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Liver and intrahepatic bile ducts-nontumor

General concepts

Fulminant hepatitis / massive hepatic necrosis

Reviewers: Komal Arora, M.D. (see Reviewers page)
Revised: 30 April 2012, last major update April 2012
Copyright: (c) 2004-2012, PathologyOutlines.com, Inc.


● Uncommon (<1%) complication of acute viral hepatitis
● Progresses from onset of symptoms to hepatic encephalopathy in 2-3 weeks in previously healthy patient
● Orderly regeneration due to massive destruction of confluent lobules
● Liver can regenerate after massive necrosis if connective tissue framework is intact
Regeneration: portal ductules increase in size and number and become dilated
● Individual hepatocytes with clear cytoplasm appear from ductules
● Ductules are transformed into hepatocytes and form round cell clusters, which organize into trabeculae with fibrosis
● Lobular architecture is established
● May become normal at 14 months (Mod Pathol 2000;13:152)
Causes: viruses (Hepatitis B, C), drugs (acetaminophen, carbon tetrachloride, halothane, isoniazid, rifampin), acute fatty liver of pregnancy, hepatic vein obstruction, hyperthermia, ischemia, tumor, Wilsonís disease
Subfulminant hepatitis: less rapid, up to 3 months to hepatic encephalopathy


● Liver transplant, auxiliary partial orthotopic liver transplant
● Mortality without liver transplant is 25-90% (Semin Liver Dis 2008;28:175)

Case reports - causes

● Acetic acid (concentrated) in 42 year old woman (Arch Pathol Lab Med 2000;124:127)
● Phenytoin and trimethoprim-sulfamethoxasole in 60 year old woman (Arch Pathol Lab Med 2000;124:1800)
● Troglitazone in 63 year old woman (Hum Pathol 2000;31:250)

Gross images

Post phenytoin-trim-sulfa: necrosis at autopsy

Micro description

● Massive necrosis of hepatocytes in all zones (possible periportal sparing) with reticulin collapse, often with minimal inflammatory reaction
● May be bile duct proliferation, lymphocytic infiltration of central veins
● Biopsies may have minimal findings due to variability of disease

Micro images

Hepatocyte necrosis, chronic inflammatory infiltrate and bile duct proliferation

Post acetic acid periportal fibrosis

Regeneration after transplant:

Days 0-7

Day 29

2-3 months

6-14 months

Additional references

Med Clin North Am 2008;92:761, Hepatology 2008;47:1401

End of Liver and intrahepatic bile ducts-nontumor > General concepts > Fulminant hepatitis / massive hepatic necrosis

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