Alcoholic Hepatitis Flashcards
Define alcoholic hepatitis.
Inflammatory liver injury caused by chronic heavy intake of alcohol.
What are the three forms of liver disease caused by excess alcohol intake?
Fatty liver – occurs in women who consume >20g or men >30g of alcohol per day. Triglycerides accumulate in the liver due to defective fatty acid (+glycerol) metabolism due to mitochondrial damage(no beta oxidation due to lack of NAD+) or impairment of receptors or enzymes involved.
Alcoholic hepatitis - Lack of NAD+ causes the deranged metabolic processes to leak oxygen free radicals - which are pro-inflammatory → tissue damage Acetaldehyde is also damaging and pro-inflammatory. This is still reversible but takes some time
Liver cirrhosis - Persistent inflammation → fibroblast infiltration→ connective tissue. Irreversible
What is the pathophysiology of alcoholic hepatitis?
Defining histological features of alcoholic hepatitis are:
- Liver cell damage - ballooning +/- Mallory Denk bodies
- Inflammation
- Fibrosis
Fatty change may also be seen due to progression from the fatty liver stage
How is alcohol metabolised in the body? (2)
Alcohol is metabolised in the liver by 2 main pathways:
- Cytochrome P450 2E1 (generates free radicals through oxidation of NADPH to NADP. 2E1 is upregulated in chronic alcohol use)
- Alcohol dehydrogenase + Aldehyde dehydrogenase (reduce NAD —> NADH. This excess NADH:NAD ratio inhibits gluconeogenesis and promotes fatty infiltration in the liver)
- Hepatic macrophages only in chronic alcohol use (–> TNFalpha and reactive species production in mitochondria. Free radicals –> lipid peroxidation –> inflammation and fibrosis)
* People with alcohol use are usually deficient in antioxidants such as glutathione and vitamin E. So oxidative stress is very damaging.*
* Acetaldehyde can bind to cellular proteins and produce antigenic adducts –> inflammation.*
How common is alcoholic hepatitis?
- 10-35% of heavy drinkers develop it
- 40% of cases of alcoholic hepatitis will develop into cirrhosis
- ALD → 3 million deaths annually worldwide.
- Generally development of ALD is more rapid and occurs at a lower dose in women than in men.
What is the typical presentation of alcoholic hepatitis?
- Hx of heavy alcohol intake (~15-20 years of excessive intake for development of alcoholic hepatitis)
- May remain asymptomatic and undetected unless they present for other reasons
- May be mild illness, nausea, malaise, epigastric pain, right hypochondriac pain and low-grade fever.
- More severe forms: jaundice, abdominal discomfort, swelling, swollen ankles, GI bleeding.
- There may be trigger events (e.g. aspiration pneumonia or injury)
What are the signs of alcoholic hepatitis on examination?
Signs of alcohol excess - malnourished, palmar erythema, Dupyutren’s contracture, facial talengiectasia, parotid enlargement, spider naevi, gynaecomastia, testicular atrophy, hepatomegaly, easy bruising
Signs of severe alcoholic hepatitis - febrile (50% patients), tachycardia, jaundice (>50%), bruising, encephalopathy*, ascites (30-60%), hepatomegaly (usually mild enlargement and tender on palpation), splenomegaly.
*(e.g. hepatic foetor, liver flap, drowsiness, unable to copy a 5 pointed star, disorientated)
What investigations would you do for alcoholic hepatitis?
Bloods
- FBC - low Hb, high MCV, high WCC, low plt,
- LFTs - AST>ALT (2:1), high Bil, low albumin, high Alk Phos, high GGT
- U&E - urea and K+ levels tend to be low unless significant renal impairment
- Clotting - prolonged PT is a sensitive marker of significant liver damage
Imaging
- US - for other causes of liver damage (e.g. maligancy)
- UGI endoscopy - for varices
- EEG - for slow-wave activity indicative of encephalopathy
Invasive
- Liver biopsy - percutaenous or transjugular (in presence of coagulopathy) may distinguish other causes of hepatitis
How do you manage alcoholic hepatitis ACUTELY?
Acute
- Parenteral thiamine, Vit C and multivitamins
- K+, Mg2+ and glucose - monitor and correct abnormalities
- Ensure adequate urine output
- Oral lactulose and phosphate enemas - for encephalopathy
- Diuretics - for ascites - furosemide/spironolactone or therapeutic paracentesis
- Glypressin and N-acetylcysteine - for hepatorenal syndrome
How do you manage alcoholic hepatitis (non-acutely)?
Treatment required:
- Supportive
- Stop alcohol
- Nutrition
- Vitamins (esp. Pabrinex containing B1 and thiamine)
- Occasionally steroids (anti-inflammatory)
Protein restriction should be avoided unless encephalopathic
What are the complications of alcoholic liver disease?
- Acute liver decompensation
- Hepatorenal syndrome (renal failure secondary to advanced liver disease)
- Cirrhosis
What is the prognosis with alcoholic hepatitis?
- Mortality in first month is 10%, 40% in first year
- If alcohol intake continues, most progress to cirrhosis in 1-3 years
What are some differentials for fatty liver disease?
- NASH
- Alcoholic hepatitis
- Kwashiorkor
What are the stages of alcoholic liver disease?
- Alcoholic hepatitis
- Chronic stable liver disease
- Resultant portal hypertension
- Liver failure (asterixis)
NB: forms are fatty liver, alcoholic hepatitis, cirrhosis.
