What is the Best Way to Care for Patients with Alcoholic Hepatitis?

Although alcohol-related liver disease is the 8th most common cause of mortality in the US and the 2nd leading cause of mortality among all gastrointestinal diseases, there are few therapeutic options for patients or resources to support identification of new therapies. However, treatment approaches are being developed; a review in the April issue of Clinical Gastroenterology and Hepatology, discusses therapeutic targets and treatment options for patients with alcoholic hepatitis (AH).

Most of the US population consumes alcohol, and 1 in 10 people report heavy drinking (≥3 drinks/day). Fortunately, only a minority of these heavy drinkers develop significant liver disease. The reasons for this are unclear, but are likely to involve genetic factors (such as polymorphisms in patatin-like phospholipase 3) as well as an individual’s sex, ethnicity, binge drinking (5 or more drinks at a time), nutrition status (obesity), or co-existing liver diseases, such as hepatitis C.

Younger people, women, and binge drinkers are more prone to develop AH, characterized by hepatic decompensation and portal hypertension. In the review article, Ashwani K. Singal, et al. describe factors that contribute to development of AH and challenges related to management.

The pathogenesis of AH is believed to involve disrupted gut barrier function that leads to translocation of bacteria and endotoxin, activation of the innate immune response in the liver, and hepatocellular apoptosis, necrosis, and injury. Researchers are working on approaches to alter specific steps in the pathogenic process (see figure).

AH develops because alcohol increases gut permeability and allows translocation of bacteria and molecules (DAMPs) that activate the toll-like receptor (TLR)4 in liver. Kupffer cells stimulate production of cytokines such as IL1, IL6, and TNFα, which promote inflammation and cell death. Caspase or IL1 inhibitors might slow or block this process.

Singal, et al. discuss methods to assess disease activity, help patients maintain abstinence from alcohol, and provide supportive care and nutrition. Potential therapies reviewed in include corticosteroids, pentoxifylline, tumor necrosis factor (TNF) inhibitors, antioxidants, oxandrolone, granulocytapheresis, and albumin dialysis. Singal, et al. also discuss the controversies over liver transplantation for patients with AH.

The National Institute on Alcohol Abuse and Alcoholism has created a multi-institutional consortia to identify new therapeutic targets and perform early-phase clinical studies to develop and test new drugs for management of AH (U01 AA021883 and U01 AA021902)

Increasing resources are therefore being allocated to advance management approaches for alcoholic liver disease, especially AH.