Liver Disease

Alcoholic Liver Disease
• Three ways alcohol (ethanol) can damage liver
• #1: Alcoholic fatty liver disease
• #2: Acute hepatitis
• #3: Cirrhosis

Alcoholic Fatty Liver Disease
• Accumulation of fatty acids (fatty infiltration of liver)
• Usually asymptomatic among heavy drinkers
• May cause hepatomegaly on exam
• Abnormal LFTs (AST>ALT)
• Often reversible with cessation of alcohol
• ↑ risk of cirrhosis

Liver Lobules

Portal Triad

Liver Zones

NAFLD
Non-alcoholic Fatty Liver Disease
• Fatty infiltration of liver not due to alcohol
• NAFL: Fatty liver
• NASH: Steatohepatitis (fat and inflammation)
• Often asymptomatic
• Abnormal LFTs (ALT>AST)
• May progress to cirrhosis
Associated with obesity
• May improve with weight loss

Alcoholic Hepatitis
• Classically occurs after heavy, binge drinking on top of long history of alcohol consumption
• Toxic effects from acetaldehyde
• Symptoms
• Fever
• Jaundice
• RUQ pain/tenderness

Mallory bodies
• Classic histopathology finding alcoholic liver disease
• Cytoplasmic inclusions
• Damaged intermediate filaments in hepatocytes

Budd Chiari Syndrome
• Thrombosis of hepatic vein
• Abdominal pain, ascites, hepatomegaly
• Zone 3 congestion, necrosis, hemorrhage
• Common causes:
• Myeloproliferative disorder (P. vera, ET, CML)
• Hepatocellular carcinoma
• OCP/Pregnancy
• Hypercoagulable states

Right Heart Failure
• “Cardiac cirrhosis”
• Rare cause of liver failure
• Chronic liver edema → cirrhosis
• Results in nutmeg liver
• Mottled liver like a nutmeg
• Also seen Budd Chiari

Reye’s Syndrome
• Rare cause of liver failure and encephalopathy
• Children with viral infections who take aspirin
• Classically chicken pox (varicella zoster) and influenza B
• Rapid, severe liver failure
• Evidence that aspirin inhibits beta oxidation
• Mitochondrial damage seen
• Fatty changes in liver (hepatomegaly)
• Vomiting, coma, death
• Avoid aspirin in children (except Kawasaki’s)

α1 Anti-trypsin Deficiency
• Inherited (autosomal co-dominant)
• Decreased or dysfunctional AAT
• AAT balances naturally occurring proteases

α1 Anti-trypsin Deficiency
• Lung
• Emphysema
• Imbalance between neutrophil elastase (destroys elastin) and elastase inhibitor AAT (protects elastin)
Liver
• Cirrhosis
• Abnormal α1 builds up in liver (endoplasmic reticulum)
• Pathologic polymerization of AAT
• Occurs in endoplasmic reticulum of hepatocytes

α1 Anti-trypsin Deficiency
AAT polymers stain with PAS
Resist resist digestion by diastase (unlike glycogen)

Liver Abscess
• Walled-off infection of the liver
• In the US usually bacteria
• Bacteremia
• Cholangitis (GN Rods; Klebsiella often identified)
• Entamoeba histolytica (protozoa)
• Cysts in contaminated water → bloody diarrhea (dysentery)
• Ascends in the biliary tree
• Echinococcus (helminth)
• Fecal-oral ingestion of eggs
• Massive liver cysts

Viral Hepatitis
• Hepatitis A, B, C, D, or E
• Very high AST/ALT
• Often >1000 (>25x normal)
• Hyperbilirubinemia and jaundice
• If severe, may see abnormal synthetic function
• Hypoglycemia, elevated PT/PTT, low albumin
• Diagnosed via viral antibody tests

Autoimmune Hepatitis
• Autoimmune inflammation of the liver
• Most common among women in 40s/50s
• Range of symptoms
• Asymptomatic → acute liver disease → cirrhosis
• Anti-nuclear antibodies (ANAs)
• Most common antibody abnormality
• Sensitive, not specific
• Anti-smooth muscle antibodies (ASMA)
• More specific for AHA
• Treatment: steroids and immunosuppressants