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News

Prednisolone increases mortality in patients with severe alcoholic hepatitis

In patients with severe alcoholic hepatitis, prednisolone increases susceptibility to infection and infection-related mortality, and is associated with high circulating levels of bacterial DNA, reports the latest issue of Gastroenterology.

News image

Infections are common in patients with severe alcoholic hepatitis, but little information is available on how to predict their development or their effects on patients. 

Prednisolone is advocated for treatment of severe alcoholic hepatitis, but can increase susceptibility to infection. 

Dr Stephen Atkinson and colleagues from the United Kingdom compared the effects of infection on clinical outcomes of patients treated with and without prednisolone, and identified risk factors for development of infection in severe alcoholic hepatitis.

The team analyzed data from 1092 patients enrolled in a double-blind placebo-controlled trial to evaluate the efficacy of treatment with prednisolone or pentoxifylline in patients with severe alcoholic hepatitis. 

There were 547 patients that received prednisalone.

10% of patients receiving prednisolone developed an infection after treatment
Gastroenterology
The team reported that 546 were treated with pentoxifylline. 

The trial was conducted from 2011 through 2014. 

Data on development of infection were collected at evaluations performed at screening, baseline, weekly during admission, on discharge, and after 90 days. 

Patients were diagnosed with infection based on published clinical and microbiologic criteria. 

Risk factors for development of infection and effects on 90-day mortality were evaluated separately in patients treated with prednisolone, and patients not treated with prednisolone using logistic regression. 

The research team measured pretreatment blood levels of bacterial DNA (bDNA) in 731 patients.

Of the 1092 patients in the study, 135 had an infection at baseline, 251 developed infections during treatment, and 89 patients developed an infection after treatment. 

The team found no association between pentoxifylline therapy, and the risk of serious infection, infection during treatment, or infection after treatment. 

Infections classified as serious were more frequent in patients treated with prednisolone. 

The research team found no association between prednisolone therapy and infection during treatment. 

The researchers found that 10% of patients receiving prednisolone developed an infection after treatment vs 6% of patients not given prednisolone. 

Development of infection was associated with increased 90-day mortality in patients with severe alcoholic hepatitis treated with prednisolone, independent of model for end-stage liver disease or Lille score. 

The team noted that high circulating bDNA predicted infection that developed within 7 days of prednisolone therapy, independent of Model for End-Stage Liver Disease and white blood cell count. 

In patients who did not receive prednisolone, the research team observed that infection was not independently associated with 90-day mortality or levels of bDNA.

Dr Atkinson's team concludes, "Patients with severe alcoholic hepatitis given prednisolone are at greater risk for developing serious infections and infections after treatment than patients not given prednisolone, which may offset its therapeutic benefit."

"Level of circulating bDNA before treatment could identify patients at high risk of infection if given prednisolone."

"These data could be used to select therapies for patients with severe alcoholic hepatitis."

Gastroenterol 2017: 152(5): 1068–1077.e4
05 April 2017

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