Cirrhosis: Causes, Development and Impact

Cirrhosis

• Cirrhosis is a chronic, progressive, and irreversible condition affecting the entire liver.
• It results in decreased liver function due to damage.
• The two main causes are viral hepatitis (typically B and C) and chronic alcohol abuse.
• In the US, chronic alcohol abuse is the most frequent cause, but worldwide, it's viral hepatitis C.
• The liver becomes fibrotic with nodules, obstructing blood flow and bile.
• This can lead to liver failure.
• Cirrhosis can take up to 40 years to develop.

Clinical Manifestations

• Portal hypertension is a significant cause or manifestation of cirrhosis.
• Portal hypertension can cause varicosities in the esophagus and abdomen.
• These varicosities can bleed, either slowly or severely, especially in the esophagus, posing a medical emergency if they burst.
• Ascites is another manifestation, resulting from hypoalbuminemia.
• The liver's inability to produce albumin causes fluid to leak into the peritoneal space, leading to a swollen abdomen.

Other Manifestations

• Altered synthetic function leads to changes in clotting factors due to decreased vitamin K synthesis.
• Muscle wasting occurs due to decreased protein levels and hypoalbuminemia.
• Hypoglycemia is common due to the liver's inability to store and release glycogen.
• Bile accumulation leads to inflammation, necrosis, and jaundice, which is the yellowing of the skin.
• Jaundice occurs because bilirubin backs up into the blood due to bile duct obstruction.
• Stools may be clay-colored, and urine may be brown due to the absence of bile in the stool and absorption through the kidneys.
• Fat-soluble vitamin deficiency (A, D, E, K) occurs because the liver cannot make or store these vitamins.
• Intense itching (pruritus) can occur due to toxin buildup.

Liver Failure

• Ammonia builds up, leading to hepatic encephalopathy.
• The liver's inability to convert ammonia into urea results in increased serum ammonia levels.
• This affects the brain, causing confusion, loss of consciousness, and eventually unconsciousness.
• Spontaneous bacterial peritonitis can occur due to decreased Kupffer cell function, leading to increased bacteria in the GI tract.

Treatment

• Complex and depends on the underlying cause.
• Antiviral agents are used for hepatitis, avoiding alcohol, drugs, and hepatotoxic medications.
• Bile-acid binding agents can be used to aid in the excretion of bile.
• Portal hypertension can be treated with surgically implanted shunts (TIPS procedure) to improve blood flow.
• Fluid restriction, a low-sodium diet, and diuretics treat ascites.
• Paracentesis may be necessary if ascites impairs breathing.
• Esophageal varices are treated with endoscopic procedures (banding, shunts, sclerotherapy).
• Encephalopathy is treated by eliminating the source of protein breakdown with a low-protein diet.
• Lactulose can promote ammonia excretion in the stool.
• Antibiotics are given to suppress intestinal flora and decrease endogenous ammonia production.
• Liver transplant is often necessary for end-stage liver disease.

Hepatitis

• Hepatitis is an inflammation of the liver, often caused by viral infections, alcohol, medications (like acetaminophen), or autoimmune diseases.
• It can be acute (reversible), chronic, or fulminant (end-stage liver failure).
• Non-viral hepatitis is not contagious, while viral hepatitis is.

Types of Viral Hepatitis

• Hepatitis A, B, C, and D are endemic to the United States, with B and C being the most common.

Hepatitis A

• Source: Feces
• Transmission: Fecal-oral route (contaminated food/water)
• Does not cause chronic infection.
• Vaccine available

Hepatitis B

• Source: Blood and body fluids
• Transmission: Mucosal contact (sex, IV drug use)
• Can become a chronic infection or clear up.
• Vaccine available

Hepatitis C

• Source: Blood and body fluids
• Transmission: Mucosal contact (sex, IV drug use)
• 80% develop chronic infection, leading to cirrhosis.
• Prevention: Blood donor screenings, behavior modification

Hepatitis D

• Source: Blood and body fluids
• Transmission: Mucosal contact
• Can cause chronic infection.
• No immunization available.
• Can only occur in someone with Hepatitis B.

Hepatitis E

• Source: Feces
• Transmission: Fecal-oral route (contaminated water)
• Does not cause chronic infection.
• Rare, primarily affects pregnant women in underdeveloped countries.

Acute vs. Chronic vs. Fulminant Hepatitis

• Acute Hepatitis has three phases of symptoms.
• Chronic Hepatitis is characterized by continued hepatic disease lasting longer than six months, severity and disease progression varies.
• Fulminant Hepatitis is a rapidly progressing form leading to liver failure or death.

Acute Hepatitis - Three Phases

• Prodromal Period: Asymptomatic, begins two weeks after the exposure.
• Icteric Period: Jaundice begins (week 2-6); enlarged, tender liver; dark urine; clay-colored stools.
• Recovery Period: Begins with the resolution of jaundice, typically 6-8 weeks after exposure.

Hepatitis Diagnosis

• History and physical exam.
• Liver profile (liver enzymes, clotting studies).
• Liver biopsy.
• Abdominal ultrasound.

Hepatitis Treatment

• Vaccinations are the cornerstone of prevention (available for A and B).
• Limit exposure to the virus (avoid unsafe sex, sharing needles).
• Hepatitis A usually resolves with no treatment.
• Other viral types can be treated with interferon injections and antiviral medications.
• Rest, nutrition, and increased hydration.
• Paracentesis for fluid accumulation.
• Liver transplant if needed.

Hepatitis Vaccines

• Hepatitis A Vaccine: Recommended for children starting at one year of age and anyone at risk for exposure (travelers, men who have sex with men, IV drug users, people with liver disease).
• Hepatitis B Vaccine: Recommended for all infants, healthcare workers, men who have sex with men, and IV drug users.
• Initiated in the early 90s to combat the rise of hepatitis B as a sexually transmitted infection.