Drug, Alcohol, and Metabolic Liver Disease Flashcards
(42 cards)
What is the most common cause of drug-induced liver injury?
acetaminophen
How is acetaminophen toxcitiy treated?
(monitoring and treatment)
- Rumack-Matthew nomogram is used to approximate likelihood of hepatic toxicity; based on plamsa acetaminophen and time post injestion
- 4 hour post-ingestion acetaminophen level is crucial
treatment is with N-acetylcysteine (NAC)
What are examples of dose-dependent hepatotoxins?
- acetaminophen
- amanita mushroom
- tetracycline
- valproic acid
What are idiosyncratic drug reactions?
What types of drugs frequently are implicated in this?
reactions to substances that are unpredicatable
- is not dose-dependnent
- not present in all people
- may illicit an immune response or be related to impaired metabloism to substance
antibiotics are the most common cause of idiosyncratic reactions
Where is damage in drug/toxin-induced liver injury commonly seen?
zone 3 (perivenular) of the lobule
- area of highest concentration of P-450
- many metabolites are directly responsible for liver damage rather than the ingested substance itself
How much alcohol consumption per day is considered “excessive”?
- >80 mg/day in males
- 30-40 mg/day in females
- above has significant risk of severe liver injury if occurs for >10 years
- >160mg/day has expected risk of severe liver damage
a “Standard Drink” contains 10g of alcohol:
- 12 fl oz beer (5%)
- 8 fl oz/half pint malt liquor (7%)
- small glass of wine (5 fl oz)
- 1.5 fl oz shot (~40%)
What are the types of alcohol-related liver disease?
- alcoholic steatosis (fatty liver)
- alcoholic steatohepatitis
- alcoholic steatofibrosis/cirrhosis
What is alcoholic steatosis?
(clinical presentation and labs)
Approximatley how much alcohol consumption is needed?
reversible, microvesicular fatty change
-can regress with cessation
can occur with as little as one day of excessive alcohol consumption (>80mg)
Presentation:
- asymptomatic hepatomegaly
- mild elevations of alk phos and bilirubin
- minimal change in AST/ALT
What is alcoholic hepatitis?
Approximatley how much alcohol consumption is needed?
reversible, inflammatory damage:
- swelling/ballooning w/ steatosis
- necrosis
- Mallory-Denk bodies (eosinophilic inclusions of keratin filaments)
- neutrophil infiltrate
acute presentation following episode(s) of heavy alcohol consumption
What is the clinical presentation and lab findings of alcoholic steatohepatitis?
Presentation:
- ranges from asymtomatic to severe liver failure depending on severity
- anorexia, nausea, vomiting, jaundice, tender hepatomegaly, RUQ pain
Labs:
- elevated AST/ALT w/ ratio of >2:1 (typcially below 400U/L)
- elevated bilirubin, alk phos, and GGT
- leukocytosis w/ left shift
- possible megaloblastic anemia (folic acid deficiency)
- thrombocytopenia (direct toxcity or hypersplenism)
- decreased LFT (increased PT/INR, decreased albumin)
What is alcoholic steatofibrosis?
Approximatley how much alcohol consumption is needed?
usually irreversible fibrotic change
- fibrosis begins around central vein and spreads through space of Disse -> “chicken wire” pattern
- irreversible with increased severity or progression to cirrhosis
-reversible in early stages with abstinence
-long-term exposure to excessive alcohol consumption (prolonged alcoholic steatosis)
-repeated attacks of alcoholic hepatitis
What is the risk of developing cirrohsis from alcohol consumption alone?
What factors increase the risk of developing cirrhosis?
10-15% of chronic alcoholics develop cirrhosis
Risk factors:
- female (more at risk despite being less prevalent)
- African American
- HBV or HCV infection
- iron overload
- malnutrition?
How does the body metabolize alcohol?
How does alcohol metabolism cause hepatocyte damage?
In the liver:
- alcohol dehydrogenase, ADH (cytoplasmic): EtOH + NAD+ -> acetaldehyde + NADH
- acetaldehyde dehydrogenase, ALDH (mitochondiral): acetaldehyde + NAD+ -> acetic acid + NADH
at high blood EtOH levels:
-microsomal P-450 pathway is used -> ROS
damage caused by:
- consumption of NAD+
- increased fat catabolism
- peroxidation of lipid by acetaldehyde
- production of ROS
- enhanced drug metabolism (P-450 activation)
What are complications of advanced alcoholic liver disease?
- infection
- GI hemorrhage (variceal hemorrhage and/or coagulopathy)
- HCC
-Wernicke encephalopathy
-Korsakoff syndrome
Decompensated cirrhosis:
- coma (hepatic encephalopathy)
- ascites (w/ SBP)
- portal HTN
- coagulopathy
- hepatorenal syndrome
What is Wernicke encephalopathy and Korsakoff syndrome?
Wernicke encephalopathy (acute and reversible):
- AMS
- ataxia
- saccadic eye movements (nystagmus, diploplia, ophthalmaplegia)
- treated with thiamine
Korsakoff syndrome (chronic and irreversible):
- severe memory issues
- confabulation
- personality/psych changes
- no response to thiamine
What lab and clinical finding are poor prognositc inidcators in alcoholic liver disease (indicate severe alcoholic hepatitis)?
- ascites
- variceal hemorrhage
- encephalopathy
- hepatorenal syndrome
severe alcoholic hepatitis:
- total bilirubin >8-10 mg/dL
- PTT > 6 sec
- hypoalbuminemia
- azotemia
What measures are used to predict prognosis of alcoholic liver disease?
Maddrey’s discrminant function (DF):
-calculated with PT and bilirubin
-value >32 is poor prognosis
Glasgow alcoholic hepatitis score:
- multivariable
- score >9 is poor prognosis
Model for End-Stage Liver Disease (MELD):
- value >14 qualifies for liver transplant
- value >21 indicates significant mortality
What are the types of aquired metabolic liver disease?
- non-alcoholic fatty liver disease (NAFLD)
- non-alcoholic seatohepatitis (NASH)
How is alcoholic liver disease treated?
Treatment:
-abstinence from alcohol (taper if needed to prevent withdrawal)
Management:
- thiamine
- folic acid
- multivitamin
- zinc
- monitor glucose and administer as need (give increased thiamine with glucose)
- correction of electrolyte deficiencies (potassium, magnesium, and phosphate)
What is NAFLD?
hepatic steatosis not attributable to alcohol consumption
assocaited with metabolic syndrome:
-one of: DM, impaired glucose tolerance, impaired fasting glucose, insulin resistance
-and-
-two of: HTN (BP > 140/90), dyslipidemia, central obesity, microalbuminemia
What is the clinical presentation and lab findings of NAFLD?
Presentation:
typically asymptomatic aside from symptoms of metabolic syndrome
Lab findings:
-liver tests normal
-abnormal lab values associated with metaboic syndrome
What is NASH?
identical histology with alcoholic hepatitis:
- swelling/ballooning w/ steatosis
- necrosis
- Mallory-Denk bodies (eosinophilic inclusions of keratin filaments)
- neutrophil infiltrate (monocytes may be more prominent)
What is the clinical presentation and lab findings of NASH?
Presentation:
- symptoms of metabolic syndrome
- possible RUQ pain
- hepatomegaly
Labs:
- mildly elevated AST/ALT (ratio of less than <1 unlike alcohoic hepatitis)
- mildly elevated alk phos
- abnormal lab values associated with metaboic syndrome
What are complications of NAFLD/NASH?
NAFLD:
-no major complicaitons beyond progression to NASH
NASH:
- cirrhosis (possible decompensation)
- HCC
