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, published 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% 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% of patients within 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% of patients died within 28 days of starting treatment. At 90 days, 29% of patients had died, and after one year 56% 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%. 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, supported by the NIHR Clinical Research Network and the NIHR Imperial Biomedical Research Centre.
