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S47: Drug-Induced Liver Disease Cheat Sheet (DRAFT) by

Drug-Induced Liver Disease

This is a draft cheat sheet. It is a work in progress and is not finished yet.

Learning Objective #1

Summarize the six major types of drug-i­nduced liver disease.
1. Cytotoxic (Direct Hepato­cel­lular Death): Drug binds covalently to intrac­ellular proteins to disrupt cellular functions. May involve formation of free radicals, ROS, or electr­ophilic radicals, leading to oxidative stress and disruption of ionic gradients, cell membranes, actin, and ATP genera­tion. Liver cells become sensitized to cytokines. Cell death may be zonal (centr­ilo­bular) or non-zonal (diffuse).
2. Immune­-me­diated: Toxins undergo biotra­nsf­orm­ation to form adducts or haptens, which travel to Kupffer cell membranes to evoke an immune response via MHC I and MHC II. Humoral and cellular immune responses lead to inflam­mation and produce liver damage.
3. Steatosis: Toxins inhibit elimin­ation of FA by inhibiting microsomal TG transfer protein (MTP), which is normally respon­sible for forming TG-rich VLDLs and mitoch­ondrial oxidation. Leads to accumu­lation of FA in the mitoch­ondria. Microv­esi­cular steatosis indicates acute injury, whereas macrov­esi­cular steatosis indicates chronic injury.
4. Choles­tatic Injury: Substances secreted into the bile canali­culus cause direct bile duct injury and disable bile salt transport proteins.
5. Vascular Injury: Veno-o­ccl­usion and congestive hepato­tox­icity. Dilation of hepatic sinusoids produce blood-­filled cavities within the liver.
6. Neopla­stic: Benign or malignant neoplasms

Learning Objective #2

List common medica­tions and herbals that are known to cause liver disease and the most likely mechanism of liver toxicity.

Learning Objective #3

List approp­riate risk factors for drug-i­nduced hepatic and choles­tatic diseases.

Learning Objective #4

Calculate an R-value for evaluating drug-i­nduced liver injury and its implic­ations.

Learning Objective #5

Outline approp­riate steps in both the prevention and management of drug-i­nduced hepatic and choles­tatic disease.

Self-A­sse­ssment Questions

1. According to the acute liver failure registry which of the following agents causes the MOST acute liver failure cases?*
A. Phenytoin
B. Acetam­inophen
C. Comple­mentary & Altern­ative Medicine
D. Antimi­cro­bials
E. Valproic Acid
2. Which of the following is/are considered a type of drug-i­nduced liver injury (DILI)? (Select all that apply)
A. Direct hepato­cel­lular
B. Immune­-me­diated
C. Steatosis
D. Choles­tatic
E. Vascular