Expert consensus on the diagnosis and treatment of intrahepatic cholestasis (2021 edition) / 中华肝脏病杂志

Intrahepatic cholestasis is a clinical syndrome due to the defect of bile acid synthesis, abnormal bile excretion, and mechanical or functional disturbance of intrahepatic bile flows caused by hepatic parenchymal cell and/or intrahepatic bile duct diseases. It commonly occurs as cholestatic liver diseases, intrahepatic cholestasis of pregnancy, and genetic/metabolic-related cholestatic diseases. In recent years, new information and progress in diagnosis and treatment of intrahepatic cholestatic diseases have been achieved. In order to provide updated clinical reference and guidance for clinicians, we organized experts to compile the Expert Consensus on the Diagnosis and Treatment of Intrahepatic Cholestasis (2021), on the basis of the 2015 edition.

Colestasis genéticas / Genetic cholestasis

Los avances en genética molecular han cambiado nuestro abordaje de los pacientes con colestasis intrahepática. La identificación de mutaciones enciertos genes nos permite hoy arribar al diagnóstico genético de varias formas de colestasis, agrupadas previamente como colestasis intrahepáticafamiliar progresiva. Las tres formas descriptas:tipos 1, 2 y 3, son el resultado de mutaciones en los genes ATP8B1, ABCB11 y ABCB4. Hallazgosclínicos, bioquímicos e histológicos nos orientan en el diagnóstico. El tratamiento tiene como objetivosaliviar los síntomas y mejorar la calidadde vida. Los errores congénitos en la síntesis de ácidos biliares representan un subgupo de las colestasis familiares. El tratamiento de reemplazo con ácido ursodesoxicólico y ácido cólico evitanla progresión de la lesión hepática.

Colestasias familiares: una causa común de hiperbilirrubinemia conjugada / Familial cholestasis: a comon cause of conjugated hyperbilurubinemia

Cholestasis is defined as a disorder affecting the production of bile resulting in the retention of its components in the liver and blood. In children, this disorder is almost always due to genetic alterations. Functionally, cholestasis may be the result of hepatic failure to secrete bile due to decrease in transport, synthesis or biliary obstruction. Extrahepatic cholestasis may be caused by biliary atresia and other obstructions of the bile ducts. Intrahepatic cholestasis may be the result of several disorders including progressive familial intrahepatic cholestasis (PFIC) types 1, 2 and 3, an autosomal recessive disease due to mutations in the genes ATP8B1, ABCBll and ABCB4 respectively. Pathophysiology and clinical presentation of this disease are now well understood. Clinically, these patients may present with jaundice, itching, anorexia, and generally unwell. Laboratory tests may disclose conjugated bilirubin over lmg/dl or larger than 20 percent of total bilirubin. Ursodeoxycholic acid, cholestiramine and biliary diversion may help in some of these conditions. Ongoing research into the mechanisms of genetic cholestasis could be key to therapy.

La Colestasia corresponde a un trastorno en la formación y excreción de la bilis que provoca retención de sus componentes y daño en hígado y sangre. La colestasia en el niño casi siempre se debe a una alteración hepática secundaria a causas ahora mayormente conocidas a nivel molecular. Desde el punto de vista funcional la colestasia resulta de una insuficiencia secretora del hígado debido a una disminución del flujo biliar por falla en los procesos de transporte o síntesis o a una obstrucción de la vía biliar. La colestasia extrahepática incluye la atresia de vías biliares y otras obstrucciones de la vía biliar. La colestasia intrahepática incluye las colestasias progresivas familiares PFIC 1, 2 y 3 causadas por fallas en los genes ATP8B1, ABCBll y ABCB4 respectivamente. Clínicamente pueden presentarse con ictericia, prurito, anorexia y compromiso del estado general. Desde el punto de vista del laboratorio las enfermedades colestásicas se caracterizan por hiperbilirrubinemia conjugada mayor a 1 mg/dl o mayor a 20 por ciento de bilirrubina total.

Colestase da gravidez: revisão de literatura / Obstetric cholestasis: review of the literature

Colestase da gravidez (CG) é uma doença hepática específica da gravidez que tipicamente ocorre a partir do final do segundo trimestre. É uma doença de etiologia heterogênea (multifatorial) com contribuição de fatores genéticos e hormonais, caracterizada por prurido generalizado intenso e alterações das provas de função hepática, estando associada ao aumento das taxas de morbidade e mortalidade fetal. A revisão de literatura realizada refere-se à epidemiologia, etiologia, manifestações clínicas, achados laboratoriais e o manejo da CG na qual se conclui que o conhecimento por parte dos profissionais sobre a doença é fundamental para que seja realizado um manejo adequado das gestantes, visando principalmente prevenir complicações fetais. Apesar do número significativo de estudos relacionados com a CG, vários aspectos da sua etiologia e patogênese não foram elucidados. O diagnóstico é feito por meio de achados clínicos e das alterações das provas de função hepática e aumento dos níveis de ácidos biliares. O ácido ursodesoxicólico é a droga atualmente utilizada na terapêutica da CG com eficácia no controle do prurido e no restabelecimento de níveis normais dos ácidos biliares. Porém, há necessidade da condução de pesquisas e ensaios clínicos para a melhor condução desta doença.

Obstetric cholestasis (OC) is a specific hepatic pathology of the pregnancy that typically happens in the end of the second trimester. It is a heterogeneous etiology (multifactorial) disease with contribution from genetic and hormonal factors, characterized by intense itch and abnormal liver function tests, being associated to the increase of perinatal morbidity and mortality. The revision of accomplished literature refers to the epidemiology, etiology, clinical manifestations, laboratory findings and of which management OC concludes that knowledge by professionals about the disease is the key to an appropriate management, undertaken by pregnant women, seeking mainly to prevent fetal complications. In spite of the significant number of studies related with OC, several aspects of its etiology and pathogenesis were not elucidated. The diagnosis is made through the clinical discoveries and abnormal liver function tests and increase of the levels of bile acids. The ursodeoxycholic acid is now the drug used in the therapeutics of OC with effectiveness in the control of the itch and in the re-establishment of normal levels of the bile acids. However, new research and clinical trials are required for best conduction of this pathology

Non-traumatic right hepatic artery pseudoaneurysm: an unusual cause of hemobilia and obstructive jaundice

Most hepatic artery pseudoaneurysms [HAPA] are post traumatic, and non-traumatic pseudoaneurysm is rarely reported. It is a potentially life threatening vascular disorder and difficult to diagnose before rupture. Early diagnosis and prompt nonoperative intervention of this lesion could be life saving. The authors report the case of a patient with hemobilia caused by ruptured right hepatic artery pseudoaneurysm and subsequently developed right hepatic duct stricture, which has not been reported previously. This patient was successfully treated with endovascular stent graft of pseudoaneurysm and endoscopic stenting of right hepatic duct stricture

[Intrahepatic cholestasis of pregnancy]

Intrahepatic cholestasis of pregnancy is a pregnancy specific hepatic disorder. It occurs mainly in the third trimester of pregnancy by pruritus and elevated serum levels of aminotransferases and total bile acid which completly regresses few days or weeks after delivery. Intrahepatic cholestasis of pregnancy is regarded as a benign disease with meaningful consequences to the mother but associated to increased perinatal risk with increased rates of preterm birth and perinatal mortality. The pathogenesis of disease is unclear yet but likely involves a genetic hypersensitivity to estrogen or progesteron metabolites. Treatment is focused on reducing symptoms in mother and to provide an adequate obstetric management in order to prevent fetal distress. Currently, only ursodeoxycholic acid treatment has been proven to be useful and safe and should be the first choice treatment

Colestasis gravidica: a propósito de un caso / Cholestasis gravidarum: a purpose of a case

La Colestasis Gravídica en un síndrome que habitualmente se produce en el tercer trimestre del embarazo y se resuelve en el embarazo. Se caracteriza clínicamente por la presencia de prurito, ictericia o ambos sin otra disfunción hepática importante. En el siguiente trabajo se reporta caso de paciente femenino de 24 años III gestas II para FUR: 12/8/06 quien refiere de 6 días de evolución orinas coluricas, prurito generalizado predominio de manos y tórax, exámenes para clínicos con aumento de un transaminasas, fosfatasas alcalinas, se diagnóstica colestasis gravídica, patología de baja incidencia de 1/300 y 1/2000 embarazos, se considera importante realizar una revisión académica del mismo.

progressive family intrahepatic cholestasis difficulty of diagnosis and taking charge in a developing country

The progressive family intrahepatic cholestasis or Byler syndrome is a group of recessive autosomic illness. It is responsible of an intra-hepatic cholestate which is secondary to an anomaly of the metabolism and the excretion of biliareses acid .In spite of progress achieved over the last few years in the understanding of the physio-pathological mechanisms and the genetics of this group of cholestasis, the hold in charge remains difficult in a developing country like Tunisia. Patient and methods: it is about a retrospective survey concerning 12 children treated in the paediatric service during a period of 18 years [1986-2003] for progressive family intrahepatic cholestate confirmed by clinical, biological and histological data. our set includes 12 children who have presented a cholestatic jaundice with dark urine and discoloured waste beginning between the ages of 3 days and 18 months with an average age of 4 months, the parental inbreeding has been noted in 10 patients, the domestic antecedents of jaundice of the infant were found in 5 cases the jaundice was in irregular all cases and partner to a prurits in 8 cases. The hyperbilirubinemy and the increase of the alkaline phosphatases were present with all patients. The rate of cholesterol was normal with all patients. The gamma GT was normal in 10 cases and increased in 2 cases, biliary acids have been measured in 10 patients, they were raised in all cases. The hepatic biopsy has been achieved in 10 cases; it showed signs of cholestase and fibrosis in all cases. Eight patients received a treatment associating acidic ursodesoxycolic [AUDC] and Rifampicin, whereas 4 patients have been treated with cholesteramin in the absence of hold social. The K vitamin by way parenterale has been prescribed for all children, whereas vitamins A and E, not available in Tunisia are taken only by 2 patients. The evolution has been made toward the death in a graph of decomposed cirrhosis in 3 patient [age ranging from 1 month to 4 years]. The other patients are treated again with thrusts of jaundice and pruritus but with no sign of serious hepato-cellular insufficiency. A lot of difficulties persist at the level the diagnosis of the PFIC in Tunisia [biliary acid dosage abroad] and especially at the therapeutic level: unavailability of fat-soluble vitamin and absence of a hepatic transplantation program

Colestasia intrahepática del embarazo / Intrahepática colestasia of the pregnancy

Analiza que la colestasia intrahepática del embarazo es una complicación rara de la gestación caracterizada por prurito e ictericia. Su etiología es desconocida. Respecto a su etiopatogenia, destaca la existencia de un estasis de la circulación biliar materna, de que derivan entre otras, una elevación anormal de los ácidos biliares en el plasma materno. No hay daño hepatocelular ni fenómenos inflamatorios en el paénquima hepático. Aparece en las últimas semanas de gestación tiende a ser recurrente en embarazos posteriores y no hay otra explicación, a parte del embarazo, para sus síntomas los cuales desaparecen espontáneamente después del parto. Siendo su pronóstico benigno para la madre, es en cambio una complicación peligrosa para el y para el recién nacido.

Colestase intra-hepática da gravidez / Cholestasis in pregnancy

A colestase intra-hepática gestacional é uma doença hepática própria da gravidez. Chile, Escandinávia, norte da Europa e Bolívia são as regióes que apresentam maior prevalência desta doença, em cuja gênese estão envolvidos fatores genéticos e hormonais. A principal manifestação clínica é o prurido, que pode ser acompanhado de icterícia, esteatorréia, acolia e colúria. Algumas alteraóes das provas de função hepática são observadas...

Litiasis intrahepática: aporte de los tratamientos percutáneos / Intrahepatic primitive lithiasis

Se presenta una serie de 82 casos de litiasis intrahepática primitiva. Esta alta cantidad rara en Occidente, se explica por tratarse en su mayoría de pacientes que han quedado con litiasis remanente y enviados para su extracción percutánea. Desde de 1964 hasta la actualidad (5.000 casos). Se analiza la etiopatogenia dando importancia capital a las estenosis prelitiásicas, presentes en el 80 por ciento, que se consiguieron dilatar en todos los casos y no recidivaron. De las 82, 16 fueron difusas, 52 del conducto hepático izquierdo y 14 del derecho. En casi todos la cirugía fue complementada con el tratamiento instrumental. Se hizo tratamiento percutáneo en 79 casos, 73 se realizaron por la vía transfistular y 6 por vía TPH. Se obtuvo un éxito global del 94 por ciento. Las complicaciones fueron del 17 por ciento y la mortalidad del 2,4 por ciento. No se realizó ninguna hepatectomía

Estenosis congénitas e idiopáticas de las vías biliares / Idiopatic and congenital biliary tract stenosis

Desde 1960 hasta 1992 se recopilaron 17 casos de estenosis de las vías biliares. De ellas 13 son consideradas idiopáticas y 4 congénitas. La edad osciló desde los 16 hasta los 47 años con un promedio de 26. La localización fue en convergencia superior 1, hepático derecho y sus ramas 5, hepático izquierdo 7, hepático común 1, convergencia cístico-coledociana 1, y colédoco intrapancreático 2. Se practicó una anastomosis biliodigestiva, 2 calibradas intraoperatoriamente y 12 calibradas y dilatads postoperatoriamente con sondas ubicadas en forma prolongada ( 15 días a 2 meses). Se trataron 2 pacientes con estenosis en ramas terciarias. Las dilataciones fueron generalmente transfisturales, siendo en un caso realizadas por vía transparietohepática. Este método dio buen resultado en todos los casos aplicados, por lo que se considera de elección

Colestasis extrahepáticas benignas / Benign extrahepatic cholestasis

Se refieren a las distintas causas de colestasis, considerando en este artículo las producidas por lesiones benignas de las vías biliares extrahepáticas. Se pasa revista somera a 87 pacientes estudiados y su terapéutica