Currently, steroids are the only treatment known to reduce death from alcoholic hepatitis within the first 28 days. However, steroids increase the risk of infection and more than 1 in 3 patients do not respond to them. Non-response to steroids (steroid resistance) predicts death within 90 days. Accurate prediction of response to steroids would therefore enable selection of appropriate patients who might benefit from steroid treatment at the same time as reducing exposure of steroids and risk of infection to steroid resistant patients. Currently, it takes 7 days of steroid treatment to determine whether it has been effective and even then, 1 in 4 patients are incorrectly classified as steroid responders. A faster and more accurate method to measure steroid resistance is required.
We have developed a new laboratory technique (the BLISS assay) to measure steroid resistance based on patients’ white blood cell responses to steroids, which takes only 2 days to run. We will assess whether this test is accurate in identifying steroid responders and non-responders in a multicentre study. In addition, we will be investigating the mechanisms of steroid resistance by looking at genetic regulation of steroid signalling within white blood cells. This work will help us improve identification of steroid resistant patients and to develop new therapies that specifically target steroid resistance.
Dr Ashwin Dhanda