alcoholic%20liver%20disease
ALCOHOLIC LIVER DISEASE
Alcoholic liver disease diagnosis is suggested by an established history of habitual alcohol intake of sufficient length and intensity.
Toxic daily threshold of alcohol consumption is 40-80 g for males and 20-40 g for females for 10-12 years.
Signs of alcohol abuse and hepatic injury include malnutrition and muscle wasting, cutaneous telangiectasia, palmar erythema, finger clubbing, Dupuytren's contracture, peripheral neuropathy, parotid gland enlargement and signs of gynecomastia and hypogonadism may also be present.

Pharmacotherapy

Corticosteroid Hormones

  • Most extensively studied pharmacological agent in patients with severe alcoholic hepatitis
  • May be considered in patients with the following:
    • Diagnosis of severe alcoholic hepatitis with a Maddrey’s discriminant function score of >32 or a Model for End-stage Liver Disease (MELD) score of >20 
    • Hepatic encephalopathy
  • Action: Reduce the pro-inflammatory response
  • Prednisolone is preferred to Prednisone
    • Prednisone needs conversion to the active form, Prednisolone, in the liver
  • Corticosteroids have not been studied and are therefore contraindicated in patients with gastrointestinal bleeding, renal failure, diabetes, pancreatitis or in patients with evidence of infection
  • N-acetylcysteine may be helpful in patients with severe alcoholic hepatitis taking corticosteroids
  • Assess response to corticosteroid therapy at 7 days utilizing the Lille score
    • If patient is unresponsive (Lille score >0.45), discontinue therapy  
  • Consider palliative therapy in patients with alcoholic hepatitis who are unresponsive to corticosteroid therapy,  with multiple organ failures and not a candidate for early liver transplantation

Pentoxifylline

  • An oral phosphodiesterase inhibitor that also inhibits tumor necrosis factor alpha production
  • In a study of patients with alcoholic hepatitis with discriminate function score >32, Pentoxifylline showed survival benefit and significant protection against the hepatorenal syndrome
    • In patients with severe alcoholic hepatitis, the use of Pentoxifylline is not supported by current evidence
  • Action: May be related to beneficial effects of the drug on microcirculation especially within the kidneys
  • Further studies are required to confirm efficacy

Points to consider before commencing treatment with Corticosteroids or Pentoxifylline:

  • Do hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) screening
  • Obtain an abdominal ultrasound to rule out other etiologies of jaundice
  • Screen for infection in blood, urine, ascites culture
  • Screen for renal failure and treat hepatorenal syndrome
  • Control hyperglycemia

Granulocyte Colony Stimulating Factor

  • Recent data show improvement of liver disease, reduction in infectious complications and patient survival with its use

Investigational Therapies

Colchicine

  • Clinical trials show conflicting results
  • Further studies are required to confirm efficacy

Propylthiouracil (PTU)

  • A recent meta-analysis found no significant effects of PTU vs placebo on mortality or liver-related mortality, complications of liver disease, or liver histology

Antioxidants

  • Metadoxine
    • Studies have shown improvement in biochemical parameters, though additional studies are needed regarding its long-term effects
  • S-adenosylmethionine (SAMe)
    • Reports suggest a decrease in mortality but other trials found no significant benefit
  • Silymarin
    • Meta-analysis showed reduction in liver-related mortality in patients with alcoholic liver disease

Anti-Tumor Necrosis Factor (TNF) Agents

  • Use of tumor necrosis factor (TNF) inhibitors Infliximab and Etanercept is currently limited to clinical trials

Vaccination

  • It is recommended for patients to have immunization against hepatitis A and B, influenza and pneumonia

Non-Pharmacological Therapy

Nutrition Therapy1

  • Most patients with alcoholic hepatitis suffer some degree of malnutrition and should be considered for nutritional supplementation
  • Severity of malnutrition generally correlates with severity of liver disease
  • Protein calorie malnutrition is associated with high risk of cirrhosis complications (eg encephalopathy, ascites, infection)
  • Nutritional assessment should be on an ongoing basis
  • Long-term aggressive nutritional therapy is necessary
  • Daily nutrition considerations
    • Emphasize multiple feedings including breakfast and nighttime snack to improve nitrogen balance
    • Regular oral diet with increased dietary intakes (1-1.5 g/kg/day protein, 35-40 kcal/kg/day for energy)
    • Fluid and vitamin replacement, if deficient
  • Nutrition during acute illness or exacerbations
    • Above-normal protein and energy seem to improve protein calorie malnutrition (1.5-2 g/kg/day protein, 40-45 kcal/kg/day for energy)
  • May use enteral supplements in those with severe disease or in anorexic, hospitalized patients (conventional amino acid preparations may be used)
  • Patients with mild-moderate alcoholic hepatitis benefit from abstinence and nutrition therapy and will likely not require nor gain from medical treatment

1Various nutritional products and supplements for alcoholic liver disease are available. Please see the latest MIMS for specific formulations and prescribing information

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