Common ABCB4 and ABCB11 genotypes are associated with idiopathic chronic cholestasis in adults

AbstractProgressive family intrahepatic cholestasis (PFIC) is an autosomal recessive disease that causes chronic cholestasis. It is associated with pathogenic variants in genes that encode proteins involved in bile secretion to canaliculus from hepatocytes. In this study, we present a 16-year-old boy who presented with severe pruritus and cholestatic jaundice. All possible infectious etiologies were negative. A liver biopsy was consistent with intrahepatic cholestasis and portal fibrosis. DNA was isolated from a peripheral blood sample, and whole exome sequencing was performed. A novel c.3484G > T/p.Glu162Ter variant in the ABCB11 gene and a c.208G> A/p.Asp70Asn variant in the ATP8B1 gene were detected. Despite traditional treatment, the patient's recurrent severe symptoms did not improve. The patient was referred for a liver transplantation. This novel c.3484G > T/p.Glu162Ter variant is associated with a severe and recurrent presentation, and the two compound variants could explain the severity of PFIC.

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PROGRESSIVE NEUROMUSCULAR DISEASE IN CHILDREN WITH CHRONIC CHOLESTASIS AND VITAMIN E DEFICIENCY: CLINICAL AND MUSCLE BIOPSY FINDINGS AND TREATMENT WITH ?-TOCOPHEROL

Annals of the New York Academy of Sciences ◽

10.1111/j.1749-6632.1982.tb31235.x ◽

1982 ◽

Vol 393 (1 Vitamin E) ◽

pp. 84-95 ◽

Cited By ~ 24

Author(s):

Mary Anne Guggenheim ◽

Steven P. Ringel ◽

Arnold Silverman ◽

Brian E. Grahert ◽

H. E. Neville

Keyword(s):

Vitamin E ◽

Muscle Biopsy ◽

Neuromuscular Disease ◽

Vitamin E Deficiency ◽

Chronic Cholestasis

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Chronic Cholestasis Associated with Turner’s Syndrome: 12 Years of Clinical and Histopathological Follow-Up

Digestion ◽

10.1159/000069702 ◽

2003 ◽

Vol 67 (1-2) ◽

pp. 96-99 ◽

Cited By ~ 8

Author(s):

Joram Wardi ◽

Boleslaw Knobel ◽

Mark Shahmurov ◽

Enrique Melamud ◽

Yona Avni ◽

...

Keyword(s):

Turner's Syndrome ◽

Turner’S Syndrome ◽

Chronic Cholestasis

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ALAGILLE SYNDROME AS A CHALLENGING CLINICAL CASE IN PEDIATRIC PRACTICE (case report)

Inter Collegas ◽

10.35339/ic.4.2.83-85 ◽

2017 ◽

Vol 4 (2) ◽

pp. 83-85

Author(s):

Nigar Hajiyeva

Keyword(s):

Clinical Case ◽

Spontaneous Mutation ◽

Pulmonary Stenosis ◽

Alagille Syndrome ◽

Final Diagnosis ◽

Autosomal Dominant Disorder ◽

Chronic Cholestasis ◽

Characteristic Features ◽

Prolonged Jaundice ◽

Peripheral Pulmonary Stenosis

Hajiyeva N.A.Alagille syndrome is a multisystem, highly variable, autosomal dominant disorder, which can be triggered by spontaneous mutation. This disease primarily affects the liver (chronic cholestasis), heart (most often peripheral pulmonary stenosis), eyes (posterior embryotoxon), face (characteristic features), and skeleton (butterfly vertebrae). The paper presents the clinical case of prolonged jaundice with an increased liver enzymes in infant and no final diagnosis for a long time.KeyWords: Alagille syndrome, chronic cholestasis, ursodeoxycholic acid СИНДРОМ АЛАЖІЛЯ, ЯК СКЛАДНИЙ КЛІНІЧНИЙ ПРИКЛАД З ПЕДІАТРІЧНОЇ ПРАКТИКИ (клінічний випадок)Хаджієва Н.А.Синдром Алажіля є мультисистемним варіабельним аутосомно-домінантним розладом, який є наслідком спонтанної мутації. Це захворювання перед усім уражує печінку (хронічний холестаз), серце (найчастіше периферичний стеноз легеневої артерії), очі (задні ембріотоксони), обличчя (характерні ознаки) і скелет (хребці у вигляді метеликів). В публікації представлений клінічний випадок тривалої жовтяниці з підвищеням печінкових ферментів у дитини раннього віку, у якої протягом тривалого часу неможливо було встановти клінічний діагноз.Ключові слова: синдром Алажіля, хронічний холестаз, урсодеоксихолєва кислота СИНДРОМ АЛАЖИЛЯ КАК СЛОЖНЫЙ КЛИНИЧЕСКИЙ ПРИМЕР ИЗ ПЕДИАТРИЧЕСКОЙ ПРАКТИКИ (клинический случай)Хаджиева Н.А.Синдром Алажиля является мультисистемным вариабельным аутосомно-доминантным расстройством, которое является следствием спонтанной мутации. Это заболевание прежде всего поражает печень (хронический холестаз), сердце (чаще всего периферический стеноз легочной артерии), глаза (задний эмбриотоксон), лицо (характерные признаки) и скелет (позвонки в виде бабочек). В публикации представлен клинический случай длительной желтухи с повышением печеночных ферментов у ребенка раннего возраста, у которого в течение длительного времени невозможно было установить клинический диагноз.Ключевые слова: синдром Алажиля, хронический холестаз, урсодеоксихолевая кислота

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Drug-Induced Vanishing Bile Duct Syndrome: From Pathogenesis to Diagnosis and Therapeutics

Seminars in Liver Disease ◽

10.1055/s-0041-1729972 ◽

2021 ◽

Author(s):

Fernando Bessone ◽

Nidia Hernández ◽

Mario Tanno ◽

Marcelo G. Roma

Keyword(s):

Bile Duct ◽

Diagnostic Tools ◽

Drug Induced ◽

Vanishing Bile Duct Syndrome ◽

Beneficial Effects ◽

Intrahepatic Bile Ducts ◽

Chronic Cholestasis ◽

Vanishing Bile Duct ◽

Therapeutic Alternatives ◽

Duct Syndrome

AbstractThe most concerned issue in the context of drug/herb-induced chronic cholestasis is vanishing bile duct syndrome. The progressive destruction of intrahepatic bile ducts leading to ductopenia is usually not dose dependent, and has a delayed onset that should be suspected when abnormal serum cholestasis enzyme levels persist despite drug withdrawal. Immune-mediated cholangiocyte injury, direct cholangiocyte damage by drugs or their metabolites once in bile, and sustained exposure to toxic bile salts when biliary epithelium protective defenses are impaired are the main mechanisms of cholangiolar damage. Current therapeutic alternatives are scarce and have not shown consistent beneficial effects so far. This review will summarize the current literature on the main diagnostic tools of ductopenia and its histological features, and the differential diagnostic with other ductopenic diseases. In addition, pathomechanisms will be addressed, as well as the connection between them and the supportive and curative strategies for ductopenia management.

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Large-duct cholangiopathies: aetiology, diagnosis and treatment

Frontline Gastroenterology ◽

10.1136/flgastro-2018-101098 ◽

2019 ◽

Vol 10 (3) ◽

pp. 284-291 ◽

Cited By ~ 1

Author(s):

Shyam Menon ◽

Andrew Holt

Keyword(s):

Bile Flow ◽

Biliary Tree ◽

Biliary Cirrhosis ◽

Caroli Disease ◽

End Stage Liver Disease ◽

Recurrent Pyogenic Cholangitis ◽

Chronic Cholestasis ◽

End Stage ◽

Extrahepatic Biliary Tree ◽

Portal Biliopathy

Cholangiopathies describe a group of conditions affecting the intrahepatic and extrahepatic biliary tree. Impairment to bile flow and chronic cholestasis cause biliary inflammation, which leads to more permanent damage such as destruction of the small bile ducts (ductopaenia) and biliary cirrhosis. Most cholangiopathies are progressive and cause end-stage liver disease unless the physical obstruction to biliary flow can be reversed. This review considers large-duct cholangiopathies, such as primary sclerosing cholangitis, ischaemic cholangiopathy, portal biliopathy, recurrent pyogenic cholangitis and Caroli disease.

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