Primary Sclerosing Cholangitis

Clinical Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease clinically characterized by fatigue, pruritus, and jaundice. The etiology is not known. It can occur at any age, including early childhood; some of these patients have had previous neonatal jaundice. Primary sclerosing cholangitis is a slowly progressing condition. The diagnosis is suspected by finding a cholestatic biochemical profile and confirmed by imaging of an abnormal biliary tract. In some, the disorder gradually progresses to cirrhosis and hepatic failure, and these patients are considered for liver transplantation. An initial diagnosis of PSC during pregnancy is probably fortuitous. Liver function does not deteriorate during pregnancy, and pregnancy does not have a negative effect on PSC progression. These patients are at increased risk of developing a cholangiocarcinoma and gallbladder adenocarcinoma.
Associated Conditions Sclerosing cholangitis does occur as an isolated condition. More typical, especially in younger patients, is an association with inflammatory bowel disease. Liver involvement in patients with ulcerative colitis is not uncommon, although the reported prevalence varies considerably. Part of the confusion is that some patients with ulcerative colitis have nonspecific inflammation surrounding bile ducts; whether such pericholangitis is a variation of sclerosing cholangitis or a separate entity is unknown. Sclerosing cholangitis developing in a setting of inflammatory bowel disease is still called primary; in spite of such an association, no evidence exists that bowel inflammation results in biliary changes. In fact, in some patients sclerosing cholangitis precedes the clinical detection of inflammatory bowel disease. In the past, some authors excluded a diagnosis of PSC if bile duct calculi were present. Yet clinically and radiologically some patients have both sclerosing cholangitis and calculi, and bile duct calculi should be considered part of the spectrum of PSC.About 10% of PSC patients have intrahepatic bile duct calculi, and a similar number have chronic pancreatitis. An MR study of patients with PSC detected pancreatic abnormalities in 46%, consisting of a hypointense pancreas on T1-weighted images, hyperintense on T2-weighted images, decreased enhancement during the arterial phase, pancreatic enlargement, pancreatic duct narrowing, and peripancreatic edema or fluid.
Some patients with autoimmune hepatitis have cholestasis and bile duct strictures similar to those found in PSC. Occasionally reported are associations of PSC with thymoma and hypogammaglobulinemia, Sjögren’s syndrome, Graves’ hyperthyroidism, systemic lupus erythematosus, and celiac sprue. Sclerosing cholangitis has developed during interferon therapy. Whether Langerhans’ cell histiocytosis, resulting in lung cysts and beaded intrahepatic ducts in infants and a rare adult, is related to PSC is conjecture. An interesting observation is that the odds of having primary sclerosing cholangitis is significantly decreased among those who smoke.
Pathology Fibro-obliterative inflammation of both intraand extrahepatic bile ducts is a constant feature of PSC. The presence of liver noncaseating and nonnecrotizing granulomas is generally considered a feature of primary biliary cirrhosis, although similar granulomas are occasionally detected in PSC. In Japan, eosinophilia is found in a large minority of patients with primary sclerosing cholangitis. Similarly, about a third of patients with PSC are antinuclear antibody positive.
Imaging Both intra- and extrahepatic bile ducts are involved. In a minority of patients only intrahepatic ducts are affected, some of the bile ducts become amputated, and the imaging appearance superficially mimics that seen with primary biliary cirrhosis.

raiology images of severe intrahepatic sclerosing cholangitis. Right lobe (A) and left lobe (B) ducts reveal numerous strictures. C: Sclerosing cholangitis in another patient involves both intra- and extrahepatic ducts (arrows). A major stricture is present at the right and left lobe junction.

A minority of patients develop diverticular-like outpouchings. These intramural diverticula appear as cyst-like structures within the bile wall and, if present, are almost pathognomonic of sclerosing cholangitis.

Radiology images of Irregular diverticular-like outpouchings (arrow) are an uncommon but characteristic finding in sclerosing cholangitis.

Classic findings in sclerosing cholangitis consist of multiple strictures varying in length and caliber. A beaded appearance to the bile ducts is not uncommon, with beading ranging from a fine, barely perceptible change in caliber to a coarse, undulating outline. Beading is difficult to evaluate with CT; dilated intrahepatic ducts, regardless of cause, often have an apparent beaded appearance as they course through different axial planes. Extensive hepatic fibrosis and bile duct wall thickening are common. On noncontrast CT fibrosis appears as hypoattenuating regions that become isoattenuating postcontrast. Duct wall thickening ranges from diffuse to focal. Periportal fibrosis results in hyperechoic portal triads. Bile duct wall thickening appears variable in echogenicity with endoluminal US.
In some studies of PSC patients, MRCP has better defined intrahepatic bile ducts and identified more strictures than ERCP. Its noninvasive nature makes it attractive for following established disease and evaluating intrahepati ducts not visualized by ERCP. Once PSC is well established, MRI identifies intrahepatic bile duct dilation, intrahepatic and extrahepatic bile duct stenosis, occasionally a resultant beaded appearance, and bile duct wall thickening and enhancement. A major function of MR is to identify underlying parenchymal damage. Magnetic resonance imaging identifies peripheral wedge-shaped hyperintense regions on T2-weighted images, regions often showing increased arterial-phase enhancement and an occasional reticular pattern. The significance of the MR parenchymal findings is not clear, and this topic is ripe for further research.
Scintigraphy confirms bile retention within bile ducts. Single photon emission computed tomography (SPECT) images reveal multiple focal regions of tracer retention due to bile stasis. In some patients an otherwise normal gallbladder fails to visualize with radiotracer. Lymph node enlargement is not uncommon, with both porta hepatis nodes and other intraabdominal sites involved. Periportal edema is also detected. Biliary abnormalities in most patients gradually progress over years; a more sudden change in a stricture should suggest an underlying cholangiocarcinoma. Eventually, cirrhosis and portal hypertension ensue. The right and left lobe atrophy, the caudate lobe hypertrophies, and the liver develops a prominent lobular appearance, a finding less commonly found with other causes of cirrhosis.
In spite of an occasional optimistic statement that cholangiocarcinomas can be detected in a setting of sclerosing cholangitis, not uncommonly an unsuspected cancer is first discovered by a pathologist after liver transplantation. Distortion by underlying disease makes detection of superimposed tumors difficult. Intraluminal polypoid cancers are least common in these patients; more often, a dominant stricture is found to consist of fibrosis with interspersed cancer cells. Even delayed CT contrast enhancement, a prominent feature with most cholangiocarcinomas, is often missing with thesecancers. Sudden, more proximal bile duct dilation should suggest a neoplastic stricture, but at that point one is already dealing with a widespread tumor. An ERCP appearance similar to intrahepatic sclerosing cholangitis has been described with polycystic liver disease; perihilar cysts can indent bile ducts sufficiently to produce an irregular outline.
Therapy
No specific medical treatment is available for primary sclerosing cholangitis. Orthotopic liver transplantation is currently the definitive therapy. Because of the risk of developing a cholangiocarcinoma, some investigators are recommending liver transplantation earlier in the course rather than waiting until hepatic failure and cirrhosis develop. Because these patients are also at increased risk for hepatocellular carcinoma, screening for hepatocellular carcinoma as well as for cholangiocarcinoma prior to orthotopic liver transplantation appears reasonable. The prognosis is very poor if a cholangiocarcinoma is found even as an incidental finding after liver transplantation. Endoscopic dilation of major duct stenoses is a temporizing measure in this generally progressive condition. In a minority of patients one extrahepatic bile duct stricture is responsible for most obstructive symptoms. Bile duct stricture dilation, especially surgical repair, should
be approached cautiously. An occasional patient develops rapid progression of sclerosing cholangitis postoperatively; whether a fibroproliferative response is induced by duct manipulation is speculative.
A stent through a major stricture provides temporary relief in some, although stent occlusion is a common long-term complication. One variant is to provide short-term stenting; interestingly, these ducts tend to remain patent for months afterward. Also of interest is that immunosuppression after liver transplantation does not influence inflammatory bowel disease in these patients. Secondary Sclerosing Cholangitis Secondary sclerosing cholangitis is associated with some infections, including HIV, bile duct ischemia, some pharmacotherapy, hepatic artery chemotherapy, and embolization and postsurgical complications. As an example, if a hydatid liver cyst communicates with the bile ducts, intracystic injection of a scolicidal solution (formaldehyde) may result in solution spread to the bile ducts and lead to secondary sclerosing cholangitis. Likewise, intraarterial infusion of chemotherapeutic agents has led to bile duct strictures; the perihilar region is most often involved, with these strictures having a smooth and symmetrical appearance. Imaging findings of secondary sclerosing cholangitis are similar to those seen with PSC.

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