Primary Sclerosing cholangitis (PSC)
What is PSC?
PSC is a chronic, cholestatic liver disease characterized by in?ammation and ?brosis of both intrahepatic and extrahepatic bile ducts, leading to the formation of multifocal bile duct strictures.
Small duct PSC is a disease variant which is characterized by typical cholestatic and histological features of PSC but normal bile ducts on cholangiography.
It primarily affects young and middle aged men.
Secondary sclerosing cholangitis (SSC) is characterized by a similar multifocal biliary stricturing process due to long-term biliary obstruction, infection (HIV), and in?ammation.
How is PSC diagnosed?
- Cholestatic LFTs- raised AP, aminotransferase (2-3 times normal) can be elevated too
- Characteristic cholangiographic changes (multifocal, short, annular strictures alternating with normal or slightly dilated segments producing a “beaded” pattern) on ERCP or MRCP and
- Secondary causes of Sclerosing cholangitis have been excluded
Patients, who present with clinical, biochemical and histological features compatible with PSC, but have a normal cholangiogram, are classi?ed as small duct PSC.
Discuss the signs and symptoms of PSC?
- Many patients are asymptomatic and the diagnosis is made incidentally when abnormal LFTs are investigated.
- Typical symptoms include right upper quadrant abdominal discomfort, fatigue, pruritus, and weight loss.
- Physical examination may reveal jaundice, hepatomegaly and splenomegaly.
- Many patients with PSC are asymptomatic with no physical abnormalities at presentation. Approximately 60%-80% of patients with PSC have concomitant IBD, most often UC.
Discuss the role of antibodies in diagnosing PSC?
Anti-neutrophil cytoplasmic antibody (ANCA) may be present in 50%–80% of PSC cases. However, this is non specific and has no role in the routine diagnosis of PSC. Other antibodies like ANA, SMA etc may be present too
Discuss role of ERCP vs. MRCP?
ERCP has been the gold standard in diagnosing PSC. However it is invasive.
MRCP has become the diagnostic imaging modality of choice when PSC is suspected. ERC and MRC have comparable diagnostic accuracy, although the visualization of bile ducts may b e less than optimal for certain patients with MRC. However, it should be noted that that patients with early changes of PSC may b e missed by MRC, and ERC still has a useful role in excluding large duct PSC where MRC views may not be optimal.
What is the role of liver biopsy?
Periductal concentric (“onion-skin”) ?brosis is a classic histopathologic ?nding of PSC; however the changes are non specific at an early stage. In the presence of an abnormal cholangiogram, a liver biopsy is therefore not required to establish a diagnosis of large duct PSC, although is essential in suspected small duct PSC, and for the assessment of possible overlap syndromes.
Discuss IgG4-associated sclerosing cholangitis?
In all patients with possible PSC, serum IgG4 levels should be measured to exclude IgG4-associated sclerosing cholangitis.
Discuss complications of PSC?
- Dominant stricture- the concern is cholangiocarcinoma. An ERCP and brush cytology is needed besides providing therapy in the form of balloon dilatation with or without stenting. Surgery may be needed if ERCP/PTC fails
- Cirrhosis and portal hypertension
- Hepatic osteodystrophy- DEXA scan is recommended at diagnosis and 2-3 yearly intervals subsequently.
- Cholangiocarcinoma (CCA) – The 10-year cumulative incidence is approximately 7%-9% in recent studies. The diagnosis of CCA in the setting of PSC remains challenging if a mass lesion is not identi?ed by imaging studies. With a negative MRI scan, CA 19-9 value 130 U/mL, and negative cytology, a dominant stricture can be assumed to be benign. Bacterial cholangitis should be absent to interpret the serum CA 19-9 level. An ERCP with brush cytology or PET scan may be performed if the index of suspicion is high. Survival following the diagnosis of CCA in the setting of PSC is dismal with 2-year survival being unusual. Even for surgically resected patients, the 3-year survival rate is 20%.
- Gall bladder cancer- there is a high risk of cancer associated with a gallbladder mass lesion. Thus annual ultrasound is recommended to detect mass lesions in the gallbladder. In patients with gallbladder mass lesions, cholecystectomy is recommended a s treatment regardless of lesion size, if the underlying liver disease permits
Discuss the natural history of PSC?
The estimated 10-year survival for patients with PSC is approximately 65% but large individual variations exist. Various prognostic models have been proposed, however their ability to predict outcomes in an individual patient is limited and thus their use is not recommended.
Discuss treatment of PSC?
UDCA use as a chemopreventative agent in PSC patients cannot be routinely recommended given the limited information available. The role for UDCA in slowing the progression of PSC-related liver disease is as yet unclear and indeed, high dose UDCA may b e harmful. Thus use of UDCA in PSC is not recommended.
Cholestyramine/rifampin may be used for pruritus.
Liver transplant is the only definitive treatment option. Indications for patients with PSC do not differ substantially from those with other forms o f chronic liver disease and relate primarily to complications of portal hypertension, impaired quality of life, and chronic liver failure. Unique liver transplant indications for patients with PSC include intractable pruritus, recurrent bacterial cholangitis, and cholangiocarcinoma.
Discuss IBD and PSC?
- The prevalence of IBD in PSC is in the range of 60-80%. Both UC and Crohn’s colitis occur, however the most frequent type of IBD in PSC is UC. Conversely, PSC has been diagnosed in less than 10% of patients with IBD.
- IBD in PSC has a unique phenotype. Characteristics of IBD associated with PSCExtensive colitis (with right sided predominance)
Rectal sparing
Backwash ileitis
Mild or quiescent course
Increased risk of colorectal neoplasia
Increased risk of pouchitis
Increased risk of peristomal varices in patients undergoing proctocolectomy with ileostomy - CD con?ned to the small bowel is not associated with PSC.
- IBD in PSC may be present with little or no clinical evidence of bowel disease and a diagnosis of IBD has implications in terms of follow-up, a full colonoscopy with multiple biopsies is recommended in all PSC patients at diagnosis.
- IBD may be diagnosed at any time during the course of PSC. In the majority of cases, the diagnosis of IBD precedes that of PSC, even by several years.
- Given the increased risk of CRC in patients with PSC, surveillance colonoscopy at one to two year intervals from the time of diagnosis of PSC in patients with colitis is recommended
- Colorectal neoplasia associated with PSC appears to have a predilection for the proximal colon, with up to 76% having a right-sided distribution.
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