L12: Alcoholic liver disease Flashcards
Blood flow in the liver
Hepatic artery→ oxygenated blood to liver→ hepatic veins→ inferior vena cava
GI tract and spleen→ Portal vein→ products of digestion to liver→ processes nutrients and filters toxins→ hepatic veins→ inferior vena cava
Stages of Alcoholic liver disease
Not distinct stages, multiple stages may be present at once
- Fatty Liver (Simple Steatosis) (present in most drinkers >60g/day)
- Alcoholic Hepatitis
- Chronic Hepatitis with fibrosis or cirrhosis
Risk factors for Alcoholic liver disease
Women→ 2x as sensitive to ETOH hepatotoxicity & develop more severe ALD at lower doses with shorter duration
African American>Hispanic> Caucasian males
Obesity→ limit to 1 drink a day
Genetic Factors→ alcoholism & ALD
Hepatitis C+ alcohol→ more rapid progression→ limit to 1 drink a day
ALD + smoking→ increased risk of hepatocellular cancer
Progression of cirrhosis/fibrosis/HCC
Normal liver + chronic alcohol use Steatosis Steatohepatitis Fibrosis Cirrhosis Hepatocellular Carcinoma
How much do you have to drink to get alcoholic liver disease?
Risk of developing cirrhosis increases with daily consumption:
Men >3 drinks/day for >5 years
Women >2 drinks/day for >5 years
Risk increased with >30 g/day
Amount of alcohol ingested→ most important risk factor
+/- Type of alcohol→ Beer or spirits > wine
Pattern of Drinking→ drinking outside meal times increases risk
Relationship to quantity is not completely linear
Fatty liver pathophysiology
Increased mobilization of free fatty acid from peripheral stores
Increased triglyceride formation
Decreased fatty acid oxidation
Reduced lipoprotein release by liver
Accumulation of fat (small or large droplets) in the cytoplasm of liver cells
Fatty liver presentation
Asymptomatic +/- hepatomegaly
Fatty liver management
Often completely reversible with 4-6 weeks of abstinence
May progress to fibrosis or cirrhosis, especially with continued drinking
Inflammation of liver characterized by necrosis (death) and fibrotic scarring
Mild (few symptoms) to severe presentation with advanced liver disease (cirrhosis in 50%)
High risk of progressive liver injury with cirrhosis developing in 50%
Alcoholic hepatitis
Alcoholic hepatitis presentation
Asymptomatic to mild to severe Severe→ marked impairment of liver function: Fever Leukocytosis Hepatic encephalopathy Spider angiomas *Jaundice* Hepatosplenomegaly with liver tenderness Edema (scrotal or LE) *Ascites* *Variceal bleeding* Oliguria
Alcoholic hepatitis labs
CBC – leukocytosis with left shift, Macrocytosis (MCV elevated), Thrombocytopenia AST/ALT ratio >2→ classic AST <500 IU/L. (2-6X ULN) ALT < 200 IU/L ALP→ mildly elevated Bilirubin→ Elevated, Direct>Indirect PT/ INR→ Elevated Albumin→ low Hyponatremia Hypokalemia GTP→ Elevated secondary to ETOH use Folate→ Low
Alcoholic hepatitis histology
Clumps of intracellular material→ Alcoholic hyaline (Mallory bodies)
Fatty infiltration
- Neutrophil infiltration* around clusters of necrotic hepatocytes
- Fibrosis* around hepatic venules→ precursor to cirrhosis
Alcoholic hepatitis diagnosis
Liver biopsy is required for diagnosis
* When there is an unclear history of alcohol use and elevated liver tests
* Confounded by other risk factors for liver disease and considering
pharmacotherapy with steroids
Alcoholic hepatitis management
Nutritional Assessment + therapy
Do not limit protein intake
Sodium restricted diet (<2000 mg/day)
Address vitamin deficiencies/malnutrition
Discontinue non-selective beta blockers (increase risk of AKI)
Treatment of Alcohol Withdrawal
Infection Surveillance
Fluid overload management→ Diuretics→ Lasix, Spironolactone
Mallory bodies
Seen on histology of alcoholic hepatitis:
Clumps of intracellular material→ Alcoholic hyaline
Folate deficiency + elevated LFTs
Alcoholic hepatitis
Discontinuing all alcohol in alcoholic hepatitis
Improve outcome Improve histological features Reduce portal pressure/complications (ascites, variceal bleeding) Decrease progression to cirrhosis Improve survival
Severe alcoholic hepatitis is defined as
MDF >32 or MELD >20
These people get a 7 day trial of steroids using MDF for starting steroids, Lillie score for discontinuing steroids
They can get a liver transplant if they meet specific criteria
Risk assessment calculators
Risk assessment calculators:
Model of End Stage Liver Disease (MELD score) → bilirubin, creatinine, INR→
> 20→ Severe, poor prognosis
Maddery (Modified) Discriminant Factor (MDF) → Protein, Protein control, bilirubin→ > 32→ Severe, Poor Prognosis (50% mortality 1 month) → steroids beneficial
Lillie Score → bilirubin, albumin, creatinine, protime at day 0→ bilirubin day 7→ Determine if steroids should be continue
If a patient is has a high mortality risk, they are hospitalized (MELD >20?)
Hepatocellular dysfunction + portosystemic shunting→ Failure of the liver to detoxify noxious agents of gut origin→ impaired brain function
Ammonia is the best known neurotoxin
Hepatic encephalopathy
Hepatic encephalopathy presentation
EEG changes
Asterixis: flapping tremor
Grading of hepatic encephalopathy
Grade I→ Subclinical or Covert Encephalopathy→ Changes in behavior, mild confusion, slurred speech,
disordered sleep pattern
Grade II→ Lethargy, moderate confusion
Grade III→ Marked confusion (stupor), incoherent speech, sleeping but can arouse.
Grade IV→ Coma, unresponsive to pain
Stroop test
Brief cognitive screening tools, which do not require psychological expertise in administration interpretation
Evaluate psychomotor speed and cognitive flexibility→ diagnose minimal hepatic encephalopathy (very sensitive + specific)
Hepatic encephalopathy treatment
Treat any precipitating factors: GI bleeding, infection, sedating
medications, electrolyte abnormalities, constipation, renal failure
Lactulose, Rifaximin
