereditária, autossômica e dominante. Caracteriza-se pela presença de colestase crônica progressiva causada por hipoplasia das vias biliares; anomalias vertebrais, oculares e cardíacas e fenótipo facial particular. Seus diagnósticos diferenciais incluem infecções, doenças endócrino-metabólicas, atresia biliar e causas idiopáticas. O prognóstico desta síndrome é variável e depende do grau de envolvimento hepático e defeitos cardiovasculares. A abordagem terapêutica geralmente é interdisciplinar e personalizada, focada no controle sintomático, prevenção da desnutrição e deficiência de vitaminas lipossolúveis. Apresentamos o caso de uma criança de 2 meses de idade em que foram estudadas as causas mais frequentes de colestase e a quem foi diagnosticada Síndrome de Alagille. Descrevemos a sua abordagem terapêutica e seguimento.

Colangitis biliar primaria: experiencia de cinco años en el Hospital Clínico de la Universidad de Chile / Primary biliary cholangitis. Experience in 179 patients

BACKGROUND: Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic disease, which can progress to cirrhosis. It mainly affects middle-aged women. Its most frequent form of presentation is asymptomatic with biochemical cholestasis and the presence of antimitochondrial antibodies (AMA). AIM: To describe the epidemiological characteristics, clinical presentation and treatment for patients with PBC at a clinical hospital. MATERIAL AND METHODS: Descriptive, observational, retrospective study, carried out between January 2015 and December 2020. Results: 179 patients (158 women) were cared in the study period. At the time of diagnosis, the median age was 54 years (range 24-76), 55% of them were asymptomatic, 45% had fatigue and 28% had pruritus. Positive AMA were present in 65% of patients, antinuclear antibodies (ANA) in 51%, and anti-smooth muscle antibodies (ASMA) in 9%. Immunoglobulin M (IgM) was elevated in 30% of the patients and 50% of patients were biopsied. Splenomegaly and esophageal varices were present in 24 and 22% of patients, respectively. PBC was associated with Sjogren's syndrome in 15%, hypothyroidism in 14%, osteoporosis in 13%, and scleroderma in 8%. CONCLUSIONS: The epidemiological characteristics of our patients agree with those published abroad. Laboratory cholestasis associated with the presence of AMA, currently allows diagnosis without the need for histological study. Ursodeoxycholic acid (UDCA) is the first-line treatment for patients with PBC. The use of biochemical response criteria is essential to identify patients who require other UDCA alternatives for isolated or combined treatment.

Terapias usuales y emergentes en colangitis biliar primaria / Conventional and emerging therapies in primary biliary cholangitis

La colangitis biliar primaria (CBP) es una enfermedad autoinmune caracterizada por daño de los conductos biliares intrahepáticos, que hasta ahora tiene mecanismos poco claros de respuesta celular inflamatoria, con la mitocondria como orgánulo blanco. Durante varias décadas han sido el control de los ácidos biliares y el tratamiento de la colestasis lo que ha permitido el manejo médico de los pacientes, logrando un impacto parcial en el curso y la progresión de la enfermedad, mejorando además la sobrevida de los individuos. Con el hallazgo de nuevos mecanismos fisiopatológicos se han iniciado estudios con terapias inmunomoduladoras, que podrían ser prometedoras en el mejoramiento de la calidad de vida de los pacientes que padecen la enfermedad. Aún los resultados son inciertos, y se hacen necesarios más estudios para aclarar el papel de los nuevos tratamientos en el arsenal terapéutico disponible para la CBP.

Primary biliary cholangitis (PBC) is an autoimmune disease characterized by damage of intrahepatic bile ducts, so far with unclear mechanisms of inflammatory cellular response with the mitochondria as the target organelle. For several decades it has been the control of bile acids and the treatment of cholestasis what has allowed the management of patients, achieving a partial impact on the course and progression of the disease, also improving the survival of individuals. With the discovery of new pathophysiological mechanisms, studies have been initiated with new immunomodulatory therapies that could be promising in improving the quality of life of patients suffering from the disease. The results are still uncertain and further studies are needed to clarify the role of the new treatments in the therapeutic arsenal available for PBC.

Colangitis biliar primaria: caracterización de una cohorte retrospectiva / Primary biliary cholangitis: characterization of a retrospective cohort

Introducción. La colangitis biliar primaria (CBP) es una enfermedad hepática crónica de origen autoinmune, caracterizada por inflamación y destrucción progresiva de las células epiteliales de los conductos biliares intralobulillares, que causa de manera secundaria colestasis, fibrosis, cirrosis e insuficiencia hepática. La historia natural de la enfermedad ha cambiado en los últimos años debido a la mejoría en los métodos diagnósticos y terapéuticos. Metodología. Estudio observacional descriptivo de cohorte retrospectivo, en el cual se efectuó la revisión y análisis de las historias clínicas de los pacientes mayores de 16 años con diagnóstico de CBP, atendidos en la Unidad de Hepatología y Trasplante Hepático del Hospital Pablo Tobón Uribe, entre los años 2013 a 2021, con el fin de obtener información sobre las características de esta patología a nivel local. Resultados. Se evaluó un total de 239 pacientes, con un promedio de edad de 61,6±12,31 años, el 97,07% fue del sexo femenino, con criterios serológicos como anticuerpos antimitocondriales (AMA) positivos en un 76,89%, el 66,95% de los pacientes presentaban alguna enfermedad autoinmune concomitante y el 31,60% tuvieron sobreposición con hepatitis autoinmune. La manifestación clínica más frecuente fue el prurito en un 61,92% de los pacientes, seguido por la astenia en un 51,88%. La presencia de hipertensión portal al diagnóstico fue del 29,29%. La colangitis no supurativa y la ductopenia en la biopsia de hígado se documentó en un 43,79% de los casos. El ácido ursodesoxicólico (UDCA) fue la terapia de primera línea en el 100% de los pacientes, se identificó refractariedad del 16,36% según criterios de París II y del 31,79% con los criterios de Toronto. La no respuesta al UDCA, se asoció de manera significativa con mayor mortalidad (p=0,039) y presencia de hepatocarcinoma (p=0,042). Conclusión. Se caracterizó la CBP en nuestra población. El diagnóstico serológico por AMA fue bajo, con altos requerimientos de biopsia hepática en el contexto de síndromes de sobreposición. Los signos de hipertensión portal al momento del diagnóstico fueron prevalentes. La refractariedad bioquímica a la terapiafue descrita en relación con mayor progresión de fibrosis, aumento de mortalidad y presencia de hepatocarcinoma.

ntroduction. Primary biliary cholangitis (PBC) is a chronic liver disease of autoimmune origin, characterized by inflammation and progressive destruction of the epithelial cells of the intralobular bile ducts, causing secondary cholestasis, fibrosis, cirrhosis, and liver failure. The natural history of the disease has changed in recent years due to the improvement in diagnostic and therapeutic methods. Methodology. Cross-sectional descriptive observational study, where the medical records of patients older than 16 years with a diagnosis of PBC, treated at the Hepatology and Liver Transplant Unit of the Pablo Tobón Uribe Hospital, between the years 2013 to 2021, were reviewed and analyzed in order to obtain information on the characteristics of this pathology at a local level. Results. A total of 239 patients were evaluated, with a mean age of 61.6±12.31 years, 97.07% were females, with serological criteria such as positive antimitochondrial antibodies (AMA) in 76.89%. Of all included patients, 66.95% had some concomitant autoimmune disease and 31.60% had an overlap with autoimmune hepatitis. The most frequent clinical manifestation was pruritus in 61.92% of the patients, followed by asthenia in 51.88%. The presence of portal hypertension at diagnosis was 29.29%. Non-suppurative cholangitis and ductopenia on liver biopsy were documented in 43.79% of the cases. Ursodeoxycholic acid (UDCA) was the first line therapy in 100% of patients, 16.36% were refractory to treatment according to the Paris II criteria and 31.79% according to the Toronto criteria. Non-response to UDCA was significantly associated with higher mortality (p=0.039) and presence of hepatocarcinoma (p=0.042). Conclusion. PBC was characterized in our population. Serological diagnosis by AMA was low, with high requirements for liver biopsy in the context of overlap syndromes. Signs of portal hypertension at diagnosis were prevalent. Biochemical refractoriness to therapy was described in relation to greater progression of fibrosis, increased mortality, and the presence of hepatocarcinoma.

N-acetilcisteína e/ou ácido ursodeoxicólico associados à metformina na esteato-hepatite não alcoólica: um estudo aberto, multicêntrico, randomizado controlado / N-acetylcysteine and/or ursodeoxycholic acid associated with metformin in non-alcoholic steatohepatitis: an open-label multicenter randomized controlled trial

ABSTRACT BACKGROUND: Nowadays, pharmacological treatment of non-alcoholic fatty liver disease (NAFLD) is still limited and it is based on the treatment of conditions associated comorbities. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. OBJECTIVE: To evaluate the efficacy of N-acetylcysteine (NAC) in combination with metformin (MTF) and/or ursodeoxycholic acid (UDCA) for treatment of non-alcoholic steatohepatitis (NASH). METHODS: Open-label multicenter randomized trial was conducted for 48 weeks. It included patients with biopsy-proven NASH. The patients were randomized into three groups: NAC (1.2 g) + UDCA (15 mg/kg) + MTF (850-1500 mg/day) (n=26); UDCA (20 mg/kg) + MTF (850-1500 mg/day) (n=13); NAC (1.2g) + MTF (850-1500 mg/day) (n=14) for 48 weeks. Clinical, laboratory and the second liver biopsies were performed after 48 weeks. RESULTS: A total of 53 patients were evaluated; 17 (32.1%) were males; median age ±54 (IQR=15, 21-71) years. In the baseline, no difference was seen between groups according clinical and histological parameters. The groups differed only in cholesterol, LDL and triglycerides. No significant differences in biochemical and histologic parameters were found between these the three groups after 48 weeks of treatment. In the intragroup analysis (intention-to-treat) comparing histological and biochemical features, there were significant improvements in the steatosis degree (P=0.014), ballooning (0.027) and, consequently, in the NAFLD Activity Score (NAS) (P=0.005), and in the ALT levels at the end of the treatment only in the NAC + MTF group. No significant evidence of modification in the liver fibrosis could be observed in any of the groups. CONCLUSION: This multicenter study suggests that the association of NAC + MTF could reduce the liver disease activity in patients with NASH. These data stimulate further controlled studies with this therapy for these patients.

RESUMO CONTEXTO: Atualmente, o tratamento farmacológico da doença hepática gordurosa não alcoólica (DHGNA) ainda é limitado e baseia-se no tratamento de condições associadas às comorbidades. O estresse oxidativo e a resistência à insulina são os mecanismos que parecem estar mais envolvidos em sua patogênese. OBJETIVO: Avaliar a eficácia da N-acetilcisteína (NAC) em associação à metformina (MTF) e/ou ácido ursodesoxicólico (UDCA) no tratamento da EHNA. MÉTODOS: Estudo randomizado, multicêntrico e aberto, conduzido por 48 semanas. Incluiu pacientes com esteato-hepatite não alcoólica (EHNA) comprovada por biópsia. Os pacientes foram distribuídos aleatoriamente em três grupos: NAC (1,2 g) + UDCA (15 mg/kg) + MTF (850-1500 mg/dia) (n=26); UDCA (20 mg/kg) + MTF (850-1500 mg/dia) (n=13); NAC (1,2 g) + MTF (850-1500 mg/dia) (n=14) durante 48 semanas. Os dados clínicos, laboratoriais e as segundas biópsias hepáticas foram realizados após 48 semanas. RESULTADOS - Um total de 53 pacientes foram avaliados; 17 (32,1%) eram do sexo masculino; idade mediana de ±54 (IQR=15, 21-71) anos. No baseline, nenhuma diferença foi observada entre os grupos de acordo com parâmetros clínicos e histológicos. Os grupos diferiram apenas em colesterol, LDL e triglicerídeos. Não foram encontradas diferenças significativas nos parâmetros bioquímicos e histológicos entre os três grupos após 48 semanas de tratamento. Contudo, na análise intragrupos (intenção de tratar) comparando características histológicas e bioquímicas, houve melhora significativa no grau de esteatose (P=0,014), balonização (P=0,027) e, consequentemente, no NAFLD Activity Score (NAS) (P=0,005), e nos níveis de ALT no final do tratamento apenas no grupo NAC+MTF. Nenhuma evidência significativa de modificaçãona fibrose hepática pôde ser observada em nenhum dos grupos. CONCLUSÃO: - Este estudo multicêntrico sugere que a associação de NAC+MTF poderia reduzir a atividade da doença hepática em pacientes com EHNA. Esses dados estimulam estudos adicionais controlados com essa terapia para esses pacientes.

O tratamento contínuo superior a cinco anos com ácido ursodesoxicólico gera benefícios na taxa de mortalidade e na taxa de transplantes em colangite biliar primária: revisão sistemática da literatura e metanálise / Continuous treatment with ursodeoxycholic acid over five years generates benefits in mortality rate and transplantation rate in primary biliary cholangitis: systematic review of the literature and meta-analysis

Objetivos: A colangite biliar primária (CBP) é uma doença hepática colestática, autoimune, inflamatória e crônica que, quando não tratada, evolui para cirrose e eventualmente insuficiência hepática em um período de 10 a 20 anos. Este estudo teve como objetivo avaliar o impacto em longo prazo do tratamento com ácido ursodesoxicólico (AUDC) em pacientes com CBP. Métodos: Uma revisão sistemática da literatura foi conduzida até maio de 2017. Os desfechos incluíram sobrevida livre de transplante (SLT) ou morte, sobrevida global (SG), taxa de mortalidade, taxa de transplantes e a taxa combinada de mortes e transplantes. A análise dos dados foi realizada por meio de um modelo de efeitos aleatórios, utilizando-se o método de DerSimonian e Laird. Resultados: Doze estudos foram incluídos na metanálise. O tratamento com AUDC apresentou aumento do tempo de SLT no acompanhamento em longo prazo a partir do quinto ano de tratamento, com resultados estatisticamente significativos para os anos de 5 e 10 (p < 0,01). Os resultados da metanálise das taxas de mortalidade, transplante e taxa combinada de mortalidade e transplante mostraram-se não significativos para os três desfechos apresentados. A inclusão dos estudos de braço comparador teórico alterou de maneira significativa os resultados da análise principal, tornando os resultados estatisticamente significativos a partir do terceiro ano de acompanhamento. Conclusões: AUDC é eficaz no aumento da SLT ou morte, com resultados estatisticamente significativos em 5 e 10 anos, quando os pacientes são tratados de maneira crônica.

Objectives: Primary biliary cholangitis (PBC) is an inflammatory and chronic autoimmune cholestatic liver disease that, when left untreated, progresses to cirrhosis and eventually liver failure in a period of 10 to 20 years. This study aimed to evaluate the long-term impact of treatment with ursodeoxycholic acid (UDCA) in patients with PBC. Methods: A systematic literature review was conducted until May 2017. The endpoints included transplant-free survival (TFS) or death, overall survival (OS), mortality rate, transplantation rates and the combined rate of deaths and transplants. Data analysis was performed using a random effects model with the DerSimonian and Laird method. Results: Twelve studies were included in the meta-analysis. Treatment with UDCA showed an increase in TFS time in the long-term follow up from the fifth year of treatment, with statistically significant results for the years 5 and 10 (p < 0.01). Meta-analysis results for mortality rates, transplantation and combined mortality and transplantation rates were not significant for the three outcomes presented. The inclusion of the theoretical comparator arm studies significantly altered the results of the main analysis, making the results statistically significant from the third year of follow-up. Conclusions: UDCA is effective in increasing TFS or death, with statistically significant results at 5 and 10 years, when patients are treated chronically

Colangitis biliar primaria. Parte 1. Actualización: generalidades, epidemiología, factores involucrados, fisiopatología y manifestaciones clínicas / Primary biliary cholangitis. Part 1. State of the art, epidemiology, physiopathology and clinical manifestations

La colangitis biliar primaria (CBP), es una colangiopatía crónica caracterizada por la destrucción selectiva de las células epiteliales biliares de conductos hepáticos de pequeño y mediano calibre, que afecta principalmente a mujeres. Los principales síntomas son la fatiga y el prurito, sin embargo, gran porcentaje de los pacientes pueden ser asintomáticos. El diagnóstico se basa en anticuerpos antimitocondriales (AMA) con títulos >1:40, fosfatasa alcalina >1,5 veces del límite superior normal por más de 24 semanas e histología hepática compatible con la patología. Se asocia con múltiples enfermedades principalmente de carácter autoinmune extra hepáticas, enfermedades tiroideas, óseas, entre otras. El tratamiento de primera línea es el ácido ursodesoxicólico (AUDC) que a pesar que no cura la enfermedad, mejora las pruebas del perfil hepático, así como el retraso en la progresión a cirrosis. Actualmente se encuentran en estudio nuevos tratamientos y terapias adyuvantes. El propósito de esta revisión es ofrecer una actualización de este tema que se presenta en los servicios de medicina interna y gastroenterología; para su realización se conformó un equipo interdisciplinario que desarrolló una búsqueda en la base Medline a través de PubMed con las palabras claves correspondientes y se procedió a una lectura crítica y analítica de títulos, resúmenes y textos completos para el filtro, extracción y síntesis de la información encontrada

Primary biliary cholangitis (PBC) is a chronic autoimmune cholangiopathy characterized by a selective destruction of biliary epithelial cells of small and medium caliber hepatic ducts, which mainly affects women. The main symptoms are fatigue and pruritus, however, a large proportion of patients may be asymptomatic. The diagnosis is based on AMA titers >1:40, alkaline phosphatase >1.5 times the upper limit for more than 24 weeks and compatible liver histology. It is associated with multiple autoimmune diseases mainly extrahepatic, thyroid diseases, bone diseases, among others. The first line treatment is ursodeoxycholic acid (UDCA), that improves liver function tests and delay the progression to cirrhosis. Currently, there are new treatments and adjuvant therapies on study. The purpose of this review is to offer an update in this topic, which is very important in gastroenterology and internal medicine. We formed an interdisciplinary team to search in the database Medline thorough PubMed with the key words describe below, we made a critical lecture of the titles and abstracts of each article to write this paper

Eficacia del ácido ursodesoxicólico en el tratamiento de la enfermedad hepática grasa no alcohólica / Efficacy of ursodeoxycholic acid in the treatment of nonalcoholic fatty liver disease

Introducción: La enfermedad hepática grasa no alcohólica (EHGNA), tiene una prevalencia del 10 % al 24 % en la población general, con una historia natural poco conocida para poder establecer sus opciones terapéuticas. El ácido ursodosoxicólico (AUDC) es una droga utilizada en enfermedades hepáticas colestásicas, la cual tiene un efecto citoprotector en la EHGNA, en donde el estrés oxidativo es uno de los mecanismos fisiopatológicos. Objetivos: evaluar la eficacia del AUDC para mejorar los valores de aminotransferasas (ALT) en un tiempo determinado. Pacientes y métodos: se realizó un estudio prospectivo, experimental, incluyendo aquellos sujetos con aumento de ALT que acudieron a la consulta de centro privado entre enero 2009 - diciembre 2011, se les indicó AUDC a 13 mg/Kg/día por 12 semanas. Para el análisis estadístico se utilizó la prueba de Kolmogorov- Smirnov con un nivel de significancia del 99 % y Chi2 con un nivel de significancia del 95 %. Resultados: del total de los casos n=53, 55 % (n=29) perteneció al sexo femenino con una media de edad de 47,1 años (DS ±13,7 años). Al comparar los promedios de ALT antes y después del tratamiento del total de la muestra, se obtuvo una media 122,3 U/L y 64,7 U/L respectivamente, siendo estas diferencias significativas (p<0,001). Al comparar según sexo, hubo diferencias significativas tanto para el femenino en los promedios ALT antes y después del tratamiento: 110,9 U/L y 53,13 U/L, como en el sexo masculino 136 U/L y 78,7 U/L respectivamente, p<0,001. Existe una relación entre las variables y tiempo de tratamiento, observándose diferencias significativas al comparar los valores de ALT a las 4,8 y 12 semanas con 34,8 %, 30 % y 80 % respectivamente, siendo mayor a las 12 semanas, p<0,05. Conclusión: en nuestro estudio se pudo determinar que el AUDC en un tiempo establecido, mostro ser eficaz para la reducción de los niveles de ALT.

The history natural is poorly unknown for focused therapeutic options. Ursodeoxycholic Acid (UDCA) has long been used in the chronic cholestatic liver diseases, in NALFD believed to have cytoprotective properties and may help to reduce oxidative stress. Objetive: to know the efficacy of UDCA for improvement the serum aminotransferase levels (ALT). Patients and Methods: a prospective, experimental study was performed between january 2009 and december 2011 all patients with elevated ALT were included received UDCA 13 mg/kg/daily for 12 weeks. Analyses were conducted using Kolmogorov-Smirnov and chi-squared test with p<0,001 and p<0,05 was considered as the level of significance respectively. Results: a total of 53 patients, 55 % were female with a mean of 47,1 years old (DS±13,7 years). To compare the mean of ALT among the patients underwent starting treatment before and after was 122,3 U/L y 64,7 U/L respectively and statistically significant p<0,001 and the mean of ALT female gender was rate of response showed difference in patients 110,9 U/L y 53,13 U/L and male gender was 136 U/L y 78,7 U/L before and after UDCA was statistically significant p<0,001. Rate of response did differ in patients treated with UDCA 4, 8 and 12 weeks was 34,8 %, 30 % y 80 % respectively being statistically significant p<0,05 % at 12 weeks. Conclusion: at the present study we determined that UDCA was effective, in a given time, for improvement the serum aminotransferase levels.

Colangite esclerosante primária / Primary sclerosing cholangitis

A colangite esclerosante primária (CEP) é uma doença hepática colestática crônica caracteriza»da por estenoses da árvore biliar intra e extra»hepática, que pode causar cirrose e colangiocar»cinoma em 10% a 30% dos pacientes. Comu»mente está associada à doença inflamatória intestinal e pode causar morte por insuficiência hepática. A CEP é considerada doença hepática imunomediada, multifatorial, multigenética de causa desconhecida. CPRE e colangiopancreato»grafia-ressonância são recomendadas para o diag»nóstico de CEPo O clássico achado em "contas de rosário" é resultado de áreas multifocais de estenoses de duetos biliares intra ou extra-hepá»ticas, intercalados com segmentos normais ou di»latados. Citologia de duetos biliares com esteno»ses e dados histológicos de material obtidos por punção possibilitam o diagnóstico de colangio»carcinoma. Não há tratamento eficaz para a CEPo O ácido ursodesoxicólico pode reduzir as eleva»ções de enzimas hepáticas; seu efeito sobre a his»tologia hepática e o prognóstico são inconclusi»vos. O transplante hepático continua sendo o único tratamento comprovado a longo prazo para a CEP, porém, com recorrência em 20% a 40% dos pacientes.

Hepatolitiasis difusa: un desafío terapéutico / The difuse iintrahepathic lithiasis: detail the therapeutic

Antecedentes: La disminución de la morbilidad y mortalidad de la duodenopancreatectomía cefálica (DPC) en los últimos años permitió extender sus indicaciones a enfermedades benignas. Objetivos: Evaluar los resultados de la DPC en pacientes con enfermedades benignas en un centro de referencia de patología pancreática. Lugar de aplicación: Hospital público. Diseño: Retrospectivo. Población: Pacientes con diagnóstico anatomopatológico de enfermedad benigna (ausencia de carcinoma) en la pieza de resección de DPC. Método: Mediante un análisis retrospectivo de una base de datos prospectiva se evalúo la forma de presentación, el diagnóstico preoperatorio, la indicación quirúrgica, el tipo de cirugía y la morbilidad y mortalidad operatoria. Resultados: En el período 1993-2005 se realizaron 289 DPC, en 110 (38%) pacientes el diagnóstico histológico fue enfermedad benigna. La neoplasia quística (n=64) y la pancreatitis crónica (n=19) fueron las patologías más frecuentes (75,4%). Fueron sintomáticos 88 (81%) pacientes y asintomáticos los restantes. Las indicaciones quirúrgicas fueron el tratamiento de enfermedad benigna conocida (n=30) y la sospecha de malignidad (n=80). Se realizaron 74 DPC con preservación pilórica y 36 sin preservación pilórica. La morbilidad fue de 31,8% y la mortalidad de 0,9%. Conclusiones: Nuestra baja morbimortalidad justifica la DPC en el tratamiento de pacientes con enfermedades benignas en cabeza de páncreas y en pacientes con sospecha de malignidad.

Cirrosis biliar primaria: experiencia de trece años en dos centros de referencia / Primary biliary cirrhosis: a thirteen years experience

Background: Primary biliary cirrhosis (PBC) is a chronic cholestatic disease, which can progress to hepatic failure. Aim: To study the clinical presentation, pathological features, treatment and outcome of a group of patients with PBC. Material and methods: Retrospective review of medical records of 115 patients (110 females, age range 30-76 years) with PBC. Clinical presentation, pathological stage, treatment, outcome and eventual use of liver transplantation, were recorded. Result: Seventy eight percent of patients were symptomatic at presentation (itching in 69% and malaise in 62%). Antimitochondrial antibodies were positive in 56%. No clinical or laboratory differences were observed between symptomatic patients or those with positive antimitochondrial antibodies and the rest of the study group. Sjögren syndrome was present in 38%, hypothyroidism in 13%, scleroderma in 7% and rheumatoid arthritis in 5%. Initially, 61% had fibrosis and/or cirrhosis, and ursodeoxycholic acid was indicated in 94% of the patients. Fifteen patients underwent liver transplantation due to upper digestive bleeding or itching. Survival has been 67% at 36 months after transplantation. In one transplanted liver, PBC recurred. Conclusions: An early diagnosis and treatment of a progressive disease such as PBC will reduce the incidence of complications and the use of costly treatments.

Mecanismos de acción y aplicaciones terapéuticas del ácido ursodeoxicólico en las enfermedades hepáticas colestásicas / Potential mechanisms of action and therapeutic applications of the ursodeoxycholic acid in cholestasis

El ácido ursodeoxicólico es un ácido biliar hidrofílico, que representa una pequeña fracción del pool de ácidos biliares. En las dos últimas décadas, numerosas enfermedades hepáticas colestásicas crónicas (cirrosis biliar primaria, colangitis esclerosante primaria, colestasia intrahepática del embarazo) han sido tratadas con AUDC. Sin embargo, hasta hoy su eficacia sólo ha sido demostrada en la cirrosis biliar primaria, siendo necesario realizar estudios que permitan definir claramente sus indicaciones. Su efecto es mediado por una disminución del daño de los ácidos biliares tóxicos retenidos sobre la membrana celular de los hepatocitos, a través de una estimulación de la secreción biliar, mejoría del flujo biliar y disminución del daño hepático mediado por el sistema inmune

O ácido ursodesoxicólico (AUDC) no tratamento das hepatites crônicas e nas colestases / Ursodeoxycholic acid (UCDA) for the treatment of chronic hepatitis and cholestasis

Como poderá observar o leitor, este assunto está em ebuliçäo, necessitando de mais trabalhos, para nos mostrar onde e como empregar o AUDC. Achamos ser o mesmo eficaz nas colestases de qualquer etiologia, e estamos empregando-o nas hepatites crônicas e cirroses, esperando trazer, em breve, nossos resultados nestas patologias

Cirrose biliar primária: relato de um caso tratado com ácido ursodesoxicólico / Primary biliar cirrhosis: a case report of a treatment with ursodesoxicholic acid

A cirrose biliar primária é de incidência rara e pouco registrada no Brasil. O prurido persistente numa mulher de meia-idade, associado a colestase detectada em laboratório, levou-nos a hipótese da doença, confirmada histologicamente. O uso do ácido ursodesoxicólico teve resposta favorável, tanto no quadro clínico como laboratorial