Diseases of the Liver and Biliary Tract: Enterohepatic Circulation

Liver Anatomy and Function

• Unique circulation of blood through the intestines and liver (enterohepatic circulation)
• Liver has a functional reserve that must suffer a large loss before becoming symptomatic
• Liver function tests (LFTs) measure enzymes (e.g., LDH, AST, ALT, ALKP, bilirubin) to assess liver function

Liver Diseases

• Chronic liver disease can lead to toxic accumulations of metabolic waste (e.g., ammonia, bilirubin), bleeding, edema, and failure to absorb intestinal fat
• Viral hepatitis (HAV, HBV, HCV, HDV, HEV) can cause acute and chronic hepatitis, cirrhosis, and liver cancer
• Autoimmune hepatitis is a chronic liver disease not associated with viral infection
• Liver abscess is a focal collection of necrotic tissue, inflammatory debris, and fluid

Hepatitis A (HAV)

• Primarily fecal-oral transmission
• Benign and self-limiting
• Incubation period is about 2-6 weeks
• Most common type of hepatitis worldwide
• Fatalities are rare
• No carrier state
• Vaccine is available

Hepatitis B (HBV)

• Detector by presence of HBsAg
• Viremia may last for many weeks
• 1st antibody to appear is anti-HBc
• Beginning of recovery marked by appearance of anti-HBs, which confers immunity
• Transmitted through blood, saliva, semen, and vertically from mother to child
• Vaccine is available

Hepatitis C (HCV)

• Major cause of chronic liver disease
• Incubation period varies from a few weeks to 6 months
• About 40,000 new cases per year
• About 2% have antibodies indicating previous infection
• Transmission is primarily through IV drug abuse, sexual contact, and infected healthcare workers
• Mutating RNA virus, making vaccine development difficult

Hepatitis D (HDV)

• Co-infects with HBV
• Mostly in IV drug abusers and hemophiliacs
• Delta virus

Hepatitis E (HEV)

• Rare in the US but most common form of epidemic hepatitis in India
• Transmitted like HAV
• Mild and self-limiting

Pathology of Hepatitis

• Carrier state: liver biopsy normal, usually
• Acute hepatitis: hydropic degeneration, chronic inflammation, necrosis of individual cells
• Fulminant hepatitis or hepatic failure: extensive necrosis
• Chronic hepatitis: more severe damage, disorganized, intense inflammatory reaction, more extensive necrosis, scar tissue

Cirrhosis

• Final, common endstage for various chronic liver diseases
• Patterned fibrosis characterized by interconnecting bands of scar tissue, dividing the liver into small nodules separated by dense fibrous tissue
• Progressive, irreversible, and incurable, usually due to alcoholic liver disease, chronic viral hepatitis, or chronic disease of the biliary tree

Alcoholic Liver Disease

• Amount necessary to produce cirrhosis: about 200gms/day for 10-16 years
• Sequence of damage: fatty liver, alcoholic hepatitis, cirrhosis, and steatohepatitis/alcoholic hepatitis
• Severe damage if: abnormal clotting tests, low albumin, signs of hepatic failure

Other Liver Diseases

• Hemochromatosis: toxic accumulation of iron in cells, especially the liver, heart, and pancreas
• Wilson disease: autosomal recessive disorder, toxic accumulation of copper mainly in the brain and liver
• Primary biliary cirrhosis: autoimmune disease, inflammatory destruction of intrahepatic bile ducts
• Hepatocellular carcinoma: usually related to HBV and HCV, high levels of alpha-fetoprotein, grim prognosis
• Metastatic carcinoma: most common neoplasm in the liver, usually from colon, lung, or breast