PSC--- Diagnosis PART 1

[Guest guest]

I know this article is very long, but it just

came out this week and I knew you would want to read it. Because you must be registered to view it,

I’m going to make it easy and post it in 3 parts. Several of the things we have been

discussing the last two weeks are addressed here. Dr Lindor is a highly respected specialist

in PSC. Barb in Texas

Primary

Sclerosing Cholangitis -- Approach to Diagnosis

Posted 04/25/2007 - Ian L. Steele, MD; Levy, MD; D. Lindor, MD

Introduction

Primary sclerosing cholangitis (PSC) is a

progressive disease of the biliary tract characterized by diffuse inflammation

and fibrosis of both intra- and extrahepatic bile ducts. According

to population-based studies, its prevalence is estimated at 1-10 per 100,000

persons in the United States.

Disease progression is slow and

highly variable, but eventually culminates in cirrhosis and complications

related to portal hypertension, with a 10-year survival of approximately 65%. Problems more specific to PSC can also

develop, such as recurrent ascending cholangitis and

cholangiocarcinoma.

Although

neither the etiology nor the pathogenesis of PSC is well understood, PSC is

thought to be an immune-mediated process and is indeed associated with other

autoimmune diseases. The vast majority of PSC cases

occur in the setting of inflammatory bowel disease (IBD) and its association

with IBD is well recognized, especially ulcerative colitis. Although

PSC occurs in approximately 5% of all patients with ulcerative colitis, up to

75% of those with PSC will have associated ulcerative colitis.

It can be

extremely difficult to diagnose PSC with confidence, particularly outside of

tertiary care centers. This article uses case

scenarios to illustrate the diagnostic process in PSC, and follows with a

review of the current understanding of how clinical presentation, laboratory

tests, endoscopy, radiology, and histology facilitate

the diagnosis of PSC.

Case 1

A

19-year-old white man was found to have abnormal serum liver biochemistry test

results 3 years ago when he was first diagnosed as having ulcerative colitis. He denied any previous transfusions, gallstone disease,

intravenous drug use, tattoos, or significant alcohol consumption. The patient had no family history of liver disease and,

with the exception of his ulcerative colitis, he reported that he was healthy. Even after stopping all medications, his liver function

test results remained abnormal. His laboratory studies

were significant for increased serum alkaline phosphatase

(ALP) and aminotransferase levels elevated to 3 times

the upper limit of normal. His bilirubin

level was normal (< 1 mg/dL). Endoscopic

retrograde cholangiopancreatography (ERCP) was

performed and showed multiple stenoses and

dilatations throughout the intrahepatic biliary system, with a pruning type

pattern. The common bile duct and extrahepatic portion

of the common hepatic duct appeared normal, without strictures. These biliary findings coupled with the presence of

inflammatory bowel disease (IBD) and the absence of any alternative etiology

led to a confident diagnosis of PSC.

Case 2

A

47-year-old white woman was found to have abnormal liver function test results

during a routine health maintenance examination. She

had always been asymptomatic and denied any social risk factors for acquired

liver disease. Laboratory studies showed the

following: serum aspartate aminotransferase

(AST), 68 U/mL (normal, 10-39 U/mL);

serum alanine aminotransferase

(ALT), 50 U/mL (normal, 10-39 U/mL);

serum total bilirubin, 0.8 mg/dL

(normal, 0.1-1.0 mg/dL); and ALP, 289 U/L (normal,

45-129 U/L). Serologic markers, including antimitochondrial antibody and antinuclear antibody, were

normal, as were immunoglobulins, including IgG4 and

carbohydrate antigen 19-9 (CA19-9). Magnetic resonance

cholangiopancreatography (MRCP) was performed and

showed hepatic ductal dilatation, with no evidence of

mass lesions. The patient subsequently underwent ERCP

at an outside facility, which showed right hepatic ductal

dilatation without visualization of the left hepatic ducts. This

finding was indicative for obstruction, and malignancy could not be ruled out. Therefore, the patient was referred to our institution for

tumor resection. A repeat MRCP was performed and

showed intrahepatic ductal dilatation with tortuous

and diffuse dilatation most consistent with PSC. Focal

obstruction at the confluence of right and left hepatic ducts was still

indicative for a Klatskin tumor. However,

repeat ERCP showed tight strictures of the left hepatic duct and the first

division of the right hepatic duct. Several smaller

strictures were noted in the smaller intrahepatic ducts. Biopsies

and cytology specimens obtained during this ERCP showed no evidence of

malignancy. This patient has been observed for 1 year

and her benign course corroborated a diagnosis of PSC.

Case 1

illustrates the classic patient with PSC: a young male with history of

ulcerative colitis who is found to have a cholestatic

pattern on serum liver biochemistry measurement. Indeed,

up to 70% of patients with PSC are male, with the mean age of 40 years at time

of diagnosis.

Case 2

demonstrates the diagnostic challenge of PSC because of its varying clinical

presentation. Approximately 15% to 40% of patients

with PSC are asymptomatic. Despite the lack of

symptoms, these patients have a decreased life expectancy compared with the

general population. This may be due to the fact that

up to 17% of asymptomatic patients are found to have cirrhosis at diagnosis.

When present,

symptoms of PSC are vague and nonspecific, and usually are of little benefit in

making the diagnosis. Typically, patients will go

through successive periods of exacerbation and remission, with the most common

complaints consisting of fatigue, right upper quadrant abdominal pain, and

pruritus. Also, particular attention should be paid to

clinical signs of infection, because these patients are at increased risk for

the development of bacterial cholangitis secondary to

biliary obstruction. Jaundice may appear during these

episodes of acute cholangitis, but unrelieved

jaundice usually means progression of the underlying disease.

In general, symptomatic patients are more likely to have advanced liver

disease as well as a decreased survival free of liver transplantation. Finally, although unusual, PSC can present as acute liver

failure. This diagnosis should especially be

considered in individuals with IBD who present with acute liver failure of

indeterminate etiology.

Elevated

serum ALP is the most common laboratory abnormality seen in PSC. ALP levels are often found to be 3 to 10 times the upper

limit of normal, whereas serum AST and ALT levels are typically 2-3 times the

upper limit of normal. The majority of patients with

PSC have a normal serum total bilirubin level. An increase in bilirubin may

result from stricturing due to advanced disease,

acute cholangitis, choledocholithiasis,

or development of malignancy. As with most liver

diseases, altered prothrombin time and serum albumin

levels reflect progression of disease.