Prepared by Ryan C. Hill, MD of the Department of Radiology, University of Arkansas for Medical Sciences, Little Rock, AR; Justin Q. Ly, MD of the Department of Radiology, Wilford Hall Medical Center, Lackland Air Force Base, TX; Thomas P. Jones, MD of the Department of Radiology, The Mayo Clinic, Rochester, MN; and Douglas P. Beall, MD of the Department of Radiology and Nuclear Medicine, The Uniformed Services Health University, Bethesda, MD.

CASE SUMMARY

A 48-year-old woman with a history of Crohn's disease presented with recurrent obstructive jaundice, pruritis, weight loss, and fatigue. Laboratory evaluation of liver function revealed moderately elevated aminotransferase and alkaline phosphatase levels. Following abdominal radiography, which showed no suspicious calcifications, sonographic evaluation of the right upper quadrant was performed (Figure 1), with further evaluation by endoscopic retrograde cholangiopancreatography (ERCP) study (Figure 2).

IMAGING FINDINGS

Sonographic evaluation revealed marked thickening of the common bile duct (Figure 1), as well as multiple mildly dilated intrahepatic ducts (Figure 1C). Diffuse intrahepatic strictures and mild dilatation of the common hepatic duct and the left and right main ducts were demonstrated on ERCP (Figure 2).

DIAGNOSIS

Primary sclerosing cholangitis (PSC)

DISCUSSION

This diagnosis is made by identifying typical cholangiographic abnormalities and excluding conditions that can mimic PSC, including previous biliary tract surgery, biliary tract malignancies, systemic diseases such as sarcoid or systemic lupus erythematosis (SLE), AIDS-related cholangiopathy, congenital biliary tract abnormalities, exposure to irritant chemicals, and other types of advanced liver disease. ¹ The diagnosis is supported by clinical, biochemical, and histologic findings, which include jaundice, pruritus, elevated alkaline phosphatase, and elevated levels of bilirubin. Low-titer autoantibodies, such as ANA, SMA, and pANCA can be present. The most common histologic finding is periductal concentric obliterative fibrosis of small interlobular bile ducts with or without proliferation of bile ducts in the portal tracts. ²

Sonography, computed tomography (CT), and magnetic resonance imaging (MRI) can also be used in the diagnosis of PSC. Typical sonographic findings are marked diffuse thickening of the common hepatic and bile ducts. Wall thickening may obliterate the lumen of the ducts and may be difficult to distinguish from intraluminal debris. One major limitation of sonography is its frequent inability to visualize the intrahepatic ducts. CT findings include mural contrast enhancement of the extrahepatic ducts in nearly all cases, along with dilatation, stenosis, wall thickening, and nodularity. Dilatation, stenosis, pruning, and beading of intrahepatic bile ducts can be detected approximately 80% of the time. ERCP remains the gold standard for diagnosis. It can be used for the treatment of strictures or the removal of debris within the ducts. Common ERCP findings include cobblestoning, stricture formation, and duct dilation. The presence of diverticula or pseudodiverticula is pathognomonic. Cholangiography is limited due to its invasiveness and may soon be replaced by MRI for the purpose of diagnosing PSC. MRI has the added ability to visualize some portions of the biliary tree not seen by cholangiography due to stricture. Other MRI findings include periportal lymphadenopathy, periportal increased T2 signal, and abnormal hyperintensity of the liver parenchyma. ³

Most cases of PSC occur in people over the age of 45, with a 2:1 male predominance. ⁴ Africans and Afro-Caribbeans may be at increased risk of developing PSC. ⁵ The etiology is unclear, but autoimmunity, portal bacteremia, viral infection, absorption of colonic toxins, toxic bile acid, and ischemic injury have been suggested as possible causes. ⁴ Association with other diseases, such as ulcerative colitis, is common. Other associated conditions include cirrhosis, chronic active hepatitis, pericholangitis, pancreatitis, osteopenic bone disease with predisposition to spontaneous fractures, retroperitoneal or mediastinal fibrosis, Peyronie disease, Riedel thyroiditis, hypothyroidism, and retro-orbital pseudotumor. The most ominous complication is cholangiocarcinoma. While the increased risk of developing hepatocellular cancer has not been demonstrated in precirrhotic cases, hepatocellular carcinoma (HCC) does occur in approximately 2% of advanced cirrhotic cases. ⁶ As liver disease progresses to end stage, portal hypertension develops, leading to peristomal varices in patients who have undergone colectomy for ulcerative colitis.

The median reported survival time in patients with primary sclerosing cholangitis is 10 to 12 years from the time of diagnosis. Surgical management of precirrhotic patients involves resection of the entire extrahepatic biliary tree, including the hepatic duct bifurcation. Intrahepatic duct dilatation, with or without stenting, leads to a longer interval of symptom improvement than does nonoperative management. These interventions may delay but do not prevent the eventual development of cirrhosis. Once cirrhosis occurs, liver transplantation is the best treatment option. ⁷ The timing of transplantation is important for improving survival, decreasing morbidity, and decreasing overall related medical costs. There is a growing tendency at many medical centers to perform transplantation earlier in the course of the disease, in view of the poorer outcome with continued deterioration and the increasing risk of cholangiocarcinoma over time. Natural history models have been proposed that help to determine the optimal timing for liver transplantation, as well as predict patient outcome. ⁸ One such model, which has become the gold standard, was developed by the Mayo Clinic and employs the presence of variceal bleeding, bilirubin, albumin, and aspartate aminotransferase levels to assess disease severity and predict outcome of liver transplantation. ⁹

SUMMARY

Primary sclerosing cholangitis is a chronic disease that eventually leads to cirrhosis and death. Sonography, CT, ERCP, and MRI can aid the clinician in achieving an early diagnosis. There are several treatment options available that can delay the inevitable, and early diagnosis can lead to decreased morbidity and mortality. Until a cure is found, early diagnosis remains the key to providing these patients with the best quality of life for the longest period of time.