Primary biliary cirrhosis

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Primary biliary cirrhosis

Primary biliary cirrhosis is an autoimmune disease

Autoimmune disease

Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body attacks its own cells....
of the liver

Liver

The liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, a few of which are detoxification, protein synthesis, and production of biochemicals necessary for digestion....
marked by the slow progressive destruction of the small bile ducts (bile canaliculi) within the liver. When these ducts are damaged, bile

Bile

Bile or gall is a bitter yellow or green fluid secreted by hepatocytes from the liver of most vertebrates. In many species, bile is stored in the gallbladder between meals and upon eating is discharged into the duodenum where the bile aids the process of digestion of lipids....
builds up in the liver (cholestasis

Cholestasis

In medicine, cholestasis is a condition where bile cannot flow from the liver to the duodenum. Bile formation is a secretory function of the liver....
) and over time damages the tissue. This can lead to scarring, fibrosis

Fibrosis

Fibrosis is the formation or development of excess fibrous connective tissue in an organ or tissue as a reparative or reactive process, as opposed to a formation of fibrous tissue as a normal constituent of an organ or tissue....
and cirrhosis

Cirrhosis

Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver Tissue by fibrous scar tissue as well as regenerative Nodule , leading to progressive loss of liver function....
.It was previously thought to be a rare disease, but more recent studies have shown that it may affect up to 1 in 3-4,000 people; the sex ratio is at least 9:1 (women to men).

following signs may be present in PBC:

iagnose PBC, distinctions should be established from other conditions with similar symptoms, such as autoimmune hepatitis

Autoimmune hepatitis

Anomalous presentation of human leukocyte antigen class II on the surface of hepatocytes, possibly due to genetic predisposition or acute liver infection; causes a cell-mediated immune response against the body's own liver, resulting in autoimmune hepatitis....
or primary sclerosing cholangitis

Primary sclerosing cholangitis

Primary sclerosing cholangitis is a chronic liver disease caused by progressive inflammation and scarring of the bile ducts of the liver. The inflammation impedes the flow of bile to the gut, which can ultimately lead to liver cirrhosis and liver failure....
(PSC).

Diagnostic blood test

Blood test

A blood test is a medical laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a hypodermic needle, or via fingerprick....
s include:

Abdominal ultrasound

Medical ultrasonography

Diagnostic sonography is an ultrasound-based diagnostic medical imaging technique used to visualize subcutaneous body structures including tendons, muscles, joints, vessels and internal organs for possible pathology or lesions....
or a CT scan is usually performed to rule out blockage to the bile ducts.

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Encyclopedia

Primary biliary cirrhosis is an autoimmune disease

Autoimmune disease

Liver

Bile

Cholestasis

Fibrosis

Cirrhosis

Signs and symptoms

The following signs may be present in PBC:

Fatigue
Fatigue (physical)

Fatigue is a weariness caused by exertion. It can describe a range of afflictions, varying from a general state of wikt:lethargy to a specific work-induced burning sensation within one's muscles....
Pruritus (itchy skin)
Jaundice
Jaundice

Jaundice, also known as icterus , is a yellowish discoloration of the skin, the conjunctival membranes over the sclera , and other mucous membranes caused by hyperbilirubinemia ....
(yellowing of the eyes and skin), due to increased bilirubin
Bilirubin

Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is formed from hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile, and its levels are elevated in certain diseases....
in the blood.
Xanthoma
Xanthoma

A xanthoma is a deposition of yellowish cholesterol-rich material in tendons and other body parts in various disease states:* Tendon xanthomas ...
(local collections of cholesterol
Cholesterol

Cholesterol is a lipidic, waxy alcohol found in the cell membranes and transported in the blood plasma of all animals. It is an essential component of mammalian cell membranes where it is required to establish proper membrane permeability and membrane fluidity....
in the skin, especially around the eyes (Xanthelasma
Xanthelasma

Xanthelasma is a sharply demarcated yellowish collection of cholesterol underneath the skin, usually on or around the eyelids. Although not harmful or painful, these minor growths may be disfiguring and can be removed....
))
Complications of cirrhosis
Cirrhosis

Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver Tissue by fibrous scar tissue as well as regenerative Nodule , leading to progressive loss of liver function....
and portal hypertension
Portal hypertension

In medicine, portal hypertension is hypertension in the portal vein and its tributaries.It is often defined as a portal pressure gradient of 5 mm Hg or greater....
:

Fluid retention in the abdomen (ascites
Ascites

In medicine , ascites is an accumulation of fluid in the peritoneal cavity. Although most commonly due to cirrhosis and severe liver disease, its presence can portend other significant medical problems....
)
Hypersplenism
Esophageal varices
Esophageal varices

In medicine , esophageal varices are extremely dilation sub-mucosal veins in the esophagus. They are most often a consequence of portal hypertension, such as may be seen with cirrhosis; patients with esophageal varices have a strong tendency to develop bleeding....
Hepatic encephalopathy
Hepatic encephalopathy

Hepatic encephalopathy is a potentially-reversible neuropsychiatric abnormality in the setting of liver failure, whether chronic , or acute liver failure....
, up to coma, in extreme cases.

Association with an extrahepatic autoimmune disorder such as Rheumatoid arthritis
Rheumatoid arthritis

Rheumatoid arthritis is a chronic, systemic disease inflammation that may affect many tissues and organs, but principally attacks the joints producing a inflammatory synovitis that often progresses to destruction of the articular cartilage and ankylosis of the joints....
or Sjögren's syndrome
Sjögren's syndrome

Sj?gren's syndrome is an autoimmunity in which immune cells attack and destroy the exocrine glands that produce tears and saliva.It is named after Swedish ophthalmology Henrik Sj?gren , who first described it....
(up to 80% incidence).

Diagnosis

To diagnose PBC, distinctions should be established from other conditions with similar symptoms, such as autoimmune hepatitis

Autoimmune hepatitis

Primary sclerosing cholangitis

Blood test

A blood test is a medical laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a hypodermic needle, or via fingerprick....
s include:

Deranged liver function tests (high alkaline phosphatase
Alkaline phosphatase

Alkaline phosphatase is a hydrolase enzyme responsible for removing phosphate groups from many types of molecules, including nucleotides, proteins, and alkaloids....
, elevated AST, ALT)
Presence of certain antibodies: antimitochondrial antibody, antinuclear antibody (the M2-IgG antimitochondrial antibody is the most specific test)

Abdominal ultrasound

Medical ultrasonography

Liver biopsy

Liver biopsy is the biopsy from the liver. It is a medical test that is done to aid medical diagnosis of liver disease, to assess the severity of known liver disease, and to monitor the progress of treatment....
, and - if uncertainty remained - endoscopic retrograde cholangiopancreatography

Endoscopic retrograde cholangiopancreatography

Endoscopic retrograde cholangiopancreatography is a technique that combines the use of endoscopy and fluoroscopy to diagnose and treat certain problems of the bile duct or pancreatic ductal systems....
(ERCP, an endoscopic

Endoscopy

Endoscopy means looking inside and typically refers to looking inside the body for medical reasons using an instrument called an endoscope....
investigation of the bile duct

Bile duct

A bile duct is any of a number of long tube-like structures that carry bile.Bile, required for the digestion of food, is excreted by the liver into passages that carry bile toward the hepatic duct, which joins with the cystic duct to form the common bile duct, which opens into the intestine....
). Now most patients are diagnosed without invasive investigation since the combination of anti-mitochondrial antibodies (see below) and typical (cholestatic) liver function tests are considered diagnostic. However, a liver biopsy is necessary to determine the stage of disease.

Anti-nuclear antibodies appear to be prognostic agents in PBC. Anti-glycoprotein-210 antibodies

Anti-glycoprotein-210 antibodies

Anti-glycoprotein-210 antibodies are directed at nucleoporin 210kDa and are found within primary biliary cirrhosis patients in high frequency....
, and to a lessor degree anti-p62 antibodies

Anti-p62 antibodies

Anti-nucleoporin 62 antibodies are found in a primary biliary cirrhosis. p62 is also more frequent in Stage IV primary biliary cirrhosis and is prognostic for severe disease. The autoantigen is the nucleoporin 62kDA protein....
correlate with progression toward end stage liver failure. Anti-centromere antibodies

Anti-centromere antibodies

Anti-centromere antibodies occur in CREST syndrome and occasionally in systemic scleroderma. They are very rare in other rheumatic conditions and in healthy persons....
correlate with developing portal hypertension.. Anti-np62 and anti-sp100 are also found in association with PBC.

Summary of stages

Stage 1 - Portal Stage: Normal sized triads; portal inflammation, subtle bile duct
Bile duct

A bile duct is any of a number of long tube-like structures that carry bile.Bile, required for the digestion of food, is excreted by the liver into passages that carry bile toward the hepatic duct, which joins with the cystic duct to form the common bile duct, which opens into the intestine....
damage. Granulomas are often detected in this stage.

Stage 2 - Periportal Stage: Enlarged triads; periportal fibrosis
Fibrosis

Fibrosis is the formation or development of excess fibrous connective tissue in an organ or tissue as a reparative or reactive process, as opposed to a formation of fibrous tissue as a normal constituent of an organ or tissue....
and/or inflammation
Inflammation

Inflammation is the complex biological response of Blood vessel tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue....
. Typically characterized by the finding of a proliferation of small bile ducts.

Stage 3 - Septal Stage: Active and/or passive fibrous septa.

Stage 4 - Biliary Cirrhosis: Nodules present; garland or jigsaw pattern.

Etiology

The cause of the disease is unknown at this time, but research indicates that there is an immunological basis for the disease

Disease

A disease or medical condition is an abnormal condition of an organism that impairs bodily functions, associated with specific symptoms and Medical signs....
, making it an autoimmune disorder. Most of the patients (>90%) seem to have anti-mitochondrial antibodies (AMAs) against pyruvate dehydrogenase complex (PDC-E2), an enzyme complex that is found in the mitochondria. In addition, a more specific test to confirm this disease from a bone disorder such as Paget's disease which also has increases in Alkaline phosphatase is the Gamma-glutamyl transpeptidase

Gamma glutamyl transpeptidase

Gamma-glutamyl transferase is primarily a liver enzyme which catalyzes the following chemical reaction:-peptide + an amino acid peptide + 5-L-glutamyl amino acid...
test (GGT). An increase in GGT could indicate presence of Primary Biliary Cirrhosis. 57% of patients with acute liver failure have anti-transglutaminase antibodies

Anti-transglutaminase antibodies

Anti-transglutaminase antibodies are antibodies found more frequently in certain autoimmune diseases. High levels of ATA are found in almost all instances of coeliac disease....
suggesting a role of gluten sensitivity

Gluten sensitivity

Gluten sensitivity encompasses a collection of medical conditions in which gluten has an adverse effect. For individuals with gluten-sensitive enteropathy, removal of gluten generally results in the restoration of Intestinal villus or lower lymphocyte count in the intestine....
in primary biliary cirrhosis, and primary biliary cirrhosis is considerably more common in gluten sensitive enteropathy

Gluten-sensitive enteropathy associated conditions

Gluten-sensitive enteropathy has a wide variety of associated conditions, however the key symptoms are typically restricted to the bowel and associated tissues....
than the normal population. In some cases of disease protein expression may cause an immune tolerance

Immune tolerance

Immune or 'immunological tolerance' is the process by which the immune system does not attack an antigen. It occurs in three forms: central tolerance, peripheral tolerance and acquired tolerance....
failure, as might be the case with gp210

Nucleoporin 210kDa

Nuclear pore glycoprotein-210 is an essential trafficking regulator in the eukaryotic nuclear pore complex. Gp-210 anchors the pore complex to the nuclear membrane....
and p62

Nucleoporin 62

Nucleoporin p62 is a protein complex associated with the nuclear envelope. The p62 protein remains associated with the nuclear pore complex-lamina fraction....
, nuclear pore proteins. Gp210 has increased expression in the bile duct of anti-gp210 positive patients. Both proteins appear to be prognostic of liver failure relative to anti-mitochondrial antibodies.

Therapy

There is no known cure, but medication may slow the progression so that a normal lifespan and quality of life may be attainable for many patients. However, specific treatment for fatigue, which may be invalidating in some patients, is unavailable. Ursodeoxycholic acid (Ursodiol

Ursodiol

Ursodiol, also known as ursodeoxycholic acid and the abbreviation UDCA, is one of the secondary bile acids, which are metabolic byproducts of intestinal bacteria....
) is the most frequently used treatment. This helps reduce the cholestasis and improves blood test results (liver function tests

Liver function tests

Liver function tests , which include liver enzymes, are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a patient's liver....
). It has a minimal effect on symptoms and whether it improves prognosis is controversial. To relieve itching caused by bile acids in circulation, which would normally be removed by the liver, cholestyramine

Cholestyramine

Cholestyramine or colestyramine is a bile acid sequestrant, which binds bile in the gastrointestinal tract to prevent its reabsorption. The resin is a strong anion exchange resin, which means that it can exchange its chloride anions with anionic bile acids in the gastrointestinal tract and bind them strongly in the resin matrix....
(a bile acid sequestrant

Bile acid sequestrant

The bile acid sequestrants are a group of medications used for binding certain components of bile in the gut. They disrupt the enterohepatic circulation of bile acids by sequestering them and preventing their reabsorption from the gut....
) may be prescribed to absorb bile acids in the gut and be eliminated, rather than re-enter the blood stream. As in all liver diseases, alcoholic beverage

Alcoholic beverage

An alcoholic beverage is a drink containing ethanol . Alcoholic beverages are divided into three general classes: beers, wines, and distilled beverage....
s are contraindicated. In advanced cases, a liver transplant, if successful, results in a favourable prognosis.

Multivitamins (esp. Vitamin D) and calcium are also recommended as patients with PBC have poor lipid-dependent absorption of Vitamins A, D, E, K.

Statistics

The female:male ratio is at least 9:1. In some areas of the US and UK the prevalence is estimated to be as high as 1 in 4000. This is much more common than in South America or Africa, which may be due to better recognition in the US and UK. First-degree relatives may have as much as a 500 times increase in prevalence, but there is debate if this risk is greater in the same generation relatives or the one that follows.

After liver transplant, the recurrence rate may be as high as 18% at 5 years, and up to 30% at 10 years. There is no consensus on risk factors for recurrence of the disease.

Medical

(State of the art; technical.)
Review article.*

General

Sanjiv Chopra. The Liver Book: A Comprehensive Guide to Diagnosis, Treatment, and Recovery, Atria, 2002, ISBN 0-7434-0585-4
Melissa Palmer. Dr. Melissa Palmer's Guide to Hepatitis and Liver Disease: What You Need to Know, Avery Publishing Group; Revised edition May 24, 2004, ISBN 1-58333-188-3. .
Howard J. Worman. The Liver Disorders Sourcebook, McGraw-Hill, 1999, ISBN 0-7373-0090-6.

Primary literature

External links

- patients' organisation

(2004)

Many research papers online.