By Abdul Hameed Jan

Alcoholic Hepatitis

OutlineOutline: 1.Intro2.Definition3.Pathogenesis4.Symptoms5.Clinical signs6.Treatment7.Complications8.References

Case Study:A 36 year old man complains of fatigue, dark urine, and abdominal swelling. He admits to drinking a few beers a day since his teen years, but he has never had major medical problems. Recently, he has been drinking more heavily while unemployed. He states that he has not had blood transfusions and does not use intravenous drugs. Physical examination findings are remarkable for tachycardia and low-grade fever. Prominent scleral icterus is noted, and the abdominal examination reveals shifting dullness. The liver span is increased on percussion.

Introduction:• Most important agent that produces toxic liver injury

is alcohol.• Excessive ethanol consumption causes more than

60% of chronic liver disease in most Western countries and accounts for 40% to 50% of deaths due to cirrhosis.

• More than 10 million Americans are alcoholics.

• Alcohol abuse causes 100,000 to 200,000 deaths annually in the United States, the • fifth leading cause of death in the US.

Definition:

Alcoholic hepatitis describes liver inflammation caused by drinking alcohol.

Some Stats:• 90-100% of alcohol consumers develop

hepatic steotosis• Out of these 10-35% develop Alcoholic

hepatitis and 8-20% develop cirrhosis

Morphology of Alcoholic hepatitis:

1.Hepatocyte Swelling/Necrosis• Single or multiple cells undergo swelling

and necrosis• Due to accumulation of fat, water and

proteins that are normally exported

Morphology of Alcoholic hepatitis:2. Mallary Bodies: • Accumulation of intermediate filaments

and other proteins• Seen as eosinophilic cytoplasmic inclusions

in dying cells

Morphology of Alcoholic hepatitis:

3. Neutrophil Infiltration• Neutrophills together with lymphocytes and

macrophages enter the liver and surround the degenerating hepatocytes

Morphology of Alcoholic hepatitis:

4. Fibrosis:• Sinusoidal and Perivenular fibrosis• Liver looks mottled red with bile stained

areas• Cholestasis and mild deposition of

hemosiderrin in Kupffer cells.

Mottled Liver

Pathogenesis:Alcohol Consumed Absorbed unchanged into blood (by the stomach and small intestine

Levels of Alcohol in the blood and their effects:• 200 mg/dL will result in drowsiness• 300 mg/dL will result in stupor• >300 mg/dL can result in comaChronic Alcoholics can tolerate up to 700 mg/dL and still not enter coma

Pathogenesis:Alcohol Metabolism: There are 3 enzyme systems involved

1.Alcohol dehydrogenase in the cytosol 2.Cytochrome P-450 in the microsomes3.Catalase in peroxisomes (minor:

metabolizes only 5%)

Pathogenesis:Alcohol Metabolism: There are 3 enzyme systems involved

1.Alcohol dehydrogenase in the cytosol • Alcohol oxidation by alcohol

dehydrogenase causes a decrease in NAD+ and an increase in NADH.

• NAD+ is required for fatty acid oxidation in the liver.

• Its deficiency is a main cause of accumulation of fat in the liver of alcoholics.

Pathogenesis:• NAD+ is also required for the

conversion of lactate into pyruvate• Increase in the NADH/NAD+ ratio in

alcoholics causes metabolic acidosis resulting from Lactic acid accumulation

• Acetaldehyde has many toxic effects and may be responsible for some of the acute effects of alcohol.

Pathogenesis:

Alcohol Metabolism: There are 3 enzyme systems involved

2. Cytochrome P-450 in the microsomes• At high blood alcohol levels, the

microsomal ethanol-oxidizing system participates in the metabolism. • Involves cytochrome P-450 enzymes,

particularly the CYP2E1 isoform, located in the smooth ER.

Pathogenesis:

• P-450 enzymes metabolizes drugs (acetaminophen, cocaine), anesthetics, carcinogens, and industrial solvents. • When alcohol is present in the

blood at high concentrations, it competes with other CYP2E1 substrates• This delays the catabolism of other

drugs, thus potentiating their effects.

Pathogenesis:

• Also produces free radicals that disrupts the cytoskeleton and membrane of the haptocytes

Clinical Symptoms:• Malaise• Anorexia, weight loss, loss of appetite and

nausea and vomiting• Upper abdominal pain and tenderness• Hepatomegaly • Fever• Ascites

Lab tests:• CBC • CT, ultrasound, or MRI of the liver• Blood test to check levels of:• Bilirubin• ALT and ASTHigh levels indicate liver necrosis

Risk Factors:• Other liver diseases like Hepatitis C• Malnutrition• Obesity and genetic factors• Sex: women are 5 times more likely to

develop this condition• Type of beverage: Beer/spirits vs wine• Binge drinking • Race: African American and Hispanic

Complications:• Increased BP in portal vein that can lead to

portal HT• Varices: bleeding into stomach and

esophagus• Ascites, Jaundice, hepatic encephalopathy• Cirrhosis• Kidney failure

Treatment: 1.Stop drinking2.Get on a healthy diet to counter any

malnourishment3.Take corticosteroids for inflammation but

beware of the adverse side effects4.Last resort liver transplant.

Case Study:A 36 year old man complains of fatigue, dark urine, and abdominal swelling. He admits to drinking a few beers a day since his teen years, but he has never had major medical problems. Recently, he has been drinking more heavily while unemployed. He states that he has not had blood transfusions and does not use intravenous drugs. Physical examination findings are remarkable for tachycardia and low-grade fever. Prominent scleral icterus is noted, and the abdominal examination reveals shifting dullness. The liver span is increased on percussion.

References:

Basic Pathology By Robins 8th edition Mayo Clinic website: http://www.mayoclinic.org/diseases-conditions/alcoholic-hepatitis/basics/treatment/con-20026160

http://books.google.ca/books?id=nStxzRQlNaAC&pg