Primary Sclerosing Cholangitis

    

    

    Figure 2:  Thick slab MRCP image showing multiple strictures in the
intrahepatic biliary ducts (arrows). And dilated left hepatic duct (arrowhead).
    
    

Diagnosis

Primary sclerosing cholangitis.

Image interpretation

MRCP demonstrated diffuse intrahepatic strictures and mild dilatation of the common hepatic duct and left and right main ducts.

Treatment and clinical course

Patient underwent liver biopsy under imaging guidance, which demonstrated mild portal hepatitis with septal fibrosis and destructive cholangitis which were compatible with the diagnosis of sclerosing cholangitis. Anaemia was treated with blood transfusion. Patient was discharged after improvement in symptoms. She was advised various drugs including Azathioprine, Prednisolone, Mesalazine and iron supplements and is on regular follow-up.

Discussion

Primary Sclerosing Cholangitis (PSC) is a chronic cholestatic liver disease of intra and/or extrahepatic bile ducts, probably of autoimmune origin [1]. This condition is commonly associated with inflammatory bowel disease [1], especially ulcerative colitis as in our patient. Other conditions which may be associated or be present along with PSC include celiac disease, diabetes mellitus, rheumatoid arthritis, Sjogren’s disease, chronic pancreatitis, cystic fibrosis and systemic lupus erythematosus [1]. The diagnosis is very important because the risk of colorectal malignancies and cholangiocarcinoma is very high in these patients [2]. Although autoimmune aetiology is likely, portal bacteraemia, viral infection, toxic bile acid and ischemic injury are some of the hypothesized causes. Certain studies have shown PSC to be more prevalent in non-smokers as compared to controls [3,4]. Males are twice more commonly affected and the peak age is around third to fifth decade [5]. Africans and Afro-Caribbean’s are at an increased risk of developing PSC due to genetic factors [5,6] and increased prevalence is also reported among Caucasians [6,7]. Exact incidence and prevalence in Singapore is not known [7]. According to Ang et al, prevalence of inflammatory bowel disease and positive pANCA is very less in patients with PSC in Singapore [7].

The clinical features are highly variable and patients may present with fatigue, abdominal discomfort, pruritus and weight loss. Liver function tests are often abnormal and patients may have background of inflammatory bowel disease. Eventually there may be signs of liver failure or they may develop cholangiocarcinoma [8].

Immunochemistry is gaining popularity with increased Immunoglobulin M (IgM) in 50% of cases and hypergammaglobuminemia in a third of the patients. Low titre autoantibodies such as Anti-Nuclear Antibody (ANA), Smooth Muscle Antibodies (SMA) and perinuclear Anti-Neutrophil Cytoplasmic Antibodies (pANCA) can be present.

Early changes can be focal and missed on liver biopsy. The most common finding is of periductal concentric ‘onion-skin’ obliterative fibrosis surrounding the bile ducts. In advanced disease, an entity called ‘vanishing bile duct syndrome’ is noted with loss of bile ducts as the central feature [9].

The diagnosis can be made on imaging by identifying the typical cholangiographic findings coupled with clinical presentation. Exclusion of conditions mimicking PSC such as cholangiocarcinoma, secondary cholangitis or stone disease is an important step in making the diagnosis [10]. The role of ultrasound is very limited and can detect changes of cirrhosis only in advanced stage. Visualization of intrahepatic biliary radicals is often difficult on ultrasound. Contrast enhanced computed tomography showing mural contrast enhancement of the extrahepatic ducts is a consistent finding, along with dilatation, stenosis, wall thickening and nodularity. ERCP is the gold standard examination and can be used for diagnosis as well as treatment of strictures and/or removal of debris within the ducts. Common findings include cobble stoning, stricture formation and duct dilatation. The presence of diverticula or pseudodiverticula is pathognomonic. Magnetic Resonance Cholangio-Pancreaticography (MRCP) is becoming investigation of choice due to inherent advantages over ERCP. The advantages of MRCP apart from being non-invasive modality, include lack of radiation, faster imaging and visualization of dilated peripheral intrahepatic ducts. Other findings in MR imaging include periportal lymphadenopathy, periportal increased T2 signal and signal changes in the liver parenchyma [11]. There are advantages of ERCP over MRCP, such as increased sensitivity in the visualization of peripheral ducts, mechanical dilatation of ducts, ability to obtain specimen for histopathological analysis and placement of stent. However the risks and complications such as haemorrhage, infection, perforation of the duct or intestine can occur. Hence MRCP is preferred diagnostic modality and ERCP is generally used for therapeutic guidance, rather than for diagnosis [12].

The median reported survival in patients with PSC is 10-12 years [13]. Early diagnosis and management is essential to delay the progress of the disease. Ursodeoxycholic Acid (UDCA), a naturally occurring bile acid, is proven to improve the liver enzyme function in PSC, but its role in improving liver histology is controversial. Surgical management of precirrhotic patients involves resection of the entire extrahepatic biliary tree, including the hepatic duct bifurcation. Ductal dilatation with/without stenting of intrahepatic ducts leads to a longer symptom free period. The interventions can delay but not prevent development of cirrhosis. Once cirrhosis has developed, liver transplantation is the treatment of choice [14].

Conclusion

Primary sclerosing cholangitis is a chronic liver disease of unknown etiology, characterised primarily by inflammation and fibrosis of the biliary tree. It is closely associated with inflammatory bowel disease and a host of other conditions, eventually leading to cirrhosis and death. Diagnosis is achieved by imaging, laboratory markers and histology. ERCP is the current gold standard investigation, although MRCP is the non-invasive investigation of choice. Early diagnosis and medical intervention slow the disease progression and decrease mortality and morbidity.

References

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