In a major trial of more than 1,000 patients, prednisolone and pentoxifylline, the key treatments recommended in international guidelines, did not achieve a statistically significant reduction in mortality rates after 28 days, 90 days or a year.
The authors of the study, which is published in the New England Journal of Medicine, say there is a critical need for more research into prevention and treatment of the illness as patients have no suitable options to improve their survival.
World-leading liver expert Professor Chris Day, Pro-Vice-Chancellor for Newcastle University’s Faculty of Medical Sciences, was part of the pioneering study.
He said: “Liver disease is the only leading cause of preventable death that is increasing in the country, yet very little research is currently being undertaken on conditions such as alcoholic hepatitis.
“The fact that prednisolone and pentoxifylline have been found to be ineffective is not a big surprise as there was previously only scant evidence supporting their use coming from old and relatively small trials.
“There is a undoubtedly a stigma around obtaining funds to study alcoholic hepatitis as funders figure that we know what causes it and therefore how to prevent it. However, there needs to be much more research as the current treatment options available do not work for those heavy drinkers unlucky enough to develop the disease.”
The study involved 1,053 patients being treated at 65 hospitals in the UK, including a significant number from Newcastle Hospitals NHS Foundation Trust’s Liver Unit at the Freeman Hospital. Patients were randomly assigned to four groups, each receiving two treatments: prednisolone and pentoxifylline, prednisolone and placebo, pentoxifylline and placebo, or both placebo.
Overall, 16 per cent of patients died within 28 days of starting treatment. At 90 days, 29 per cent of patients had died, and after one year 56 per cent had either died or had a liver transplant. The differences in mortality rates between the treatment groups were not statistically significant.
Professor Mark Thursz, from the Department of Medicine at Imperial College London, who led the study, said: “This study is four times larger than any previous trial in patients with severe alcoholic hepatitis, so it provides much stronger data on how effective the drugs are.
“We urgently need to invest in research into the mechanisms of disease, to identify targets for new treatments, and develop better strategies to stop people drinking.”
Deaths from liver disease increased by 40 per cent in England and Wales from 2001 to 2012, partly driven by a rise in alcohol consumption. Alcoholic liver disease was responsible for 4,425 deaths in 2012.
Excessive alcohol consumption first causes fat to build up in the liver, which is potentially reversible. Alcoholic hepatitis is a dramatic manifestation of alcohol-related liver disease, associated with jaundice and liver failure. It is caused by inflammation of the liver and may cause death in up to 30 per cent of patients with a month.
Professor Thursz added: “One reason why we might not have seen a significant effect is that the drugs increase the risk of infection. Another reason is that many patients return to drinking, and suffer further attacks or complications of cirrhosis.
“Some older studies found a mortality rate after 28 days above 30 per cent. It was much lower in this study, which suggests that even though the treatments are ineffective, we are looking after patients better than we used to.”
The study was funded by the National Institute for Health Research Health Technology Assessment programme.
Photo caption: Professor Chris Day, Pro-Vice-Chancellor for Newcastle University’s Faculty of Medical Sciences
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