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Toronto Notes 2019 Biliary Tract Gilbert’s Syndrome
Definition
• milddecreaseinglucuronyltransferaseactivityleadingtodefectiveconjugationofbilirubin • anabnormalityofbilirubinmetabolismwithnoclinicalrelevance
Etiology/Epidemiology
• somepatientshavedecreasedhepatobiliaryuptake
• affects7%ofpopulation,especiallymales
• autosomaldominant,70%duetoamutationintheUGTgene
Clinical Features
• presentsinteens-20s,oftenanincidentalfinding
• onlymanifestationisintermittentjaundicewithincreasedserumunconjugatedbilirubindeveloping
most characteristically while fasting, or at times of acute illness; no other clinical implications
Treatment
• noneindicated(entirelybenign)
Primary Sclerosing Cholangitis
Definition
• narrowingofbiliarytree(intraand/orextrahepaticbileducts)fromscarring
Etiology
• primary/idiopathic(mostcommon)
■ associated with IBD, more commonly UC, in up to 70% of patients (usually male) ■ one of the most common indications for liver transplant
• secondary(lesscommon)
■ long-termcholedocholithiasis
■ cholangiocarcinoma
■ surgical/traumatic injury (iatrogenic)
■ contiguous inflammatory process
■ post-ERCP
■ associatedwithHIV/AIDS(“HIVcholangiopathy”) ■ IgG4-related disease
Signs and Symptoms
• ofteninsidious,maypresentwithfatigueandpruritus
• maypresentwithsignsofepisodicbacterialcholangitissecondarytobiliaryobstruction
Investigations
• increasedALP(hallmark),lessoftenincreasedbilirubin
• mildlyincreasedAST,usually<300U/L
• p-ANCA(30-80%),elevatedIgM(40-50%)
• MRCPandERCPshowsnarrowinganddilatationsofbileductsthatmayresultin“beading”,both
intrahepatic and extrahepatic bile ducts
■ if intrahepatic narrowing only, do anti-mitochondrial antibody to rule out PBC
Complications
• repeatedboutsofcholangitismayleadtocompletebiliaryobstructionwithresultantsecondarybiliary cirrhosis and hepatic failure
• increasedincidenceofcholangiocarcinoma(10-15%):difficulttodiagnoseandtreat
Treatment
• imagebileduct(MRCP)atleastannuallyforearlydetectionofcholangiocarcinoma(controversial) • endoscopicsphincterotomy,biliarystentinselectedcasesofdominantCBDstricture
• antibioticsforcholangitis
• suppurativecholangitisrequiresemergencydrainageofpusinCBD
• livertransplantationappearstobethebesttreatmentforadvancedsclerosingcholangitis(nearly90%1 yr survival; mean follow-up time from diagnosis to need for transplant is 10 yr)
• ursodiol:previouslyrecommended,butstudiessuggestthatatleastinhighdosesitincreasesmortality
Prognosis
• unfavourableregardlessoftreatment
• meansurvivalafterdiagnosisremains4-10yr
Gastroenterology G41
Gilbert’s Syndrome vs. Crigler-Najjar Syndrome
Gilbert’s Syndrome: mild decrease in glucuronyltransferase activity Crigler-Najjar Syndrome: complete deficiency of glucuronyltransferase