Medical liver disease

From Libre Pathology
Revision as of 13:21, 19 October 2010 by Michael (talk | contribs) (→‎Common: more)
Jump to navigation Jump to search

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" -- if it isn't clearly malignancy.

Liver neoplasms are dealt with in the liver neoplasms article.

Hepatitis A

  • Infection is self-limited, i.e. not persistent.
  • Usually asymptomatic in children.[1]
  • Serology is diagnostic.

Hepatitis B

General

  • May lead to hepatocellular carcinoma without cirrhosis.
  • High prevalence.
  • Diagnosis is by serology.

Histology

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.

Histology

  • Lobular inflammation - this is non-specific finding.
  • Periportal steatosis in genotype 3.[2]
    • Steatosis in hepatitis C is usually a secondary pathology, i.e. a separate pathologic process.[3]

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.[4]

Gross

  • "Nutmeg" liver - yellow spotted appearance.

Histologic

Features:[5]

  • 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.[6]

Image: Congestive hepatopathy (WC).

Alcoholic liver disease

  • Acute and/or chronic liver changes due to alcohol use.
  • Includes ASH (alcoholic steatohepatitis).

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.

Histopathology

See:

Features:

  • Often zone III damage.
  • Neutrophils (often helpful to differentiate) -- few other things have PMNs.
  • Cholestatsis common, i.e. yellow staining.
  • Fibrosis starts at central veins.

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.[7]
  • Some consider alcoholic liver disease a clinical diagnosis, i.e. as a pathologist one does not diagnose it.[8]

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

General

  • Steatohepatitis is a label for a set of histopathologic findings.
    • May arise due to numerous etiologies, e.g. alcoholic steatohepatitis (ASH), non-alcoholic steatohepatitis (NASH).
  • Fat accumulation in hepatocytes.
    • It may be a pattern seen in drug toxicity, e.g. methotrexate toxicity.[9]

Microscopic

Features:

  • Steatosis (usually macrovesicular) - key feature.
    • If less than 10% ... consider alt. diagnosis/disease process.
  • Hepatocyte injury:
    • Ballooning degeneration - key feature (see introduction to liver).
    • Mallory bodies.
      • Mallory body wannabes: "occasional cytoplasmic clumping".
  • +/-Chicken-wire perisinusoidal fibrosis +/- zone III (centrilobular) fibrosis (early).
    • Late-stage disease - portal bridging.[10]

Image: Steatohepatitis (WC).

Grading steatohepatitis

Grading inflammation:[11]

  • Grade 1 - steatosis, occasional ballooning degeneration, PMNs.
  • Grade 2 - obvious ballooning, obvious PMNs, chronic inflammation.
  • Grade 3 - panacinar steatosis.

Autoimmune hepatitis

General

  • Abbreviated AIH.
  • Several criteria exist to diagnose.

Diagnosis

Simplifed diagnostic criteria (2008):[12]

  1. Antibody titer.
  2. Elevated IgG.
  3. Liver pathology.
  4. Exclusion of viral hepatitis.

Details (scoring):[12]

  • ANA or SMA 1:40 1 point.
  • ANA or SMA 1:80 2 points.
  • LKM 1:40 2 points.
  • IgG upper normal 1 point.
  • IgG 1.1x upper limit 2 points.
  • Histology compatible 1 point.
  • Typical AIH histo. 2 points.
  • No viral hepatsis 2 points.

Interpretation: Definite >= 7. Probable = 6.

Notes:

  • Autoantibodies may be seen in HCV.[12]
  • A normal IgG is very unusual in AIH - but may be seen in atypical variants with zone III involvment.

Abbreviations:

  • ANA = anti-nuclear antibody.
  • SMA = smooth muscle antibody.
  • LKM-1 = liver kidney microsomal type 1 antibody.

Histology

Classification:[12]

  • Typical:
    • Interface hepatitis (zone 1).
      • Lymphocytic/lymphoplasmacytic infiltration of portal tracts + lobule.
    • Emperipolesis - one cell penetrates into another one.
    • Hepatic rosette.
  • Compatible
    • Chronic hepatitis - with lymphocytic dominant.
  • Atypical:
    • Signs of other disease.

Notes:

  • PAS may be useful - find plasma cells. (???)
  • Atypical Autoimmune hepatitis may have zone III involvment (lymphoplasmacytic infiltrate)[13] and a normal IgG.[14]

Micrographs:

Treatment

  • Immunosuppresants (prednisone, azathioprine).[13]

Primary biliary cirrhosis

  • Abbreviated PBC.

Epidemiology

  • Female>male (~9:1).[15]
  • Usually middle age.
  • Associated with other autoimmune conditions (Sjogren's syndrome, progressive systemic sclerosis, celiac).

Etiology

  • Autoimmune.

Serology

  • AMA+.

Classic presentation

  • Pruritis.

Pathophysiology

  • Septal bile duct attacked.

Histopathology

  • Intraepithelial lymphocytes - in bile duct key feature.
  • Bile duct epithelial cells with eosinophilic cytoplasm.[16]
  • Plasma cells.
  • Granulomas - close to bile duct.
    • Seen in classic presentation -- often not present or poorly formed.
  • Focal damage (may be missed on biopsy -- due to sampling).
  • "Garland" cirrhosis -- has irregular border (unlike in EtOH).
    • Garland originally "wreath of flowers" (in French).[17]

Images:

DDx:[18]

  • Sarcoidosis (if granulomas present).
  • PSC, viral hepatitis, AIH, drugs, Hodgkin's lymphoma[19]

Staging

PBC is staged according to Ludwig:[20]

  • Stage 1: Portal - inflammation or bile duct abnormalities.
  • Stage 2: Periportal - periportal fibrosis (enlargement of portal tracts) +/- inflammation.
  • Stage 3: Septal - septal fibrosis +/-inflammation in septa.
  • Stage 4: Cirrhosis - nodules of hepatocytes +/- inflammation.

Notes:

  • There can be significant variation in staging on biopsy - due to variability of fibrosis in a PBC liver.[21]
    • "Worst area" in biopsy specimen is used to determine stage.

Treatment

  • Ursodeoxycholic acid.
  • May be indication for transplant.


Autoimmune hepatitis-primary biliary cirrhosis overlap syndrome (AIH-PBC OS)

Epidemiology

  • Rare.

Serology

  • AMA+, anti-dsDNA+.[22]


Primary sclerosing cholangitis

Diagnosis

  • Diagnosed radiologically.
  • Liver biopsy is rarely useful diagnostically[25] - as the disease may be patchy.
    • The utility of the biopsy is staging.

Treatment

  • None very good.
  • May be indication for transplant.

Histopathology

  • Classic: "onion-skinning" - cells layer around the bile ducts; "onion skin" present in approx. 40% of cases.[26]
    • Not pathognomonic for PSC[26] - but not too much else looks like this on microscopy (ergo good fellowship exam question).
  • +/-Ductopenia.
  • +/-Ductal proliferation.

DDx:

  • Big.

Micrographs:

Staging

Features:[27]

  • Stage I - focal portal inflammation, +/- duct abnormalities, no fibrosis.
  • Stage II - portal enlargement (fibrosis), +/- inflammation.
  • Stage III - bridging fibrosis + necrosis.
  • Stage IV - cirrhosis.

Notes:

  • Similar to PBC staging.

Hereditary hemochromatosis

Epidemiology/General

  • Genetic defect.
    • One mutation (C282Y mutation) in up to 12.5% of people in populations of northern and central European origin.[28]
  • Onset in males earlier than females (due to menses).
  • Mutation thought to confer survival advantage - several theories (increased resistance to TB, S. typhi vs. decr. iron def./incr. iron absorption)[28]
  • May lead to restrictive cardiomyopathy.

Pathophysiology

  • Iron overload --> cirrhosis.

Microscopic

  • Periportal changes (early), i.e. no iron centrilobular.
    • Late stage disease has diffuse iron deposition.
  • Brown granular -- may vaguely look like lipofuscin on H&E.

Diagnosis suggested by positive iron stain.

  • Light blue haze is not enough.
    • NOT siderosis -- in Kupffer cells.

Image: Hemosiderosis - iron stain (WC).

Notes:

  • Iron in the bile ducts and endothelium used to be though specific of hereditary hemochromatosis.[29]
    • It is now thought to just reflect the severity of iron deposition, i.e. if the bile ducts and endothelium have iron - it is severe.

DDx

  • Myelodysplastic syndrome.
  • Chronic hemolysis.
  • Alcohol.

Wilson's disease

Epidemiology

  • Rare autosomal recessive - mutation in copper-transporting adenosine triphosphatase (ATPase) gene (ATP7B).[30]
    • Heterozygote carrier rate approximately 1/100 persons.[30]
  • 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.

Histopathology

  • Nothing specific.
  • Steatosis.
  • Portal fibrosis.

Staining:

  • Copper staining positive in ONLY 15%.
    • Other stains: rhodinine, orecin.


Alpha-1 antitrypsin deficiency

General

  • AKA 'alpha1-antiprotease inhibitor deficiency'.

Etiology

  • Genetic defect.

Causes

  • Lung and liver injury.
    • Lung -> emphysema.

Histopathology

  • Pink globules in zone 1.
    • Globules not seen in children.
    • May not be present in late stage (cirrhotic).
    • Best seen on PAS-diastase.
    • Can be seen on H&E -- if one looks carefully.

Drug toxicity

  • Can do almost anything; may include: granulomata, bile duct injury, cholestasis, ischemic type injury.
  • Effects can be delayed -- temporal relationship not always obvious.

Microscopic:

  • Non-specific findings.
    • +/-Eosinophils.[31]
    • +/-Steatosis - periportal macrovesicular, microvesicular.

Common

Acute hepatits:

  • Related to Rx - most often antibiotics.

Acetaminophen:

  • Zone 3 necrosis.
    • Tx: N-acetylcysteine (NAC).[32]
    • Toxicity due to N-acetyl-p-benzoquinoneimine (NAPQI) due to depletion of glutathione.[32]

Methotrexate - chronic use:

  • Histology:[33]
    • Features of steatohepatitis.
      • Zone III steatosis.
      • Ballooning degeneration.
    • Portal inflammation with mixed population (lymphocytes, macrophages, PMNs).
    • Nuclear atypia (hyperchromasia, pleomorphism, vacuolation).
      • Described as just nuclear size variation by some.[34]

Focal nodular hyperplasia

  • Abbreviated FNH.
  • Not commonly seen by pathologists.
  • Benign lesions.
  • Associated with oral contraceptive pill (OCP) use.

Imaging

  • FNH enhances on the arterial phase in triphasic imaging, i.e. triphasic CT or MRI.[35]

Gross

Features:[36]

  • Well circumscribed, but no capsule.
  • Lighter than surrounding parenchyma, may be yellow.
  • +/-Stellate central scar with thick vessels.

Note: Usually a solitary lesion.[35]

Histopathology

Features:[37]

  • Stellate scar has large arteries with fibromuscular hyperplasia.
    • Thin fibrous septa radiate from the central scar - surrounded by lymphocytes & bile ductules.
      • Normal hepatocytes between fibrous septae.

DDx

  • May be difficult to distinguish from hepatic adenoma if no scar and no ductal proliferation.[38]


Nodular regenerative hyperplasia

  • Associated with renal transplants, bone marrow transplants and vasculitities.[39]
  • Can lead to portal hypertension and many of the associated complications.

Etiology

  • Arterial hypervascularity secondary to loss of hepatic vein radicles (loss of central venule in hepatic lobule).[40]

ASIDE: radicle = ramulus - smallest branch or vessel or nerve.[41]

Gross

  • Diffuse nodularity - whole liver.

Histopathology

Features:[42]

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


Sinuosoidal obstruction syndrome

  • Term for obstruction due to toxicity from a chemotherapeutic agent.[43]
  • May be referred to as Hepatic veno-occlusive disease.[44]

Polycystic kidney disease and the liver

Complications of PKD in the liver:[45]

  1. Infected cyst.
  2. Cholangiocarcinoma.
  3. Cholestasis/obstruction due to duct compression.[46]

Cysts:

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

Microscopic

Features:[47]

  • Von Meyenburg complexes (bile duct hamartoma):
    • Cluster of dilated ducts with "altered" bile.
    • Surrounded by collagenous stroma.
    • Separate from the portal areas.[48]

Images:

Notes:

  • Appearance on ultrasound[49] and CT (hypodense)[50] - similar to metastases.

See also

References

  1. ↑ Jeong SH, Lee HS (2010). "Hepatitis A: clinical manifestations and management". Intervirology 53 (1): 15–9. doi:10.1159/000252779. PMID 20068336.
  2. ↑ 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.
  3. ↑ OA. September 2009.
  4. ↑ URL: http://emedicine.medscape.com/article/151792-overview. Accessed on: 17 June 2010.
  5. ↑ URL: http://emedicine.medscape.com/article/151792-diagnosis. Accessed on: 17 June 2010.
  6. ↑ Suggested by OA. September 2009.
  7. ↑ Jensen K, Gluud C (November 1994). "The Mallory body: theories on development and pathological significance (Part 2 of a literature survey)". Hepatology 20 (5): 1330-42. PMID 7927269.
  8. ↑ MG. September 2009.
  9. ↑ MG. 22 September 2009.
  10. ↑ Gramlich, T.; Kleiner, DE.; McCullough, AJ.; Matteoni, CA.; Boparai, N.; Younossi, ZM. (Feb 2004). "Pathologic features associated with fibrosis in nonalcoholic fatty liver disease.". Hum Pathol 35 (2): 196-9. PMID 14991537.
  11. ↑ Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR. Am J Gastroenterol. 1999 Sep;94(9):2467-74. PMID 10484010.
  12. ↑ 12.0 12.1 12.2 12.3 Scoring systems for the diagnosis of autoimmune hepatitis: past, present, and future. Wiegard C, Schramm C, Lohse AW. Semin Liver Dis. 2009 Aug;29(3):254-61. Epub 2009 Aug 12. PMID 19675998
  13. ↑ 13.0 13.1 Non-classical phenotypes of autoimmune hepatitis and advances in diagnosis and treatment. Czaja AJ, Bayraktar Y. World J Gastroenterol. 2009 May 21;15(19):2314-28. Review. PMID 19452572.
  14. ↑ FW. 21 September 2009.
  15. ↑ Tadrous, Paul.J. Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum (1st ed.). Wiley. pp. 162. ISBN 978-0470519035.
  16. ↑ OA. 11 September 2009.
  17. ↑ http://dictionary.reference.com/browse/garland
  18. ↑ Tadrous, Paul.J. Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum (1st ed.). Wiley. pp. 163. ISBN 978-0470519035.
  19. ↑ Vanishing bile duct syndrome and Hodgkin disease: a case series and review of the literature. Pass AK, McLin VA, Rushton JR, Kearney DL, Hastings CA, Margolin JF. J Pediatr Hematol Oncol. 2008 Dec;30(12):976-80. PMID 19131796.
  20. ↑ PBC. eMedicine.com. URL: http://emedicine.medscape.com/article/171117-diagnosis. Accessed on: 22 September 2009.
  21. ↑ J Clin Pathol. 1996 July; 49(7): 556-559. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=500569. Accessed on: September 22, 2009.
  22. ↑ The serological profile of the autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. Muratori P, Granito A, Pappas G, Pendino GM, Quarneti C, Cicola R, Menichella R, Ferri S, Cassani F, Bianchi FB, Lenzi M, Muratori L. Am J Gastroenterol. 2009 Jun;104(6):1420-5. Epub 2009 Apr 28. PMID 19491855.
  23. ↑ Khurana V, Singh T. Primary sclerosing cholangitis. eMedicine.com. URL: http://emedicine.medscape.com/article/187724-overview. Accessed on: 29 November 2009.
  24. ↑ Jesudian, AB.; Jacobson, IM. (2009). "Screening and diagnosis of cholangiocarcinoma in patients with primary sclerosing cholangitis.". Rev Gastroenterol Disord 9 (2): E41-7. PMID 19668124.
  25. ↑ Khurana V, Singh T. Primary sclerosing cholangitis. eMedicine.com. URL: http://emedicine.medscape.com/article/187724-diagnosis. Accessed on: 29 November 2009.
  26. ↑ 26.0 26.1 Steele et al. URL: http://www.medscape.com/viewarticle/552500_6. Accessed on: 29 November 2009.
  27. ↑ Steele et al. URL: http://www.medscape.com/viewarticle/552500_6. Accessed on: 29 November 2009.
  28. ↑ 28.0 28.1 Weinberg ED (2008). "Survival advantage of the hemochromatosis C282Y mutation". Perspect. Biol. Med. 51 (1): 98-102. doi:10.1353/pbm.2008.0001. PMID 18192769.
  29. ↑ MG. 17 September 2009.
  30. ↑ 30.0 30.1 http://emedicine.medscape.com/article/183456-overview
  31. ↑ Tadrous, Paul.J. Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum (1st ed.). Wiley. pp. 166. ISBN 978-0470519035.
  32. ↑ 32.0 32.1 Millea PJ (August 2009). "N-acetylcysteine: multiple clinical applications". Am Fam Physician 80 (3): 265–9. PMID 19621836.
  33. ↑ Burt, Alastair D.;Portmann, Bernard C.;Ferrell, Linda D. (2006). MacSween's Pathology of the Liver (5th ed.). Churchill Livingstone. pp. 715. ISBN 978-0-443-10012-3.
  34. ↑ MG. 23 September 2009.
  35. ↑ 35.0 35.1 http://emedicine.medscape.com/article/368377-overview
  36. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 922. ISBN 0-7216-0187-1.
  37. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 922. ISBN 0-7216-0187-1.
  38. ↑ STC. 19 Jan 2009.
  39. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 922. ISBN 0-7216-0187-1.
  40. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 922. ISBN 0-7216-0187-1.
  41. ↑ Dorland's Medical Dictionary. 30th Ed.
  42. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 922. ISBN 0-7216-0187-1.
  43. ↑ Review article: updates in the pathogenesis and therapy of hepatic sinusoidal obstruction syndrome. Helmy A. Aliment Pharmacol Ther. 2006 Jan 1;23(1):11-25. Review. PMID 16393276.
  44. ↑ Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). DeLeve LD, Shulman HM, McDonald GB. Semin Liver Dis. 2002 Feb;22(1):27-42. Review. PMID 11928077.
  45. ↑ Burt, Alastair D.;Portmann, Bernard C.;Ferrell, Linda D. (2006). MacSween's Pathology of the Liver (5th ed.). Churchill Livingstone. pp. 174-5. ISBN 978-0-443-10012-3.
  46. ↑ URL: http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868. Accessed on: 23 September 2009.
  47. ↑ Burt, Alastair D.;Portmann, Bernard C.;Ferrell, Linda D. (2006). MacSween's Pathology of the Liver (5th ed.). Churchill Livingstone. pp. 176. ISBN 978-0-443-10012-3.
  48. ↑ Meyenburg complex. Stedman's Medical Dictionary. 27th Ed.
  49. ↑ Bile duct hamartomas--the von Meyenburg complex. Salles VJ, Marotta A, Netto JM, Speranzini MB, Martins MR. Hepatobiliary Pancreat Dis Int. 2007 Feb;6(1):108-9. PMID 17287178.
  50. ↑ [The von Meyenburg complex] Schwab SA, Bautz W, Uder M, Kuefner MA. Rontgenpraxis. 2008;56(6):241-4. German. PMID 19294869.
Retrieved from "https://librepathology.org/w/index.php?title=Medical_liver_disease&oldid=2307"