Long‐term outcome in patients with severe alcoholic hepatitis can be reliably determined using an in vitro measure of steroid sensitivity
Authors: Ashwin D. Dhanda, Alex J. di Mambro, Vicky L. Hunt, C. Anne McCune, Colin M. Dayan, Andrew D. Dick, Richard W.J. Lee, Peter L. Collins
Journal: Hepatology (2014)

Severe alcoholic hepatitis (SAH) has an overall mortality of 40% and is widely treated with steroids. However, a proportion of patients are steroid resistant and ultimately die from liver failure. Currently, the only existing model to predict response to steroids relies on laboratory parameters at baseline and after 7 days of steroid treatment and has 75% sensitivity in predicting death at 6 months.1 We have previously reported on a 48-hour in vitro measure of steroid sensitivity (known as the dexamethasone inhibition of lymphocyte proliferation assay [DILPA]) that predicts 6-month survival with 78% sensitivity.2 Here, we present results of a validation study performed in an independent cohort of 26 patients with SAH. Consecutive patients with SAH (defined as recent-onset jaundice with a bilirubin level >80 µmol/L and coagulopathy in patients heavily consuming alcohol with a Maddrey discriminant function [DF] >32) were recruited. All patients were treated with 4 weeks of prednisolone 40 mg daily (other therapies, including pentoxifylline and N-acetylcisteine, were not used). The DILPA was performed as previously described2 as soon as possible after admission and before prednisolone treatment. The maximum suppression of proliferation (Imax) was determined and a threshold of less than 60% was set to define steroid resistance, as previously described.3 DILPA was performed in 46 patients with SAH. Median Imax was 87% in survivors versus 43% in nonsurvivors at 6 months (P < 0.001). A threshold of Imax of 60% (dotted line) has a 91% sensitivity in predicting 6-month survival. Twenty-six patients were recruited between February 2010 and September 2012 (median age: 46; 23% female; median baseline DF: 49.7; 72% had ascites and 23% had overt hepatic encephalopathy) and followed up for at least 1 year (median time: 889 days). The accuracy of the DILPA in predicting 6-month survival, assessed by area under the receiver operating characteristic (AUROC), was 0.86. Combining this recent cohort with our previously published data set resulted in an AUROC of 0.84 for prediction of both 6- and 12-month survival, which exceeds the AUROC for the Lille score of 0.73 and 0.71 at 6 months and 1 year, respectively. An Imax >60% had a 91% sensitivity in predicting 6-month survival (Fig. 1). Six-month and 1-year mortality in patients with Imax <60% was 74% versus 9% in those with Imax >60% (hazard ratio: 6.5). Overall 6-month mortality was 43% (14% at 28 days). The few subjects with outlying DILPA values did not have any specific clinical characteristics to explain their results and should be considered false positives and negatives. These results confirm that in vitro steroid sensitivity is a good measure of clinical steroid responsiveness and demonstrate the potential value of the DILPA as a rapid bioassay that can be performed at an early stage to accurately determine long-term outcome of patients with SAH, in particular to identify patients with a poor prognosis where alternative treatment strategies may be indicated. Ashwin D. Dhanda, MRCP1,2 Alex J. di Mambro, M.D., MRCP3 Vicky L. Hunt, B.Sc.2 C. Anne McCune, M.D., FRCP2 Colin M. Dayan, Ph.D., FRCP4 Andrew D. Dick, FRCS, F.R.C.Ophth., FRCP, M.D., F.Med.Sci.1 Richard W.J. Lee, MRCS, M.R.C.Ophth., Ph.D.1 Peter L. Collins, M.D., FRCP2 1School of Clinical Sciences University of Bristol Bristol, UK 2Department of Liver Medicine University Hospitals Bristol NHS Foundation Trust Bristol, UK 3Department of Gastroenterology Gloucestershire Hospitals NHS Foundation Trust Cheltenham, UK 4Institute of Molecular and Experimental Medicine Cardiff University School of Medicine Cardiff, UK