Is pentoxyphyllin (pentoxifylline) useful in treating alcoholic hepatitis?

Pentoxifylline in Alcoholic Hepatitis Treatment

Pentoxifylline is not a first-line treatment for alcoholic hepatitis, as corticosteroids have demonstrated superior efficacy with a higher 1-month survival rate of 87.0% compared to 74.5% for pentoxifylline. 1

Efficacy of Pentoxifylline vs. Corticosteroids

• First-line treatment: Corticosteroids (prednisolone 40 mg daily for 28 days) remain the preferred first-line treatment for severe alcoholic hepatitis with Maddrey Discriminant Function (mDF) ≥32 1
• Survival rates: A Korean randomized controlled trial showed that the 1-month survival rate with pentoxifylline (74.5%) was inferior to prednisolone (87.0%) 1
• Largest clinical evidence: The STOPAH trial (2015) found that pentoxifylline did not improve survival in patients with alcoholic hepatitis, with 28-day mortality rates of 19% for pentoxifylline vs. 17% for placebo 2

Role of Pentoxifylline as Alternative Therapy

Pentoxifylline (400 mg three times daily for 28 days) should be reserved as an alternative treatment only when:

1. Corticosteroids are contraindicated (e.g., uncontrolled infections, acute kidney injury, gastrointestinal bleeding) 3
2. Insurance constraints prevent access to prednisolone 3

Mechanism and Benefits of Pentoxifylline

• Mechanism: Acts as a selective phosphodiesterase inhibitor that increases intracellular cAMP levels, decreasing expression of cytokines such as TNF-α, IL-8, and macrophage inflammatory protein-1a 1
• Hepatorenal syndrome prevention: The main benefit of pentoxifylline appears to be reduction in hepatorenal syndrome incidence rather than overall mortality improvement 1, 4
  • One study showed hepatorenal syndrome occurred in 50% of deaths in the pentoxifylline group versus 92% in the placebo group 1
  • A systematic review confirmed pentoxifylline reduces fatal hepatorenal syndrome compared to placebo (RR: 0.47, p=0.01) 5

Combination Therapy Considerations

• No added benefit: Combination therapy of corticosteroids plus pentoxifylline shows no survival benefit at 4 weeks or 6 months compared to corticosteroid monotherapy 1, 6
• Potential benefits: Despite no survival advantage, dual therapy may decrease the incidence of hepatorenal syndrome/acute kidney injury (OR=0.47) and infection risk (OR=0.63) compared to corticosteroid monotherapy 7

Treatment Algorithm for Severe Alcoholic Hepatitis

1. Assess disease severity: Use mDF score (≥32 indicates severe disease requiring treatment) 1
2. First-line treatment: Prednisolone 40 mg daily for 28 days if no contraindications 1
3. Alternative treatment: Pentoxifylline 400 mg three times daily for 28 days if corticosteroids are contraindicated 1, 3
4. Treatment monitoring: Assess response after 7 days using Lille model or Early Change in Bilirubin Level (ECBL) 1
   • If Lille score ≥0.56 or no ECBL, consider discontinuing steroids and evaluating for liver transplantation 1
5. Cornerstone of treatment: Complete alcohol abstinence regardless of pharmacological intervention 1, 3

Important Caveats

• Pentoxifylline should not be used as rescue therapy for steroid non-responders, as studies show no benefit in this scenario 1
• Anti-TNF-α agents (infliximab, etanercept) should be avoided due to higher mortality rates 1, 3
• Regular screening for infections before and during treatment is crucial, particularly with corticosteroid therapy 3