Compound Pentoxifylline Shown to Improve Survival for Severe Acute Alcoholic Hepatitis

Compound Pentoxifylline Shown to Improve Survival for Severe Acute Alcoholic Hepatitis

i-stethoscopeAlcoholism takes its toll in so many ways. For compounding pharmacist, Tara, getting more involved in understanding the clinical effects of acute alcoholic hepatitis and becoming more active in her patients’ healthcare teams helped her offer her patients better therapies.

Weary of only seeing patients with advanced acute alcoholic hepatitis and with orders from specialists for corticosteroid treatments, she proactively pursued better relationships with patients’ specialists and physicians, and worked toward introducing other off-label and compounded therapies, including nutritional supplements and the phosphodiesterase inhibitor pentoxifylline.

For patients like 63-year-old Steve, a 30-year heavy drinker suffering through liver damage from acute alcoholic hepatitis, working with a compounding pharmacist like Tara to receive pentoxifylline rather than corticosteroids helped him recover some liver function and quality of life.1

Treating Acute Alcoholic Hepatitis with Pentoxifylline v. Corticosteroids

Overall, mortality rates for acute alcoholic hepatitis vary widely depending on additional health factors. While chronic conditions like cirrhosis also develop from alcohol abuse, alcoholic hepatitis as a condition does not always lead to death. However, the onset of hepatitis or a hepatorenal infection becomes much more likely for patients with alcoholic hepatitis.2

Pentoxifylline (Oxpentifylline) was first applied for patients with acute alcoholic hepatitis in the early 2000s when researchers thought it might reduce the chances of patients developing hepatorenal syndrome, a leading cause of death.

The phosphodiesterase inhibitor works by modulating transcription of the TNF-α gene, thereby inhibiting production of TNF-α. In a small early trial, fewer than one-quarter of the patients who received daily pentoxifylline died, compared with half in the placebo group. Hepatorenal syndrome accounted for more than 90 percent of the deaths in the placebo group and 50 percent of the deaths in the pentoxifylline group.3

Many specialist groups recommend corticosteroids for treating severe alcoholic hepatitis. While corticosteroids have undoubtedly demonstrated effectiveness in short-term survival, they can result in a high risk of fatal gastrointestinal bleeding and sepsis.

For pharmacists whose patients cannot risk the high likelihood of side effects with corticosteroids, pentoxifylline via oral doses is another effective option for short-term survival benefits.

Additional health indicators such as obesity can have an effect on how well pentoxifylline works when compared to glucocorticosteroid treatments and prednisolone, which is included along with pentoxifylline in The American Association for the Study of Liver Disease treatment guidelines.4

It should also be noted that a 2008 study in the Journal of Hepatology found that up to 40 percent of alcoholic hepatitis patients will be categorized as “non-responders” when treated with corticosteroids, deriving no measurable benefit from the treatment. For these non-responders, switching to a regimen of pentoxifylline also yielded no benefits. The study was inconclusive regarding how to treat non-responding alcoholic hepatitis patients who proved resistant to both corticosteroids alone and corticosteroids followed by a switch to pentoxifylline. The conclusion also made no comment on the efficacy of pentoxifylline alone for non-responders.5

The Role of Pharmacists in Acute Alcoholic Hepatitis Treatment

Managing acute hepatitis treatment should always be done in concert with a patient’s existing doctors and specialists, but the compounding pharmacist has a definite role to play as part of a patient’s healthcare team.

The process of acute alcoholic hepatitis is difficult to reverse once begun. For patients who show inclinations toward alcohol abuse, early-intervention treatments can show strong results. Pharmacists should be educated regarding behavioral signs for patients who may show tendencies toward alcohol abuse, since many often have more interactions with patients than other physicians. Pharmacists are also in a position to recommend off-label treatments like compound baclofen.

Once acute alcoholic hepatitis has progressed, a pharmacist could work with a patient’s healthcare team through several potential therapies, including:

  • Corticosteroids
  • TNF modulation with pentoxifylline
  • Propylthiouracil
  • Antioxidant therapy for cirrhosis
  • Nutritional supplements

Pharmacists should also be on the lookout for malnourishment in patients with alcoholic hepatitis. If you have a limited background in nutrition, you might recommend adding a nutritionist to the patient’s healthcare team.

While studies are divided on whether nutritional support helps reduce early mortality rates for patients with acute alcoholic hepatitis, the largest peer-reviewed study comparing therapies found that total enteral nutrition proved as effective as corticosteroids as a treatment method. Ultimately, that might not be saying much considering that pentoxifylline beats out corticosteroids as a treatment method in every study, but it’s unlikely that nutritional support resulting in serum albumin improvements would result in adverse effects.6

Acute alcoholic hepatitis rarely occurs in a vacuum and rarely is the only condition in a patient who was probably a heavy drinker for an extended period of time. Pharmacists who are well-versed in leading off-label treatments like pentoxifylline, as well as various other treatments, will be in a position to become a much more active member of a patient’s healthcare team. Like pharmacist Tara did for patient Steve, you’ll be better able to improve your patient’s quality of life, no matter the situation.

Pharmaceutica North America is a leading provider of high-quality active pharmaceutical ingredients and custom compounding kits. Contact us to learn more about our available bulk pentoxifylline and how we can help you provide high-quality patient care.

Show 6 footnotes

  1. “Current Management of Alcoholic Liver Disease,” July 2004, http://www.medscape.com/viewarticle/472652_6
  2. “Alcoholic hepatitis: Natural history and management,” Oct. 7, 2015, http://www.uptodate.com/contents/alcoholic-hepatitis-natural-history-and-management
  3. “Systematic review: pentoxifylline for the treatment of severe alcoholic hepatitis,” March 13, 2013, http://onlinelibrary.wiley.com/enhanced/doi/10.1111/apt.12279
  4. “Prednisolone or Pentoxifylline for Alcoholic Hepatitis,” April 23, 2015, http://www.nejm.org/doi/full/10.1056/NEJMoa1412278#t=article
  5. “Early switch to pentoxifylline in patients with severe alcoholic hepatitis is inefficient in non-responders to corticosteroids,” March 2008, http://www.sciencedirect.com/science/article/pii/S0168827807005934
  6. “Current Management of Alcoholic Liver Disease,” ibid.
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