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A. Pathophysiology

  1. Immunological injury (? MHC linkage for susceptibility to damage)
  2. Metabolism of Alcohol
    1. Alcohol dehydrogenase (ADH)
    2. Microsomal ethanol-oxidizing system (MEOS; induced by EtOH)
  3. Toxic effects of metabolites, especially acetaldehyde (highly reactive with biomolecules)
  4. Apoptosis [11]
    1. Acidophilic bodies found in biopsies from alcoholic hepatitis are apoptotic bodies
    2. Oxidative stress likely a major inducer of apoptosis
    3. Liver cells particularly sensitive to Fas induced apoptosis as well
    4. TGFß1 also involved in apoptosis as well as fibrosis
  5. Avoid acetaminophen, which can lead to severe encephalopathy and failure in alcoholics
  6. Safe drinking level depends on tolerance, weight, metabolism; ~40gm/day [2]
  7. Moderate alcohol intake is beneficial []

B. Symptoms and Signs

  1. Hepatomegaly
  2. Jaundice
  3. Ascites
  4. Weight Loss
  5. Alcohol withdrawal
  6. Splenomegaly
  7. Abdominal Pain
  8. Encephalopathy
  9. Fever
  10. Stigmata of chronic liver disease
    1. Spider angiomata
    2. Palmer erythema
    3. Gynecomastia
    4. Ascites
  11. Screen for additional problems: CAGE Questions

C. Effects on Liver

  1. Transaminase Elevation
    1. Aspartate Aminotransferase (AST, SGOT) is mildly elevated
    2. Alanine Aminotransferase (ALT, SGPT) may not be elevated
    3. Typically AST:ALT > 2
    4. AST increase due to disproportional damage to mitochondria releasing AST
  2. Jaundice may occur in early moderate or severe disease
  3. Fatty Liver (Steatohepatitis, Steatosis) [3,12]
    1. Probably most common change even with moderate alcohol intake
    2. Also found in obese patients who do not drink; exacerbated in obese alcoholics
    3. Obesity is probably more important risk factor than alcohol intake [10]
    4. Hepatomegaly is most common finding
    5. Cirrhosis and/or fibrosis occurs in >15% of patients with pure fatty liver in 10 years
    6. Progression to cirrhosis and/or carcinoma may depend on TNFa production [12]
  4. Micronodular cirrhosis and fatty liver may be seen on biopsy specimens
  5. Women more at risk for alcoholic complications compared with men at given EtOH doses [4]
    1. Cirrhosis occurs in women at ~40gm EtOH/d x >10 years
    2. Cirrhosis occurs in men at ~80gm EtOH/d x >10 years
  6. Increased risk of hepatocellular carcinoma in patients with alcoholic cirrhosis
  7. Alcohol abuse increases risk of cirrhosis ~8 fold in hepatitis C virus infected patients [13]
  8. Alcoholic hepatitis with cirrhosis may progress to hepatorenal syndrome (HRS)

D. Treatment of Alcoholic Hepatitis with Encephalopathy

  1. Supportive care as above
  2. Replace vitamin deficiencies: Thiamine, Folate, Multivitamin
  3. Assess for Iron Deficiency
  4. Consider aspiration pneumonia
    1. Mixed infection with anaerobes and G- rods
    2. Increased risk of Klebsiella
  5. Glucocorticoids are beneficial in patients with alcholic hepatitis with encephalopathy [5]

E. Glucocorticoids in Alcoholic Hepatitis [5,6]

  1. Useful only in setting of encephalopathy or severe disease
  2. Also useful when "descriminant function" is >32; DF = 4.63·(PT-Control) + Serum Bili
  3. Dose is 40-60mg of prednisone equivalent per day
  4. Routine use of glucocorticoids for alcoholic hepatitis is not recommended [7]

F. Additional Considerations

  1. Must include alcoholic rehabilitation
  2. Avoid Non-Steroidal Anti-Inflammatory Agents (NSAIDs) [8]
  3. Acetaminophen use should be <2gm / day
  4. Fasting also increases risks of acetaminophen toxicity in alcoholics [9]
  5. Pentoxyfylline (Trental®) 400mg po tid reduces risk of HRS and mortality in severe alcoholic hepatitis with cirrhosis [15]

Resources

calcHepatitis Discriminant Function

References

  1. Lieber CS. 1994. Gastroenterol. 106:1085 abstract
  2. Sherlock S. 1995. Lancet. 345(8944):227 abstract
  3. Teli MR, Day CP, Burt AD, et al. 1995. Lancet. 346:987 abstract
  4. Batey RG, Burns T, Benson RJ, Byth K. 1992. Med J Austral. 156(6):413 abstract
  5. Imperiale TF and McCullough AJ. 1990. Ann Intern Med. 113(4):299 abstract
  6. Ramond MJ, Poynard T, Rueff B, et al. 1992. NEJM. 326(8):507 abstract
  7. Christensen E and Gluud C. 1995. Gut. 37:113 abstract
  8. Henry D, Dobson A, Turner C. 1993. Gastroenterol. 105(4):1078 abstract
  9. Whitcomb DC and Block GD. 1994. JAMA. 272(23):1845 abstract
  10. Bellentani S, Saccoccio G, Masutti F, et al. 2000. Ann Intern Med. 132(2):112 abstract
  11. Rust C and Gores GJ. 2000. Am J Med. 108(7):567 abstract
  12. Tilg H and Diehl AM. 2000. NEJM. 343(20):1467 abstract
  13. Harris DR, Gonin R, Alter HJ, et al. 2001. Ann Intern Med. 134(2):120 abstract
  14. Mukamal KJ, Conigrave KM, Mittleman MA, et al. 2003. NEJM. 348(2):109 abstract
  15. Gines P, Guevara M, Arroyo V, Rodes J. 2003. Lancet. 362(9398):1819 abstract