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Liver pathology (view source)

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This article is an introduction to liver pathology. Liver neoplasms are dealt with in the ''[[liver neoplasms]]'' article.  Medical liver diseases (e.g. viral hepatitis) is dealt with in the ''[[medical liver disease]]'' article.
This article is an introduction to liver pathology. Liver neoplasms are dealt with in the ''[[liver neoplasms]]'' article.  Medical liver diseases (e.g. viral hepatitis) is dealt with in the ''[[medical liver disease]]'' article.
Liver biopsies are quite often non-specific, as the liver has the same appearance for many mechanisms of injury, especially when the injury is marked.
Almost every differential in liver pathology has "drugs" -- if it isn't clearly malignancy.


=Review of liver blood work=
=Review of liver blood work=
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=Liver biopsy=
=Liver biopsy=
==Medical liver biopsy adequacy==
==Medical liver biopsy adequacy==
Liver biopsy specimens should be:<ref>{{Ref MacSween|418}}</ref>
*This is covered in the ''[[Medical_liver_disease#Medical_liver_biopsy_adequacy|medical liver disease]]'' article.
*2.0 cm in length and contain 11-15 portal tracts,
*The core should be deeper than 1.0 cm from the liver capsule; specimens close to the capsule may lead to over grading of fibrosis.


==Reporting==
==Reporting==
{{Main|Pathology reports}}
{{Main|Pathology reports}}
<pre>
*This is covered in the ''[[Medical_liver_disease#Reporting|medical liver disease]]'' article.
Specimen, procedure:
- Diagnosis.
</pre>
The diagnosis usually contains grading and staging information, e.g. ''activity 2 /4, Laennec fibrosis stage 1 /4''.
 
In the context of medical liver disease:
*Grade = inflammation/activity.
*Stage = severity of fibrosis/architectural changes.
 
Notes:
*The term "acute" is infrequently used in liver pathology.
*In the liver: neutrophils ''is not'' acute -- unlike most elsewhere in the body.<ref>OA. September 2009.</ref>
 
===A microscopic checklist===
<pre>
Size of biopsy: Adequate
Fragmentation: Absent
Fibrosis: Stage 2-3/4, mostly stage 2
Fibrous septa: Present
Septa with curved contours: Present – focally only
Large droplet steatosis (% of hepatocytes): Present, moderate 60%
Ballooning of hepatocytes: Present, rare
Mallory-Denk bodies: Present, rare
Portal inflammation: Present
Interface activity: Minimal (0-1/4)
Lobular necroinflammation: Minimal
Ducts: Present in normal numbers
Duct injury: Absent
Ductular reaction: Absent
Cholestasis: Absent
Terminal hepatic venules: Present
Iron stain: Absent
Ground glass cells with routine stains: Absent
PASD for alpha-1 antitrypsin droplets: Negative
</pre>


=Liver injury terms/histologic findings=
=Liver injury terms/histologic findings=
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Image:Von_Meyenburg_complex_low_mag.jpg | Von Meyenburg complex - bile duct hamartoma (WC)
Image:Von_Meyenburg_complex_low_mag.jpg | Von Meyenburg complex - bile duct hamartoma (WC)
Image:Bile_duct_hamartoma_intermed_mag.jpg | Bile duct hamartoma - intermed. mag. (WC)
Image:Bile_duct_hamartoma_intermed_mag.jpg | Bile duct hamartoma - intermed. mag. (WC)
Image:Von_Meyenburg_complex_liver.jpg | Von Meyenburg complex / bile duct hamartoma (WC)
</gallery>
</gallery>
www:
www:
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===Ground glass hepatocytes===
===Ground glass hepatocytes===
*Eosinophilic dull/hazy, somewhat irregular cytoplasm.
{{Main|Ground glass hepatocyte}}
**Ground glass<ref>URL: [http://en.wikipedia.org/wiki/Ground_glass http://en.wikipedia.org/wiki/Ground_glass]. Accessed on: 7 June 2010.</ref> = glass with a rough/flat finish; glass that is translucent and has a matte finish.
***The term is frequently used in radiology to describe hazy radiodense areas in the lung.<ref>URL: [http://www.healthsystem.virginia.edu/internet/radiology/educ/groundglass.cfm http://www.healthsystem.virginia.edu/internet/radiology/educ/groundglass.cfm]. Accessed on: 7 June 2010.</ref>
*Usually suggests '''chronic''' [[HBV]] infection.
**Pattern NOT seen in acute HBV.
**Caused by virion particles.
 
DDx:
*Pseudo-Lafora bodies in patients on disulfiram (anatabuse) - rare.
 
====Classification====
*GGHs are not routinely classified.
 
Notes:
*Several different types of GGHs are recognized.<ref name=pmid14633616>Wang HC, Wu HC, Chen CF, Fausto N, Lei HY, Su IJ. Different types of ground glass hepatocytes in chronic hepatitis B virus infection contain specific pre-S mutants that may induce endoplasmic reticulum stress. Am J Pathol. 2003 Dec;163(6):2441-9. PMID 14633616. Available at: [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=14633616 http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=14633616]. Accessed on: September 11, 2009.</ref>
 
Classification:<ref>Wang HC, Wu HC, Chen CF, Fausto N, Lei HY, Su IJ. Different types of ground glass hepatocytes in chronic hepatitis B virus infection contain specific pre-S mutants that may induce endoplasmic reticulum stress. Am J Pathol. 2003 Dec;163(6):2441-9. PMID 14633616. Available at: [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1892360&rendertype=figure&id=f1
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1892360&rendertype=figure&id=f1]. Accessed on: 17 September 2009.</ref>
*Type I ground glass hepatocytes (GGHs).
**Weak Pre-S2 positive immunostaining; morphology: GGHs scattered singly.
*Type II GGHs.
**Pre-S2 negative immunostaining; morphology: GGHs in clusters.
 
There is some suggestion that type II GGHs predispose to [[HCC]], based on data in children<ref name=pmid19719772>Pre-S2 deletion mutants of hepatitis B virus could have an important role in hepatocarcinogenesis in Asian children. Abe K, Thung SN, Wu HC, Tran TT, Le Hoang P, Truong KD, Inui A, Jang JJ, Su IJ. Cancer Sci. 2009 Aug 6. [Epub ahead of print] PMID 19719772.</ref> and based on an animal model.<ref name=pmid18505413>Ground glass hepatocytes contain pre-S mutants and represent preneoplastic lesions in chronic hepatitis B virus infection. Su IJ, Wang HC, Wu HC, Huang WY. J Gastroenterol Hepatol. 2008 Aug;23(8 Pt 1):1169-74. Epub 2008 May 26. Review. PMID 18505413.</ref>
 
Micrographs of GGHs:
<gallery>
Image:Ground_glass_hepatocytes_high_mag_cropped_2.jpg | Ground glass hepatocytes. (WC/Nephron)
Image:Ground_glass_hepatocytes_high_mag_cropped.jpg | Ground glass hepatocyte. (WC/Nephron)
</gallery>
www:
*[http://www.consultantlive.com/aids/article/1145619/1363027 Ground glass hepatocytes (consultantlive.com)].
*[http://www.biomedcentral.com/1471-230X/5/36/figure/F1 Ground glass hepatocytes (biomedcentral.com)].
*[http://pathology.osu.edu/paxit/deptbase/Paxit/Images/10534/PAXIT052.JPG Ground glass hepatocyte (pathology.osu.edu)].


===Mallory bodies===
===Mallory bodies===
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*Inflammation disrupts the "limiting plate", i.e. there is disruption of the hepatocytes that separate the portal tracts from the lobules.
*Inflammation disrupts the "limiting plate", i.e. there is disruption of the hepatocytes that separate the portal tracts from the lobules.


Micrograph:
=====Images=====
<gallery>
Image: Interface hepatitis -- high mag.jpg | IH (mild) - high mag. (WC)
Image: Interface hepatitis -- very high mag.jpg | IH (mild) - very high mag. (WC)
</gallery>
www:
*[http://www.pathologyatlas.ro/viral-chronic-moderate-hepatitis.php Interface hepatitis (pathologyatlas.ro)].
*[http://www.pathologyatlas.ro/viral-chronic-moderate-hepatitis.php Interface hepatitis (pathologyatlas.ro)].
*[http://www.nature.com/modpathol/journal/v20/n1s/fig_tab/3800693f1.html#figure-title Interface hepatitis (nature.com)].<ref name=pmid17486049>{{Cite journal | last1 = Theise | first1 = ND. | title = Liver biopsy assessment in chronic viral hepatitis: a personal, practical approach. | journal = Mod Pathol | volume = 20 Suppl 1 | issue = | pages = S3-14 | month = Feb | year = 2007 | doi = 10.1038/modpathol.3800693 | PMID = 17486049 }}</ref>
*[http://www.nature.com/modpathol/journal/v20/n1s/fig_tab/3800693f1.html#figure-title Interface hepatitis (nature.com)].<ref name=pmid17486049>{{cite journal |author=Theise ND |title=Liver biopsy assessment in chronic viral hepatitis: a personal, practical approach |journal=Mod. Pathol. |volume=20 Suppl 1 |issue= |pages=S3-14 |year=2007 |month=February |pmid=17486049 |doi=10.1038/modpathol.3800693 |url=http://www.nature.com/modpathol/journal/v20/n1s/full/3800693a.html}}</ref>


===Liver fibrosis===
===Liver fibrosis===
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===Cirrhosis===
===Cirrhosis===
*Cirrhosis ''is'' stage 4 (Laennec).
{{Main|Cirrhosis}}
**The formal Robbins definitions is:<ref name=Ref_PCPBoD8_439>{{Ref PCPBoD8|439}}</ref> (1) bridging fibrosis, (2) nodule formation, and (3) disruption of the hepatic architecture.
*The etiology of late stage fibrosis (cirrhosis), may be impossible to determine.
*Perisinusoidal fibrosis may suggest congestive hepatopathy.<ref>OA. September 15, 2009.</ref>
*In NAFLD portal-to-portal fibrosis (septal/bridging fibrosis) tends to be more common than perivenular fibrosis.<ref name=pmid14991537>Pathologic features associated with fibrosis in nonalcoholic fatty liver disease. Gramlich T, Kleiner DE, McCullough AJ, Matteoni CA, Boparai N, Younossi ZM. Hum Pathol. 2004 Feb;35(2):196-9. PMID 14991537.</ref>
*The classic teaching is that cirrhosis is irreversible; however, there is increasing evidence that it regresses.<ref name=pmid11079009>{{Cite journal  | last1 = Wanless | first1 = IR. | last2 = Nakashima | first2 = E. | last3 = Sherman | first3 = M. | title = Regression of human cirrhosis. Morphologic features and the genesis of incomplete septal cirrhosis. | journal = Arch Pathol Lab Med | volume = 124 | issue = 11 | pages = 1599-607 | month = Nov | year = 2000 | doi = 10.1043/0003-9985(2000)1241599:ROHC2.0.CO;2 | PMID = 11079009 }}</ref><ref name=pmid21286337>{{Cite journal  | last1 = Kim | first1 = SU. | last2 = Park | first2 = JY. | last3 = Kim | first3 = do Y. | last4 = Ahn | first4 = SH. | last5 = Choi | first5 = EH. | last6 = Seok | first6 = JY. | last7 = Lee | first7 = JM. | last8 = Park | first8 = YN. | last9 = Chon | first9 = CY. | title = Non-invasive assessment of changes in liver fibrosis via liver stiffness measurement in patients with chronic hepatitis B: impact of antiviral treatment on fibrosis regression. | journal = Hepatol Int | volume = 4 | issue = 4 | pages = 673-80 | month =  | year = 2010 | doi = 10.1007/s12072-010-9201-7 | PMID = 21286337 }}</ref><ref name=pmid24304452>{{Cite journal  | last1 = Casado | first1 = JL. | last2 = Quereda | first2 = C. | last3 = Moreno | first3 = A. | last4 = Pérez-Elías | first4 = MJ. | last5 = Martí-Belda | first5 = P. | last6 = Moreno | first6 = S. | title = Regression of liver fibrosis is progressive after sustained virological response to HCV therapy in patients with hepatitis C and HIV coinfection. | journal = J Viral Hepat | volume = 20 | issue = 12 | pages = 829-37 | month = Dec | year = 2013 | doi = 10.1111/jvh.12108 | PMID = 24304452 }}</ref>
 
Special types:
*Garland cirrhosis ([[AKA]] holly leaf cirrhosis) - see ''[[primary biliary cirrhosis]]''.
====Gross====
Cirrhosis can be divided (in gross pathology) into:
*Micronodular cirrhosis - classically due to [[alcohol]].
**Uniform, diffuse.
*Macronodular cirrhosis - classically due to viral hepatitis.
**Irregular.
 
Images:
*[http://www.meddean.luc.edu/lumen/MedEd/orfpath/cirhosis.htm Cirrhosis - macronodular & micronodular (meddean.luc.edu)].
<gallery>
Image:Cirrhosis_high_mag.jpg | Cirrhotic liver - trichrome stain. (WC/Nephron)
</gallery>


===Steatosis===
===Steatosis===
Mark
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