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Viral Hepatitis

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Liver Biopsy

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Liver Biopsy

Liver biopsy is an important diagnostic tool in assessing the nature and severity of liver disease. Liver biopsy provides information concerning

  • the cause of the liver damage
  • the degree of ongoing liver injury
  • the extent of chronic liver damage

Liver biopsy provides the clinician with confirmation of the diagnosis of hepatitis C, as well as a determination of the amount of inflammation and fibrosis. In HCV infection, there is a poor correlation between symptoms or levels of alanine aminotransferase and histologic features of the liver. Thus, patients with HCV infection may have normal levels of liver enzymes and have significant fibrosis on biopsy. Conversely, patients may also have elevated serum ALT and trivial liver disease.(1)

Risks

Liver biopsy carries a small risk of complications. If performed correctly, most patients do not feel pain during the biopsy. Some of the risks include the following:

  • Bleeding requiring
    • transfusion in less than one per thousand biopsies
    • surgery in less than per thousand biopsies
  • Penetration of other organs such as lung, kidney, gallbladder, intestine
  • Fatality in less than one per ten thousand biopsies

Because of the small risk of complications, liver biopsy should only be performed when the information will be useful for optimal patient care and only after written informed consent has been obtained. In hepatitis C, this would include

  • prior to starting HCV treatment
  • determination of extent of liver damage, particularly in patients with persistent, significant elevations in ALT

Procedure

A liver biopsy can usually be safely performed as an outpatient procedure. A physician trained and experienced in the procedure should perform the liver biopsy. Prior to the procedure, patients should discontinue all anticoagulants (e.g., coumadin) for at least a week and should not take aspirin or other non-steroidal anti-inflammatory medicines for about a week (patients can take acetaminophen). Additional contraindications to percutaneous liver biopsy include the following:(2)

Absolute Contraindications

  • Uncooperative patient
  • History of unexplained bleeding
  • Tendency to bleed*
    • Prothrombin time 3-5 sec more than control
    • Platelet count <50,000/mm3
    • Prolonged bleeding time (10 minutes)
    • Use of NSAID within previous 7-10 days
  • Blood for Transfusion unavailable
  • Suspected hemangioma or other vascular tumor
  • Inability to identify an appropriate site for biopsy by percussion or ultrasonography
  • Suspected echinococcal cysts in the liver

Relative Contraindications

  • Morbid obesity
  • Ascites
  • Hemophilia
  • Infection in the right pleural cavity or below the right hemidiaphragm
*Although these criteria are considered absolute contra-indications by most hepatologists, they can be corrected by transfusions of platelets or fresh-frozen plasma and are therefore not truly absolute.
Source: Bravo AA, Sheth SG, Chopra S. Current Concepts: Liver Biopsy. N Engl J Medicine 2001; 344: 498, Table 2; Use of aspirin within 7-10 days is an absolute contraindication to liver biopsy. Use of other NSAIDS within the previous 3 days is generally an absolute contraindication.

For the procedure:

  • Patients must provide written informed consent
  • Patients are placed flat in bed and the liver is localized in the right mid-axillary line
  • Localization of the liver can be performed by percussion/palpation or by ultrasound
  • Some physicians administer conscious sedation prior to the liver biopsy
  • The skin over the biopsy site is cleaned with betadine or another suitable antiseptic, and lidocaine is injected locally to anesthetize the skin and the capsule of the liver
  • Liver biopsy is performed by quickly inserting and then withdrawing a 15 to 18-gauge needle into the liver. A successful biopsy obtains a piece of liver tissue approximately the diameter of the lead in a pencil and 1 inch long

Post-Procedure:

  • The patient lies on his/her right side for 1-2 hours and then on his/her back for 3-5 hours (total observation after liver biopsy is 4-6 hours)
  • Blood pressure and heart rate are checked frequently during this time
  • Patients are allowed to go home if they can follow instructions reliably and have easy access to a hospital should they develop bleeding or other complications
  • Patients should remain off anti-coagulants, aspirin and NSAIDs for at least one week
  • Patients should be advised to refrain from heavy lifting or strenuous exercise for one to two weeks following the procedure

Histopathology

Liver biopsy provides the best information available concerning the amount of hepatic fibrosis and the amount of ongoing inflammation and necrosis. Inflammation is characteristically predominantly located in the portal area and consists of a mixture of mononuclear cells and lymphocytes. In more severe cases, inflammation and necrosis of the lobular parenchyma is present. Fibrosis usually begins in the portal area in HCV and in the central vein in alcoholic liver disease. Bridging fibrosis refers to the presence of fibrosis that reaches from a portal area to another portal area. Cirrhosis consists of extensive bridging fibrosis in the presence of regeneration such that normal portal areas and normal central veins cannot be identified.

One grading system used for assessing inflammation and fibrosis is that of Batts and Ludwig.(3)

Inflammation (Grade)
GradeDescriptionPiecemeal NecrosisLobular Inflammation and Necrosis
0No activityNoneNone
1MinimalMinimal, patchyMinimal; occasional spotty necrosis
2MildMild; involving some or all portal tractsMild; little hepatocellular damage
3ModerateModerate; involving all portal tractsModerate; with noticeable hepatocellular damage
4SevereSevere; may have bridging fibrosisSevere, with prominent diffuse hepatocellular damage

Print table

Fibrosis (Stage)
StageDescriptionCriteria
Source: Batts and Ludwig (Am J Surg Pathol 1995) (Table)
0No fibrosisNormal connective tissue
1Portal fibrosisFibrous portal expansion
2Periportal fibrosisPeriportal or rare portal-portal septa
3Septal fibrosisFibrous septa with architectural distortion; no obvious cirrhosis
4CirrhosisCirrhosis

Print table

Other grading systems include Metavir and Histologic Activity Index (Knodell Score).

References

  1. Bravo AA, Sheth SG, Chopra S. Current Concepts: Liver BiopsyLink will take you outside the VA website.. N Engl J Medicine 2001; 344(7):495-500.
  2. Ibid., 498 (table 2).
  3. Batts KP, Ludwig J. Chronic hepatitis. An update on terminology and reportingLink will take you outside the VA website.. Am J Surg Pathol 1995;19(12): 1409-17.

Suggested Reading

  1. Ludwig J, Batts KP, Moyer TP, Poterucha JJ. Advances in liver biopsy diagnosis. Mayo Clin Proc 1994 Jul;69(7):677-8.