Editing Primary sclerosing cholangitis

Chronic inflammatory disease characterised by strictures of the intrahepatic and extrahepatic biliary tree

* Generally progressive

== Pathophysiology ==

* Poorly understood
* Likely autoimmune
* ?Bacterial translocation and infection
* Genetic factors, although complex and polygenetic, exist

== Aetiology ==

* 2/3 male
* Average age 40s

=== Associated with: ===

** UC (most common - 60-90% of cases)
** Crohns
** T1DM
** Thyroiditis
** Autoimmune hepatitis
** Ankylosing spondylitis
** Coeliac disease
** Acute pancreatitis
** Pancreatic adenocarcinoma
** Gallstones
** GB polyps/cancer
*** Some recommend annual biliary USS
*** Cholecystectomy for ANY size polyp
** Colorectal adenocarcinoma - need frequent surveillance
** Cholangiocarcinoma (as high as 15%)
*** Not associated with duration of PSC disease or presence of cirrhosis
*** No high-risk group has been identified to target with screening protocols
*** Screening consists of serial MRCP and CA 19-9 (can be falsely elevated in setting of jaundice though)
*** ERCP for those with increasing CA 19-9 or those in whom dominant strictures develop or progress
*** Need complete resection to manage
** HCC

== Distribution ==

* Intra and extrahepatic 75%
* Only intrahepatic 15%
* Only extrahepatic 10%
* 'Dominant stricture' = a narrowing 1.5mm or less in CBD or 1mm or less in CHD

== Presentation ==

* Non-specific
* Often asymptomatic
* Often recurrent cholangitis leading to secondary biliary cirrhosis and not uncommonly, biliary malignancy
* Can lead to end-stage liver disease/portal HTN
* Present intra and extra hepatic ducts in 70%, just intra-hepatic in 25% and just extra-hepatic in <5%
* Can be classic biliary - RUQ pain, pruritis, fatigue
* Can be deranged LFTs/liver failure, especially if intrahepatic disease primarily

== Diagnosis ==

* MRCP is gold standard
* ERCP

== Workup ==

* Need liver biopsy to document degree of fibrosis
* Colonoscopy (exclude CRC and diagnose IBD)

== Medical therapy ==

* No drug has slowed disease progression, prolonged survival or improved outcomes in patients with PSC
* Future therapies?
** Antifibrotic agents
** TNF-a inhibitors
** T-cell modulators
** Inhibitors of 'toxic bile' formation (Farnesoid X agonists)

== Endoscopic/IR therapies ==

* ERCP best treatment methodology
* Opportunity for cholangioscopy/EUS - better chance of identifying CCA
* Balloon dilation - 80% get a good clinical response
* If no response: endobiliary stents
** Need to remove after 6-8 weeks
** Complications - bleeding, perforation, pancreatitis, cholangitis
* The role of PTC is mostly limited to those with previous RYGB or other biliary bypass

== Surgical resection ==

* Should generally be avoided in PSC - limited impact on survival, significant morbidity, increased scarring in porta hepatis which may complicate future transplant
* Only exception would be patients with early disease, but a dominant extrahepatic stricture, who may be eligible for biliary reconstruction (hepaticojejunostomy)

== Liver transplant ==

* Use Mayo Model to predict optimal timing of transplant
** Bilirubin
** Degree of fibrosis
** Presence of splenomegaly
** Age
* Recurrent PSC in 25% (IBD and intact colon puts them at risk)
* If unsuspecting small CCA (<1cm) is found at explant, the long-term prognosis seems to be unaffected

== Complications ==

* CCA (lifetime risk 10-20%) - annual MRCP and CA19-9 is a sensible screening pattern)
* Cholelithiasis/GB CA
* Cholestasis-associated problems
** Metabolic bone disease
** Fat-soluble vitamin deficiencies
** Choledocholithiasis
* Higher risk of CRC


== Prognosis ==

* Average survival from diagnosis to death/transplantation is 12-18 years

[[Category:Biliary]]