Alcoholic hepatitis treatments fail to keep patients alive

The main drugs used to treat alcoholic hepatitis are not effective at increasing patients' survival, a major study has found.

In a trial of over 1,000 patients, prednisolone and pentoxifylline, treatments recommended in international guidelines, did not achieve a statistically significant reduction in mortality after 28 days, 90 days or a year.

The authors of the study, which is published today in the New England Journal of Medicine, say there is an urgent need for more research into prevention and treatment of alcohol-related liver disease.

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 Mark Thursz from the Department of Medicine at Imperial College London, who led the study, said: "Liver disease is the only major cause of preventable death that is increasing in England, but generally falling in other comparable European nations.

"The treatments we looked at are widely used, but the evidence supporting them comes from a few relatively small trials. 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 were surprised to find that neither treatment had a significant effect on survival after the first month, and the mortality rate after one year is alarmingly high. 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."

The study involved 1,053 patients being treated at 65 hospitals in the UK. 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 Thursz said: "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 (NIHR) Health Technology Assessment programme. It was also supported by the NIHR Clinical Research Network and the NIHR Imperial Biomedical Research Centre.

For more information please contact:

Sam Wong
Research Media Officer
Imperial College London
Email: sam.wong@imperial.ac.uk
Tel: +44(0)20 7594 2198
Out of hours duty press officer: +44(0)7803 886 248

For a comment from the Alcohol Health Alliance UK, contact Paul Jordan: paul.jordan@rcplondon.ac.uk 0203 075 1726

1. M.R. Thursz et al. 'Prednisolone or Pentoxifylline for Alcoholic Hepatitis.' N Engl J Med 2015;372:1619-28. DOI: 10.1056/NEJMoa1412278

2. About Imperial College London

Imperial College London is one of the world's leading universities. The College's 14,000 students and 7,500 staff are expanding the frontiers of knowledge in science, medicine, engineering and business, and translating their discoveries into benefits for society.

Founded in 1907, Imperial builds on a distinguished past - having pioneered penicillin, holography and fibre optics - to shape the future. Imperial researchers work across disciplines to improve global health, tackle climate change, develop sustainable energy technology and address security challenges. This blend of academic excellence and its real-world application feeds into Imperial's exceptional learning environment, where students participate in research to push the limits of their degrees.

Imperial nurtures a dynamic enterprise culture, where collaborations with industrial, healthcare and international partners are the norm. In 2007, Imperial College London and Imperial College Healthcare NHS Trust formed the UK's first Academic Health Science Centre. This unique partnership aims to improve the quality of life of patients and populations by taking new discoveries and translating them into new therapies as quickly as possible.

Imperial has nine London campuses, including Imperial West: a new 25 acre research and innovation centre in White City, west London. At Imperial West, researchers, businesses and higher education partners will co-locate to create value from ideas on a global scale. http://www.imperial.ac.uk

3. The National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme funds research about the effectiveness, costs, and broader impact of health technologies for those who use, manage and provide care in the NHS. It is the largest NIHR programme and publishes the results of its research in the Health Technology Assessment journal, with over 700 issues published to date. The journal's 2013 Impact Factor (5.116) ranked it two out of 85 publications in the Health Care Sciences and Services category. All issues are available for download, free of charge, from the website. The HTA Programme is funded by the NIHR, with contributions from the CSO in Scotland, NISCHR in Wales, and the HSC R&D Division, Public Health Agency in Northern Ireland. http://www.nets.nihr.ac.uk/programmes/hta

4. The National Institute for Health Research (NIHR) is funded by the Department of Health to improve the health and wealth of the nation through research. Since its establishment in April 2006, the NIHR has transformed research in the NHS. It has increased the volume of applied health research for the benefit of patients and the public, driven faster translation of basic science discoveries into tangible benefits for patients and the economy, and developed and supported the people who conduct and contribute to applied health research. The NIHR plays a key role in the Government's strategy for economic growth, attracting investment by the life-sciences industries through its world-class infrastructure for health research. Together, the NIHR people, programmes, centres of excellence and systems represent the most integrated health research system in the world. For further information, visit the NIHR website (http://www.nihr.ac.uk).

This article presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.