Difference between revisions of "Medical liver disease"

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[[Image:Ground glass hepatocytes high mag cropped 2.jpg|thumb|right|[[Micrograph]] showing ground glass hepatocytes, as seen in chronic [[hepatitis B]]. [[H&E stain]].]]
This article deals with '''medical [[liver]] disease'''.  An introduction to the liver and approach is found in the ''[[liver]]'' article.
This article deals with '''medical [[liver]] disease'''.  An introduction to the liver and approach is found in the ''[[liver]]'' article.



Revision as of 07:10, 9 December 2014

Micrograph showing ground glass hepatocytes, as seen in chronic hepatitis B. H&E stain.

This article deals with medical liver disease. An introduction to the liver and approach is found in the liver article.

Every differential in liver pathology has "drugs"[1] -- if it isn't clearly malignancy.

Liver neoplasms are dealt with in the liver neoplasms article.

Viral hepatitis

These are common. The diagnoses are based on serology. The serology is covered in the viral hepatitis section in the liver pathology article.

Typically classified as:[2][3]

  1. Acute < 6 months duration.
  2. Chronic > 6 months duration.

Hepatitis A

  • Infection is self-limited, i.e. not persistent.
  • Usually asymptomatic in children.[4]
  • Serology is diagnostic.

Hepatitis B

Hepatitis B virus, abbreviated HBV, redirects here.

General

Associated pathology:

Microscopic

Features:

  • Lobular inflammation - this is non-specific finding.
    • Hepatocyte necrosis:
      • Necrotic hepatocytes look a lot like neutrophils - however:
        • Cytoplasm is more pink.
        • Round apoptotic bodies.
  • Ground glass hepatocytes - see liver pathology article.

DDx:

Image

IHC

Hepatitis C

General

  • Leads to hepatocellular carcinoma in the setting of cirrhosis.
  • Tends to be chronic; the "C" in "hepatitis C" stands for chronic.
  • Diagnosis is by serology.

Associated pathology:

Microscopic

Features:

  • Lobular inflammation - this is non-specific finding.
    • Usually Grade 1, rarely Grade 2 and almost never Grade 3 or Grade 4.[5]
  • Periportal steatosis in genotype 3.[6]
    • Steatosis in hepatitis C is usually a secondary pathology, i.e. a separate pathologic process.[7]

DDx:

Other infections

  • Hydatid disease (Hydatid cyst).
  • Ascaris.
  • Fasciola

Hydatid disease

  • AKA hydatid cyst.

General

Microscopic

Features:

Images

www:

Metabolic and toxic

Alcoholic liver disease

General

Classic lab findings in EtOH abusers

  • AST & ALT elevated with AST:ALT=2:1.
  • GGT elevated.
  • MCV increased.

Gross pathology/radiologic findings

  • Classically micronodular pattern.
    • May be macronodular.

Microscopic

See:

Features:

  • Often zone III damage.
  • Cholestatsis common, i.e. yellow staining.
    • NASH (non-alcoholic steatohepatitis) usu. does not have cholestasis.[11]
  • Fibrosis starts at central veins.
  • Neutrophils (often helpful) -- few other things have PMNs. (???)
    • Neutrophils cluster around cells with Mallory hyaline.

Notes:

  • If portal inflammatory infiltrates more than mild, r/o other causes i.e. viral hepatitis.
  • Mallory bodies once thought to be characteristic; now considered non-specific and generally poorly understood.[12]
  • Some consider alcoholic liver disease a clinical diagnosis, i.e. as a pathologist one does not diagnose it.[13]

Non-alcoholic fatty liver disease

  • Abbreviated NAFLD.
  • Fatty liver that is not due to alcohol; includes obesity-related fatty liver, metabolic disease/diabetes-related fatty liver.

NASH

  • Non-alcoholic steatohepatitis - see steatohepatitis section.
  • Histologically indistinguishable from ASH.
  • NASH is a clinical diagnosis based on exclusion of alcohol.

Steatohepatitis

Autoimmune

Autoimmune hepatitis

  • Abbreviated AIH.

Primary biliary cirrhosis

  • Abbreviated PBC.

Autoimmune hepatitis-primary biliary cirrhosis overlap syndrome

  • Abbreviation AIH-PBC OS.

General

Epidemiology:

  • Rare.

Serology:[14]

  • AMA +ve.
  • Anti-dsDNA +ve.

Microscopic

See: autoimmune hepatitis and primary biliary cirrhosis.

Primary sclerosing cholangitis

  • Abbreviated PSC.

Hereditary

Caroli disease

General

Clinical:[17]

Note:

  • Caroli syndrome = Caroli disease + congenital hepatic fibrosis.[20]

Gross

  • Dilated bile ducts.[15]

Microscopic

Features:[17]

  • Dilated bile ducts.
  • Periductal fibrosis. (???)
  • +/-Fibrosis.

Image:

Hereditary hemochromatosis

For secondary causes see secondary hemochromatosis.

Wilson disease

General

Epidemiology:

  • Rare autosomal recessive - mutation in copper-transporting adenosine triphosphatase (ATPase) gene (ATP7B).[22][23]
    • Heterozygote carrier rate approximately 1/100 persons.[22]
  • Young individuals - usually 12-23 years old.

Clinical:

  • Kayser-Fleischer rings --> on slit-lamp examination (green eyes).
  • May present to psychiatry or appear to be abusing EtOH.
  • Serum ceruloplasmin - lower than normal.

Etiology:

  • Excess copper -- due to genetic defect.

Microscopic

Features:

  • Nothing specific - known as the great mimicker of live pathology.
  • Steatosis.
  • Portal fibrosis.

Stains

  • Copper staining positive - only 15% of cases.
    • Other stains: rhodinine (red/orange granules = positive), orecin.

Notes:

  • Copper staining is a non-specific finding seen in many liver diseases; it is associated with impaired bile secretion.[24]

Additional testing

  • Mass spectrometry - determine portion of copper.

Alpha-1 antitrypsin deficiency

  • AKA alpha1-antiprotease inhibitor deficiency.

Other

Budd-Chiari syndrome

  • AKA hepatic vein obstruction.

General

  • Hepatic outflow obstruction.

Clinical triad:[25]

  • Ascites.
  • Abdominal pain.
  • Hepatomegaly.

Etiology:

Clinical DDx:

Microscopic

Features:[27]

  • Sinusoidal dilation in zone III (congestion).
  • +/-Hepatocyte drop-out.
  • +/-Centrilobular fibrosis.

DDx congestion:

Vanishing bile duct syndrome

General

  • Fatal.

DDx:[29]

Microscopic

Features:[29]

  • Loss of intrahepatitic bile ducts - key feature.
  • Cholestasis.

Note:

  • May occur without fibrosis and inflammation; thus, can be easy to miss.

IHC

  • CK7 -ve.
    • Marks bile ducts.

Congestive hepatopathy

General

  • Liver failure due to (right) heart failure.
  • AKA cardiac cirrhosis - a term used by clinicians.
    • Generally, it does not satisfy pathologic criteria for cirrhosis.[32]

Gross

  • "Nutmeg" liver - yellow spotted appearance.

Microscopic

Features:[33]

  • Zone III atrophy.
  • Portal venule (central vein) distension.
  • Perisinusoidal fibrosis - progresses to centrilobular fibrosis and then diffuse fibrosis.
  • Dilation of sinusoids in all zone III areas - key feature.[34]

Image: Congestive hepatopathy (WC).

Drug-induced liver disease

  • AKA drug-induced liver toxicity.

Focal nodular hyperplasia

  • Abbreviated FNH.

Nodular regenerative hyperplasia

General

Etiology

  • Arterial hypervascularity secondary to loss of hepatic vein radicles (loss of central venule in hepatic lobule).[35]

ASIDE: radicle = ramulus - smallest branch or vessel or nerve.[37]

Gross

  • Diffuse nodularity - whole liver.

Microscopic

Features:[35]

  • "Plump" hepatocytes surrounded by atrophic ones.
  • No fibrosis.

Sinuosoidal obstruction syndrome

  • May be referred to as Hepatic veno-occlusive disease.[38]

General

  • Term for obstruction due to toxicity from a chemotherapeutic agent.[39][27]

Clinical DDx:

Microscopic

Features:[27]

  • Subendothelial swelling in hepatic venules.

Negatives:

  • No thrombosis.

Polycystic kidney disease and the liver

General

Complications of PKD in the liver:[40]

  1. Infected cyst.
  2. Cholangiocarcinoma.
  3. Cholestasis/obstruction due to duct compression.[41]

Cysts:

  • Cysts in the liver, like the kidney, are thought to enlarge with age.

Microscopic

Features:[42]

  • Von Meyenburg complexes (bile duct hamartoma):
    • Cluster of dilated ducts with "altered" bile.
    • Surrounded by collagenous stroma.
    • Separate from the portal areas.[43]

Images:

Notes:

  • Appearance on ultrasound[44] and CT (hypodense)[45] - similar to metastases.

Peliosis hepatis

General

  • Associated with:
    • Infections.
    • Malignancy.
    • Other stuff.
  • Rarely biopsied.

Microscopic

Features:

  • Cyst lined by endothelium.
    • Usu. incomplete.
  • Blood.

Total parenteral nutrition

  • Abbreviated TPN.

General

  • Indication: short gut syndrome, others.

Microscopic

Variable - may range from: steatosis, steatohepatitis, cholestasis, fibrosis and cirrhosis.[46]

Features (classic):[47][48]

  • Steatosis (periportal) - early.
  • Cholestasis - late.

Giant cell hepatitis

  • AKA neonatal giant cell hepatitis.
See: Giant cell hepatitis.

Hepatic amyloidosis

  • AKA liver amyloidosis.
  • AKA amyloidosis of the liver.

General

Microscopic

Features:

  • Amorphous extracellular pink stuff on H&E - see amyloid article.

DDx:

Images

Stains

Fulminant hepatic necrosis

General

Etiology:

Microscopic

Features:

  • Hepatocyte necrosis.
  • Bile duct proliferation.

DDx:

Secondary hemochromatosis

For the hereditary one see hereditary hemochromatosis.

General

  • Iron overload secondary to blood transfusions for hereditary or acquired anemia.[50]
  • Imaging considered the best test, as iron deposition is patchy.[50]

Selected hereditary causes:[50]

Selected acquired causes:[50]

Microscopic

See hereditary hemochromatosis.

See also

References

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  2. "Terminology of chronic hepatitis, hepatic allograft rejection, and nodular lesions of the liver: summary of recommendations developed by an international working party, supported by the World Congresses of Gastroenterology, Los Angeles, 1994.". Am J Gastroenterol 89 (8 Suppl): S177-81. Aug 1994. PMID 8048409.
  3. URL: http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html. Accessed on: 2 May 2012.
  4. Jeong SH, Lee HS (2010). "Hepatitis A: clinical manifestations and management". Intervirology 53 (1): 15–9. doi:10.1159/000252779. PMID 20068336.
  5. STC. 6 December 2010.
  6. Yoon EJ, Hu KQ. Hepatitis C virus (HCV) infection and hepatic steatosis. Int J Med Sci. 2006;3(2):53-6. Epub 2006 Apr 1. PMID 16614743. Avialable at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1415843. Accessed on: September 9, 2009.
  7. OA. September 2009.
  8. Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 448. ISBN 978-1416054542.
  9. URL: http://emedicine.medscape.com/article/170539-overview. Accessed on: 3 May 2012.
  10. STC. 6 December 2010.
  11. STC. 6 December 2010.
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  13. MG. September 2009.
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  15. 15.0 15.1 Online 'Mendelian Inheritance in Man' (OMIM) 263200
  16. Online 'Mendelian Inheritance in Man' (OMIM) 600643
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  18. Yonem, O.; Bayraktar, Y. (Apr 2007). "Clinical characteristics of Caroli's disease.". World J Gastroenterol 13 (13): 1930-3. PMID 17461492.
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  21. URL: http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm. Accessed on: 1 December 2011.
  22. 22.0 22.1 http://emedicine.medscape.com/article/183456-overview
  23. Online 'Mendelian Inheritance in Man' (OMIM) 606882
  24. Miyamura H, Nakanuma Y, Kono N (December 1988). "Survey of copper granules in liver biopsy specimens from various liver abnormalities other than Wilson's disease and biliary diseases". Gastroenterol. Jpn. 23 (6): 633–8. PMID 2464523.
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  34. Suggested by OA. September 2009.
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  45. [The von Meyenburg complex] Schwab SA, Bautz W, Uder M, Kuefner MA. Rontgenpraxis. 2008;56(6):241-4. German. PMID 19294869.
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  49. Bion, E.; Brenard, R.; Pariente, EA.; Lebrec, D.; Degott, C.; Maitre, F.; Benhamou, JP. (Feb 1991). "Sinusoidal portal hypertension in hepatic amyloidosis.". Gut 32 (2): 227-30. PMC 1378815. PMID 1864548. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/.
  50. 50.0 50.1 50.2 50.3 Gattermann, N. (Jul 2009). "The treatment of secondary hemochromatosis.". Dtsch Arztebl Int 106 (30): 499-504, I. doi:10.3238/arztebl.2009.0499. PMC 2735704. PMID 19727383. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2735704/.