alcohol-related%20liver%20disease
ALCOHOL-RELATED LIVER DISEASE

Alcoholic liver disease diagnosis is suggested by an established history of habitual alcohol intake of sufficient length and intensity.
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. Patient may also be asymptomatic.

 

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 Discriminant Function (MDF) score of ≥32, a Glasgow Alcoholic Hepatitis Score (GAHS) of ≥9, 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 are contraindicated in patients with gastrointestinal bleeding, acute kidney injury, acute pancreatitis, drug-induced liver injury, hepatocellular carcinoma, uncontrolled infection, or multiorgan failure or shock
  • N-acetylcysteine may be helpful in patients with severe alcoholic hepatitis taking corticosteroids
  • Assess response to corticosteroid therapy after 7 days utilizing the Lille score
    • If patient is responsive (Lille score <0.45), continue Prednisolone for a total of 28 days 
    • If patient is unresponsive (Lille score ≥0.45), discontinue therapy and evaluate patient for early liver transplantation
  • Consider palliative therapy in patients with alcoholic hepatitis who are unresponsive to corticosteroid therapy, with multiple organ failures, and who are not candidates for early liver transplantation

Pentoxifylline

  • An oral phosphodiesterase inhibitor that also inhibits tumor necrosis factor (TNF) alpha production
  • In a study of patients with severe alcoholic hepatitis, Pentoxifylline, when compared with placebo, showed survival benefit related to a decrease in the incidence of hepatorenal syndrome
  • 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 cultures and chest X-ray
  • Screen for renal failure and treat hepatorenal syndrome
  • Control hyperglycemia

Granulocyte Colony Stimulating Factor (GCSF)

  • Recent data show improvement of liver disease, reduction in infectious complications and patient survival with its use
  • Further studies are required prior to recommending its use for treatment

Investigational Therapies

  • Colchicine, Propylthiouracil, S-adenosyl-L-methionine and Silymarin have been tested in patients with ALD cirrhosis but clinical endpoints did not show consistent benefits

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 versus 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-adenosyl-L-methionine (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 ALD

Anti-Tumor Necrosis Factor (TNF) Agents

  • Use of 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

Other Treatment Measures

  • Lactulose and Rifaximin may be considered for the treatment of hepatic encephalopathy in patients with alcoholic hepatitis 
  • Due to the potential risk of developing acute kidney injury in patients with severe alcoholic hepatitis, it is recommended to avoid diuretics and nephrotoxic drugs to prevent development of renal failure 
  • In patients with decompensated cirrhosis, stem-cell based therapies showed similar efficacy as standard of care while GCSF and Erythropoietin were shown to reduce 1-year mortality when compared to standard of care

Non-Pharmacological Therapy

Nutrition Therapy1

  • Most patients with alcoholic hepatitis suffer some degree of malnutrition and should be considered for enteral nutrition and 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 (1.2-1.5 g/kg/day protein, 35-40 kcal/kg/day for energy)
    • Salt restriction is advised for the treatment of ascites
    • Vitamin and nutrient supplementation; fluid replacement if deficient
      • Vitamin B-complex supplementation is recommended due to the potential risk of Wernicke’s encephalopathy; may also consider therapeutic doses of zinc in patients with moderate and severe alcoholic hepatitis
  • 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 alcohol-related liver disease are available. Please see the latest MIMS for specific formulations and prescribing information

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