Alcoholic Liver Disease


Summary 1) Wikipedia

Alcoholic liver disease is a term that encompasses the liver manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with liver fibrosis or cirrhosis.

Pathophysiology 2) Robbins Basic Pathology by Vinay Kumar

Short-term ingestion of as much as 80 g of ethanol per day (56 beers or 89 ounces of 80-proof liquor) generally produces mild, reversible hepatic changes, such as fatty liver. Chronic intake of 40 to 80 g/day is considered a borderline risk factor for severe injury. For reasons that may relate to decreased gastric metabolism of ethanol and differences in body composition, women are more susceptible than men to hepatic injury. It seems that how often and what one drinks may affect the risk of liver disease development. For example, binge drinking causes more liver injury than that associated with steady, lower level consumption. Individual, possibly genetic risk factors must exist, but no reliable markers of susceptibility are known. In the absence of a clear understanding of the factors that influence liver damage, no safe upper limit for alcohol consumption can be proposed. The induction of cytochrome P-450 by chronic alcohol use leads to augmented transformation of other drugs to toxic metabolites. In particular, this effect can accelerate the metabolism of acetaminophen into highly toxic metabolites and increase the risk of liver injury even with therapeutic doses.

Causes 3) Robbins Basic Pathology by Vinay Kumar

  • Acetaldehyde (a major metabolite of ethanol) induces lipid peroxidation and acetaldehyde-protein adduct formation, which may disrupt cytoskeleton and membrane function.
  • Alcohol directly affects cytoskeleton organization (as illustrated by Mallory-Denk bodies), mitochondrial function, and membrane fluidity.
  • Reactive oxygen species generated during oxidation of ethanol by the microsomal ethanol oxidizing system react with and damage membranes and proteins. Reactive oxygen species also are produced by neutrophils, which infiltrate areas of hepatocyte necrosis.
  • Cytokine-mediated inflammation and cell injury is a major feature of alcoholic hepatitis and alcoholic liver disease in general. TNF is considered to be the main effect or of injury; IL-1, IL-6, and IL-8 may also contribute. The main stimuli for the production of cytokines in alcoholic liver disease are the reactive oxygen species, mentioned earlier, and microbial products (e.g., endotoxin) derived from gut bacteria.

Symptoms 4)

  • Gastrointestinal – abdominal discomfort, nausea, dark bowel movements, loss of appetite and weight loss 
  • Skin changes – darkening or lightening of the skin, jaundice, red hands or feet and swelling in the legs and abdomen and enlarged breasts (in men) 
  • Changes in mental status  confusion, fainting, fatigue, mood swings, slow movements 
  • Bleeding problems  nosebleeds and bleeding gums

Alcoholic cirrhosis

Diagnosis 5)USMLE Step 1 Secrets by Thomas Brown6)

  • Laboratory Findings – AST elevation that is ≥2 × ALT
  • Ultrasound – hypertrophy of the caudate lobe and lateral segments of left lobe (segments II & III) with concomitant atrophy of the posterior segments (VI & VII) of the right lobe

Treatment 7) Wikipedia

  • Liver transplant – when all else fails and the liver is severely damaged 
  • AntiTumor Necrosis Factor Therapy  prevents liver damage 
  • Corticosteroids  reduces inflammation

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