Hepatitis

Question 1

Liver Basics

Answer 1

• Largest organ in the body
• Weighs 1-1.5 kg
• Held in place by ligamentous attachments to the diaphragm, peritoneum, great vessels, and upper GI organs
• Receives a dual blood supply: hepatic artery and portal vein
• Majority of the cells are hepatocytes
  
  • synthesize serum proteins (albumin, coagulation factors, hormonal and growth factors)
  • produce bile
  • regulate nutrients

Question 2

Patterns of Liver Disease

Answer 2

1. Hepatocellular: viral hepatitis, alcohol induced liver disease
   
   • liver injury and inflammation
   • elevated AST, ALT
2. Cholestatic (obstructive): obstruction, PBC, PSC, drug-induced
   
   • inhibition of flow is the primary issue
   • elevated bilirubin, alk phos
3. Combination

Question 3

Presenting Symptoms

Answer 3

• Scleral icterus
• Fatigue & malaise
• Itching
• RUQ pain
• Abdominal distention
• Nausea & vomiting
• Lack of appetite
• Alcoholic stools, steatorrhea
• Dark or cola colored urine

Question 4

ALT/AST

Answer 4

• Located in hepatocytes
• Markers of liver cell injury - leak with ongoing inflammation and injury
• Present at low levels at all times
• Male levels > female levels, obese levels > normal BMI
• Very high with viral, toxin, ischemia (>1000)
• ALT: more specific to the liver
• AST: decreasing order of concentration - liver, cardiac muscle, skeletal muscle, kidneys, brain, pancreas, lungs

Question 5

Alkaline Phosphatase

Answer 5

• Located in hepatocyte membrane bordering bile canaliculi
• Also in bone and placenta
• Iso enzymes or GGT to specify
• Higher elevations from drugs, intra- or extra-hepatic obstruction
• Lower levels from chronic liver disease

Question 6

Bilirubin

Answer 6

• Water soluble product of heme metabolism
• Direct (conjugated), Indirect (unconjugated)
• Formation: heme catabolism, heme disassociated from globin, broken down into biliverdin, reduced to bilirubin (unconjugated)
• Excretion: unconjugated is poorly absorbed, binds with albumin, taken up by hepatocyte, conjugated with glucoronic acid, now water soluble and excreted through biliary system
• Unconjugated:
  
  • Elevated in Gilberts: lack of conjugation enzyme, higher with fasting, illness and stress
  • Hemolysis
• Conjugated:
  
  • Liver dysfunction
  • Obstruction

Question 7

Albumin

Answer 7

• Measures synthetic function
• Half-life 20 days
• Level affected by many factors - nutrition, liver synthesis, malabsorption, protein loss from GI or urinary system

Question 8

PT/INR

Answer 8

• Coagulation factors II, V, VII, and X are synthesized in the liver
• Mesaures liver function
• With hepatic dysfunction, cannot synthesize coagulation factors despite adequate vitamin K

Question 9

DDx of Elevated LFTs

Answer 9

• Hepatitis A, B, C
• Fatty infiltration of the liver (NAFLD, NASH)
• Autoimmune hepatitis
• Hemochromatosis
• Celiac sprue
• Idiopathic
• Ischemia
• Wilson’s disease
• Other viral - CME, EBV
• Primary sclerosing cholangitis
• Primary biliary cirrhosis
• Thyroid dysfunction
• Cancer - primary liver, metastatic disease, pancreatic cancer, cholangiocarcinoma
• Biliary etiology - gallstones
• Alcohol
• Toxins
• Medication effect

Question 10

When is Liver Biopsy Indicated?

Answer 10

• Serologic workup for elevated LFTs and imaging unrevealing and persistently elevated LFTs (greater than 2x normal)
• Assess fibrosis level of the liver to determine timing/necessity of treatment if labs and imaging are not helpful
• To confirm certain diagnoses:
  
  • Autoimmune
  • Wilson’s
  • PBC
  • Hemochromatosis
• Assess if treatment is effective

Question 11

Acute vs Chronic Hepatitis

Answer 11

• Acute:
  
  • Weeks - 6 months
  • Jaundice present
  • Sx include anorexia, malaise, dark urine, fever, abdominal pain
• Chronic:
  
  • Often no symptoms, risk of cirrhosis, HCC
  • fatigue
  • sometimes symptoms of cirrhosis

Question 12

Fulminent Liver Failure

Answer 12

• Defined as presence of acute liver failure within 8 weeks of the onset of jaundice in a patient without previous liver disease
• Need transplant
• Includes:
  
  • Any degree of encephalopathy
  • Increased INR (> 1.5)
  • In a patient without cirrhosis with an illness less than 26 weeks duration
• Causes: Acetaminophen, Idiopathic, Idosyncratic drug reaction, Hep B, Ischemia, Hep A
• Symptoms: mailaise, jaundice, nausea
• Labs: very high AST/ALT with the exception of wilson’s disease (mild elevations), elevated total bilirubin, elevated INR
• Treatment: eliminate offending agent and treat with medications if able, transplant!