Primary biliary cirrhosis

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{{#if: | {{#if: | {{#if: K74.3| {{#if: 571.6| {{#if: | {{#if: | {{#if: 10615| {{#if: | {{#if: med| {{#if: D008105| {{#if: |
Primary biliary cirrhosis
Classification & external resources
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ICD-10 K74.3}}
ICD-9 571.6}}
ICD-O: }}
OMIM [3] }}
DiseasesDB 10615 }}
MedlinePlus [4] }}
eMedicine search | topic list | med/223 }} }}
MeSH D008105 }}
MeSH {{{MeshNumber}}}}}

Primary biliary cirrhosis is an autoimmune disease of the liver marked by the slow progressive destruction of the small bile ducts (bile canaliculi) within the liver. When these ducts are damaged bile builds up in the liver (cholestasis) and over time damages the tissue. This can lead to scarring, fibrosis, cirrhosis, and ultimately liver failure. 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 not less than 9 to 1, women to men (reference: Medical care of the Liver Trasplant Patient, 3rd Edition published 2006, editied by Paul G. Killenberg, page 155).

Contents

Signs and symptoms

The following signs may be present in PBC:

Diagnosis

To diagnose PBC, distinctions should be established from other conditions with similar symptoms, such as autoimmune hepatitis or primary sclerosing cholangitis (PSC).

Diagnostic blood tests include:

Abdominal ultrasound or a CT scan is usually performed to rule out blockage to the bile ducts. Previously most suspected sufferers underwent a liver biopsy, and - if uncertainty remained - endoscopic retrograde cholangiopancreatography (ERCP, an endoscopic investigation of the bile duct). 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, and to a lessor degree anti-p62 antibodies correlate with progression toward end stage liver failure. Anti-centromere antibodies correlate with developing portal hypertension.[1]. Anti-np62[2] 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 damage. Granulomas are often detected in this stage.
  • Stage 2 - Periportal Stage: Enlarged triads; periportal fibrosis and/or inflammation. 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, 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 of bone) which also has increases in Alkaline phosphatase is the Gamma-glutamyl trans peptidase test (GGTP). An increase in GGTP could indicate presence of Primary Biliary Cirrhosis. 57% of patients with acute liver failure have anti-transglutaminase antibodies[3] suggesting a role of gluten sensitivity in primary biliary cirrhosis, and primary biliary cirrhosis is considerable more common in gluten sensitive enteropathy than the normal population.[4][5] In some cases of disease protein expression may cause an immune tolerance failure, as might be the case with gp210 and p62, nuclear pore proteins. Gp210 has increased expression in the bile duct of anti-gp210 positive patients.[6] 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) is the most frequently used treatment. This helps reduce the cholestasis and improves blood test results (liver function tests). It has a minimal effect of 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 (a bile acid sequestrant) 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 beverages 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 not less than 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. (reference: Medical care of the Liver Trasplant Patient, 3rd Edition published 2006, editied by Paul G. Killenberg, page 155).

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 (reference: Medical care of the Liver Trasplant Patient, 3rd Edition published 2006, editied by Paul G. Killenberg, page 429).

References

Medical

  • Online 'Mendelian Inheritance in Man' (OMIM) {{#if: |{{{2}}} - }}109720
  • M. Eric Gershwin, John M. Vierling, Michael P. Manns, eds. Liver Immunology. Philadelphia, Pa.: Hanley and Belfus, 2003. ISBN 1-56053-499-0. (State of the art; technical.)
  • Marshall M. Kaplan, and M. Eric Gershwin, "Primary Biliary Cirrhosis", New Engl. J. of Medicine, 353:1261-1273 September 22, 2005 Number 12 . Review article
  • Carlo Selmi, Ross L. Coppel, and M. Eric Gershwin, "Primary Biliary Cirrhosis", in Noel R. Rose, Ian R. Mackey, eds, The Autoimmune Diseases, 4th edition, Academic Press, 2006

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. her webpage.
  • Howard J. Worman. The Liver Disorders Sourcebook, McGraw-Hill, 1999, ISBN 0-7373-0090-6.

Primary literature

  1. ↑ {{#if:Nakamura M, Kondo H, Mori T, et al 
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     |Nakamura M, Kondo H, Mori T, et al
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}}{{#if:
 |[{{{url}}} Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis]
 |Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis

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    }}{{#if:10.1002/hep.21472 

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    }}{{#if:17187436 

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  2. ↑ {{#if:Nesher G, Margalit R, Ashkenazi YJ |{{#if: |[[{{{authorlink}}}|{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Nesher G, Margalit R, Ashkenazi YJ }}]] |{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Nesher G, Margalit R, Ashkenazi YJ }} }} }}{{#if:Nesher G, Margalit R, Ashkenazi YJ |{{#if: | ; {{{coauthors}}} }} }}{{#if: | ({{{date}}}) |{{#if:2001 |{{#if: | ({{{month}}} 2001) | (2001) }} }} }}{{#if:Nesher G, Margalit R, Ashkenazi YJ | . }}{{#if:Nesher G, Margalit R, Ashkenazi YJ2001 | }}{{#ifeq: | no | | {{#if: |“|"}} }}{{#if: |[{{{url}}} Anti-nuclear envelope antibodies: Clinical associations] |Anti-nuclear envelope antibodies: Clinical associations }}{{#ifeq: | no | | {{#if:|”|"}} }}{{#if: | (in {{{language}}}) }}{{#if: | ({{{format}}}) }}{{#if:Semin. Arthritis Rheum. |. Semin. Arthritis Rheum. }}{{#if:30 | 30 }}{{#if:5 | (5) }}{{#if:313-20 |: 313-20 }}{{#if: |. {{#if: |{{{location}}}: }}{{{publisher}}} }}{{#if:10.1053/sarh.2001.20266 |. doi:10.1053/sarh.2001.20266 }}{{#if: |. ISSN {{{issn}}} }}{{#if:11303304 |. PMID 11303304 }}{{#if: |. Bibcode: {{{bibcode}}} }}{{#if: |. OCLC {{{oclc}}} }}{{#if: |. {{{id}}} }}{{#if: |. Retrieved on [[{{{accessdate}}}]]{{#if: | , [[{{{accessyear}}}]] }} }}{{#if: | Retrieved on {{{accessmonthday}}}, {{{accessyear}}} }}{{#if: | Retrieved on {{{accessdaymonth}}} {{{accessyear}}} }}{{#if: |. [{{{laysummary}}} Lay summary]{{#if: | – {{{laysource}}}}} }}{{#if: | ([[{{{laydate}}}]]) }}.{{#if: | “{{{quote}}}” }}
  3. ↑ {{#if:Leung PS, Rossaro L, Davis PA, et al |{{#if: |[[{{{authorlink}}}|{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Leung PS, Rossaro L, Davis PA, et al }}]] |{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Leung PS, Rossaro L, Davis PA, et al }} }} }}{{#if:Leung PS, Rossaro L, Davis PA, et al |{{#if: | ; {{{coauthors}}} }} }}{{#if: | ({{{date}}}) |{{#if:2007 |{{#if: | ({{{month}}} 2007) | (2007) }} }} }}{{#if:Leung PS, Rossaro L, Davis PA, et al | . }}{{#if:Leung PS, Rossaro L, Davis PA, et al2007 | }}{{#ifeq: | no | | {{#if: |“|"}} }}{{#if: |[{{{url}}} Antimitochondrial antibodies in acute liver failure: Implications for primary biliary cirrhosis] |Antimitochondrial antibodies in acute liver failure: Implications for primary biliary cirrhosis }}{{#ifeq: | no | | {{#if:|”|"}} }}{{#if: | (in {{{language}}}) }}{{#if: | ({{{format}}}) }}{{#if: |. ' }}{{#if: | ' }}{{#if: | () }}{{#if: |: }}{{#if: |. {{#if: |{{{location}}}: }}{{{publisher}}} }}{{#if:10.1002/hep.21828 |. doi:10.1002/hep.21828 }}{{#if: |. ISSN {{{issn}}} }}{{#if:17657817 |. PMID 17657817 }}{{#if: |. Bibcode: {{{bibcode}}} }}{{#if: |. OCLC {{{oclc}}} }}{{#if: |. {{{id}}} }}{{#if: |. Retrieved on [[{{{accessdate}}}]]{{#if: | , [[{{{accessyear}}}]] }} }}{{#if: | Retrieved on {{{accessmonthday}}}, {{{accessyear}}} }}{{#if: | Retrieved on {{{accessdaymonth}}} {{{accessyear}}} }}{{#if: |. [{{{laysummary}}} Lay summary]{{#if: | – {{{laysource}}}}} }}{{#if: | ([[{{{laydate}}}]]) }}.{{#if: | “{{{quote}}}” }}
  4. ↑ {{#if:Logan RF, Ferguson A, Finlayson ND, Weir DG |{{#if: |[[{{{authorlink}}}|{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Logan RF, Ferguson A, Finlayson ND, Weir DG }}]] |{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Logan RF, Ferguson A, Finlayson ND, Weir DG }} }} }}{{#if:Logan RF, Ferguson A, Finlayson ND, Weir DG |{{#if: | ; {{{coauthors}}} }} }}{{#if: | ({{{date}}}) |{{#if:1978 |{{#if: | ({{{month}}} 1978) | (1978) }} }} }}{{#if:Logan RF, Ferguson A, Finlayson ND, Weir DG | . }}{{#if:Logan RF, Ferguson A, Finlayson ND, Weir DG1978 | }}{{#ifeq: | no | | {{#if: |“|"}} }}{{#if: |[{{{url}}} Primary biliary cirrhosis and coeliac disease: an association?] |Primary biliary cirrhosis and coeliac disease: an association? }}{{#ifeq: | no | | {{#if:|”|"}} }}{{#if: | (in {{{language}}}) }}{{#if: | ({{{format}}}) }}{{#if:Lancet |. Lancet }}{{#if:1 | 1 }}{{#if:8058 | (8058) }}{{#if:230-3 |: 230-3 }}{{#if: |. {{#if: |{{{location}}}: }}{{{publisher}}} }}{{#if: |. doi:[1] }}{{#if: |. ISSN {{{issn}}} }}{{#if:74661 |. PMID 74661 }}{{#if: |. Bibcode: {{{bibcode}}} }}{{#if: |. OCLC {{{oclc}}} }}{{#if: |. {{{id}}} }}{{#if: |. Retrieved on [[{{{accessdate}}}]]{{#if: | , [[{{{accessyear}}}]] }} }}{{#if: | Retrieved on {{{accessmonthday}}}, {{{accessyear}}} }}{{#if: | Retrieved on {{{accessdaymonth}}} {{{accessyear}}} }}{{#if: |. [{{{laysummary}}} Lay summary]{{#if: | – {{{laysource}}}}} }}{{#if: | ([[{{{laydate}}}]]) }}.{{#if: | “{{{quote}}}” }}
  5. ↑ {{#if:Volta U, Rodrigo L, Granito A, et al |{{#if: |[[{{{authorlink}}}|{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Volta U, Rodrigo L, Granito A, et al }}]] |{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Volta U, Rodrigo L, Granito A, et al }} }} }}{{#if:Volta U, Rodrigo L, Granito A, et al |{{#if: | ; {{{coauthors}}} }} }}{{#if: | ({{{date}}}) |{{#if:2002 |{{#if: | ({{{month}}} 2002) | (2002) }} }} }}{{#if:Volta U, Rodrigo L, Granito A, et al | . }}{{#if:Volta U, Rodrigo L, Granito A, et al2002 | }}{{#ifeq: | no | | {{#if: |“|"}} }}{{#if: |[{{{url}}} Celiac disease in autoimmune cholestatic liver disorders] |Celiac disease in autoimmune cholestatic liver disorders }}{{#ifeq: | no | | {{#if:|”|"}} }}{{#if: | (in {{{language}}}) }}{{#if: | ({{{format}}}) }}{{#if:Am. J. Gastroenterol. |. Am. J. Gastroenterol. }}{{#if:97 | 97 }}{{#if:10 | (10) }}{{#if:2609-13 |: 2609-13 }}{{#if: |. {{#if: |{{{location}}}: }}{{{publisher}}} }}{{#if: |. doi:[2] }}{{#if: |. ISSN {{{issn}}} }}{{#if:12385447 |. PMID 12385447 }}{{#if: |. Bibcode: {{{bibcode}}} }}{{#if: |. OCLC {{{oclc}}} }}{{#if: |. {{{id}}} }}{{#if: |. Retrieved on [[{{{accessdate}}}]]{{#if: | , [[{{{accessyear}}}]] }} }}{{#if: | Retrieved on {{{accessmonthday}}}, {{{accessyear}}} }}{{#if: | Retrieved on {{{accessdaymonth}}} {{{accessyear}}} }}{{#if: |. [{{{laysummary}}} Lay summary]{{#if: | – {{{laysource}}}}} }}{{#if: | ([[{{{laydate}}}]]) }}.{{#if: | “{{{quote}}}” }}
  6. ↑ {{#if:Nakamura M, Takii Y, Ito M, et al |{{#if: |[[{{{authorlink}}}|{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Nakamura M, Takii Y, Ito M, et al }}]] |{{#if: |{{{last}}}{{#if: |, {{{first}}} }} |Nakamura M, Takii Y, Ito M, et al }} }} }}{{#if:Nakamura M, Takii Y, Ito M, et al |{{#if: | ; {{{coauthors}}} }} }}{{#if: | ({{{date}}}) |{{#if:2006 |{{#if: | ({{{month}}} 2006) | (2006) }} }} }}{{#if:Nakamura M, Takii Y, Ito M, et al | . }}{{#if:Nakamura M, Takii Y, Ito M, et al2006 | }}{{#ifeq: | no | | {{#if: |“|"}} }}{{#if: |[{{{url}}} Increased expression of nuclear envelope gp210 antigen in small bile ducts in primary biliary cirrhosis] |Increased expression of nuclear envelope gp210 antigen in small bile ducts in primary biliary cirrhosis }}{{#ifeq: | no | | {{#if:|”|"}} }}{{#if: | (in {{{language}}}) }}{{#if: | ({{{format}}}) }}{{#if:J. Autoimmun. |. J. Autoimmun. }}{{#if:26 | 26 }}{{#if:2 | (2) }}{{#if:138-45 |: 138-45 }}{{#if: |. {{#if: |{{{location}}}: }}{{{publisher}}} }}{{#if:10.1016/j.jaut.2005.10.007 |. doi:10.1016/j.jaut.2005.10.007 }}{{#if: |. ISSN {{{issn}}} }}{{#if:16337775 |. PMID 16337775 }}{{#if: |. Bibcode: {{{bibcode}}} }}{{#if: |. OCLC {{{oclc}}} }}{{#if: |. {{{id}}} }}{{#if: |. Retrieved on [[{{{accessdate}}}]]{{#if: | , [[{{{accessyear}}}]] }} }}{{#if: | Retrieved on {{{accessmonthday}}}, {{{accessyear}}} }}{{#if: | Retrieved on {{{accessdaymonth}}} {{{accessyear}}} }}{{#if: |. [{{{laysummary}}} Lay summary]{{#if: | – {{{laysource}}}}} }}{{#if: | ([[{{{laydate}}}]]) }}.{{#if: | “{{{quote}}}” }}

See also

External links

{{#if:|}}{{#if:Esophagitis - GERD - Achalasia - Boerhaave syndrome - Nutcracker esophagus - Zenker's diverticulum - Mallory-Weiss syndrome - Barrett's esophagus|{{#if:|{{#ifeq:{{#if:EsophagusStomach/
duodenumHerniaNoninfective enteritis and colitisOther intestinalLiver/hepatitisAccessory digestiveOther/general|false|true}}|true|}}}}{{#if:Esophagus|}}{{#if:|}}}}{{#if:Peptic (gastric/duodenal) ulcer - Gastritis - Gastroenteritis - Duodenitis - Dyspepsia - Pyloric stenosis - Achlorhydria - Gastroparesis - Gastroptosis - Portal hypertensive gastropathy|{{#if:Stomach/
duodenum|}}}}{{#if:Inguinal (Indirect, Direct) - Femoral - Umbilical - Incisional - Diaphragmatic - Hiatus|{{#if:Hernia|}}}}{{#if:IBD (Crohn's, Ulcerative colitis) - noninfective gastroenteritis|{{#if:Noninfective enteritis and colitis|}}}}{{#if:vascular (Abdominal angina, Mesenteric ischemia, Ischemic colitis, Angiodysplasia) - Ileus/Bowel obstruction (Intussusception, Volvulus) - Diverticulitis/Diverticulosis - IBS
other functional intestinal disorders (Constipation, Diarrhea, Megacolon/Toxic megacolon, Proctalgia fugax) - Anal fissure/Anal fistula - Anal abscess - Rectal prolapse - Proctitis (Radiation proctitis)|{{#if:Other intestinal|}}}}{{#if:Alcoholic liver disease - Liver failure (Acute liver failure) - Cirrhosis - PBC - NASH - Fatty liver - Peliosis hepatis - Portal hypertension - Hepatorenal syndrome|{{#if:Liver/hepatitis|}}}}{{#if:Gallbladder (Gallstones, Choledocholithiasis, Cholecystitis, Cholesterolosis, Rokitansky-Aschoff sinuses)

Biliary tree (Cholangitis, Cholestasis/Mirizzi's syndrome, PSC, Biliary fistula, Ascending cholangitis)

Pancreas (Acute pancreatitis, Chronic pancreatitis, Pancreatic pseudocyst, Hereditary pancreatitis)|{{#if:Accessory digestive|}}}}{{#if:Appendicitis - Peritonitis (Spontaneous bacterial peritonitis) Malabsorption (celiac, Tropical sprue, Blind loop syndrome, Whipple's) postprocedural:Gastric dumping syndrome - Postcholecystectomy syndromebleeding:Hematemesis - Melena - Gastrointestinal bleeding (Upper, Lower)|{{#if:Other/general|}}}}{{#if:See also congenital|{{#if:|}}}}{{#if:|{{#if:|}}}}{{#if:|{{#if:|}}}}{{#if:|{{#if:|}}}}{{#if:|{{#if:|}}}}{{#if:|{{#if:|}}}}{{#if:|{{#if:|}}}}{{#if:|{{#if:|}}}}{{#if:|{{#if:|}}}}{{#if:|{{#if:|}}}}{{#if:|{{#if:|}}}}{{#if:|{{#if:|}}}}{{#if:|}}
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}} }}
Digestive system - Gastroenterology (primarily K20-K93, 530-579)
EsophagusEsophagitis - GERD - Achalasia - Boerhaave syndrome - Nutcracker esophagus - Zenker's diverticulum - Mallory-Weiss syndrome - Barrett's esophagus
Stomach/
duodenum		Peptic (gastric/duodenal) ulcer - Gastritis - Gastroenteritis - Duodenitis - Dyspepsia - Pyloric stenosis - Achlorhydria - Gastroparesis - Gastroptosis - Portal hypertensive gastropathy
HerniaInguinal (Indirect, Direct) - Femoral - Umbilical - Incisional - Diaphragmatic - Hiatus
Noninfective enteritis and colitisIBD (Crohn's, Ulcerative colitis) - noninfective gastroenteritis
Other intestinalvascular (Abdominal angina, Mesenteric ischemia, Ischemic colitis, Angiodysplasia) - Ileus/Bowel obstruction (Intussusception, Volvulus) - Diverticulitis/Diverticulosis - IBS
other functional intestinal disorders (Constipation, Diarrhea, Megacolon/Toxic megacolon, Proctalgia fugax) - Anal fissure/Anal fistula - Anal abscess - Rectal prolapse - Proctitis (Radiation proctitis)
Liver/hepatitisAlcoholic liver disease - Liver failure (Acute liver failure) - Cirrhosis - PBC - NASH - Fatty liver - Peliosis hepatis - Portal hypertension - Hepatorenal syndrome
Accessory digestiveGallbladder (Gallstones, Choledocholithiasis, Cholecystitis, Cholesterolosis, Rokitansky-Aschoff sinuses)

Biliary tree (Cholangitis, Cholestasis/Mirizzi's syndrome, PSC, Biliary fistula, Ascending cholangitis)

Pancreas (Acute pancreatitis, Chronic pancreatitis, Pancreatic pseudocyst, Hereditary pancreatitis)
Other/generalAppendicitis - Peritonitis (Spontaneous bacterial peritonitis)

Malabsorption (celiac, Tropical sprue, Blind loop syndrome, Whipple's)

postprocedural: Gastric dumping syndrome - Postcholecystectomy syndrome

bleeding: Hematemesis - Melena - Gastrointestinal bleeding (Upper, Lower)
See also congenital
]]de:Primär biliäre Zirrhose

pl:Pierwotna marskość żółciowa wątroby sv:primär biliär cirrhos

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