An Excellent article on PSC

[Guest guest]

Hi:

This article came from a liver group I belong to. It gets very informative

later in the article.

Judy

From: LiverInfo1@...

Source: The Liver Disorders Sourcebook, 1999

By: Dr. J. Worman, MD

Lowell House, Los Angeles

ISBN: 0737300906

PRIMARY SCLEROSING CHOLANGITIS

DEFINITION AND SYMPTOMS

Primary sclerosing cholangitis is often referred to as PSC. It is a chronic

liver disease characterized by inflammation, destruction, and fibrosis of the

large bile

ducts within the liver, as well as bile ducts outside the liver. The cause

of PSC is unknown, but most investigators agree that it is an autoimmune

disease. Other causes such as infectious agents, toxins or recurrent

infections of the bile ducts, have not been absolutely excluded. PSC's

worldwide prevalance is approximately

3 in 100,000 individuals. About 70% of patients with PSC are men. The

strong association of PSC with inflammatory bowel disease also suggests it is

an

autoimmune disorder. About 75% of patients with PSC have inflammatory bowel

disease, mainly ulcerative colitis.

Inflammation of the larger bile ducts in PSC can lead to strictures or

" narrowing. "

Sometimes bile can get plugged in these strictures resulting in acute and

almost complete blockage of bile flow. In such instances patients will

develop jaundice.

These recurrent bouts of bile duct obstruction, along with destruction of

bile ducts within the liver, eventually lead to biliary cirrhosis in most

patients. Patients with

PSC also often have recurrent episodes of bacterial cholangitis, which is an

infection of the bile ducts with bacteria. Patients with bacterial

cholangitis often

have jaundice, fever, and right upper quadrant abdominal pain. In some

patients, recurrent episodes of bacterial cholangitis, which can be fatal,

are a very significant

problem before cirrhosis develops. In other patients, bacterial cholangitis

is not a frequent problem. Patients with PSC also bear an increased risk of

cholangiocarinoma or primary bile duct cancer. The average survival or time

until

liver transplantation, in patients with PSC is around ten years from time of

diagnosis.

DIAGNOSIS

Many patients with PSC are diagnosed by discovering elevated alkaline

phosphatase and GGTP activities in blood tests taken for other reasons. This

testing may be part of an evaluation for inflammatory bowel disease, from

which most patients with PSC also suffer. Some patients present with itching

(pruritus),

jaundice (yellowing of skin and whites of eyes), fatigue, fever, weight loss,

or signs of complications from cirrhosis. Others present for the first time

with signs and symptoms of bacterial cholangitis such as fever, chills, and

right upper quadrant

abdominal pain.

Blood tests for PSC virtually always indicate elevated akaline phosphatase

and GGTP activities with lesser or no elevations in the aminotransferase

activities.

Early in the course of disease, the bilirubin concentration is usually normal

or slightly elevated but it becomes markedly elevated late in the course of

disease.

Large fluctuations in blood bilirubin concentrations can also occur, even

early in the disease, as a result of intermittent bile duct obstructions or

bacterial cholangitis.

Both albumin concentration and prothrombin time are normal in the disease's

early stage. Later, when cirrhosis develops, albumin concentration falls and

prothrombin

time can be prolonged. The prothrombin time can also be prolonged prior to

the development of cirrhosis secondary to decreased Vitamin K absorption, in

which case it will correct with injection of Vitamin K.

Immunological abnormalities are often, but not invariably detectable in

patients with

PSC. None of them is specific to the dignosis. About 30% of affected

individuals have elevated blood gamma-globulin concentrations and about half

have elevated total blood IgM concentrations. About 50% of patient's have a

particular type of autoantibody known as antineutrophil cytoplasmic

antibodies or ANCA. These can

also be detected in patients with inflammatory bowel disease without PSC. In

PSC and inflammatory bowel disease, the ANCA are different than the classical

ANCA found in patients with certain vasculitic diseases. Some patients with

PSC may also have antismooth muscle or antinuclear antibodies.

Diagnosis of PSC is most reliably made by endoscopic retrograde

cholangiopancreatography (ERCP). The findings include strictures and

dilatations of the medium-sized and large bile ducts inside and outside the

liver. The characteristic pattern is often described as " beads on a string "

caused by the

alternating widening and narrowing of the bile ducts. Liver biopsy in PSC is

usually

confirmatory, but rarely diagnostic. Sometimes a very characteristic finding

known as an " onion skin " lesion (layers of fibrosis tissue surrounding a bile

duct) is seen on liver biopsy. Liver biopsy in PSC is also important in

determining if the patient has cirrhosis.

Secondary causes of sclerosing cholangitis must be ruled out when making the

diagnosis of PSC. Causes of secondary sclerosing cholangitis include drugs,

bile duct cancers, and past biliary tree surgery. Infections of the bile

ducts with cytomegalovirus (CMV) and crytosporidia in patients with AIDS can

also result in a picture similar to PSC. The causes of secondary sclerosing

cholangitis can usually be eliminated based on patient history, physical

examination and appropriate laboratory tests.

TREATMENT AND FOLLOW-UP

Current medical therapy does not have a significant impact on PSC. Ursodiol

(Actigall or Urso) improves laboratory test results but studies have

demonstrated that is does not prolong survival until liver transplantation is

necessary. Itching can

be treated with bile acid-binding resins such as cholestyramine and the opioid

antagonist naltrexone. Deficiencies in fat-soluable vitamins, such as

vitamin K and vitamin D are treated by supplementation.

Episodes of bacterial cholangitis can be life threatening, and immediate

antibiotic

therapy in the hospital is necessary. There may be some role in dilatation

of dominant bile duct strictures by ERCP in some cases of PSC, but there have

been no controlled trials proving that this is effective. If such a

procedure is recommended a physician with considerable experience in treating

patients with PSC should be consulted. Inappropriate or improperly

procedures to dilate ducts can be dangerous and lead to additional damage,

worsening the patient's prognosis. As there is an increased incidence of

cholangiocarcinoma in patients with PSC this should always be suspected,

especially in patients with

long-standing disease whose condition worsens. Therefore, ERCP or CAT scan

to look for bile duct cancer may be necessary in a patient whose condition

deteriorates.

Liver transplantation is highly effective in the treatment of patients with

advanced liver disease caused by PSC. Indictations for liver transplantation

are complications of cirrhosis. In some cases, patients with PSC and

recurrent,

life-threatening episodes of bacterial cholangitis warrant considerations for

liver transplantation.

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