Steroids for Alcoholic Hepatitis

In 1978, Maddrey and colleagues published a randomized trial of prednisolone versus placebo in alcoholic hepatitis. They found the laboratory markers (bilirubin/prothrombin time) could predict which patients would benefit from corticosteroid therapy, where patients with a score >32 had a mortality benefit at thirty days. Thirty-five years, and over a dozen RCT's and meta-analyses later, the use of steroids remains controversial.

Prednisolone is the most widely studied corticosteroid and is preferred over prednisone, considering prednisone is converted to prednisolone following hepatic metabolism. Forty milligrams per day is the most widely used dose and is continued for 28 days duration, followed by a 2 week taper. The populations studied tended to have isolated alcoholic hepatitis, and patients with GI bleeding, pancreatitis and active infection tended to be excluded from study. The small sample sizes and heterogeneity of studies has made it difficult to determine the effect of pharmacotherapy. A systematic review found no mortality benefit in patients with mild to moderate hepatitis, but found a mortality benefit with steroids in those at highest risk (Rambaldi et al. 2008). Interestingly this therapeutic effect may have a threshold, where patients with a Maddrey descrimant function score (MDF) >54, were found to have increased mortality with steroids.

Given a mortality rate of over 30% in patients with severe alcoholic hepatitis, combination therapy trials have been designed with the hope of improving outcomes. Prednisolone +/- N-acetylcysteine (NAC) were compared in a randomized control trial published in NEJM (Nguyen-Kach et al. 2011). There was no significant difference in mortality at 6 months, but there was improvement in survival at 1 month. Patients in the combination group were also less likely to develop hepatorenal syndrome and infection. Recommendations for NAC were not included in the recent update of the American Association for the Study of Liver Disease (AASLD) guidelines.

An additional score (Lille score) was developed and found to be helpful in determining if patients with alcoholic hepatitis were to be responsive to corticosteroid therapy. This score predicted six month mortality by comparing using laboratory data over time. Patients with chronic liver disease often have multiple causes contributing to disease progression. It is important to take a detailed alcohol history and consider pharmacotherapy in the appropriate clinical context.

Steroids and NAC - NEJM