Excerpt
Alcoholic liver disease (ALD) is the main cause of cirrhosis worldwide [
1]. Despite its high prevalence, ALD has received little attention in the liver community and there is a clear lack of programs for early detection and novel targeted therapies for advanced forms. ALD encloses a wide spectrum of features, ranging from simple steatosis, steatohepatitis, and cirrhosis to hepatocellular carcinoma [
2]. Patients with underlying ALD and heavy alcohol intake can develop an episode of alcoholic hepatitis (AH), the most severe form of ALD [
3]. AH is characterized by an abrupt onset of jaundice and/or liver decompensation. Patients with AH often show signs of systemic inflammation at admission, and are prone to infections and kidney injury, which can lead to multi-organ dysfunction within a few days [
4]. In its severe form, AH can result in 20–50 % mortality at 3 months. The only available therapies that improve survival are corticosteroids and liver transplantation [
5,
6]. The efficacy of pentoxifylline is debatable, based on recent large clinical trials [
6]. The efficacy of prednisolone has been shown in meta-analyses of individual data and was partially confirmed in the recent STOPAH trial [
6,
7]. Unfortunately, many patients do not respond to prednisolone and performing salvage liver transplantation is not feasible in most centers. Therefore, there is an urgent need to provide these patients with novel targeted therapies. In the last two decades, there have been several attempts to test old and novel drugs in patients with severe AH, ranging from classic drugs [
8] to monoclonal antibodies [
9] or stimulating factors [
10] to bone marrow transplantation [
11]. While some of them have improved short-term mortality, the results have not yet been confirmed in independent cohorts. Since prednisolone consistently improves the 1-month survival in patients with severe AH, a common strategy is to add other drugs that could target some pathogenic driver in this disease such as anti-TNF drugs like Infliximab, which have been tested in combination with prednisolone [
9]. While the initial results were encouraging, the usage of a high dose of TNF blocking agents increased the patient’s mortality, likely through the increase of severe bacterial infections [
12]. …
