eMedicine Specialties > Radiology > Gastrointestinal

Cholangitis, Primary Sclerosing

Author: Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR, LRCP, Chairman of Medical Imaging, Professor of Radiology, NGHA, King Fahad National Guard Hospital, King Abdulaziz Medical City, Riyadh, Saudi Arabia
Coauthor(s): Sumaira MacDonald, MBChB, PhD, MRCP, FRCR, Lecturer, Sheffield University Medical School; Endovascular Fellow, Sheffield Vascular Institute; Aali J Sheen, MBChB, FRCS, Specialist Registrar, Department of HPB Surgery, Manchester Royal Infirmary Oxford Road Manchester UK
Contributor Information and Disclosures

Updated: Jan 4, 2008

Introduction

Background

Primary sclerosing cholangitis (PSC) is a chronic, progressive, inflammatory disease characterized by fibrosis of the bile ducts. The cause is unknown, but a hypersensitivity reaction is implicated. Patients present with abnormalities of liver function tests and progressive intermittent obstructive jaundice, which may be associated with fever chills, night sweats, pain, and itching. A liver biopsy, endoscopic retrograde cholangiopancreatogram (ERCP), or percutaneous cholangiogram can help achieve diagnosis. The term primary is used to distinguish this condition from bile duct strictures that are secondary to bile duct injury, cholelithiasis, ischemia, and chemical injury.^1,2,3,4,5

See also the following topics in eMedicine:
Cholangitis [Emergency Medicine]
Cholangitis [Gastroenterology]
Primary Sclerosing Cholangitis [Gastroenterology]

See also the following topics in Medscape:
Resource Center Inflammatory Bowel Disease
Resource Center Gallbladder and Biliary Disease
Resource Center Liver & Intestine Transplant
Resource Center Pancreatitis
CME Inflammatory Bowel Disease
CME Therapy for Inflammatory Bowel Disease

Pathophysiology

PSC is a progressive inflammatory disease causing multifocal strictures of both the intrahepatic and extrahepatic bile ducts. The etiology is unknown, but a hypersensitivity reaction is speculated. PSC is often associated with inflammatory bowel disease, such as ulcerative colitis (50-74%) and Crohn disease (13%).⁶ This may account for the genetic predilection. Other associations include cirrhosis, chronic active hepatitis, pericholangitis, steatosis of the liver, pancreatitis, retroperitoneal and mediastinal fibrosis, Peyronie disease, Riedel thyroiditis, hypothyroidism, and retro-orbital pseudotumor.¹

The distribution of biliary system involvement varies, but the common bile duct (CBD) is almost always involved, with or without involvement of the intrahepatic bile ducts and, in some patients, the gallbladder and pancreas. Intrahepatic pigment stones are present in 8% of patients.⁶  

Histologically, the disease can be classified into 4 stages.

• Stage 1: Histologic analysis in stage 1 disease identifies degeneration of the epithelial cells lining the bile ducts associated with inflammatory cell ductal and periportal triad infiltration and scarring.
• Stage 2: Stage 2 disease is characterized by fibrosis, paucity of bile ductules, periportal inflammatory cell infiltration, and piecemeal necrosis of the periportal hepatocytes.
• Stage 3: In stage 3 disease, severe degenerative changes are associated with disappearance of the bile ducts, portal-to-portal fibrous septa, and periportal cholestasis.
• Stage 4: Stage 4 depicts end-stage disease characterized by secondary biliary cirrhosis.

Frequency

United States

Prevalence of the disease in the general population is 1%, as compared with 4% in patients with inflammatory bowel disease.^6,7

Mortality/Morbidity

The course of PSC is prolonged, with progressive jaundice. Death eventually ensues as a result of secondary biliary cirrhosis. The mainstay of treatment remains unsatisfactory, with conventional surgery rarely contemplated and steroid therapy of little use. Avoid surgical procedures, because they may complicate or even preclude future liver transplantation. Prolonged biliary drainage and bile duct dilatation by percutaneous transhepatic biliary stenting or ERCP may provide relief of symptoms. Over the past decade, liver transplantation has emerged as the treatment of choice for patients with end-stage primary sclerosing cholangitis, with many centers reporting 1-year patient and graft survival of 90-97% and 85-88%, respectively. However, specific complications to primary sclerosing cholangitis remain a problem.^8,9

Inflammatory bowel disease complicates approximately 75% of the patients with primary sclerosing cholangitis, with an increased risk of large bowel cancer both pretransplantation and posttransplantation. Furthermore, symptoms from inflammatory bowel disease may become more severe following transplantation prompting proctocolectomy. The results of liver transplantation in patients with primary sclerosing cholangitis complicated by cholangiocarcinoma are disappointing. However, patients who are found to have an incidental cholangiocarcinoma have a low incidence of recurrence. The incidence of both acute and chronic rejection, hepatic artery thrombosis, and subsequent bile duct strictures appears to be higher in patients undergoing liver transplantation for primary sclerosing cholangitis. At least 20% of patients undergoing liver transplantation develop recurrentprimarysclerosingcholangitiswithin5 years.⁸

See also the following related topics in Medscape:
Resource Center Inflammatory Bowel Disease
Resource Center Colorectal Cancer

Race

No racial predilection exists, although the Japanese have reported 2 age peaks in their population at 20-30 years and 50-70 years.^7,10

Sex

Male-to-female ratio is 7:3.⁶

Age

Most patients are younger than 45 years, with an age range of 21-67 years.⁶

Anatomy

The right and left hepatic ducts unite at the porta hepatis to form the common hepatic duct (CHD), which enters the free edge of the lesser omentum. The CHD is joined by the cystic duct, forming the CBD. The main left and right bile ducts lie anterior to the left and right portal veins. The hepatic artery branch usually lies anterior to the right portal vein but is often posterior to the left portal vein. In the liver, the bile ducts run with the portal vein and hepatic artery branches in a common sheath (ie, the portal triad).

The CBD is approximately 8 cm long. It lies in the free edge of the lesser omentum, usually situated anterolateral to the portal vein. It then passes behind the superior part of the second part of duodenum and traverses the head of the pancreas to the end at the duodenal papilla. Behind the duodenum, the CBD lies anterior to the portal vein with the gastroduodenal artery on its left side. Behind the head of the pancreas, the CBD lies on the inferior vena cava. At this point, the CBD receives the common pancreatic duct and turns to the right to enter the duodenum. Just below the porta hepatis, the right branch of the hepatic artery is usually visible passing between the CHD anteriorly and the portal vein posteriorly.

The upper limit of the normal diameter for the CBD is 5 mm; 6-7 mm is regarded as equivocal, and greater than 7 mm usually is pathologic, although bile duct diameter increases in elderly persons and post cholecystectomy. The normal bile duct is 4 mm or less in diameter in 95% of the adult population. In 98% of the adult population, the CHD is 5 mm or less in diameter at the porta hepatis, while at the head of the pancreas, the CBD normally shows slight narrowing. The intrahepatic duct just proximal to the CHD measures 2-3 mm in diameter. The cystic duct lies posterior to the CBD in 95% of the population and anterior to the CBD in 5%. The cystic duct runs in a common sheath with the CBD before their lumina unite; thus, cholecystectomy leaves a variable length of cystic duct in situ.

The CBD is distensible and responsive to fluctuation in prandial bile flow. It enlarges slowly with age at a pace equal to that of the hepatic artery and equal to half that of the portal vein. The duct is slightly larger in children with contracted gallbladder, in contrast to findings in adults. Often, a discrepancy exists between the CBD diameter measurements demonstrated using ERCP and ultrasound (US). This finding has been attributed to the variable cross section of the CBD, which is oval in 70% of patients.

Standard US technique involves measuring the anteroposterior (AP) diameter of the CBD. The AP diameter for oval and round ducts is similar, but the transverse diameter of an oval duct is greater. Thus, a discrepancy is found between ERCP and US findings when AP diameters are measured on US and conventionally transverse diameters are measured on ERCP. In addition, ERCP involves the injection of contrast, during which the biliary system is stretched by the pressure of injection. Since transverse CBD measurements using US correlate better with disease than conventional AP diameters, transverse measurements can be useful in confirming or excluding bile duct dilatation when AP diameters are larger than normal.

Postcholecystectomy CHD and CBD dimensions usually are slightly greater than they are prior to surgery. The normal postcholecystectomy CHD mean diameter is 0.52 cm at the porta hepatis and 0.62 cm at the CBD. Patients with gallstones also tend to have larger extrahepatic bile ducts, although this does not always mean that gallstones are noted within the bile ducts at the same examination.

See also the following related topics in eMedicine:
Gallbladder Disease
Bedside Ultrasonography, Gallbladder Disease
Bladder Stones

See also the following related topics in Medscape:
Resource Center Gallbladder and Biliary Disease
Resource Center Stone Disease

Presentation

Initially, patients come under observation because of abnormal liver function test results demonstrating raised alkaline phosphatase, gamma-glutamyltransferase, and mildly elevated bilirubin levels. All patients eventually present with chronic obstructive jaundice. Patients with known inflammatory bowel disease may present with raised liver enzymes before the onset of jaundice. Of patients with PSC, 10-15% may present with fever, night sweats, chills, itching, and right upper quadrant pain. In 53% of patients, a history of previous biliary surgery and/or recurrent pancreatitis also is found.⁶

Preferred Examination

US is the initial examination of choice in patients presenting with jaundice and right upper quadrant pain. The liver may demonstrate nonspecific abnormalities on US, which infrequently leads to definitive diagnosis. The primary role of US is in helping clinicians make the diagnosis of other bile duct mechanical obstructions, such as gallstones and neoplasia.¹¹

ERCP and percutaneous transhepatic cholangiography (PTC) remain the preferred investigations. Advances in software have improved the diagnostic quality of magnetic resonance cholangiopancreatography (MRCP),¹² and although preliminary studies indicate that MRCP may be sensitive and specific in PSC, larger studies are required before it replaces traditional invasive methods.^{11,13,14,15,16,17,18}

Limitations of Techniques

Both ERCP and PTC are invasive and can potentially cause ascending cholangitis. Recent technical advances have improved MRCP such that third- and fourth-order intrahepatic bile ducts can be resolved, but appearances remain nonspecific.

CT scans also demonstrate nonspecific changes. Indistinguishable features may occur with cholangiocarcinoma and other forms of cholangitis.

Differential Diagnoses

Chemotherapy-induced Cholangitis
Cholangitis, Recurrent Pyogenic
Cholelithiasis
Crohn Disease
Ulcerative Colitis

Other Problems to Be Considered

Sclerosing cholangiocarcinoma
Acute ascending cholangitis
Primary biliary cirrhosis
AIDS-related cholangiopathy

• Search for CME/CE on This Topic »

• Cholangitis (Emergency Medicine)
• Primary Sclerosing Cholangitis (Pediatrics: General Medicine)
• Primary Sclerosing Cholangitis (Gastroenterology)
• Pericholangitis (Gastroenterology)

• Endoscopic and Surgical Management of Primary Sclerosing Cholangitis
• The Medical Management of Primary Sclerosing Cholangitis
• Review: Current Status of Therapy in Autoimmune Liver Disease