Drug-induced liver disease

Drug-induced liver disease, also drug-induced liver toxicity and drug liver injury, is relatively common.

Drug reactions in general are dealt with in drug toxicity.

General

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

Microscopic

Features:

Non-specific findings.
- +/-Eosinophils^[1] - significant suggestive finding.
- +/-Steatosis - periportal macrovesicular, microvesicular.
- +/-Vanishing bile duct syndrome.
- +/-Granulomas.

Images

Drug-induced hepatitis - low mag. (WC)
Drug-induced hepatitis - intermed. mag. (WC)
Drug-induced hepatitis - high mag. (WC)

Specific patterns

Acute hepatits:

Related to Rx - most often antibiotics.

Steatohepatitis/steatosis:^[2]

Amiodarone - cardiac arrhythmias.
Tamoxifen - breast cancer.
Carbamazepine - seizures.

Cholestasis:

Venlafaxine - depression.^[3]
Thalidomide - multiple myeloma.^[4]

Specific drugs

Acetaminophen:

Zone 3 necrosis.
- Tx: N-acetylcysteine (NAC).^[5]
  - NAC is an endogenous precursor to glutathione.^[6]
- Hepatotoxicity from N-acetyl-p-benzoquinoneimine (NAPQI) due to depletion of glutathione.^[5]

Methotrexate - chronic use:

Histology:^[7]
- 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.^[8]

Sign out

LIVER, MEDICAL CORE BIOPSIES:
- MILD STEATOHEPATITIS AND MILD FIBROSIS (1/4).
- MILD TO MODERATE STEATOSIS.

COMMENT:
The findings are compatible with nonalcoholic steatohepatitis (NASH), alcoholic
steatohepatitis (ASH) or drug effect. The steatosis is periportal predominant; this 
is not typical for NASH or ASH. Clinical correlation and review of medications 
is suggested.

References

↑ Tadrous, Paul.J. Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum (1st ed.). Wiley. pp. 166. ISBN 978-0470519035.
↑ Grieco, A.; Forgione, A.; Miele, L.; Vero, V.; Greco, AV.; Gasbarrini, A.; Gasbarrini, G.. "Fatty liver and drugs.". Eur Rev Med Pharmacol Sci 9 (5): 261-3. PMID 16237810.
↑ Stadlmann, S.; Portmann, S.; Tschopp, S.; Terracciano, LM. (Nov 2012). "Venlafaxine-induced cholestatic hepatitis: case report and review of literature.". Am J Surg Pathol 36 (11): 1724-8. doi:10.1097/PAS.0b013e31826af296. PMID 23073329.
↑ Vilas-Boas, F.; Gonçalves, R.; Sobrinho Simões, M.; Lopes, J.; Macedo, G. (Oct 2012). "Thalidomide-induced acute cholestatic hepatitis: case report and review of the literature.". Gastroenterol Hepatol 35 (8): 560-6. doi:10.1016/j.gastrohep.2012.05.007. PMID 22789729.
↑ ^5.0 ^5.1 Millea PJ (August 2009). "N-acetylcysteine: multiple clinical applications". Am Fam Physician 80 (3): 265–9. PMID 19621836.
↑ URL: http://www.mskcc.org/mskcc/html/69310.cfm. Accessed on: 19 October 2010.
↑ 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.
↑ MG. 23 September 2009.

External links

Drug-liver toxicity (nih.gov).

[1] Tadrous, Paul.J. Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum (1st ed.). Wiley. pp. 166. ISBN 978-0470519035.

[pmid16237810-2] Grieco, A.; Forgione, A.; Miele, L.; Vero, V.; Greco, AV.; Gasbarrini, A.; Gasbarrini, G.. "Fatty liver and drugs.". Eur Rev Med Pharmacol Sci 9 (5): 261-3. PMID 16237810.

[pmid23073329-3] Stadlmann, S.; Portmann, S.; Tschopp, S.; Terracciano, LM. (Nov 2012). "Venlafaxine-induced cholestatic hepatitis: case report and review of literature.". Am J Surg Pathol 36 (11): 1724-8. doi:10.1097/PAS.0b013e31826af296. PMID 23073329.

[pmid22789729-4] Vilas-Boas, F.; Gonçalves, R.; Sobrinho Simões, M.; Lopes, J.; Macedo, G. (Oct 2012). "Thalidomide-induced acute cholestatic hepatitis: case report and review of the literature.". Gastroenterol Hepatol 35 (8): 560-6. doi:10.1016/j.gastrohep.2012.05.007. PMID 22789729.

[pmid19621836-5] 5.0 ^5.1 Millea PJ (August 2009). "N-acetylcysteine: multiple clinical applications". Am Fam Physician 80 (3): 265–9. PMID 19621836.

[6] URL: http://www.mskcc.org/mskcc/html/69310.cfm. Accessed on: 19 October 2010.

[7] 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.

[8] MG. 23 September 2009.

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Drug-induced liver disease

Contents