Alcoholic Hepatitis and TNF-α Antagonists: The Rise and Fall

Alcoholic liver disease (ALD) is the most prevalent cause of advanced liver disease. The disease spectrum ranges from mild steatohepatitis to progressive fibrosis and finally hepatocellular carcinoma. In 2015 in the United States liver cirrhosis was the 12th leading cause of death. The crude death rate from alcohol-related cirrhosis was 6.6 deaths per 100,000 population. Keywords: Alcoholic Hepatitis (AH); TNF-α Antagonists Inflammatory cytokines have an important role in the pathogenesis of ALD and drugs targeting inflammatory cytokines like tumor necrosis factor alpha (TNF-α) have been used. Corticosteroid treatment in Alcoholic Hepatitis have been argued for and against many times over the last few decades. Corticosteroids treatment for severe AH as a reference treatment has been established in the last two decades after multiple metanalyses of randomized controlled trials concluded that corticosteroids improved the short-term survival of patients with severe Alcoholic Hepatitis (AH). Experimental and clinical evidence indicates that TNF-α and its downstream inflammatory cytokines correlate with disease severity and may contribute to the pathogenesis and clinical sequelae of alcoholic hepatitis thereby implicating a possible role for inhibition of TNF-α in the treatment of alcoholic hepatitis. In the early 21st century, an initial pilot study demonstrated the ability of TNF-α Antagonists to augment the treatment of steroid. However further studies have shown TNF-α to not be helpful in Moderate or Severe AH. Newer therapeutic strategies including Pentoxifylline to improve outcomes are being developed and trialed in the population