Treatment of Alcohol Use Disorder in Patients with Alcoholic Liver Disease

Leggio, Lorenzo; Lee, Mary R.

doi:10.1016/j.amjmed.2016.10.004

Cited by 133 publications

(149 citation statements)

References 80 publications

Supporting

Mentioning

142

Contrasting

Unclassified

Order By: Relevance

“…Chronic alcohol consumption is a leading cause of liver disease worldwide (Leggio and Lee, ). Alcohol‐related liver disease ranges in severity from mild and reversible fatty liver (steatohepatitis) to more severe forms including hepatitis, cirrhosis, or even hepatic failure (Leggio and Lee, ). In terms of mechanisms, both oxidative stress and inflammation have been implicated in the induction of alcohol‐related liver injury, including steatohepatitis.…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, while CBD presents a good safety profile (Bergamaschi et al., ), the FDA has recommended a dose adjustment in those with hepatic impairment based on transaminase elevations observed in patients receiving 20 mg/kg/d (FDA, ). Liver damage is commonly seen in AUD patients (Leggio and Lee, ), and the FDA recommends a maximum dosage of 10 mg/kg/d for patients with moderate hepatic impairment making this an appropriate target for AUD. Interestingly, the studies on hepatotoxicity as discussed in the current review revealed that CBD was able to prevent development of signs of liver pathology noted with excessive alcohol exposure (Wang et al., ; Yang et al., ), and safety data from Devinsky and colleagues () also revealed that patients with elevated transaminase levels received concomitant valproate.…”

Section: Discussionmentioning

confidence: 99%

“…It is a highly disabling condition and represents a serious public health concern. The FDA has approved 3 medications for treating AUD including naltrexone (both oral and intramuscular formulation), acamprosate, and disulfiram (Leggio and Lee, ); however, meta‐analytic evidence only supports the use of acamprosate and naltrexone (Jonas et al., ). The European Medicines Agency has also approved nalmefene for AUD (Paille and Martini, ).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Cannabidiol as a Novel Candidate Alcohol Use Disorder Pharmacotherapy: A Systematic Review

Turna

Syan

Frey

et al. 2019

Alcoholism Clin & Exp Res

View full text Add to dashboard Cite

There is substantial interest in the therapeutic potential of cannabidiol (CBD), a nonpsychoactive cannabinoid found in plants of the genus Cannabis. The goal of the current systematic review was to characterize the existing literature on this topic and to evaluate the credibility of CBD as a candidate pharmacotherapy for alcohol use disorder (AUD). Using a comprehensive search strategy, 303 unique potential articles were identified and 12 ultimately met criteria for inclusion (8 using rodent models, 3 using healthy adult volunteers, and 1 using cell culture). In both rodent and cell culture models, CBD was found to exert a neuroprotective effect against adverse alcohol consequences on the hippocampus. In rodent models, CBD was found to attenuate alcohol-induced hepatotoxicity, specifically, alcoholinduced steatosis. Finally, findings from preclinical rodent models also indicate that CBD attenuates cue-elicited and stress-elicited alcohol seeking, alcohol self-administration, withdrawal-induced convulsions, and impulsive discounting of delayed rewards. In human studies, CBD was well tolerated and did not interact with the subjective effects of alcohol. Collectively, given its favorable effects on alcoholrelated harms and addiction phenotypes in preclinical models, CBD appears to have promise as a candidate AUD pharmacotherapy. This is further bolstered by the absence of abuse liability and its general tolerability. A clear limitation to the literature is the paucity of human investigations. Human preclinical and clinical studies are needed to determine whether these positive effects in model systems substantively translate into clinically relevant outcomes.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Cannabidiol as a Novel Candidate Alcohol Use Disorder Pharmacotherapy: A Systematic Review

Turna

Syan

Frey

et al. 2019

Alcoholism Clin & Exp Res

View full text Add to dashboard Cite

show abstract

“…Because posttransplant resumption of alcohol use can compromise long‐term survival, comprehensive alcohol use disorder (AUD) treatment is a crucial element of pre‐ and posttransplantation procedures . While select pharmacotherapies (eg, acamprosate, baclofen) may be safely prescribed to ALD patients to help maintain abstinence, the extent to which behavioral alcohol interventions (a critical element of evidence‐based alcohol treatment approaches) are effective for ALD patients is uncertain. ALD patients represent a unique subpopulation of those with AUD, often presenting with a chronic and severe history of alcohol addiction and variable insight and motivation into alcohol problems .…”

Section: Introductionmentioning

confidence: 99%

A review of behavioral alcohol interventions for transplant candidates and recipients with alcohol-related liver disease

Schlagintweit

Lynch

Hendershot

2019

American Journal of Transplantation

View full text Add to dashboard Cite

Alcohol‐related liver disease (ALD) is a common indication for liver transplantation. Reflecting growing consensus that early transplant (ie, prior to sustained abstinence) can be a viable option for acute alcoholic hepatitis, access to liver transplantation for ALD patients has increased. Prevention of alcohol relapse is critical to pretransplant stabilization and posttransplant survival. Behavioral interventions are a fundamental component of alcohol use disorder treatment, but have rarely been studied in the transplant context. This scoping review summarizes published reports of behavioral and psychosocial alcohol interventions conducted with ALD patients who were liver transplant candidates and/or recipients. A structured review identified 11 eligible reports (3 original research studies, 8 descriptive papers). Intervention characteristics and clinical outcomes were summarized. Interventions varied significantly in orientation, content, delivery format, and timing/duration. Observational findings illustrate the importance of situating alcohol interventions within a multidisciplinary treatment context, and suggest the potential efficacy of cognitive‐behavioral and motivational enhancement interventions. However, given extremely limited research evaluating behavioral alcohol interventions among ALD patients, the efficacy of behavioral interventions for pre‐ and posttransplant alcohol relapse remains to be established.

show abstract

“…Improving the treatment of patients with alcohol use disorder (AUD) and alcohol-related liver disease (ALD) is of vital importance from a clinical and public health standpoint (1). Only three medications have been approved by the FDA to treat AUD -the last approval took place almost 15 years ago.…”

Section: Introductionmentioning

confidence: 99%

Leveraging genetic data to investigate molecular targets and drug repurposing candidates for treating alcohol use disorder and hepatotoxicity

Gray

Murphy

Leggio

2019

Preprint

Self Cite

View full text Add to dashboard Cite

Novel treatments for alcohol use disorder (AUD) and alcohol-related liver disease (ALD) are greatly needed. We utilized a recently developed Bayesian approach, Integrative Risk Gene Selector (iRIGS), to identify high-confidence risk genes (HRGs) for alcohol consumption using SNPs from the largest alcohol consumption GWAS to date (N = 941,280). We subsequently used the Target Central Resource Database (TCRD) to search for drug-protein interactions for these HRGs and previously identified risk genes for alcohol consumption. We identified several HRGs for alcohol consumption that are novel contributions to the previously published alcohol consumption GWAS. Namely, ACVR2A, codes for activin receptor type-2A, which is critical for liver function, and PRKCE, codes for protein kinase C epsilon, which has been linked to alcohol consumption. Furthermore, several previously identified risk genes for alcohol consumption code for proteins that are implicated in liver function and are targeted by drugs that are promising candidates for managing hepatotoxicity (e.g., metformin), highlighting potential candidates for drug repurposing. This study demonstrates the value of incorporating regulatory information and drug-protein interaction data to highlight promising molecular targets and drugs for treating AUD and ALD.

show abstract

Treatment of Alcohol Use Disorder in Patients with Alcoholic Liver Disease

Cited by 133 publications

References 80 publications

Cannabidiol as a Novel Candidate Alcohol Use Disorder Pharmacotherapy: A Systematic Review

Cannabidiol as a Novel Candidate Alcohol Use Disorder Pharmacotherapy: A Systematic Review

A review of behavioral alcohol interventions for transplant candidates and recipients with alcohol-related liver disease

Leveraging genetic data to investigate molecular targets and drug repurposing candidates for treating alcohol use disorder and hepatotoxicity

Contact Info

Product

Resources

About