Cirrhosis

Etiology

Ethanol metabolism

Acetaldehyde is a reactive metabolite that causes injury to the liver

Genetic Factors

-Human leukocyte antigen (HLA) groups
-Genetic polymorphisms of collagen (ADH, ALDH, and CYP2E1)
-Genetic predilection has been identified, however, exact mechanisms are less clear

Malnutrition

Protein-energy malnutrition (PEM)

Pathogenesis

Toxic effects on cell membranes

Acetaldehyde (metabolite of alcohol)

Hypermetabolic state of the hepatocyte

Induced by alcohol

Generation of free radicals and oxidative injury

-Free radicals, superoxides and hydroperoxides as byproducts of alcohol metabolism
-Antioxidant defenses against this process reduced in this patients

Steatosis

accumulation of fat within the hepatocytes

Formation of acetaldehyde adducts

Triggers immune response through the formation of neoantigens

Immune Mechanisms triggered

-Increased levels of immunoglobulin A (IgA)
-Formation of autoantibodies
-B & T lymphocytes noted in portal and periportal areas
-NK cells noted around hyalin-containing hepatocytes
-Decreased peripheral lymphocyte counts (lymphocytes engaged in cell mediated inflammatory process)

Cytokines

-Tumor necrosis factor-alpha (TNF-alpha)
-Inflammatory cytokines (TNF, IL-1, IL-8)

Concomitant viral disease

-Concomitant hepatitis C virus infection in 20% of patients

Acetaminophen-alcohol interactions

potentiates acetaminophen toxicity

Epidemiology

-2 million affected in the USA (1% of population)
-No predilection amongst race, but more common in native Americans
-Women are more susceptible than men

Clinical Manifestations

-Fatigue
-Bleeding easily
-Bruising easily
-Itchy skin
-Yellow discoloration in the skin and eyes (jaundice)
-Fluid accumulation in your abdomen (ascites)
-Loss of appetite
-Nausea
-Swelling in your legs
-Weight loss
-Confusion, drowsiness and slurred speech (hepatic encephalopathy)
-Spiderlike blood vessels on your skin
-Redness in the palms of the hands
-Testicular atrophy in men
-Breast enlargement in men (gynecomastia)

Treatment and management

Diagnosis

Laboratory Tests

-Liver function tests
-Kidney function tests
-Test for hepatitis B or C
-Clotting

Imaging

-Magnetic resonance elastography
-MRI
-CT
-Biopsy

Treatment

-Treatment for alcohol dependency
-Weight loss
-Medication to control hepatitis
-Medications to control other causes and symptoms of cirrhosis