drug induced liver disease

drug induced liver injury

• a term to describe a spectrum of pathological responses in the liver after exposure to potentially hepatotoxic chemical compounds.

acute liver failure

• drug induced liver injury is leading cause of ____

host factors for drug induced liver injury

• Age

• Sex

• Pregnancy

• Malnutrition

• Obesity

• Diabetes

• Comorbidities

• Indication for therapy

environmental factors for drug induced liver injury

• smoking

• alcohol consumption

• infection

• inflammatory epidoses

drug related factors for drug induced liver injury

• daily dose

• metabolic profile

• class effect

• drug interactions

• polypharmacy

intrinsic, idiosyncratic

• two major types of DILI

intrinsic DILI

• predictable

• typically dose related

• occurs in large proportion of patients exposed

• onset within a short time span (hours-days)

idiosyncratic DILI

• unpredictable and spontaneous

• not usually dose-related

• rare, not reproducible in animal models

• variable latency (days to weeks)

hepatocellular injury

• key marker = elevations in ALT

• associated with poor prognosis

• injury pattern more common with idiosyncratic DILI

• acute liver injury characterized with hepatocyte necrosis, chronic injury more often display fibrosis

• R > 5

cholestatic injury

• key marker = elevations in ALP

• present with abnormal biliary secretory function

• R < 2

mixed injury

• combine characteristics of hepatocyte damage, bile duct obstruction, degradation or problems with bile secretions

• 2 < R < 5

R value equation

• ALT/45 / ALP/91

hepatocellular DILI

• R > 5

mixed DILI

• 2 < R < 5

cholestatic DILI

• R < 2

5As predominantly associated with DILI

• alcohol

• antibiotics

• antiepileptics

• atorva(statins)

• acetaminophen

do not discontinue medications until

• ALT ≥ 5x ULN

• ALP ≥ 2x ULN

• ALT ≥ 3x ULN and Tbili ≥ 2x ULN

N-acetylcysteine

• precursor of glutathione

• only approved agent for acetaminophen induced DILI

ursodiol

• hydrophobic bile acid that decreases the cholesterol content of bile

cholestyramine

• recommended for hepatotoxicity caused by leflunomide and terbinafine

L-carnitine

• potential treatment for valproic acid hepatotoxic agent

folic acid

• potential treatment for hepatotoxic methotrexate

adverse clinical outcomes for DILI

• acute liver failure

• vanishing bile duct syndrome (gradual loss of bile ducts)

• cirrhosis

• need for liver transplant