Drug-Related Acute Hepatitis

 Minority of cases progress to chronic hepatitis and rarely cirrhosis


image Jaundice, high AST levels, and preexisting chronic liver disease are adverse prognostic factors





Microscopic




• Most medications produce inflammation-predominant pattern

• Most toxins & a few medications like acetaminophen produce necrosis-predominant pattern

• Concomitant bile duct injury, eosinophils, granulomas, perivenular necrosis, and cholestasis out of proportion to hepatocellular injury suggest DILI, but none of these are specific


Top Differential Diagnoses




• Inflammation-predominant pattern: Acute viral hepatitis, autoimmune hepatitis, Wilson disease

• Necrosis-predominant pattern: Herpes/adenoviral hepatitis, ischemic necrosis, acute venous outflow obstruction

image
Portal and Interface Inflammation
The inflammation-predominant pattern of drug-related acute hepatitis features dense lymphoplasmacytic infiltrate and interface hepatocellular injury.


image
Prominent Plasma Cells
Numerous plasma cells image can be seen in drug-induced liver injury and do not necessarily indicate autoimmune hepatitis.

image
Trichrome Stain
The collagen in the portal tracts is coarse and stains darkly image, while the periportal area with ductular reaction shows light staining image. The latter indicates confluent necrosis rather than fibrosis.

image
Orcein Stain
The elastic fibers are highlighted in the portal tract image, while the area of confluent necrosis is negative image. The combination of trichrome and elastic stains help in distinguishing confluent necrosis (acute hepatitis) from fibrosis (chronic hepatitis).


TERMINOLOGY


Abbreviations




• Drug-induced liver injury (DILI)


ETIOLOGY/PATHOGENESIS


2 Chief Mechanisms




• Intrinsic hepatotoxicity
image Predictable, dose-dependent hepatocellular damage

– Industrial, household, or environmental toxins

image Typically shows necrosis with negligible inflammation

• Idiosyncratic hepatotoxicity
image Majority of adverse drug reactions fall in this category

image Metabolic and immunological categories
– Metabolic: Drug is metabolized into toxic metabolite in predisposed individuals

– Immunological: Drug allergy or hypersensitivity following sensitization to drug

image Typically shows inflammation-predominant liver injury


Herbals/Botanicals




• Important but often overlooked cause of hepatotoxicity

• Not regulated by Food and Drug Administration and hence not subject to rigorous testing

• Nearly 20% of American adults have used herbal remedies, and > 5 billion dollars are spent on these annually

• Heavy metal contaminants in these agents (arsenic, cadmium, lead, mercury) can also lead to liver toxicity


CLINICAL ISSUES


Presentation




• 3 clinical patterns
image Hepatitic

– Acute hepatitis with autoimmune markers may mimic autoimmune hepatitis (AIH)

– May have features of hypersensitivity like rash, arthralgia, and peripheral eosinophilia

– Progression to chronic hepatitis with fibrosis and even cirrhosis can occur

image Cholestatic

image Mixed

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Apr 20, 2017 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Drug-Related Acute Hepatitis
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