Integrated Treatment of Alcohol Use Disorder in Patients With Alcohol‐Associated Liver Disease: An Evolving Story
Authors: Michael R. Lucey, Ashwani K. Singal
Journal: Hepatology (2020)

Potential conflict of interest: Dr. Lucey consults for Novartis and received grants from Pharmasolutions. See Article on Page 1894 and 2080 Alcohol‐associated liver disease (ALD) contributes to 50% of cases of cirrhosis worldwide.(1) Despite this burden of disease, the resources devoted to either research into or treatment of ALD have lagged compared with liver diseases from other etiologies.(2,3) Progress has been hampered by the isolation of addiction medical services from internal medicine, family medicine, and gastroenterology‐hepatology. As a result, around the world, ALD is recognized late in its course, even in specialist centers.(4) Furthermore, most patients with a new diagnosis of ALD report prior interactions with health care providers over their lifetime, when opportunities for screening for alcohol use disorder (AUD) and detecting ALD at an early stage were missed.(5) Recent guidelines into the management of ALD have highlighted the need for better communication between practitioners in addiction, and those in general and specialized medicine and surgery.(2,3) However, we take hope from two papers in this issue of Hepatology that point to the future for better care for patients with ALD.(6,7) In the first study, Preoschold‐Bell et al. compared Screening, Brief Intervention, and Referral to Treatment (SBIRT) with SBIRT and enhanced treatment of AUD, with an aim to reduce alcohol consumption in patients with hepatitis C virus (HCV) infection.(7) Subjects attending three out‐patient clinics from October 2014 to September 2017 were identified as candidates for the study using the AUD Identification Test questionnaire. The primary outcome of abstinence from alcohol at 6 months improved similarly in both groups. For example, abstinence at month 6 in the SBIRT‐only group improved to 20.5% from 7.1% at day 0, and the SBIRT plus intensive treatment of AUD group improved to 23.3% from 4.2% at baseline. Similar results were obtained for evaluation on heavy drinking days, number of heavy drinking days per month, decreasing the amount of alcohol consumption per week, and use of other recreational drugs. This study makes the important point that improvements in drinking behavior are possible with concerted medical intervention. It should be acknowledged that this study included patients with mild AUD, limiting the applicability to the patients usually seen in liver units. Furthermore, all patients in this study received screening for AUD, raising awareness, which is not the standard of care for HCV infection treatment in routine practice. Apart from SBIRT, two other psychosocial interventions for managing more severe AUD or alcohol dependence include cognitive behavioral therapy (12‐step abstinence‐based program that involves Alcoholics Anonymous, focusing on identifying triggers that endanger relapse and how to deal with these) and motivational enhancement therapy (technique dealing with the patient dilemma, focusing on the decision to stop or modify drinking behavior). The study by Rogal et al. provides a fascinating retrospective account of treatments of AUD in patients with cirrhosis in the U.S. Veterans Affairs (VA) integrated health system.(6) Among a cohort of almost 100,000 subjects with cirrhosis, 35,682 were identified with a new diagnosis of AUD. The authors showed that only 14% received treatment for AUD within 180 days of the index diagnosis of AUD, with 12% receiving behavioral therapy alone, 0.4% pharmacotherapy alone, and 1% both behavioral and pharmacotherapy. A further important insight from this study provides the main reason for continuing efforts to promote treatment of AUD in patients with ALD. Their data showed that treatment for AUD was associated with reduction in the hepatic decompensation by 37%, with 13% reducing long‐term all‐cause mortality.(6) The low use of AUD treatment in the VA is in line with national experience. For example, data from the National Epidemiologic Survey on Alcohol and Related Conditions III, a survey of 36,309 U.S. noninstitutionalized civilian adults (2012‐2013), collected through face‐to‐face interview, revealed that only 19.8% with diagnosis of AUD during their lifetime ever received AUD treatment.(8) In another study, Mellinger et al. examined an insurance‐based U.S. cohort of 66,053 individuals with alcohol‐associated cirrhosis, and discovered that only 10% received a face‐to‐face mental health or substance abuse visit, with only 0.8% receiving U.S. Food and Drug Administration–approved medication for AUD within 1 year of index diagnosis.(9) These data are particularly disappointing given that 72% of the cohort had specific coverage for treatment of substance abuse disorders. What are the barriers that hamper treatment of AUD in patients with ALD, despite guidelines recommending clinical care models for addicted patients with liver disease that integrate hepatology and addiction medicine? We speculate that the barriers exist at many levels, including, but not limited to, logistics of health system infrastructure, a lack of professional addiction medicine expertise among physicians including hepatologists, and poor patient acceptance of AUD treatment. The curricula of internal medicine and surgical residencies, and fellowships in gastroenterology, transplant hepatology and transplant surgery, all should include dedicated experience in addiction medicine. Patients with ALD often express resistance to treatment of AUD, for reasons that they no longer have cravings for alcohol, skepticism regarding the available treatments, or being too sick for participation in counseling sessions.(10,11) We need to convince ourselves first and overcome other infrastructure barriers before convincing our patients about the value of treatment of AUD as a basis for improving their outcomes and survival. The same barriers regarding skepticism and recruitment are compounded by critical decisions regarding choice of intervention in the treatment and control groups, when planning clinical trials of AUD treatment in patients with ALD. There is also a momentum for changing endpoints from traditional absolute endpoints of abstinence to more qualitative ones, such as reduction in drinking parameters.(12) For example, in Weinrieb's randomized controlled trial comparing motivational enhancement therapy (MET) with treatment as usual (TAU) in patients with advanced ALD, it was found that 25% in each group relapsed to alcohol use.(11) However, after "excluding an extreme outlier," the MET‐treated group had significantly fewer drinks per drinking days than subjects in the TAU group. The article in this issue by Proeschold‐Bell et al. eschewed TAU as the comparative therapy, on the grounds that SBIRT had become standard of care.(7) However, one explanation for their observed outcome is that the two treatment arms were essentially the same. In summary, two papers in this issue of Hepatology address treatment of AUD as a basis for prevention of ALD or its progression with consequent improved outcomes. These emerging data also provide real grounds for hope that we are on the crest of a new treatment paradigm for patients with AUD and ALD, diagnosing each at an earlier stage, and integrating AUD management into the care of patients with alcohol‐associated cirrhosis and/or alcoholic hepatitis. We propose a simple algorithm to help providers to accomplish these goals (Fig. 1). In addition, we need better education about AUD for gastroenterology and hepatology trainees, better integration of AUD treatment into liver units, and more prospective studies of AUD in patients with ALD. We believe that adoption of these ideas would be cost‐effective in macroeconomic terms, given the high mortality due to ALD, affecting patients in the most productive period of their lives. Furthermore, this integrated care will hopefully reduce morbidity and mortality among patients at risk or with established ALD.(1)Fig. 1: Screening for AUD using the AUD Identification Test (AUDIT) questionnaire, to identify high‐risk individuals and to select patients with ALD for the integrated care model.