Alcoholic steatohepatitis (ASH) and alcoholic hepatitis (AH): cascade of events, clinical aspects, and pharmacotherapy options

ABSTRACT

Introduction: Clinicians caring for patients with alcoholic hepatitis (AH) are often confronted with the question of the best pharmacotherapy to be used.

Areas covered: This article covers metabolic aspects of alcohol as the basis of understanding pharmacotherapy and to facilitate choosing the drug therapeutic options for patients with severe AH.

Expert opinion: Alcoholic steatohepatitis (ASH) and alcoholic hepatitis (AH) as terms are often used interchangeably in scientific literature but a stringent differentiation is recommended for proper clarity. As opposed to ASH, the clinical course of AH is often severe and requires an effective drug treatment strategy, in addition to absolute alcohol abstinence and nutritional support. Drug options include corticosteroids as a first choice and pentoxifylline, an inhibitor of phosphodiesterase, as a second line therapy, especially in patients with contraindications for a corticosteroid therapy such as infections or sepsis. At seven days under corticosteroids, treatment should be terminated in non-responders, and patients must then be evaluated for liver transplantation. Pentoxifylline is not effective as a rescue therapy for these patients. Other treatments such as infliximab, propylthiouracil, N-acetylcysteine, silymarin, colchicine, insulin and glucagon, oxandrolone, testosterone, and polyunsaturated lecithin are not effective in severe AH. For liver transplantation, few patients will be eligible.

KEYWORDS:

• Alcohol dehydrogenase
• alcoholic hepatitis
• alcoholic liver disease
• alcohol metabolism
• alcoholic steatohepatitis
• corticosteroids
• microsomal ethanol-oxidizing system
• pentoxifylline
• pharmacotherapy options

Article highlights

● Alcoholic steatohepatitis (ASH) and alcoholic hepatitis (AH) as terms are often used interchangeably in the scientific literature but a stringent differentiation is recommended for reasons of clarity.

● Corticosteroids are the most commonly used drugs, recommended as first line treatment in severe AH

● Pentoxifylline, a non-selective inhibitor of phosphodiesterase with properties to reduce TNF formation and serum levels, is a second line therapy of severe AH

● Other phosphodiesterase inhibitors had been used as anticytokine therapeuticals for severe AH but results were disappointing, including those with infliximab, a monoclonal chimeric anti-TNF antibody, which alone or combined with prednisolone caused a high rate of lethality.

● Etanercept, propylthiouracil, vitamin E, N-acetylcysteine, silymarin, colchicine, polyunsaturated lecithin, and anabolic steroids such as oxandrolone and testosterone have also disappointed as treatment strategies.

● Liver transplantation for severe AH should be considered in face of a critical clinical course and unsuccessful pharmacotherapy, but indications remain a matter of debate and a case-by-case decision.

This box summarizes key points contained in the article.

Declaration of interest

R Teschke has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This manuscript has not been funded.