Primary biliary cirrhosis pathophysiology: Difference between revisions

	Primary Biliary Cirrhosis Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Primary Biliary Cirrhosis from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Study of Choice
History and Symptoms
Physical Examination
Laboratory Findings
Electrocardiogram
X Ray
CT
MRI
Ultrasound
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Primary biliary cirrhosis pathophysiology On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Primary biliary cirrhosis pathophysiology All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Primary biliary cirrhosis pathophysiology
CDC on Primary biliary cirrhosis pathophysiology
Primary biliary cirrhosis pathophysiology in the news
Blogs on Primary biliary cirrhosis pathophysiology
Directions to Hospitals Treating Primary biliary cirrhosis
Risk calculators and risk factors for Primary biliary cirrhosis pathophysiology

VisualWikitext

Latest revision as of 23:49, 29 July 2020

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2]

Overview

Primary biliary cirrhosis also known as primary biliary cholangitis is an autoimmune cholestatic disease. The disease is chronic and slowly progressive. The exact pathogenesis of primary biliary cirrhosis is not fully understood. It is postulated that primary biliary cirrhosis is the result of antimitochondrial antibodies (AMAs), directed to the E2 component of the pyruvate dehydrogenase complex (PDC-E2). Overexpression of Bcl-2 in small apoptotic biliary epithelial cells and cell lineage-specific lack of glutathione prevents loss of immunogenicity of the PDC-E2 component after apoptosis of biliary epithelial cells which finally results in autoimmunity. Primary biliary cirrhosis may be familial and is related to factors inherited maternally. Primary biliary cirrhosis is strongly associated with a variety of rheumatologic conditions, most commonly Sjogren's syndrome. On gross pathology, characteristic findings of primary biliary cirrhosis include hepatomegaly, splenomegaly, and cirrhosis (in late stage). On microscopic histopathological analysis, asymmetric destruction of the intralobular bile ducts within portal triads is characteristic findings of primary biliary cirrhosis.

Pathophysiology

Pathogenesis

The exact pathogenesis of primary biliary cirrhosis is not fully understood.
It is thought that primary biliary cirrhosis is the result of antimitochondrial antibodies (AMAs), directed to the E2 component of the pyruvate dehydrogenase complex (PDC-E2).^[1]

Algorithm showing postulated hypothesis of pathogenesis of primary biliary cirrhosis^[2]^[3]^[4]^[5]

Biliary epithelial cells (BEC)

Overexpression of Bcl-2 in small apoptotic BEC

Cell lineage specific lack of glutathione

Inhibition of PDC-E2 glutathiolation

Prevents loss of immunogenicity after apoptosis of BEC

PDC-E2 component remains intact and antigenic in apoptotic blebs of BEC

Antigenic PDC-E2 are engulfed by intrahepatic dendritic cells

Dendritic cells transfer antigenic PDC-E2 to regional lymph nodes

Antigenic PDC-E2 is recognized by MHC class I restricted CD8⁺ T cells

Initiates autoimmunity

Primary biliary cirrhosis

Genetics

Primary biliary cirrhosis may be familial and is related to factors inherited maternally.^[6]
Primary biliary cirrhosis tends to present at an earlier age in the second generation.

Associated Conditions

Conditions associated with primary biliary cirrhosis include:^[7]^[8]^[9]

Gross Pathology

On gross pathology, characteristic findings of primary biliary cirrhosis include:^[7]
- Hepatomegaly
- Splenomegaly
- Cirrhosis (late stages)

Microscopic Pathology

On microscopic histopathological analysis, asymmetric destruction of the intralobular bile ducts within portal triads is characteristic findings of primary biliary cirrhosis.
Primary biliary cirrhosis can be classified into four stages according to histological classification of Ludwig. According to Ludwig classification, all four stages may be present on a single liver biopsy.^[10]^[11]
It can also be classified into four stages according to the histological classification of P. Scheuer.^[12]

Classification of Primary biliary cirrhosis on the basis of histology
Stage	Histologic appearance
Stage	Ludwig classification	Scheuer's classification
Stage 1	Portal inflammation	Florid duct lesion or chronic non-suppurative destructive cholangitis
Stage 2	Extension of inflammation beyond portal tracts into surrounding parenchyma with or without ductal loss	Proliferation of the small bile ductules
Stage 3	Presence of fibrous septa linking adjacent portal tracts	Fibrosis or scarring
Stage 4	Cirrhosis	Cirrhosis

References

↑ Matsumura S, Van De Water J, Leung P, Odin JA, Yamamoto K, Gores GJ; et al. (2004). "Caspase induction by IgA antimitochondrial antibody: IgA-mediated biliary injury in primary biliary cirrhosis". Hepatology. 39 (5): 1415–22. doi:10.1002/hep.20175. PMID 15122771.
↑ Lleo A, Selmi C, Invernizzi P, Podda M, Coppel RL, Mackay IR; et al. (2009). "Apotopes and the biliary specificity of primary biliary cirrhosis". Hepatology. 49 (3): 871–9. doi:10.1002/hep.22736. PMC 2665925. PMID 19185000.
↑ Odin JA, Huebert RC, Casciola-Rosen L, LaRusso NF, Rosen A (2001). "Bcl-2-dependent oxidation of pyruvate dehydrogenase-E2, a primary biliary cirrhosis autoantigen, during apoptosis". J Clin Invest. 108 (2): 223–32. doi:10.1172/JCI10716. PMC 203018. PMID 11457875.
↑ Charlotte F, L'Herminé A, Martin N, Geleyn Y, Nollet M, Gaulard P; et al. (1994). "Immunohistochemical detection of bcl-2 protein in normal and pathological human liver". Am J Pathol. 144 (3): 460–5. PMC 1887102. PMID 8129031.
↑ Shimoda S, Harada K, Niiro H, Yoshizumi T, Soejima Y, Taketomi A; et al. (2008). "Biliary epithelial cells and primary biliary cirrhosis: the role of liver-infiltrating mononuclear cells". Hepatology. 47 (3): 958–65. doi:10.1002/hep.22102. PMID 18181218.
↑ Brind AM, Bray GP, Portmann BC, Williams R (1995). "Prevalence and pattern of familial disease in primary biliary cirrhosis". Gut. 36 (4): 615–7. PMC 1382507. PMID 7737573.
↑ ^7.0 ^7.1 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.
↑ Watt FE, James OF, Jones DE (2004). "Patterns of autoimmunity in primary biliary cirrhosis patients and their families: a population-based cohort study". QJM. 97 (7): 397–406. PMID 15208427.
↑ Tsianos EV, Hoofnagle JH, Fox PC, Alspaugh M, Jones EA, Schafer DF; et al. (1990). "Sjögren's syndrome in patients with primary biliary cirrhosis". Hepatology. 11 (5): 730–4. PMID 2347546.
↑ Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ; et al. (2009). "Primary biliary cirrhosis". Hepatology. 50 (1): 291–308. doi:10.1002/hep.22906. PMID 19554543.
↑ Ludwig J, Dickson ER, McDonald GS (1978). "Staging of chronic nonsuppurative destructive cholangitis (syndrome of primary biliary cirrhosis)". Virchows Arch A Pathol Anat Histol. 379 (2): 103–12. PMID 150690.
↑ Scheuer P (1967). "Primary biliary cirrhosis". Proc R Soc Med. 60 (12): 1257–60. PMC 1901478. PMID 6066569.

Template:WH Template:WS

[pmid15122771-1] Matsumura S, Van De Water J, Leung P, Odin JA, Yamamoto K, Gores GJ; et al. (2004). "Caspase induction by IgA antimitochondrial antibody: IgA-mediated biliary injury in primary biliary cirrhosis". Hepatology. 39 (5): 1415–22. doi:10.1002/hep.20175. PMID 15122771.

[pmid19185000-2] Lleo A, Selmi C, Invernizzi P, Podda M, Coppel RL, Mackay IR; et al. (2009). "Apotopes and the biliary specificity of primary biliary cirrhosis". Hepatology. 49 (3): 871–9. doi:10.1002/hep.22736. PMC 2665925. PMID 19185000.

[pmid11457875-3] Odin JA, Huebert RC, Casciola-Rosen L, LaRusso NF, Rosen A (2001). "Bcl-2-dependent oxidation of pyruvate dehydrogenase-E2, a primary biliary cirrhosis autoantigen, during apoptosis". J Clin Invest. 108 (2): 223–32. doi:10.1172/JCI10716. PMC 203018. PMID 11457875.

[pmid8129031-4] Charlotte F, L'Herminé A, Martin N, Geleyn Y, Nollet M, Gaulard P; et al. (1994). "Immunohistochemical detection of bcl-2 protein in normal and pathological human liver". Am J Pathol. 144 (3): 460–5. PMC 1887102. PMID 8129031.

[pmid18181218-5] Shimoda S, Harada K, Niiro H, Yoshizumi T, Soejima Y, Taketomi A; et al. (2008). "Biliary epithelial cells and primary biliary cirrhosis: the role of liver-infiltrating mononuclear cells". Hepatology. 47 (3): 958–65. doi:10.1002/hep.22102. PMID 18181218.

[pmid7737573-6] Brind AM, Bray GP, Portmann BC, Williams R (1995). "Prevalence and pattern of familial disease in primary biliary cirrhosis". Gut. 36 (4): 615–7. PMC 1382507. PMID 7737573.

[pmid18215315-7] 7.0 ^7.1 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.

[pmid15208427-8] Watt FE, James OF, Jones DE (2004). "Patterns of autoimmunity in primary biliary cirrhosis patients and their families: a population-based cohort study". QJM. 97 (7): 397–406. PMID 15208427.

[pmid2347546-9] Tsianos EV, Hoofnagle JH, Fox PC, Alspaugh M, Jones EA, Schafer DF; et al. (1990). "Sjögren's syndrome in patients with primary biliary cirrhosis". Hepatology. 11 (5): 730–4. PMID 2347546.

[pmid19554543-10] Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ; et al. (2009). "Primary biliary cirrhosis". Hepatology. 50 (1): 291–308. doi:10.1002/hep.22906. PMID 19554543.

[pmid150690-11] Ludwig J, Dickson ER, McDonald GS (1978). "Staging of chronic nonsuppurative destructive cholangitis (syndrome of primary biliary cirrhosis)". Virchows Arch A Pathol Anat Histol. 379 (2): 103–12. PMID 150690.

[pmid6066569-12] Scheuer P (1967). "Primary biliary cirrhosis". Proc R Soc Med. 60 (12): 1257–60. PMC 1901478. PMID 6066569.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

@@ Line 3: / Line 3: @@
 {{Primary biliary cirrhosis}}
-<div style="-webkit-user-select: none;">
+{| class="infobox" style="position: fixed; top: 65%; right: 10px; margin: 0 0 0 0; border: 0; float: right;"
-{|class="infobox" style="position: fixed; top: 65%; right: 10px; margin: 0 0 0 0; border: 0; float: right;
 |-
 | {{#ev:youtube|https://https://www.youtube.com/watch?v=CQtHOMzLzwU|350}}
@@ Line 10: / Line 9: @@
 |}
-{{CMG}}; {{AE}}
+{{CMG}}; {{AE}}{{Anmol}}
 ==Overview==
-The exact pathogenesis of [disease name] is not fully understood.
+Primary biliary cirrhosis also known as primary biliary cholangitis is an [[autoimmune]] [[cholestatic]] disease. The disease is [[Chronic (medical)|chronic]] and slowly progressive. The exact pathogenesis of primary biliary cirrhosis is not fully understood. It is postulated that primary biliary cirrhosis is the result of [[antimitochondrial antibodies]] (AMAs), directed to the E2 component of the [[pyruvate dehydrogenase complex]] (PDC-E2). Overexpression of [[Bcl-2]] in small [[apoptotic]] [[biliary]] [[epithelial]] [[cells]] and cell lineage-specific lack of [[glutathione]] prevents loss of [[immunogenicity]] of the PDC-E2 component after [[apoptosis]] of biliary epithelial cells which finally results in [[autoimmunity]]. Primary biliary cirrhosis may be [[familial]] and is related to factors inherited maternally. Primary biliary cirrhosis is strongly associated with a variety of [[Rheumatology|rheumatologic]] conditions, most commonly [[Sjogren's syndrome]]. On gross pathology, characteristic findings of primary biliary cirrhosis include [[hepatomegaly]], [[splenomegaly]], and [[cirrhosis]] (in late stage). On [[microscopic]] [[histopathological]] analysis, asymmetric destruction of the [[Bile ducts|intralobular bile ducts]] within [[Portal triad|portal triads]] is characteristic findings of primary biliary cirrhosis.
-OR
-It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
-OR
-[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
-OR
-Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
-OR
-[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
-OR
-The progression to [disease name] usually involves the [molecular pathway].
-OR
-The pathophysiology of [disease/malignancy] depends on the histological subtype.
 ==Pathophysiology==
 ===Pathogenesis===
-*The exact pathogenesis of [disease name] is not fully understood.
+*The exact pathogenesis of primary biliary cirrhosis is not fully understood.
-OR
+*It is thought that primary biliary cirrhosis is the result of [[antimitochondrial antibodies]] (AMAs), directed to the E2 component of the [[pyruvate dehydrogenase complex]] (PDC-E2).<ref name="pmid15122771">{{cite journal| author=Matsumura S, Van De Water J, Leung P, Odin JA, Yamamoto K, Gores GJ et al.| title=Caspase induction by IgA antimitochondrial antibody: IgA-mediated biliary injury in primary biliary cirrhosis. | journal=Hepatology | year= 2004 | volume= 39 | issue= 5 | pages= 1415-22 | pmid=15122771 | doi=10.1002/hep.20175 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15122771  }} </ref>
-*It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
-*[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
+<br>
-*Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
+<div style="text-align: center;">'''Algorithm showing postulated hypothesis of pathogenesis of primary biliary cirrhosis'''<ref name="pmid19185000">{{cite journal| author=Lleo A, Selmi C, Invernizzi P, Podda M, Coppel RL, Mackay IR et al.| title=Apotopes and the biliary specificity of primary biliary cirrhosis. | journal=Hepatology | year= 2009 | volume= 49 | issue= 3 | pages= 871-9 | pmid=19185000 | doi=10.1002/hep.22736 | pmc=2665925 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19185000  }} </ref><ref name="pmid11457875">{{cite journal| author=Odin JA, Huebert RC, Casciola-Rosen L, LaRusso NF, Rosen A| title=Bcl-2-dependent oxidation of pyruvate dehydrogenase-E2, a primary biliary cirrhosis autoantigen, during apoptosis. | journal=J Clin Invest | year= 2001 | volume= 108 | issue= 2 | pages= 223-32 | pmid=11457875 | doi=10.1172/JCI10716 | pmc=203018 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11457875  }} </ref><ref name="pmid8129031">{{cite journal| author=Charlotte F, L'Herminé A, Martin N, Geleyn Y, Nollet M, Gaulard P et al.| title=Immunohistochemical detection of bcl-2 protein in normal and pathological human liver. | journal=Am J Pathol | year= 1994 | volume= 144 | issue= 3 | pages= 460-5 | pmid=8129031 | doi= | pmc=1887102 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8129031  }} </ref><ref name="pmid18181218">{{cite journal| author=Shimoda S, Harada K, Niiro H, Yoshizumi T, Soejima Y, Taketomi A et al.| title=Biliary epithelial cells and primary biliary cirrhosis: the role of liver-infiltrating mononuclear cells. | journal=Hepatology | year= 2008 | volume= 47 | issue= 3 | pages= 958-65 | pmid=18181218 | doi=10.1002/hep.22102 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18181218  }} </ref></div>
-*[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
+<br>
-*The progression to [disease name] usually involves the [molecular pathway].
+{{Family tree/start}}
-*The pathophysiology of [disease/malignancy] depends on the histological subtype.
+{{Family tree | | | | | | | | | | | | A01 | | | | | | | | | | | A01=Biliary epithelial cells (BEC) }}
+{{Family tree | | | | | | | | |,|-|-|-|^|-|-|-|.| | | | | | | | }}
+{{Family tree | | | | | | | | B01 | | | | | | B02 | | | | | | | B01=Overexpression of [[Bcl-2]] in small apoptotic BEC|B02=Cell lineage specific lack of [[glutathione]]}}
+{{Family tree | | | | | | | | |!| | | | | | | |!| | | | | | | | }}
+{{Family tree | | | | | | | | |!| | | | | | | C01 | | | | | | | C01=Inhibition of PDC-E2 glutathiolation}}
+{{Family tree | | | | | | | | |`|-|-|-|v|-|-|-|'| | | | | | | | }}
+{{Family tree | | | | | | | | | | | | D01 | | | | | | | | | | | D01=Prevents loss of [[immunogenicity]] after [[apoptosis]] of BEC}}
+{{Family tree | | | | | | | | | | | | |!| | | | | | | | | | | | }}
+{{Family tree | | | | | | | | | | | | E01 | | | | | | | | | | | E01=PDC-E2 component remains intact and [[antigenic]] in [[apoptotic]] blebs of BEC}}
+{{Family tree | | | | | | | | | | | | |!| | | | | | | | | | | | }}
+{{Family tree | | | | | | | | | | | | F01 | | | | | | | | | | | F01=[[Antigenic]] PDC-E2 are engulfed by intrahepatic [[dendritic cells]]}}
+{{Family tree | | | | | | | | | | | | |!| | | | | | | | | | | | }}
+{{Family tree | | | | | | | | | | | | G01 | | | | | | | | | | | G01=[[Dendritic cells]] transfer [[antigenic]] PDC-E2 to regional [[lymph nodes]]}}
+{{Family tree | | | | | | | | | | | | |!| | | | | | | | | | | | }}
+{{Family tree | | | | | | | | | | | | H01 | | | | | | | | | | | H01=[[Antigenic]] PDC-E2 is recognized by [[MHC class I]] restricted CD8<sup>+</sup> T cells}}
+{{Family tree | | | | | | | | | | | | |!| | | | | | | | | | | | }}
+{{Family tree | | | | | | | | | | | | J01 | | | | | | | | | | | J01=Initiates [[autoimmunity]]}}
+{{Family tree | | | | | | | | | | | | |!| | | | | | | | | | | | }}
+{{Family tree | | | | | | | | | | | | K01 | | | | | | | | | | | K01=Primary biliary cirrhosis}}
+{{Family tree/end}}
 ==Genetics==
-*[Disease name] is transmitted in [mode of genetic transmission] pattern.
+*Primary biliary cirrhosis may be [[familial]] and is related to factors inherited maternally.<ref name="pmid7737573">{{cite journal| author=Brind AM, Bray GP, Portmann BC, Williams R| title=Prevalence and pattern of familial disease in primary biliary cirrhosis. | journal=Gut | year= 1995 | volume= 36 | issue= 4 | pages= 615-7 | pmid=7737573 | doi= | pmc=1382507 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7737573  }} </ref>
-*Genes involved in the pathogenesis of [disease name] include [gene1], [gene2], and [gene3].
+*Primary biliary cirrhosis tends to present at an earlier age in the second generation.
-*The development of [disease name] is the result of multiple genetic mutations.
 ==Associated Conditions==
+Conditions associated with primary biliary cirrhosis include:<ref name="pmid18215315">{{cite journal| author=Kumagi T, Heathcote EJ| title=Primary biliary cirrhosis. | journal=Orphanet J Rare Dis | year= 2008 | volume= 3 | issue=  | pages= 1 | pmid=18215315 | doi=10.1186/1750-1172-3-1 | pmc=2266722 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18215315  }} </ref><ref name="pmid15208427">{{cite journal| author=Watt FE, James OF, Jones DE| title=Patterns of autoimmunity in primary biliary cirrhosis patients and their families: a population-based cohort study. | journal=QJM | year= 2004 | volume= 97 | issue= 7 | pages= 397-406 | pmid=15208427 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15208427  }} </ref><ref name="pmid2347546">{{cite journal| author=Tsianos EV, Hoofnagle JH, Fox PC, Alspaugh M, Jones EA, Schafer DF et al.| title=Sjögren's syndrome in patients with primary biliary cirrhosis. | journal=Hepatology | year= 1990 | volume= 11 | issue= 5 | pages= 730-4 | pmid=2347546 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2347546  }} </ref>
+*[[Addison's disease]]
+*[[Immune thrombocytopenic purpura|Autoimmune thrombocytopenic purpura]]
+*[[Celiac disease]]
+*[[CREST syndrome]]
+*[[Crohn's disease]]
+*[[Dermatomyositis]]
+*[[Diabetes mellitus type 1]]
+*[[Gallstones]]
+*[[Glomerulonephritis]]
+*[[Grave's disease]]
+*[[Hashimoto's thyroiditis]]
+*[[Lichen planus]]
+*[[Mixed connective tissue disorder]]
+*[[Myasthenia gravis]]
+*[[Pemphigoid]]
+*[[Pernicious anemia]]
+*[[Polymyositis]]
+*[[Psoriasis]]
+*[[Pulmonary fibrosis]]
+*[[Raynaud's disease]]
+*[[Rheumatoid arthritis]]
+*[[Sarcoidosis]]
+*[[Scleroderma]]
+*[[Sjogren's syndrome]]
+*[[Systemic lupus erythematosus]]
+*[[Ulcerative colitis]]
 ==Gross Pathology==
-*On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
+*On gross pathology, characteristic findings of primary biliary cirrhosis include:<ref name="pmid18215315">{{cite journal| author=Kumagi T, Heathcote EJ| title=Primary biliary cirrhosis. | journal=Orphanet J Rare Dis | year= 2008 | volume= 3 | issue=  | pages= 1 | pmid=18215315 | doi=10.1186/1750-1172-3-1 | pmc=2266722 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18215315  }} </ref>
+**[[Hepatomegaly]]
+**[[Splenomegaly]]
+**[[Cirrhosis]] (late stages)
 ==Microscopic Pathology==
-*On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
+*On microscopic histopathological analysis, asymmetric destruction of the intralobular [[bile ducts]] within [[portal triads]] is characteristic findings of primary biliary cirrhosis.
+*Primary biliary cirrhosis can be classified into four stages according to histological classification of Ludwig. According to Ludwig classification, all four stages may be present on a single [[liver biopsy]].<ref name="pmid19554543">{{cite journal| author=Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ et al.| title=Primary biliary cirrhosis. | journal=Hepatology | year= 2009 | volume= 50 | issue= 1 | pages= 291-308 | pmid=19554543 | doi=10.1002/hep.22906 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19554543  }} </ref><ref name="pmid150690">{{cite journal| author=Ludwig J, Dickson ER, McDonald GS| title=Staging of chronic nonsuppurative destructive cholangitis (syndrome of primary biliary cirrhosis). | journal=Virchows Arch A Pathol Anat Histol | year= 1978 | volume= 379 | issue= 2 | pages= 103-12 | pmid=150690 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=150690  }} </ref>
-===Histopathology===
+* It can also be classified into four stages according to the histological classification of P. Scheuer.<ref name="pmid6066569">{{cite journal| author=Scheuer P| title=Primary biliary cirrhosis. | journal=Proc R Soc Med | year= 1967 | volume= 60 | issue= 12 | pages= 1257-60 | pmid=6066569 | doi= | pmc=1901478 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6066569  }}</ref>
+<br>
+{|
+! colspan="3" style="background:#4479BA; color: #FFFFFF;" align="center" + | Classification of Primary biliary cirrhosis on the basis of histology
+|-
+! rowspan="2" style="background:#4479BA; color: #FFFFFF;" align="center" + |Stage
+! colspan="2" style="background:#4479BA; color: #FFFFFF;" align="center" + | Histologic appearance
+|-
+! style="background:#7d7d7d; color: #FFFFFF;" align="center" + |Ludwig classification
+! style="background:#7d7d7d; color: #FFFFFF;" align="center" + |Scheuer's classification
+|-
+| style="background:#DCDCDC;" align="center" + |Stage 1
+| style="background:#F5F5F5;" + |[[Portal]] [[inflammation]]
+| style="background:#F5F5F5;" + |Florid duct lesion or chronic non-suppurative destructive [[cholangitis]]
+|-
+| style="background:#DCDCDC;" align="center" + |Stage 2
+| style="background:#F5F5F5;" + |Extension of [[inflammation]] beyond [[portal]] tracts into surrounding [[parenchyma]] with or without ductal loss
+| style="background:#F5F5F5;" + |Proliferation of the small [[Bile duct|bile ductules]]
+|-
+| style="background:#DCDCDC;" align="center" + |Stage 3
+| style="background:#F5F5F5;" + |Presence of fibrous septa linking adjacent [[portal]] tracts
+| style="background:#F5F5F5;" + |Fibrosis or scarring
+|-
+| style="background:#DCDCDC;" align="center" + |Stage 4
+| style="background:#F5F5F5;" + |[[Cirrhosis]]
+| style="background:#F5F5F5;" + |[[Cirrhosis]]
+|}
 ==References==
 {{reflist|2}}
+{{WH}}
+{{WS}}
 [[Category:Gastroenterology]]
 [[Category:Hepatology]]
 [[Category:Disease]]
-[[Category:Needs overview]]
+[[Category:Rheumatology]]
+[[Category:Medicine]]
-{{WH}}
+[[Category:Up-To-Date]]
-{{WS}}