N-acetyl cysteine in the treatment of alcohol use disorder in patients with liver disease: Rationale for further research

ABSTRACT

Introduction: Alcoholic liver disease (ALD) is the leading cause of alcohol-related death and one of the most common forms of liver disease. Abstinence from alcohol is crucial to reducing morbidity and mortality associated with the disease. However, there are few pharmacotherapies for alcohol use disorder suitable for those with significant liver disease.

Areas Covered: This paper presents a rationale for investigating the use of N-acetyl cysteine (NAC) to promote abstinence or reduce heavy alcohol consumption for patients with an alcohol use disorder, particularly in the presence of liver disease. NAC is an antioxidant with glutamatergic modulating and anti-inflammatory properties. Evidence is emerging that oxidative stress, neuro-inflammation and dysregulation of glutamatergic neurotransmission play a key role in alcohol use disorder. Similarly, oxidative stress is known to contribute to ALD. We outline the studies that have investigated NAC to reduce alcohol consumption including preclinical and clinical studies. We also review the evidence for NAC in other addictions as well as psychiatric and physical comorbidities associated with alcohol use disorders.

Expert Opinion: NAC is low cost, well-tolerated and could have promise for the treatment of alcohol use disorder in the presence of liver disease. Clinical trials directly examining efficacy in this population are required.

KEYWORDS:

• Alcoholic liver disease
• N-acetyl cysteine
• alcohol use disorder
• pharmacotherapy
• comorbidity

Article highlights

• Alcoholic liver disease (ALD) is the leading cause of alcohol-related death and one of the most common forms of liver disease.

• Abstinence from alcohol is crucial to reducing morbidity and mortality associated with the disease yet there are few treatment options for those with significant liver disease.

• N-acetyl cysteine (NAC) is an antioxidant with glutamatergic modulating and anti-inflammatory properties that is low cost and well-tolerated.

• Animal studies demonstrate efficacy of N-acetyl cysteine (NAC) for preventing relapse to alcohol consumption and improving liver function.

• Preliminary evidence in humans is emerging to show significant benefits of NAC to increase abstinence from alcohol.Clinical trials directly examining efficacy in this clinical population are required.

Declaration of interest

The authors have no other 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 apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

KC Morley is supported by a NSW Health Translational Research Fellowship. Kate Chitty is supported by an NHMRC Research Fellowship.