Approach to the patient with cholestasis and jaundice syndrome. Joint AMH, AMG, and AMEG scientific position statement.

The term cholestasis refers to bile acid retention, whether within the hepatocyte or in the bile ducts of any caliber. Biochemically, it is defined by a level of alkaline phosphatase that is 1.67-times higher than the upper limit of normal. Cholestatic diseases can be associated with an inflammatory process of the liver that destroys hepatocytes (hepatitis), withjaundice (yellowing of the skin and mucus membranes, associated with elevated serum bilirubin levels), or with both, albeit the three concepts should not be considered synonymous. Cholestatic diseases can be classified as intrahepatic or extrahepatic, depending on their etiology. Knowing the cause of the condition is important for choosing the adequate diagnostic studies and appropriate treatment in each case. A complete medical history, together with a thorough physical examination and basic initial studies, such as liver ultrasound and liver function tests, aid the clinician in deciding which path to follow, when managing the patient with cholestasis. In a joint effort, the Asociación Mexicana de Hepatología (AMH), the Asociación Mexicana de Gastroenterología (AMG) and the Asociación Mexicana de Endoscopia Gastrointestinal (AMEG) developed the first Mexican scientific position statement on said theme.

Analysis of predictive response scores to treatment with ursodeoxycholic acid in patients with primary biliary cholangitis. / Análisis de los índices predictores de respuesta al tratamiento con ácido ursodeoxicólico en pacientes con colangitis biliar primaria.

BACKGROUND AND OBJECTIVES: Primary biliary cholangitis (PBC) is an autoimmune disease that affects the small bile ducts. The only treatments currently approved in our country are ursodeoxycholic acid (UDCA) and obeticholic acid. Different indices evaluate the response after one year of treatment. The aim of our study was to evaluate the different predictive scores and prognostic factors of response to UDCA. MATERIAL AND METHODS: Retrospective single-centre study in which clinical and analytical data of patients diagnosed with PBC were collected from January 1987 to December 2015. The response after one year of treatment was evaluated using the different response scores and their concordance degree using the Kappa index. The area under the receiver operating characteristic curve (AUROC) was calculated to determine the predictive capacity of the scores. Likewise, the prognostic factors of response to treatment were analysed. RESULTS: We included 153 patients. The bivariate analysis showed a statistically significant relationship between the initial high levels of alkaline phosphatase and cholesterol and the poor response to treatment. The best AUROC was in Paris-I score (0.81). The concordance between the different scores was low. The GLOBE score was valid to evaluate the prognosis. CONCLUSION: Basal alkaline phosphatase and cholesterol were predictors of poor outcome. The best predictive qualitative score in our cohort patients was Paris-I. There was a poor concordance between the different predictive scores. GLOBE score is valid to evaluate prognosis.

Primary biliary cholangitis. / Colangitis biliar primaria.

Primary cholangitis (cirrhosis) is a chronic cholestatic disease with an unquestionable female predominance. It is characterised by inflammation of the small and medium size bile ducts, and can eventually progress to cirrhosis. Most patients remain asymptomatic and are diagnosed by the casual finding of an anicteric biochemical cholestasis with increased alkaline phosphatase. The pathogenesis is unknown and of presumed autoimmune origin in genetic susceptible subjects. M2-type antimitochondrial antibodies, and specific antinuclear antibodies (gp210 and Sp100) are typical and specific of the disease. The positivity of these antibodies and a biochemical cholestasis are sufficient for diagnosis, without the need for liver biopsy. Ursodeoxycholic acid is the specific treatment with an excellent response in more than 60% of patients. When this optimal response is not observed, it can be combined with new agents, but those that have shown to be effective are those that improve cholestasis such as fibrates and obeticholic acid.

Nuevas terapias para la colestasis / New therapies in cholestasis

The introduction of ursodeoxycholic acid (UDCA) in the treatment of patients with cholestasis enabled remarkable progress and improvements in hepatic inflammatory activity, progression to cirrhosis and quality of life. However, the benefits of UDCA are particularly evident in patients with primary biliary cirrhosis and also 30 percent of patients have sub optimal response. For this reason, in order to improve the number of people with complete responses to therapy, new pharmacological alternatives have been investigated to add to UDCA treatment. This review aims to show potential new therapies against cholestasis that have been investigated by systematizing them depending on the receptor or target on which they act. Finally, a special reference will be made in relation to the treatment of pruritus associated with cholestasis.

La introducción del ácido ursodeoxicólico (AUDC) en el tratamiento de los pacientes con colestasia permitió notables avances con mejoras en la actividad inflamatoria hepática, progresión hacia la cirrosis y calidad de vida. Sin embargo, los beneficios de AUDC se aprecian especialmente en pacientes con cirrosis biliar primaria y además, 30 por ciento de los pacientes tiene una respuesta sub óptima. Por esta razón, con la finalidad de mejorar el número de personas con respuestas completas a la terapia, se han investigado nuevas alternativas farmacológicas para adicionar al tratamiento con AUDC. La presente revisión pretende mostrar las nuevas posibles terapias contra la colestasia estudiadas sistematizándolas según el tipo de receptor o diana sobre el que actúan. Finalmente se hará referencia especial en relación al tratamiento del prurito asociado a la colestasia.

¿Beneficio o riesgo del uso de ácido ursodeoxicólico en prevención de cáncer colorrectal en pacientes con colangitis esclerosante primaria/colitis ulcerosa? / Benefit or risk from the use of ursodeoxycholic acid in prevention of colorectal

cancer in patients with primary sclerosing cholangitis/ulcerative colitis? Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and fibrosis of intra-and extrahepatic bile ducts. About 70 percent of patients with CEP have idiopathic ulcerative colitis (IUC). PSC is considered a premalignant condition with an increased risk of colorectal cancer (CC). Individuals with PSC and IUC have higher risk of developing CC than IUC patients. There are different positions between American and European experts in the fields of hepatology and inflammatory bowel disease regarding the use of ursodeoxycholic acid (UDCA) in PSC and IUC as a chemo preventive. Studies have shown mixed results about the use of UDCA in preventing CC. The following is an update on the role of UDCA as a chemo preventive in this group of patients.

La colangitis esclerosante primaria (CEP) es una enfermedad crónica hepática colestásica caracterizada por inflamación y fibrosis de ductos biliares intra y extrahepáticos. Alrededor de 70 por ciento de los pacientes con CEP presenta colitis ulcerosa idiopática (CUI). La CEP es considerada una condición premaligna con un incremento del riesgo de cáncer colorrectal (CCR). Individuos con CEP más CUI tienen mayor riesgo de desarrollar CCR que pacientes con sólo CUI. Existen distintas posturas a nivel mundial entre expertos americanos y europeos tanto en el área de la hepatología como en el área de las EII (enfermedades inflamatorias intestinales) frente al uso de ácido ursodeoxicólico (AUDOC) en CEP y CUI como quimioprotector. Estudios han mostrado resultados contradictorios para el uso de AUDOC en la prevención de CCR. Se expone una revisión actualizada sobre el rol de AUDOC como quimioprotector en este grupo de pacientes.

Novedades en enfermedades colestásicas / Latest advances in cholestatic diseases

Cholestatic liver diseases arise from impaired hepatobiliary production and excretion of bile. They have some common clinical manifestations and pathogenic features, but at the same time differences that require a special approach. Intrahepatic cholestasis of pregnancy and drug induced liver cholestasis are the most common reversible intrahepatic cholestasis. Primary biliary cirrhosis and primary sclerosing cholangitis are chronic cholestatic diseases. This review will be focused on these two types, in particular their clinical and therapeutic management and complications. While in recent years there has not been much change in the basic clinical approach of these diseases, every day we receive more information from both the basic and clinical science studies, which has enabled to develop new therapeutic lines and reject others that have not confirmed effectiveness.

Las enfermedades colestásicas se caracterizan por la disminución de la formación o excreción del flujo de bilis. Ellas tienen ciertas manifestaciones clínicas y mecanismos patogénicos comunes, pero a su vez diferencias que requieren un enfrentamiento no siempre similar. La colestasia intrahepática del embarazo(CIE) y la colestasia secundaria a fármacos son las más frecuentes dentro de las colestasias intrahepáticas reversibles. La cirrosis biliar primaria (CBP) y la colangitis esclerosante primaria (CEP), son las enfermedades colestásicas crónicas en que centramos esta revisión, en particular en los aspectos clínicos y de manejo terapéutico tanto de éstas, como de sus complicaciones. Si bien en los últimos años no ha habido un cambio significativo en el manejo fundamental de estas enfermedades, cada vez tenemos más información tanto en el área de ciencias básicas como en aspectos clínicos, lo que ha permitido ir desarrollando nuevas líneas terapéuticas y descartando otras que no han confirmado efectividad.

Cirrosis biliar primaria: presentación de un caso clínico y revisión bibliográfica / Primary biliary cirrhosis: presentation of a case report and literature review

La Cirrosis Biliar Primaria (CBP) es una enfermedad hepática colestásica-crónica y progresiva de patogenia autoinmune, que ha aumentado su prevalencia en los últimos años. En el presente trabajo exponemos un caso clínico sobre una paciente femenina con síndrome colestásico, anticuerpos anti-mitocondriales (AMA) positivo y el informe anatomopatológico compatible con CBP cirrosis biliar primaria en tercer estadío. Su tratamiento principal fue farmacológico con ácido ursodeoxicólico (AUDC).

Primary biliary cirrhosis (PBC) is a chronic-cholestatic and progressive liver disease with autoimmune pathogenesis, which has increased in prevalence in recent years. In this paper we present a case of a female patient with cholestatic syndrome, anti-mitochondrial antibody (AMA) positive and the pathology report compatible with PBC primary biliary cirrhosis in the third stage. Her main treatment was with the drug called ursodeoxycholic acid (UDCA).