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Researchers recommend need for more effective treatments for alcoholic hepatitis

Alcoholic hepatitis is one of the leading causes of morbidity and mortality in a subset of patients who consume copious amounts of alcohol. Although treatment options are available, outcomes have been poor for patients.

In a new report, researchers Maneerat Chayanupatkul, MD, division of gastroenterology/hepatology, Baylor College of Medicine, Texas, and Suthat Liangpunsakul, MD, division of gastroenterology and hepatology, Indiana University Medical Center, review the current pathogenesis, predictors for mortality, available therapies and their limitations.

Maneerat Chayanupatkul

Pathogenesis

Current data on alcoholic hepatitis (AH) suggest damage from the disease may be a result of the combination of ethanol metabolism, inflammation and innate immunity. Ethanol metabolism generates acetaldehyde, and malondialdehyde is one of the results of lipid peroxidation. Both bind to cellular proteins to form adducts that trigger a variable immune response. This response may be a contributing factor to a patient’s susceptibility to AH. Increased levels of endotoxemia also have been found in patients with AH, most likely due to increased intestinal permeability.

Predictors

An ideal scoring system to predict mortality rate should be simple, accurate, validated and able to guide treatment initiation and response, the researchers wrote. Currently, no one system does all of those, but clinicians have several scoring system options: the Child-Turcotte-Pugh score (CTP), Maddrey discriminant function (DF), Lille Model, model for end stage liver disease (MELD) and the Glasgow alcoholic hepatitis score (GAHS). CTP testing is typically used for cirrhotic patients and is not used often for assessing the severity of AH, although it did predict mortality at 3 and 6 months. Current practice guidelines recommend that AH patients who have a modified discriminate score of at least 32 on the DF test be considered for corticosteroid therapy. Although the test has been validated in multiple trials, it has limitations. The Lille score test is accurate in predicting survival, according to previous research.  However, it does not guide initiation of steroid treatment at the time of admission. MELD had similar efficacy in predicting survival to the DF test. The GAHS scoring system is equivalent to MELD accuracy in predicting 28-day mortality. Currently, modified DF score continues to be used for initiating treatment and the Lille score for guiding treatment response, according to the researchers.

Treatment

In order to generally treat AH, ascites, if present, must be addressed by restricting sodium and diuretics should be initiated. Clinicians have multiple pharmacological therapies to treat AH, including corticosteroids for those with severe cases; pentoxifylline for severe cases and patients with contraindications to corticosteroids.

Anabolic steroids, propythiouracil, S-adenosyl-L-methionine, N-acetylcysteine are not recommended because previous studies showed a lack of benefit or increased survival rate.  Liver transplantation is not recommended according to the current guidelines.

Suthat Liangpunsakul

“Alcoholic hepatitis continues to be a major alcohol-related liver disease in the US with significant morbidity and mortality. However, the outcome from the current treatment options, notably with corticosteroids or pentoxifylline is very poor,” Liangpunsakul told Healio.com. “Undoubtedly, there is a critical need for the newer and more effective pharmacological agents to treat AH. There are several ongoing studies supported by the National Institutes of Health through multi-institutional consortia to test several novel compounds for alcoholic hepatitis, and we hope that the results from these trials will lead to the advancement in the therapy for patients with AH.”

Disclosure: The researchers report no relevant financial disclosures.