WordNet

of first rank or importance or value; direct and immediate rather than secondary; "primary goals"; "a primary effect"; "primary sources"; "a primary interest"
a preliminary election where delegates or nominees are chosen (同)primary_election
one of the main flight feathers projecting along the outer edge of a birds wing (同)primary feather, primary quill
(astronomy) a celestial body (especially a star) relative to other objects in orbit around it
not derived from or reducible to something else; basic; "a primary instinct"
a chronic disease interfering with the normal functioning of the liver; the major cause is chronic alcoholism (同)cirrhosis of the liver
relating to the bile ducts or the gallbladder

PrepTutorEJDIC

『第一の』,『主要な』 / 『初期の』,『初等の』,初級の / 『根本的な』,基本的な,本来の,直接的な / 《名詞の前にのみ用いて》(回路・コイル・巻き・電流などが)一次の / 原色(三原色の一つ) / 《米》=primary election
肝硬変

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/07/08 03:31:02」(JST)

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Primary biliary cirrhosis, often abbreviated PBC, is an autoimmune disease of the liver^[1]^[2] marked by the slow progressive destruction of the small bile ducts of the liver, with the intralobular ducts (Canals of Hering) affected early in the disease.^[3] When these ducts are damaged, bile builds up in the liver (cholestasis) and over time damages the tissue. This can lead to scarring, fibrosis and cirrhosis. 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 (female to male).^[4]

Signs and symptoms

Individuals with PBC may present with the following:

Fatigue
Pruritus (itchy skin)
Jaundice (yellowing of the eyes and skin), due to increased bilirubin in the blood.
Xanthoma (local collections of cholesterol in the skin, especially around the eyes (xanthelasma))
Complications of cirrhosis and portal hypertension:
- Fluid retention in the abdomen (ascites)
- Hypersplenism
- Esophageal varices
- Hepatic encephalopathy, including coma in extreme cases.
Association with an extrahepatic autoimmune disorder such as rheumatoid arthritis or Sjögren's syndrome (in up to 80% of cases).

Causes

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.

Primary biliary cirrhosis is considerably more common in those with gluten sensitive enteropathy than the normal population.^[5]^[6] 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.^[7] Both proteins appear to be prognostic of liver failure relative to anti-mitochondrial antibodies.

A genetic predisposition to disease has been thought important for some time, as evident by cases of PBC in family members, concordance in identical twins, and clustering of autoimmune diseases. In 2009 a Canadian led group of investigators reported in the New England Journal of Medicine results from the first PBC genome-wide association study.^[8]^[9] This research revealed parts of the IL12 signaling cascade, particularly IL12A and IL12RB2 polymorphisms, to be important in the etiology of the disease in addition to the HLA region. In 2012, two independent PBC association studies increased the total number of genomic regions associated to 26, implicating many genes involved in cytokine regulation such as TYK2, SH2B3 and TNFSF11.^[10]^[11]

In 2003 it was reported that an environmental Gram negative alphabacterium — Novosphingobium aromaticivorans^[12] was strongly associated with this disease. Subsequent reports appear to have confirmed this finding suggesting an aetiological role for this organism.^[13]^[14]^[15] The mechanism appears to be a cross reaction between the proteins of the bacterium and the mitochondrial proteins of the liver cells.^[16] The gene encoding CD101 may also play a role in host susceptibility to this disease.^[17]

Diagnosis

Intermediate magnification micrograph of PBC showing bile duct inflammation and periductal granulomas. Liver biopsy. H&E stain.

Immunofluorescence staining pattern of sp100 antibodies (nuclear dots) and AMA.

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:

Deranged liver function tests (elevated gamma-glutamyl transferase and alkaline phosphatase)
Presence of certain antibodies: antimitochondrial antibody (AMA), antinuclear antibody (ANA)

Abdominal ultrasound or a CT scan is usually performed to rule out blockage to the bile ducts. Most suspected cases have a liver biopsy performed, and if uncertainty remains an endoscopic retrograde cholangiopancreatography or ERCP, where an endoscopic investigation of the bile duct is performed. Most patients now^[when?] are diagnosed without invasive investigation, as 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 lesser degree anti-p62 antibodies, correlate with the disease's progression toward end stage liver failure. Anti-centromere antibodies often correlate with developing portal hypertension.^[18] Anti-np62^[19] and anti-sp100 are also found in association with PBC.

Biopsy

Primary biliary cirrhosis is characterized by interlobular bile duct destruction. Histopathologic findings of primary biliary cirrhosis include the following:^[20]

Inflammation of the bile ducts, characterized by intraepithelial lymphocytes, and
Periductal epithelioid granulomata.

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 puzzle pattern.

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. Specific treatment for fatigue, which may be debilitating in some patients, is limited and currently undergoing trials.

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 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 (a bile acid sequestrant) may be prescribed to absorb bile acids in the gut and be eliminated, rather than re-enter the blood stream. Alternative agents include naltrexone and rifampicin.

To relieve fatigue associated with primary biliary cirrhosis, current studies indicate that Provigil (modafinil) may be effective without damaging the liver.^[21] Though off-patent, the limiting factor in the use of modafinil in the U.S. is cost. The manufacturer, Cephalon, has made agreements with manufacturers of generic modafinil to provide payments in exchange for delaying their sale of modafinil.^[22] The FTC has filed suit against Cephalon alleging anti-competitive behavior.^[23]

Patients with PBC have poor lipid-dependent absorption of Vitamins A, D, E, K.^[24] Appropriate supplementation is recommended when bilirubin is elevated.^[25]

Patients with PBC are at elevated risk of developing osteoporosis^[26] and esophageal varices^[27] as compared to the general population and others with liver disease. Screening and treatment of these complications is an important part of the management of PBC.

As in all liver diseases, excessive consumption of alcohol is contraindicated.

In advanced cases, a liver transplant, if successful, results in a favorable prognosis.

Obeticholic acid is in phase III clinical trials for PBC.^[28]

Epidemiology

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.^[4]

Prognosis

The serum bilirubin level is an indicator of the prognosis of primary biliary cirrhosis, with levels of 2–6 mg/dL having a mean survival time of 4.1 years, 6–10 mg/dL having 2.1 years and those above 10 mg/dL having a mean survival time of 1.4 years.^[29]

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.^[30]

Patients with primary biliary cirrhosis have an increased risk of hepatocellular carcinoma.

History

Addison and Gull in 1851 described the clinical picture of progressive obstructive jaundice in the absence of mechanical obstruction of the large bile ducts. Ahrens et al in 1950 coined the term primary biliary cirrhosis for this disease. The association with anti-mitochondrial antibodies was first reported in 1965.^[31] In 1986, the presence of anti-mitochondrial antibodies as a marker of early, pre-cirrhotic disease was recognised.^[32]

Additional images

Low magnification micrograph of PBC. H&E stain.

References

^ Hirschfield, GM; Gershwin, ME (Jan 24, 2013). "The immunobiology and pathophysiology of primary biliary cirrhosis.". Annual review of pathology 8: 303–30. doi:10.1146/annurev-pathol-020712-164014. PMID 23347352. Cite uses deprecated parameters (help)
^ Dancygier, Henryk (2010). Clinical Hepatology Principles and Practice of. Springer. pp. 895–. ISBN 978-3-642-04509-7. Retrieved 29 June 2010.
^ Saxena R, Theise N (February 2004). "Canals of Hering: recent insights and current knowledge". Semin. Liver Dis. 24 (1): 43–8. doi:10.1055/s-2004-823100. PMID 15085485.
^ ^a ^b Clavien, Pierre-Alain; Killenberg, Paul G. (2006). Medical Care of the Liver Transplant Patient: Total Pre-, Intra- and Post-Operative Management. Wiley-Blackwell. p. 155. ISBN 1-4051-3032-6.
^ Logan RF, Ferguson A, Finlayson ND, Weir DG (1978). "Primary biliary cirrhosis and coeliac disease: an association?". Lancet 1 (8058): 230–3. doi:10.1016/S0140-6736(78)90480-4. PMID 74661.
^ Volta U, Rodrigo L, Granito A, et al. (2002). "Celiac disease in autoimmune cholestatic liver disorders". Am. J. Gastroenterol. 97 (10): 2609–13. doi:10.1111/j.1572-0241.2002.06031.x. PMID 12385447.
^ Nakamura M, Takii Y, Ito M, et al. (2006). "Increased expression of nuclear envelope gp210 antigen in small bile ducts in primary biliary cirrhosis". J. Autoimmun. 26 (2): 138–45. doi:10.1016/j.jaut.2005.10.007. PMID 16337775.
^ Hirschfield GM, Liu X, Xu C, et al. (June 2009). "Primary biliary cirrhosis associated with HLA, IL12A, and IL12RB2 variants". N. Engl. J. Med. 360 (24): 2544–55. doi:10.1056/NEJMoa0810440. PMC 2857316. PMID 19458352.
^ http://www.uk-pbc.com
^ Liu JZ, Almarri MA, Gaffney DJ, et al. (October 2012). "Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis". Nat. Genet. 44 (10): 1137–41. doi:10.1038/ng.2395. PMC 3459817. PMID 22961000.
^ Juran BD, Hirschfield GM, Invernizzi P, et al. (December 2012). "Immunochip analyses identify a novel risk locus for primary biliary cirrhosis at 13q14, multiple independent associations at four established risk loci and epistasis between 1p31 and 7q32 risk variants". Hum. Mol. Genet. 21 (23): 5209–21. doi:10.1093/hmg/dds359. PMC 3490520. PMID 22936693.
^ Selmi C, Balkwill DL, Invernizzi P, et al. (November 2003). "Patients with primary biliary cirrhosis react against a ubiquitous xenobiotic-metabolizing bacterium". Hepatology 38 (5): 1250–7. doi:10.1053/jhep.2003.50446. PMID 14578864.
^ Mohammed JP, Mattner J (July 2009). "Autoimmune disease triggered by infection with alphaproteobacteria". Expert Rev Clin Immunol 5 (4): 369–379. doi:10.1586/ECI.09.23. PMC 2742979. PMID 20161124.
^ Kaplan MM (November 2004). "Novosphingobium aromaticivorans: a potential initiator of primary biliary cirrhosis". Am. J. Gastroenterol. 99 (11): 2147–9. doi:10.1111/j.1572-0241.2004.41121.x. PMID 15554995.
^ Selmi C, Gershwin ME (July 2004). "Bacteria and human autoimmunity: the case of primary biliary cirrhosis". Curr Opin Rheumatol 16 (4): 406–10. doi:10.1097/01.bor.0000130538.76808.c2. PMID 15201604.
^ Mattner J, Savage PB, Leung P, et al. (May 2008). "Liver autoimmunity triggered by microbial activation of natural killer T cells". Cell Host Microbe 3 (5): 304–15. doi:10.1016/j.chom.2008.03.009. PMC 2453520. PMID 18474357.
^ Mohammed JP, Fusakio ME, Rainbow DB, et al. (July 2011). "Identification of Cd101 as a susceptibility gene for Novosphingobium aromaticivorans-induced liver autoimmunity". J. Immunol. 187 (1): 337–49. doi:10.4049/jimmunol.1003525. PMC 3134939. PMID 21613619.
^ Nakamura M, Kondo H, Mori T, et al. (2007). "Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis". Hepatology 45 (1): 118–127. doi:10.1002/hep.21472. PMID 17187436.
^ Nesher G, Margalit R, Ashkenazi YJ (2001). "Anti-nuclear envelope antibodies: Clinical associations". Semin. Arthritis Rheum. 30 (5): 313–320. doi:10.1053/sarh.2001.20266. PMID 11303304.
^ Nakanuma Y, Tsuneyama K, Sasaki M, Harada K (August 2000). "Destruction of bile ducts in primary biliary cirrhosis". Baillieres Best Pract Res Clin Gastroenterol 14 (4): 549–70. doi:10.1053/bega.2000.0103. PMID 10976014.
^ Modafinil#Primary biliary cirrhosis
Ian Gan S, de Jongh M, Kaplan MM (October 2009). "Modafinil in the treatment of debilitating fatigue in primary biliary cirrhosis: a clinical experience". Dig. Dis. Sci. 54 (10): 2242–6. doi:10.1007/s10620-008-0613-3. PMID 19082890.
Kumagi T, Heathcote EJ (2008). "Primary biliary cirrhosis". Orphanet J Rare Dis 3: 1. doi:10.1186/1750-1172-3-1. PMC 2266722. PMID 18215315. "Ref 157 viz:"
Jones DE, Newton JL (February 2007). "An open study of modafinil for the treatment of daytime somnolence and fatigue in primary biliary cirrhosis". Aliment. Pharmacol. Ther. 25 (4): 471–6. doi:10.1111/j.1365-2036.2006.03223.x. PMID 17270003.
^ Modafinil#Patent protection and antitrust litigation
Carrier MA (2011). "Provigil: A Case Study of Anticompetitive Behavior" (PDF). Hastings Science & Technology Law Journal 3 (2): 441–452.
^ http://www.ftc.gov/os/caselist/0610182/080213complaint.pdf
^ Bruce R. Bacon; John G. O'Grady (2006). Comprehensive clinical hepatology. Elsevier Health Sciences. pp. 283–. ISBN 978-0-323-03675-7. Retrieved 29 June 2010.
^ Lindor, KD; Gershwin, ME; Poupon, R; Kaplan, M; Bergasa, NV; Heathcote, EJ; American Association for Study of Liver, Diseases (July 2009). "Primary biliary cirrhosis". Hepatology (Baltimore, Md.) 50 (1): 291–308. doi:10.1002/hep.22906. PMID 19554543. Cite uses deprecated parameters (help)
^ Collier, Jane (2002). "Guidelines on the management of osteoporosis associated with chronic liver disease". Gut 50 (Suppl 1): i1–i9. doi:10.1136/gut.50.suppl_1.i1. PMC 1867644. PMID 11788576.
^ Ali, AH; Sinakos, E; Silveira, MG; Jorgensen, RA; Angulo, P; Lindor, KD (August 2011). "Varices in early histological stage primary biliary cirrhosis". Journal of Clinical Gastroenterology 45 (7): e66–71. doi:10.1097/MCG.0b013e3181f18c4e. PMID 20856137. Cite uses deprecated parameters (help)
^ http://www.genengnews.com/gen-news-highlights/dainippon-sumitomo-pays-intercept-15m-for-phase-iii-liver-disease-drug/81244901/
^ Primary Biliary Cirrhosis~followup at eMedicine
^ Clavien & Killenberg 2006, p. 429
^ WALKER, JG; DONIACH, D; ROITT, IM; SHERLOCK, S (Apr 17, 1965). "SEROLOGICAL TESTS IN DIAGNOSIS OF PRIMARY BILIARY CIRRHOSIS". Lancet 1 (7390): 827–31. PMID 14263538. Cite uses deprecated parameters (help)
^ Mitchison HC, Bassendine MF, Hendrick A, et al. (1986). "Positive antimitochondrial antibody but normal alkaline phosphatase: is this primary biliary cirrhosis?". Hepatology 6 (6): 1279–84. doi:10.1002/hep.1840060609. PMID 3793004.

External links

Primary Biliary Cirrhosis page from the National Digestive Diseases Information Clearinghouse
Primary Biliary Cirrhosis page from the American Liver Foundation
PBCers.org — patients' organisation
PBC-Society.ca — Canadian PBC patient and research support
PBC Foundation UK
UK PBC - UK PBC research

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 原発性胆汁性肝硬変の臨床症状、診断、および自然経過 clinical manifestations diagnosis and natural history of primary biliary cirrhosis
2. 原発性胆汁性肝硬変の治療の概要 overview of the treatment of primary biliary cirrhosis
3. 原発性胆汁性肝硬変の病因 pathogenesis of primary biliary cirrhosis
4. 原発性胆汁性肝硬変における肝移植 liver transplantation in primary biliary cirrhosis
5. 原発性胆汁性肝硬変における高コレステロール血症およびアテローム性動脈硬化症 hypercholesterolemia and atherosclerosis in primary biliary cirrhosis

English Journal

Cancer risk among patients with coal workers' pneumoconiosis in Taiwan: A nationwide population-based study.

Hung YP1, Teng CJ, Liu CJ, Hu YW, Hung MH, Tzeng CH, Liu CY, Yeh CM, Chen TJ, Chiou TJ.Author information 1Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.AbstractThis study is aimed to evaluate the cancer risk among patients with coal workers' pneumoconiosis (CWP) using a nationwide population-based dataset. Patients without previous cancer who had been diagnosed with CWP and followed-up for more than 1 year between 1997 and 2006 were recruited from the Taiwan National Health Insurance database. Standardized incidence ratios (SIRs) of cancers in CWP patients were calculated and compared to the cancer incidence in the general population. Risk factors for cancer development were also analyzed. After a median follow-up of 9.68 years, 954 cancers developed among 8,051 recruited CWP patients, with a follow-up of 69,398 person-years. The SIR for all cancers was 1.12 [95% confidence interval (CI) 1.04-1.18]. Males older than 80 years had a SIR of 1.27 (95% CI: 1.06-1.51). The SIRs of esophageal (1.76, 95% CI: 1.24-2.44), gastric (1.42, 95% CI: 1.13-1.76), liver and biliary tract (1.18, 95% CI: 1.01-1.37) and lung and mediastinal (1.45, 95% CI: 1.26-1.66) cancers were significantly higher in the CWP group than in the general population. Multivariate analysis showed that age ≥ 60 years [hazard ratio (HR) 1.70, 95% CI: 1.41-2.05), male gender (HR = 1.79, 95% CI: 1.44-2.23) and liver cirrhosis (HR = 3.99, 95% CI: 2.89-5.51) were significant predictors of cancer development in patients with CWP. We concluded that patients with CWP, especially elderly males, were at increased risk of cancer. Age, male gender and liver cirrhosis were independent risk factors for cancer development.
International journal of cancer. Journal international du cancer.Int J Cancer.2014 Jun 15;134(12):2910-6. doi: 10.1002/ijc.28611. Epub 2014 Feb 26.
This study is aimed to evaluate the cancer risk among patients with coal workers' pneumoconiosis (CWP) using a nationwide population-based dataset. Patients without previous cancer who had been diagnosed with CWP and followed-up for more than 1 year between 1997 and 2006 were recruited from the Taiw
PMID 24242366

Primary biliary cirrhosis in 2014.

Flores A1, Mayo MJ.Author information 1Division of Digestive and Liver Diseases, University of Texas Southwestern, Dallas, Texas, USA.AbstractPURPOSE OF REVIEW: Primary biliary cirrhosis (PBC) was first described in the 1950s as a clinical syndrome of progressive cholestatic liver disease resulting from chronic inflammatory destruction of the intrahepatic bile ducts. In the 1980s, the autoimmune nature of the disease was appreciated with the discovery of disease-specific loss of immune tolerance to the pyruvate dehydrogenase complex and subsequent development of antimitochondrial antibodies and autoreactive T cells. Then, in the 1990s, multiple clinical trials demonstrating the efficacy of ursodiol as a treatment for PBC were published, although it has been clear that ursodiol is not a cure and only delays progression in some patients.
Current opinion in gastroenterology.Curr Opin Gastroenterol.2014 May;30(3):245-52. doi: 10.1097/MOG.0000000000000058.
PURPOSE OF REVIEW: Primary biliary cirrhosis (PBC) was first described in the 1950s as a clinical syndrome of progressive cholestatic liver disease resulting from chronic inflammatory destruction of the intrahepatic bile ducts. In the 1980s, the autoimmune nature of the disease was appreciated with
PMID 24671010

Fibrate treatment for primary biliary cirrhosis.

Cuperus FJ1, Halilbasic E, Trauner M.Author information 1Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Wien, Austria.AbstractPURPOSE OF REVIEW: Primary biliary cirrhosis (PBC) can lead to end-stage liver disease and death. Ursodeoxycholic acid (UDCA) treatment can normalize serum liver enzymes in PBC, and such UDCA-responsive patients have a similar life expectancy as age and sex-matched controls. Nearly up to 50% of the patients with PBC, depending on sex and age at diagnosis, show an incomplete biochemical response to UDCA and require additional/alternative treatment. The purpose of this review is to critically evaluate the molecular mechanisms and clinical benefit of fibrate treatment in these patients.
Current opinion in gastroenterology.Curr Opin Gastroenterol.2014 May;30(3):279-86. doi: 10.1097/MOG.0000000000000056.
PURPOSE OF REVIEW: Primary biliary cirrhosis (PBC) can lead to end-stage liver disease and death. Ursodeoxycholic acid (UDCA) treatment can normalize serum liver enzymes in PBC, and such UDCA-responsive patients have a similar life expectancy as age and sex-matched controls. Nearly up to 50% of the
PMID 24625898

Japanese Journal

Primary Biliary Cholangitis: Its Pathological Characteristics and Immunopathological Mechanisms

The Journal of Medical Investigation 64(1.2), 7-13, 2017
NAID 130005501980

レビー小体型認知症と鑑別を要した原発性胆汁性肝硬変に合併した肝性脳症の1例

大阪医科大学雑誌 75(3), 141-144, 2016-12
NAID 40021065068

Editorial : PBCの病名変更 : 「原発性胆汁性肝硬変」から「原発性胆汁性胆管炎」へ

肝臓 57(7), 309-311, 2016-07
NAID 40020886671

Related Pictures

★リンクテーブル★

リンク元	「原発性硬化性胆管炎」「原発性胆汁性肝硬変」「secondary biliary cirrhosis」「biliary liver cirrhosis」「PBC」
関連記事	「primary」「biliary」「cirrhosis」

「原発性硬化性胆管炎」

Primary biliary cirrhosis
	Classification and external resources
	Micrograph of primary biliary cirrhosis showing bile duct inflammation and injury. H&E stain.
ICD-10	K74.3
ICD-9	571.6
OMIM	109720
DiseasesDB	10615
MedlinePlus	000282
eMedicine	med/223
MeSH	D008105

　　[★]

英: primary sclerosing cholangitis, PSC
関: 硬化性胆管炎、胆管炎

概念

稀で原因不明の疾患。
肝内・肝外胆管に原因不明の線維性狭窄を来し、持続性あるいは再発性(反復性)の閉塞性黄疸を来す疾患。 (YN.B-73)
炎症により胆管壁の周囲に結合織が増生・硬化・狭窄し、胆管の狭窄により胆汁うっ滞による症状を呈し、慢性経過で胆管炎による胆汁うっ滞性肝硬変に進展。

病因

原因不明

自己免疫が関連？HLA-B8

疫学

20歳代、50-60歳代にピーク
男女比=2:1

遺伝形式

病理

胆管を取り巻く線維化(線維性閉塞性胆管炎)(YN.B-73)

病態

胆管壁の全長～一部に線維性の肥厚が生じて内腔が狭窄する。肝外胆管と肝内胆管の比較的太い部位に限局する(⇔原発性胆汁性肝硬変: 肝内胆管の細胆管の障害)

進行性であり、胆汁性肝硬変に至り、肝硬変や食道静脈瘤破裂により死亡。

症状

本症の7-50%は全く無症状。症状があるものでは、体重減少(35-80%)、黄疸(25-75%)、掻痒感(10-70%)、右季肋部痛・心窩部痛(75%)、全身倦怠感、発熱。(NSU.643)
閉塞性黄疸：消長を繰り返す(SSUR.615)
胆管炎：胆管の閉塞・狭窄による

検査

MRCP、ERCP、(PTC: 今ではあんまりやらない？。肝内胆管周囲の線維化のために不成功に終わる事が多い(NSU.643))

肝内・肝外胆管の限局性の狭窄と正常部が交互に現れる：びまん性の数珠状の狭窄　→　beaded appearance (NSU.643 SSUR.615)
肝内胆管の細枝が狭窄: pruned tree appearance

血液：胆道系酵素
血清学的検査：P-ANCA：陽性、AMA：90%以上の症例で陰性

診断

閉塞性黄疸の検査所見(胆道系酵素上昇、直接ビリルビン上昇)、胆道造影、血清学的検査(AMA陰性)

鑑別診断

胆管癌

合併症

YN.B-73

治療

対症療法：

副腎皮質ホルモン、免疫抑制薬、(肝庇護)ウルソデオキシコール酸、
胆道ドレナージ
胆道内瘻化術
肝外胆管切除術
胆管空腸吻合術

根治療法：(肝不全に陥った症例)肝移植

予後

肝移植後の5年生存率：85-90%(YN.B-73)
経過中に胆管癌(9-15)が発生しうる。(YN.B-73)

see BPT.659

Table 16-7. Main Features of Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis
Parameter	primary biliary cirrhosis	primary sclerosing cholangitis
Age	Median age 50 years (30-70)	Median age 30 years
Gender	90% female	70% male
Clinical course	Progressive	Unpredictable but progressive
Associated conditions	Sjogren syndrome (70%)	inflammatory bowel disease (70%)
	scleroderma (5%)	pancreatitis (?25%)
	thyroid disease (20%)	idiopathic fibrosing disease (retroperitoneal fibrosis)
Serology	95% AMA positive	0% to 5% AMA positive (low titer)
	20% ANA positive	6% ANA positive
	60% ANCA positive	82% ANCA positive
Radiology	normal	strictures and beading of large bile ducts; pruning of smaller ducts
duct lesion	florid duct lesion; loss of small ducts	concentric periductal fibrosis; loss of small ducts

参考

原発性硬化性胆管炎
primary sclerosing cholangitis（PSC）

http://www.nurs.or.jp/~academy/igaku/s5/s555.htm

http://www.geekymedics.com/body-systems/hepatology/primary-sclerosing-cholangitis/

http://emedicine.medscape.com/article/365202-imaging

http://radiographics.rsna.org/content/20/4/959/F4.expansion.html

-primary sclerosing cholangitis

同: PSC

「原発性胆汁性肝硬変」

　　[★]

英: primary biliary cirrhosis, PBC
関: 胆汁性肝硬変、続発性胆汁性肝硬変、慢性非化膿性破壊性胆管炎、無症候性原発性胆汁性肝硬変; 難病

歴史

診断の改善に伴い、肝硬変をきたしていないPBCが多く見られるようになったため、2016年に日本で病名変更が承認された。

→ 原発性胆汁性胆管炎

「secondary biliary cirrhosis」

　　[★]

続発性胆汁性肝硬変、二次性胆汁性肝硬変

関: biliary cirrhosis、biliary liver cirrhosis、chronic nonsuppurative destructive cholangitis、primary biliary cirrhosis

「biliary liver cirrhosis」

　　[★]

胆汁性肝硬変

関: biliary cirrhosis、chronic nonsuppurative destructive cholangitis、primary biliary cirrhosis、secondary biliary cirrhosis

「PBC」

　　[★] 原発性胆汁性肝硬変 primary biliary cirrhosis　→　原発性胆汁性胆管炎 primary biliary cholangitis

「primary」

　　[★]

adj.

一次の、第一次の、主要な、(化学)第一級の、一級の、初生の、(病名)原発性の、原発の、プライマリーの

関: cardinal、chief、first-order、foremost、main、mainly、major、master、primarily、principal、principally

「biliary」

　　[★]

adj.

胆汁の

関: bile、cholic、gall

「cirrhosis」

　　[★]

cirrho(=tawny yellow)

n.

肝硬変

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[Dancygier2010-2] Dancygier, Henryk (2010). Clinical Hepatology Principles and Practice of. Springer. pp. 895–. ISBN 978-3-642-04509-7. Retrieved 29 June 2010.

[3] Saxena R, Theise N (February 2004). "Canals of Hering: recent insights and current knowledge". Semin. Liver Dis. 24 (1): 43–8. doi:10.1055/s-2004-823100. PMID 15085485.

[k.26c-p155-4] Clavien, Pierre-Alain; Killenberg, Paul G. (2006). Medical Care of the Liver Transplant Patient: Total Pre-, Intra- and Post-Operative Management. Wiley-Blackwell. p. 155. ISBN 1-4051-3032-6.

[pmid74661-5] Logan RF, Ferguson A, Finlayson ND, Weir DG (1978). "Primary biliary cirrhosis and coeliac disease: an association?". Lancet 1 (8058): 230–3. doi:10.1016/S0140-6736(78)90480-4. PMID 74661.

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[pmid16337775-7] Nakamura M, Takii Y, Ito M, et al. (2006). "Increased expression of nuclear envelope gp210 antigen in small bile ducts in primary biliary cirrhosis". J. Autoimmun. 26 (2): 138–45. doi:10.1016/j.jaut.2005.10.007. PMID 16337775.

[8] Hirschfield GM, Liu X, Xu C, et al. (June 2009). "Primary biliary cirrhosis associated with HLA, IL12A, and IL12RB2 variants". N. Engl. J. Med. 360 (24): 2544–55. doi:10.1056/NEJMoa0810440. PMC 2857316. PMID 19458352.

[9] ttp://www.uk-pbc.com

[10] Liu JZ, Almarri MA, Gaffney DJ, et al. (October 2012). "Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis". Nat. Genet. 44 (10): 1137–41. doi:10.1038/ng.2395. PMC 3459817. PMID 22961000.

[11] Juran BD, Hirschfield GM, Invernizzi P, et al. (December 2012). "Immunochip analyses identify a novel risk locus for primary biliary cirrhosis at 13q14, multiple independent associations at four established risk loci and epistasis between 1p31 and 7q32 risk variants". Hum. Mol. Genet. 21 (23): 5209–21. doi:10.1093/hmg/dds359. PMC 3490520. PMID 22936693.

[Selmi2003-12] Selmi C, Balkwill DL, Invernizzi P, et al. (November 2003). "Patients with primary biliary cirrhosis react against a ubiquitous xenobiotic-metabolizing bacterium". Hepatology 38 (5): 1250–7. doi:10.1053/jhep.2003.50446. PMID 14578864.

[Mohammed2009-13] Mohammed JP, Mattner J (July 2009). "Autoimmune disease triggered by infection with alphaproteobacteria". Expert Rev Clin Immunol 5 (4): 369–379. doi:10.1586/ECI.09.23. PMC 2742979. PMID 20161124.

[Kaplan2004-14] Kaplan MM (November 2004). "Novosphingobium aromaticivorans: a potential initiator of primary biliary cirrhosis". Am. J. Gastroenterol. 99 (11): 2147–9. doi:10.1111/j.1572-0241.2004.41121.x. PMID 15554995.

[Selmi2004-15] Selmi C, Gershwin ME (July 2004). "Bacteria and human autoimmunity: the case of primary biliary cirrhosis". Curr Opin Rheumatol 16 (4): 406–10. doi:10.1097/01.bor.0000130538.76808.c2. PMID 15201604.

[Mattner2008-16] Mattner J, Savage PB, Leung P, et al. (May 2008). "Liver autoimmunity triggered by microbial activation of natural killer T cells". Cell Host Microbe 3 (5): 304–15. doi:10.1016/j.chom.2008.03.009. PMC 2453520. PMID 18474357.

[Mohammed2003-17] Mohammed JP, Fusakio ME, Rainbow DB, et al. (July 2011). "Identification of Cd101 as a susceptibility gene for Novosphingobium aromaticivorans-induced liver autoimmunity". J. Immunol. 187 (1): 337–49. doi:10.4049/jimmunol.1003525. PMC 3134939. PMID 21613619.

[pmid17187436-18] Nakamura M, Kondo H, Mori T, et al. (2007). "Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis". Hepatology 45 (1): 118–127. doi:10.1002/hep.21472. PMID 17187436.

[pmid11303304-19] Nesher G, Margalit R, Ashkenazi YJ (2001). "Anti-nuclear envelope antibodies: Clinical associations". Semin. Arthritis Rheum. 30 (5): 313–320. doi:10.1053/sarh.2001.20266. PMID 11303304.

[pmid10976014-20] Nakanuma Y, Tsuneyama K, Sasaki M, Harada K (August 2000). "Destruction of bile ducts in primary biliary cirrhosis". Baillieres Best Pract Res Clin Gastroenterol 14 (4): 549–70. doi:10.1053/bega.2000.0103. PMID 10976014.

[21] Modafinil#Primary biliary cirrhosis
Ian Gan S, de Jongh M, Kaplan MM (October 2009). "Modafinil in the treatment of debilitating fatigue in primary biliary cirrhosis: a clinical experience". Dig. Dis. Sci. 54 (10): 2242–6. doi:10.1007/s10620-008-0613-3. PMID 19082890.
Kumagi T, Heathcote EJ (2008). "Primary biliary cirrhosis". Orphanet J Rare Dis 3: 1. doi:10.1186/1750-1172-3-1. PMC 2266722. PMID 18215315. "Ref 157 viz:"
Jones DE, Newton JL (February 2007). "An open study of modafinil for the treatment of daytime somnolence and fatigue in primary biliary cirrhosis". Aliment. Pharmacol. Ther. 25 (4): 471–6. doi:10.1111/j.1365-2036.2006.03223.x. PMID 17270003.

[22] Modafinil#Patent protection and antitrust litigation
Carrier MA (2011). "Provigil: A Case Study of Anticompetitive Behavior" (PDF). Hastings Science & Technology Law Journal 3 (2): 441–452.

[23] ttp://www.ftc.gov/os/caselist/0610182/080213complaint.pdf

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[25] Lindor, KD; Gershwin, ME; Poupon, R; Kaplan, M; Bergasa, NV; Heathcote, EJ; American Association for Study of Liver, Diseases (July 2009). "Primary biliary cirrhosis". Hepatology (Baltimore, Md.) 50 (1): 291–308. doi:10.1002/hep.22906. PMID 19554543. Cite uses deprecated parameters (help)

[26] Collier, Jane (2002). "Guidelines on the management of osteoporosis associated with chronic liver disease". Gut 50 (Suppl 1): i1–i9. doi:10.1136/gut.50.suppl_1.i1. PMC 1867644. PMID 11788576.

[27] Ali, AH; Sinakos, E; Silveira, MG; Jorgensen, RA; Angulo, P; Lindor, KD (August 2011). "Varices in early histological stage primary biliary cirrhosis". Journal of Clinical Gastroenterology 45 (7): e66–71. doi:10.1097/MCG.0b013e3181f18c4e. PMID 20856137. Cite uses deprecated parameters (help)

[28] ttp://www.genengnews.com/gen-news-highlights/dainippon-sumitomo-pays-intercept-15m-for-phase-iii-liver-disease-drug/81244901/

[29] Primary Biliary Cirrhosis~followup at eMedicine

[k.26c-p429-30] Clavien & Killenberg 2006, p. 429

[31] WALKER, JG; DONIACH, D; ROITT, IM; SHERLOCK, S (Apr 17, 1965). "SEROLOGICAL TESTS IN DIAGNOSIS OF PRIMARY BILIARY CIRRHOSIS". Lancet 1 (7390): 827–31. PMID 14263538. Cite uses deprecated parameters (help)

[Mitchison1986-32] Mitchison HC, Bassendine MF, Hendrick A, et al. (1986). "Positive antimitochondrial antibody but normal alkaline phosphatase: is this primary biliary cirrhosis?". Hepatology 6 (6): 1279–84. doi:10.1002/hep.1840060609. PMID 3793004.

Primary biliary cirrhosis
Classification and external resources
Micrograph of primary biliary cirrhosis showing bile duct inflammation and injury. H&E stain.
ICD-10	K74.3
ICD-9	571.6
OMIM	109720
DiseasesDB	10615
MedlinePlus	000282
eMedicine	med/223
MeSH	D008105

匿名

検索

案内

primary biliary cirrhosis