Clinical

Pentoxifylline may be effective for severe alcoholic hepatitis

Last Updated: 2013-04-05 16:06:24 -0400 (Reuters Health)

By Will Boggs, MD

NEW YORK (Reuters Health) - Pentoxifylline may be effective in severe alcoholic hepatitis, but the evidence is sparse, UK researchers say.

"The main message of this research is the lack of data regarding pentoxifylline, which does not really support its enthusiastic support from many physicians and indeed guideline writers," Dr. Richard Parker from the University of Birmingham told Reuters Health. "Nevertheless it may be a useful therapeutic agent."

One of those enthusiastic supporters is Dr. Bruce A. Runyon from Santa Monica/UCLA Medical Center in California, who told Reuters Health that he conceived of using pentoxifylline for alcoholic hepatitis in the late 1980s. "Most authors of alcoholic hepatitis papers do not see enough patients themselves, or they would know that steroids are a disaster in alcoholic hepatitis," he said. "At Santa Monica/UCLA, I have up to five inpatients at a time with alcoholic hepatitis."

As others have reported, high levels of tumor necrosis factor alpha predict poor survival in alcoholic hepatitis - and pentoxifylline is a TNF-alpha suppressor.

Dr. Parker and colleagues examined the use of pentoxifylline for the treatment of severe alcoholic hepatitis in a systematic review of data from 10 randomized trials. They reported their findings March 13 online in Alimentary Pharmacology & Therapeutics.

In the trials that compared pentoxifylline with placebo, fatal hepatorenal syndrome was 53% lower with pentoxifylline than with placebo (p=0.01), but there was no significant difference in overall mortality at 28 days.

In trials of pentoxifylline vs corticosteroids, there were no significant differences in 28-day mortality, six-month mortality, or incidence of hepatorenal syndrome.

There were similarly no significant differences in those endpoints in trials that compared dual therapy with pentoxifylline plus corticosteroids vs corticosteroid monotherapy.

There was significant heterogeneity between the trials, leading the investigators to conclude that "the role of pentoxifylline remains uncertain."

"Whilst pentoxifylline has not shown any superiority over steroids or in combination with steroids over steroids alone, it is probably better than placebo," Dr. Parker said. "Given the relative wealth of data regarding steroids, I would regard pentoxifylline as a treatment for those with contra-indications to steroid use."

"I would only use pentoxifylline on its own. If a patient were suitable for corticosteroids, I'd use steroids on their own," Dr. Parker said.

"Further studies are required," Dr. Parker added. "STOPAH in the UK should be useful."

"STOPAH is a 1,200-patient randomized controlled trial in the UK of pentoxifylline vs corticosteroids vs both versus neither," Dr. Runyon said. "Almost no one knows about this ongoing RCT that should answer the question once and for all." (More information about the trial is at www.stopah.com.)

In the meantime, Dr. Runyon said, "Use pentoxifylline. Forget steroids."

But Dr. Sandeep S. Sidhu, a professor of gastroenterology from Dayanand Medical College & Hospital in Punjab, India agreed with Dr. Parker. He told Reuters Health that he favors pentoxifylline "if glucocorticoids are contraindicated due to sepsis, gastrointestinal bleed, renal failure, or pancreatitis."

SOURCE: http://bit.ly/ZEbW6J

Aliment Pharmacol Ther 2013.