Abstract
Primary sclerosing cholangitis (PSC) is a progressive liver disease characterized by inflammation and fibrosis of the bile ducts, leading to bile duct strictures and cholestasis, which can result in liver fibrosis and cirrhosis. This case study explores recent advancements in the diagnosis and management of PSC, emphasizing the challenges faced by health care providers in early diagnosis and the underutilization of sonography with elastography, as a monitoring tool. This case of a 71-year-old woman with symptoms and laboratory abnormalities, indicative of PSC, highlights the role of sonography and magnetic resonance imaging in the diagnostic process. Despite technological advancements, diagnosing PSC remains challenging and is often delayed until later stages. While magnetic resonance cholangiopancreatography (MRCP) is the current standard for surveillance, this case would suggest an increased use of sonography with elastography. It would offer a cost-effective and patient-centered alternative for monitoring disease progression. Further research is needed to establish guidelines for effective sonographic evaluation in PSC, potentially improving early diagnosis and patient outcomes.
Primary sclerosing cholangitis (PSC) is a progressive disease that causes inflammatory fibrosis of the bile ducts leading to obstruction of bile from the liver and gallbladder into the intestinal tract. Cholestasis associated with biliary obstruction leads to liver fibrosis and eventually cirrhosis. 1 Primary sclerosing cholangitis is often associated with inflammatory bowel disease (IBD), which suggests that PSC may be immune-related.2,3 A review of population-based studies conducted in 2022 found that the incidence and prevalence vary worldwide with a mean incidence of 0.7 per 100 000, a mean prevalence of 10.0 per 100 000, and a rising prevalence across Europe and North America.3,4
Recent improvements in medical imaging and technology have changed the diagnostic process and management of disease in PSC.2,4,5 However, this diagnosis continues to be a challenge for medical providers and is often delayed until later stages of disease.2,5 A case demonstrating high-resolution sonographic and magnetic resonance imaging (MRI) examples is provided. It is important for sonographers to understand the clinical features of PSC and sonographic appearance and to use elastography when available for improved diagnostics.
Case Report
A 71-year-old woman with a history of recent jaundice, elevated liver function tests, and right upper quadrant abdominal pain presented to the sonography department for a right upper quadrant sonographic examination. The patient’s laboratory values showed several abnormalities. The patient’s white blood cell count was 10.67 × 109/L, alanine aminotransferase (ALT) value was 82 U/L, aspartate aminotransferase (AST) was 172 U/L, alkaline phosphatase (ALP) was 439 U/L, and the total bilirubin was 16.3 mg/dL, which were all elevated. The patient had no other relevant clinical history. The sonogram was performed using a EPIQ 7 ultrasound equipment system (Philips Medical, Andover, Massachusetts) and equipped with a 5 MHz curvilinear array transducer.
The abdominal sonogram revealed an irregular gallbladder with a mobile, shadowing, echogenic focus within the gallbladder (See Figure 1). A medium-level echogenic material that was variable with patient position was also visualized within the gallbladder that was thought to be gallbladder sludge (See Figure 1). The gallbladder wall was thickened and irregular, measuring 10.7 mm (See Figure 2). The echogenic focus within the gallbladder measured 2.51 cm in length, 1.88 cm in height, and 2.25 cm in width (See Figure 3). The pancreatic duct was visible and measured 2.6 mm (See Figure 4). Multiple dilated intrahepatic bile ducts were visualized (See Figure 5), and color Doppler was utilized to show that there was no blood flow within the structures (See Figure 6). The common bile duct was dilated and measured 9.39 mm and appeared to have a thickened irregular wall (See Figure 7). At the age of 71, the common bile duct should measure less than 8 mm. The patient presented with a positive Murphy’s sign during the initial sonographic assessment. An incidental finding of a simple cyst of the right kidney was also noted. The official diagnoses made by the interpreting physician included cholecystitis, cholelithiasis, and biliary obstruction.
A longitudinal view of the gallbladder, with the patient in supine position, demonstrated cholelithiasis and gallbladder sludge (see white arrow).
A transverse view of the gallbladder, with the patient in the left lateral decubitus position, indicated a thickened gallbladder wall (see white arrow) and cholelithiasis (note the star).
Dual screen imaging of the longitudinal and transverse gallbladder, with the patient in a left lateral decubitus position, demonstrated the measurement of the stone, within the gallbladder.
A transverse sonographic view of the pancreas demonstrated a prominent pancreatic duct.
This transverse view of the right lobe of the liver demonstrated the presence of dilated intrahepatic ducts. This has been referred to as the “too many tubes” sonographic diagnostic sign.
This transverse view of the right lobe of the liver demonstrates not only the dilated intrahepatic ducts, but with color Doppler these structures are confirmed as ducts and not vessels.
The sagittal sonographic view of the right lobe of the liver demonstrates the dilated common bile duct, with thickened irregular ductal walls.
An MRI examination, with gadolinium contrast, was ordered for more detailed information about the exact location(s) of biliary obstruction for preoperative planning. The MRI showed multiple calculi within the gallbladder (See Figure 8), wall thickening, tandem fusiform stenoses of the common hepatic duct and common bile duct (See Figure 9), and intrahepatic biliary ductal dilatation (See Figure 10). The patient was given an additional diagnosis of sclerosing cholangitis. Treatment included endoscopic retrograde cholangiopancreatography (ERCP), to have a stent placed in the common bile duct and a laparoscopic cholecystectomy.
This axial slice from a magnetic resonance imaging study showed multiple calculi within the gallbladder (see red circle).
An axial slice from a magnetic resonance imaging study showed dilatation, wall thickening and stenosis, of the common bile duct (see arrow).
An axial slice from a magnetic resonance imaging study that showed intrahepatic biliary ductal dilatation (see arrows).
Discussion
The pathophysiology of PSC is not well understood, but has been linked to an environmental exposure that triggers an autoimmune response, in genetically predisposed individuals.6,7 Inflammatory bowel disease has been found in more than 50% of patients with PSC, which have genetic features similar to those with autoimmune diseases.3,6,8 Inflammation of the biliary epithelial cells results in fibrosis of the intra- and extrahepatic bile ducts, which leads to narrowing of the bile duct lumen. 2 Differential diagnoses for PSC include any cause of secondary sclerosing cholangitis, such as cholangiocarcinoma, histiocytosis, autoimmune hepatitis, and HIV syndrome. 8
The clinical presentation of PSC varies depending on severity of disease and ranges from asymptomatic, to signs of advanced liver disease. 4 In early disease, symptoms are rare which is why so many patients are diagnosed in later stages. 2 In many cases, investigation is prompted by abnormal laboratory values during a routine health evaluation or screening in patients with IBD.2,6,8 Liver tests identify cholestasis with elevated ALP and gamma-glutamyl transferase (GGT).2,8 In addition, serum bilirubin, AST, and ALT may also be elevated.2,8 When symptoms develop, they are due to biliary obstruction and include sudden onset of pruritis, jaundice, fever, and abdominal pain.6,8 The presentation of variceal bleeding and abdominal distention, from ascites, indicates the progression to end-stage liver disease.6,8 Patients with IBD often present with abdominal pain, diarrhea, gastrointestinal bleeding, and abnormal liver biochemistry; however, the gastrointestinal bleeding may be caused by IBD or portal hypertension.6,8
The extent of biliary obstruction determines the progression of disease. Many patients with PSC develop dominant strictures, which often trigger the symptoms of biliary obstruction including jaundice, pruritis, and cholangitis.6,8 Patients with PSC are at an increased risk of bacterial cholangitis, especially in cases of dominant stricture or after dilation procedures. 6 Prolonged biliary obstruction causes parenchymal injury, resulting in liver fibrosis, cirrhosis, portal hypertension, and eventually liver failure.1,6,8 Gastroesophageal varices and variceal bleeding are the result of portal hypertension. 8 A common complication of chronic cholestasis is metabolic bone disease, such as osteopenia and osteoporosis.2,8 PSC is a strong risk factor for developing cholangiocarcinoma and gallbladder carcinoma.2,9
The prognosis varies widely for patients with PSC and is better for asymptomatic patients.2,5 The prognosis is based on the stage of disease and the presence of complications.2,5 There are no approved medical therapies for PSC.2,4,6,8 Magnetic resonance cholangiopancreatography (MRCP) is currently used for follow-up to determine progression of liver fibrosis and evaluate for cirrhosis, particularly when a patient has increasingly abnormal liver function tests and/or symptoms. 2 The only definitive treatment for PSC is liver transplantation and outcomes post transplantation are excellent.8,10,11 According to a retrospective study consisting of patients with PSC, who received a liver transplant during January 2010 and December 2021, the 10-year survival rate was 74.6%. 11 The same study found that recurrence rates were low at 7.9% and only occurred in patients with ulcerative colitis, a type of IBD.
Sonography is typically the first imaging technique for evaluation of abnormal liver function tests and its primary role in PSC is to negate other causes of biliary obstruction.2,5,8 Due to the inherent connection between the liver and biliary system, best practices for sonographic imaging protocols include both the liver and biliary system. The sonographic appearance of PSC includes extrahepatic bile duct thickening with or without bile duct dilation and echogenic portal triads. 5 Other than the common hepatic duct, the intrahepatic bile ducts are often not visualized with sonography, unless they are dilated. It is important to note that the normal common bile duct measurement varies with age. Historically, resolution limitations hindered the capability of sonography to be useful in the diagnosis of PSC. In addition, a small percentage of patients with PSC have what is referred to as small duct PSC. This refers to the extrahepatic bile ducts appearing normal while the intrahepatic ducts are affected, but difficult to visualize sonographically. 8 Computed tomography (CT) has the same challenges as sonography in the diagnosis of PSC. Computed tomography may demonstrate bile duct thickening and be useful in negating other causes of biliary obstruction. 5
Endoscopic retrograde cholangiopancreatography along with liver biopsy was previously considered the diagnostic gold standard for detecting PSC. 2 Endoscopic retrograde cholangiopancreatography showed the typical beaded appearance of the bile ducts caused by multifocal strictures.2,5,6 Liver biopsy reveals the classic histological finding of PSC, which is concentric periductal fibrosis called “onion-skin fibrosis.”2,5,6 Due to the risks of such invasive procedures, ERCP and liver biopsy have been replaced by MRCP as a safer method of diagnosis.2,4,5 Endoscopic retrograde cholangiopancreatography is now reserved for therapeutic intervention of significant strictures. 2 Liver biopsy is currently only used for clarification of possible small duct PSC, or when the diagnosis is uncertain. 2
Elastography is emerging as a successful non-invasive technique for determining liver stiffness, which correlates well with the extent of liver fibrosis. 5 Elastography can be performed with sonography and MRI. Since fibrosis in PSC can be patchy, magnetic resonance elastography (MRE) provides better assessment of overall liver fibrosis because of the ability to image larger areas of liver parenchyma. 5 Currently, there are few studies conducted, which utilize sonography, with elastography, specifically for PSC, so best practice protocols have not been established. 1 A study in 2020 compared three different sonography systems’ elastography capabilities with excellent correlation results. 1 Shear wave elastography with gray scale sonography has the added benefit of simultaneous imaging of the liver and surrounding structures. 5 Sonography with elastography is not currently being utilized as an option for the surveillance of patients with PSC, after MRCP.
Conclusion
Primary sclerosing cholangitis is a progressive disease that is difficult to diagnose. The current method of diagnosis and surveillance of advancing liver fibrosis is MRCP. However, sonographic image resolution has greatly improved recently, due to the advent of new image processing techniques which may allow for better visualization of bile duct thickening. Sonographers conducting liver examinations for elevated liver function tests need to be aware of their role in differentiating various causes of biliary obstruction. When dilated bile ducts are visualized without evidence of the cause of obstruction, sonographers should attempt to obtain high-resolution images of the bile ducts to identify the presence of bile duct wall thickening, which can assist medical providers in earlier diagnosis of PSC.
Sonography with elastography is currently being underutilized for evaluation of the progression of liver fibrosis. Because sonography is more cost effective and comfortable for patients than MRI, sonography with elastography has the potential to become a reliable option for the surveillance of patients with PSC. The patchy nature of liver fibrosis in PSC would require multiple elastography sample areas. More research should be conducted to determine guidelines for effective sonographic evaluation for PSC follow-up. Correlation studies with MRE could assist in determining such guidelines.
Footnotes
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