Barriers to Alcohol Use Disorder Treatment in Patients with Alcohol-Associated Liver Disease

INTRODUCTION

Prolonged abstinence is critically important, and the ideal goal is to decrease mortality in alcohol-associated liver disease (ALD). Historically, total abstinence has been a requirement to be eligible for liver transplantation (LT)^1,2, although a significant shift in paradigm has taken place in the last decade³. Any alcohol consumption in patients with liver-related decompensation and/or alcohol-associated hepatitis and even in patients with compensated cirrhosis is not advisable⁴. After the first ALD-related hospitalization, rates of returning to alcohol use are 40–70%^5–8. After LT, in a mean follow-up period of 48.4 ± 24.7 months, rates of alcohol relapse and heavy alcohol relapse were 22 % and 14 %, respectively⁹. Mortality is 3-fold higher during a 10-year follow-up in those patients who relapse into alcohol drinking¹⁰. Still, only a very small portion of patients with ALD receive any therapeutic intervention for alcohol use disorder (AUD). For example, in a retrospective cohort study among Veterans with liver cirrhosis and comorbid AUD, only 14% received AUD treatment, including 12% receiving solely behavioral therapy, 0.4 % receiving pharmacotherapy, and 1 % receiving combined therapy¹¹. The same study showed the benefits of receiving AUD therapy as it resulted in lower risk of hepatic decompensation (adjusted odds ratio – AOR 0.63) and reduced long-term mortality (AOR 0.87)¹¹. Integrative care models, like multidisciplinary ALD clinics, are critical for patients with ALD. In such clinics, hepatology and addiction teams work jointly to treat ALD and AUD simultaneously^12,13. These multidisciplinary approaches allow a holistic and unified management of patients with AUD/ALD and facilitate an earlier diagnosis of relapse, hence allowing for timely interventions and reduced mortality^13–16. Nevertheless, implementing this approach in clinical practice is challenging, and widespread adoption of these recommended models is poor^1,11,17–19.

In this article, we outline the barriers to AUD treatment in patients with ALD. Consistent with DiMartini et al.²⁰, we categorize them into three groups: patient-, clinician-, and system-level barriers. Furthermore, we discuss strategies to overcome these obstacles. We summarized this information in Table 1.

Table 1.

Barriers to AUD treatment in individuals with ALD and possible strategies to overcome these challenges

Identified barriers	Strategies to overcome
1. Patient-level barriers
Misconceptions about the chronicity of AUD and the risk of relapse	Patient education
Stigmatization	Educational campaigns from the appropriate organizations to overcome stigma Avoid using stigmatizing language by health care providers
Underreporting alcohol consumption	Using direct or indirect biomarkers of alcohol consumption Revise the 6-months abstinence criterion for LT
Lack of information and discomfort about AUD treatment options	Provide information about treatment options Integrated care with addiction and hepatology specialists Collaborative attitude toward the patient
Insufficient motivation to reduce or stop alcohol consumption	Motivational interviewing
Lack of social / family support	Include social workers and case managers in the medical team. Family therapy and psychoeducation of the family
2. Clinician-level barriers
Inadequate identification of AUD	Education about useful screening / diagnostic tools (eg., AUDIT) Consensus about the definition of relapse
Imprecise quantification of alcohol use	Reduce stigmatization of individuals with AUD Provide extra-time for patient history taking
Lack of knowledge about AUD treatment options Choosing inappropriate treatments for AUD Discomfort in AUD treatment	Educational symposia and campaigns by addiction experts Distribute propagable, concise educational materials among health care providers Incorporating addiction medicine training in the hepatology fellowship curriculum
3. System-level barriers
Geographically separated addiction medicine and hepatology units	Facilitate funding for integrated care Increase communication between clinicians from different units (e.g., hepatology, internal medicine, addiction medicine, psychiatry) Facilitate the use of tele-health
Insufficient human and technical resources	Increase funding for mental health staff and clinics
Private health insurances do not facilitate integrated care	Increase federal and state-level funding for integrated care models
Difficulties in combined billing, separate administrative systems	Develop integrated care models
Gender, racial/ethnic and socioeconomic inequities	Uniform protocols, screening, monitoring Increase availability of mental health care in marginalized and socially deprived communities

DISCUSSION

1. PATIENT-LEVEL BARRIERS

1.1. Lack of insight of AUD diagnosis and inaccurate information about AUD

At the time of the initial visit with a hepatologist, a patient with ALD may not be aware of having an AUD, and an AUD diagnosis could come as a surprise. Facing the information that AUD and the related problematic/hazardous alcohol consumption is the cause of their liver disease may lead to denial of the AUD diagnosis in the first place²⁰. Awareness of having a drinking problem is a crucial step toward readiness to change and accept any AUD treatment. As shown by a study, in more than half of individuals with AUD, lack of insight of drinking problems was the reason for not seeking treatment²¹. In patients with ALD, younger age, higher drinking severity and higher self-stigma predict stronger self-awareness of the individual’s drinking problems²². Many of them do not believe that alcohol consumption is a significant problem for themselves, therefore, they refuse having an diagnosis²³. Even if a patient accepts the diagnosis, they may not understand that it is a chronic medical disease with a high potential to relapse. They may think that if they reach abstinence once, then no more sustained treatment is necessary, and there is no risk of relapse^20,23–26. Furthermore, patients also tend to prioritize ALD treatment and decline simultaneous AUD treatment because they feel liver problems are more important and a higher priority than AUD^23,25, hence not appreciating that in actuality AUD is the underlying cause of ALD. Of note, a recent study showed some gender disparity in some of these misconceptions, e.g., more women (18% of women vs. 10% of men) think incorrectly that women have to drink more alcohol than men to get ALD, and ~20% of women (8% of men) believe that women in general do not have to worry about having AUD²⁴.

1.2. Tendency to minimize/underestimate the use of alcohol.

A remarkable group of patients underreport their actual alcohol consumption or belittle their alcohol use²⁷. An important reason for this behavior is that they may feel discomforted discussing their illness with healthcare providers as well as feeling that their condition ‘disappoints’ them²⁴. Some people may also be afraid of AUD inpatient care, should they be honest about their actual alcohol use²⁸. For patients with AUD and ALD requiring LT, some of them may conceal their relapse because they fear a penalty or being removed from the waiting list²⁹. Patients may perceive stigma not only about having AUD but also about having liver disease. The association between alcohol and liver disease is so strong that in a survey study, 82% of liver disease patients perceived stigma from society, healthcare providers, and family for being an “alcoholic”; however, only 12 % of them had ALD³⁰. Society often blames ALD patients for their behavior leading to the illness, which prevents them from accurately self-reporting the actual alcohol consumption^31,32.

1.3. Lack of information, misconceptions, and discomfort about AUD treatment options

Even if a patient accepts the diagnosis of AUD and accurately reports their alcohol consumption, s/he may be reluctant against AUD treatment. Numerous patients feel they don’t need therapy because, in their opinion, it’s ineffective and a waste of time²⁴. Pharmacotherapy is the least well-known type of AUD treatment, and there is a lack of knowledge about its side effects and benefits as well^28,29. Patients may not appreciate that AUD treatment may also improve their mental/emotional health and social relationships. They think that it is too late to treat AUD when symptoms of advanced liver disease are present, which is also a frequent misconception. Receiving AUD treatment is perceived to be stigmatizing because of its associations with character weakness, personal failure, or signs of poor commitment to abstinence²⁹. In addition, there is a solid perception of the “ideal ALD transplant patient” who is invincible and able to avoid any relapse without getting help²⁹. Many patients prefer to deal with a relapse themselves before involving any staff because they think that they “should be strong enough to handle it alone”²⁸. There is also a reluctance to group therapy, mainly due to social anxiety, concerns about the perceived negative influence of groups that include active drinkers, and maintaining anonymity, especially in smaller towns and other small communities²⁴.

1.4. Insufficient motivation to change

The motivation to change any health behavior is a balance between the potential benefits and subjective inconveniences/disadvantages. To reach abstinence, patients must consider ending drinking-related social relationships or abstaining from the various effects (e.g., rewarding, euphoric, sedative, anxiolytic, pain-relieving) of alcohol. This decision-making is influenced by the person’s preferences and core values^20,33. The behavioral change begins with pre-contemplation, followed by contemplation and taking action to change³⁴. Many patients with ALD are in the pre-contemplation phase, and they have to go through the three steps mentioned above to become able to change their behavior and cut down alcohol consumption²⁰. That shows how difficult it may be to accept the advice of immediate abstinence. Most benefits are long-term, but disadvantages, such as withdrawal symptoms or the disappearance of drinking-related social networks, are instantaneous.

1.5. Lack of social and family support

The main driver for maintaining abstinence is support from the family as identified by 66% of LT patients in a survey study²⁹. Accordingly, those who relapsed blamed the lack of social and family support, which often drops after a successful LT²⁹. If ALD patients are not ready to reduce drinking or become abstinent, it can destroy family relationships²⁰. They may also miss their drinking partners; however, such social networks may place the patient at risk for relapse^20,29.

2. STRATEGIES TO SURMOUNT PATIENT-LEVEL BARRIERS

Appropriate screening is key to identify timely which patient needs AUD treatment and those who are abstinent with a high risk of relapse. The use of the AUD identification test (AUDIT) is highly recommended by the US Preventive Services Task Force to diagnose AUD with a sensitivity of 70% and a specificity of 85% and to assess the severity of AUD³⁵. AUDIT is validated widely across different demographic groups. A score of ≥ 8 is considered to indicate hazardous or harmful alcohol use. Before and after LT, evaluation of risk factors helps early intervention to prevent or at least mitigate the effects of alcohol relapse. The risk of relapse is higher with younger age, family history of AUD, history of previous treatment for AUD, shorter length of pre-transplantation abstinence, poor social support, smoking, comorbid mental health and substance use disorders, and non-compliance with clinic visits¹². For a proper risk evaluation, clinicians can use the Sustained Alcohol Use Post-Liver Transplant (SALT) score (range 0–11) based on the abovementioned risk factors. The SALT score includes 4 points for >10 drinks per day at initial hospitalization, 4 points for multiple prior rehabilitation attempts, 2 points for prior alcohol-related legal issues, and one point for previous substance use. This score has a good sensitivity, but its specificity is low. A SALT score of <5 has a 95% negative predictive value and a score of ≥5 has only a 25% positive predictive value for sustained alcohol use after liver transplantation³⁶. However, SALT scoring is a convenient tool to evaluate the chance of a relapse; it also has a disadvantage, namely the portion of false positives is high, thereby potentially stigmatizing numerous ALD patients.

Underreported alcohol use can be addressed by measuring biomarkers of alcohol consumption. Indirect markers, like serum levels of γ-glutamyltransferase, mean corpuscular volume, aspartate aminotransferase, or carbohydrate deficient transferrin are widely used by clinicians, but their specificity is low¹². Direct markers of alcohol metabolism are more specific, and enhancing their availability would alleviate the detection of relapse and getting proper information about actual alcohol consumption. Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are non-volatile, water-soluble metabolites produced during the elimination of ethanol, and they’re detectible in urine up to 90 hours after alcohol consumption³⁷. Urinary EtG shows an 89.3% sensitivity and a 98.9% specificity for actual alcohol drinking³⁸, and EtG can also be measured in hair and fingernails as markers of long-term alcohol use^39,40. Phosphatidylethanol (PEth) can be identified in whole blood samples and is formed only in the presence of alcohol. Therefore, its detection indicates alcohol consumption in the last 28 days, with a sensitivity of 90–99% and specificity of 100%⁴¹. A promising state-of-the-art technology is to use ankle bracelets containing a transdermal electrochemical sensor that detects alcohol vapors closely to the skin^42,43.

Reducing stigma can also help to overcome many patient-level barriers. Patients with ALD are sensitive to shame, guilt, and judgment about their alcohol use²⁴, which leads to underreporting it and rejecting treatment when it is offered. An important step to reduce stigma was the recent name change from “alcoholic” liver disease to alcohol-associated liver disease, because of the disgrace associated with the word ‘alcoholic’⁴⁴. Clinicians encountering ALD patients need to behave with a nonthreatening, nonjudgmental approach in order to gain the patient’s confidence. Such demeanor facilitates candid conversations with the patient about alcohol use, and psychoeducation about AUD^45,46. To overcome misconceptions and false beliefs about AUD, education about alcohol-related harms and amounts of alcohol which can cause liver damage is essential. Furthermore, providing information about the chronic relapsing-remitting course of AUD and treatment options (both pharmacological and behavioral) need to be included in the counseling, since many patients are not aware of them²⁰. Regarding the gender disparities in misconceptions about AUD, women-targeted motivational interventions need to address stronger reluctance of acknowledging problematic use of alcohol, higher risk for ALD and need for treatment²⁸.

Integrated care with a multidisciplinary team of hepatologists and addiction specialists, showed higher efficacy in the treatment of AUD in patients with ALD^12,16,17. Mental health specialists are able to provide motivational interviewing and recommend the type of AUD treatment. Patients with a tendency for high self-confidence in maintaining abstinence may work collaboratively with addiction specialists without feeling their self-sufficiency threatened²⁹. Social workers and case managers can provide help with insurance and transportation issues. Recovery from AUD and ALD includes not just abstinence from alcohol but also aspects of patients’ self-image, functional status, social relationships, life goals, and coping skills²⁴.

3. CLINICIAN-LEVEL BARRIERS

3.1. Inadequate identification or quantification of alcohol use

An accurate history of quantity, frequency, and duration of alcohol use is required for the diagnosis of ALD, and also to detect the comorbid AUD. A significant barrier is that clinicians who first encounter the patient (e.g., primary care providers (PCPs)), may not be trained enough to collect all this detailed information. They may feel uncomfortable asking those questions, be preoccupied and overwhelmed with other medical issues, or simply forget to ask, since many PCPs do not screen routinely for AUD. Even if information is gathered from the patient, the clinician may not contact family members, friends or significant others asking about alcohol-related patient history^47,48. Time pressure, and lack of space, clinical knowledge and training are the most frequent reasons for inadequate screening and identification of AUD. Still, most patients and providers think that PCPs should play a key role in AUD screening and treatment⁴⁸. After the appropriate screening, AUD diagnosis is the next step, which requires a structured clinical assessment of behavioral, physiological, and social consequences of alcohol consumption, including harm to users and others. Diagnostics and treatment planning takes significant time, because of the comprehensive interview addressing the severity of AUD, prior alcohol use, possible AUD treatment history and social environment of the patient. This needs to be conducted by trained mental health care providers, who are specialized and devote enough time and resources for the examination²⁰.

3.2. Insufficient knowledge about AUD treatment or inadequate therapy for AUD

A recent retrospective cohort study found that only 37% of hepatology notes documented discussions about AUD treatment options⁴⁹. In addition, when discussed, treatment recommendations are often not evidence-based and rarely include pharmacotherapy options⁴⁹. In a survey of 408 healthcare providers (the majority were hepatologists and gastroenterologists, and 80% worked in a tertiary LT center), 60% reported referring the patient to an addiction specialist for behavioral therapy, but 71% never prescribed AUD pharmacotherapy, and 77% complained about the lack of education in addiction medicine⁵⁰. Clinicians often recommend abstaining from alcohol, which is important to reach any improvement in ALD, but they provide no clear directions about how to achieve it. Having a candid conversation about alcohol use and educating the patient about the importance of abstinence is critically important, but it’s only the starting point, not the treatment for AUD. Without any behavioral or pharmacological therapy or help from a mental health care provider, it’s entirely up to the patient to comply with the doctor’s advice^20,49. If a patient with ALD has a moderate to severe AUD, it requires specific AUD treatment from addiction experts²⁰. On one hand, some internists may feel uncomfortable about treating any psychiatric issue and tend to stigmatize patients with AUD for ‘their responsibility for becoming ill’, or feel they morally don’t deserve the treatment which is a waste of time and resources. On the other hand, some mental health care providers may be enormously afraid of admitting patients with any severe somatic illness, and tend to prioritize medical stabilization of the patient before providing any AUD treatment, even though they should be simultaneous¹⁹.

4. STRATEGIES TO SURMOUNT CLINICIAN-LEVEL BARRIERS

Lack of knowledge among clinicians about how to diagnose and treat AUD properly is one of the main reasons behind clinician-level barriers. Educational symposia and campaigns by addiction experts are required to address this problem. Propagable, concise educational materials containing up-to-date information need to be developed. The distributed documents must include the most important points that a general medical staff should know about harmful alcohol use, ALD, and pharmacological and behavioral therapy options. Earlier, we discussed the AUDIT questionnaire among patient-level barriers. AUDIT use needs to be used routinely and broadly by clinicians, and it should be included in patient examinations. Knowledge about AUD can be increased by incorporating addiction medicine training in the hepatology fellowship curriculum. That way, hepatologists would also become more comfortable discussing alcohol-related issues with the patient and providing them with adequate help. In addition, they can acquire motivational interviewing and assess how open the patient is to a behavioral change regarding alcohol drinking. However, using all these skills, screening for AUD, and discussing therapy during a medical visit requires significant time commitment; therefore, current practices need to be changed to provide extra time for healthcare providers for an adequate and thorough examination.

The appropriate and meaningful definition of relapse is also required for the adequate treatment of ALD patients. After a consensus, three levels of relapse were defined: mild relapse with occasional ‘slips’ (less than once per month); moderate relapse with continuous drinking within the recommended weekly and daily NIAAA standards (≤14 drinks per week for men, and ≤7 drinks per week for women); severe relapse with regular use of alcohol above the NIAAA standards, or appearance of alcohol-related morbidity (e.g., pancreatitis, graft loss, alcohol-associated hepatitis)¹². However, any drinking with liver-related decompensation and/or alcohol-associated hepatitis and even in patients with compensated cirrhosis should be considered harmful⁴; after LT, there is no evidence that mild relapse is associated with patient or graft survival^12,51. In summary, relapse to drinking is not the same as relapse to AUD, and it’s possible that harm reduction (e.g., reducing the episodes of heavy drinking) would be a valuable end point, at least in patients with early stages of ALD.

5. SYSTEM-LEVEL BARRIERS

5.1. Organizational and logistic barriers

Even if appropriate training is provided, no medical specialty can handle alone comorbid ALD and AUD, therefore, integrated care is required. Nevertheless, a significant barrier for integrated care is the lack of support from health care systems²⁰. Separate and isolated care, with no collaboration between different specialists, results in piecemeal care and mixed/conflicting messages to the patient¹⁹. In a disintegrated system, referrals to other specialists do not happen on a regular basis, and even if happens, it is not sufficient to create an integrated treatment plan. During these types of referrals, there is always a great risk to miss important information, which again can be overcome by an integrated model⁵². The profit-oriented business healthcare model pushes to see as many patients as possible per day. This time pressure doesn’t allow to dedicate sufficient time for thorough examination, or meaningful consultation with other specialists²⁰. Mental health care providers, especially those in addiction units are often logistically disconnected from the acute medical environments. Hepatology and addiction medicine are often separated in different departments and buildings (e.g., Medicaid mental health care and liver specialty care are commonly distant), resulting in difficult collaboration and access to both services^19,53. The travel distance also negatively affects AUD treatment utilization⁵⁴. A possible reason for this isolation is that addiction services are stigmatized, and other departments want them to be separate, distant. The latter also means that hepatology and addiction medicine services may utilize different electronic system, and have different administrative teams^19,53.

5.2. Health insurance barriers

Systems based on private health insurances do not facilitate integrated care. Combined billing is difficult, administrative staff must know a wide range of medical and psychiatric diagnostic codes and encounter types, many of which require separate insurance authorization¹⁹. A possible strategy to overcome physical distance of hepatology and addictology services would be tele-health, but it is currently underdeveloped²⁰. Public health care and socialized health care systems better provide services for socially deprived populations (e.g., homeless people), where AUD and ALD may be more frequent⁵⁵. While the first multidisciplinary ALD clinic in the USA was launched in 2018¹⁹, such approaches have been developed much earlier in European countries with socialized health care systems like Italy^13,16 and France⁵⁶. There are significant racial/ethnic disparities in the effects of structural barriers. African Americans and Latinx are more likely than Whites to underutilize AUD treatment because of structural barriers²⁸. That means, Whites are more likely than Latinx or African Americans to receive treatment (37.6%, 22.4%, and 25.0%, respectively)⁵⁷.

6. STRATEGIES TO SURMOUNT SYSTEM-LEVEL BARRIERS

The development of more integrated care centers is essential to overcome the structural barriers mentioned above. National policies are required to increase federal and state level funding for mental health care and integrated care of AUD and ALD. Funding for attending multidisciplinary conferences, and for getting multidisciplinary board certifications (e.g., addiction medicine for a hepatologist) would facilitate integrated care and collaboration between medical specialties¹⁹. Closer collaboration would be important between professional societies and organizations across the hepatology and addiction fields. Research funding needs to target developing new AUD relapse prevention medications and diagnostic practices (e.g., biomarkers), relapse risk evaluation, cost-effectiveness of integrated care and implementation of multidisciplinary clinics. Addressing health insurance barriers, coverage should also include specialty AUD and ALD care. Combined billing and integrated administration, electronic systems, are also required for an appropriate multidisciplinary care. Health inequities, and racial disparities are such system-level barriers which need to be addressed by federal or state social programs and local initiatives.

7. SUMMARY

AUD is the underlying etiology that leads to the development of ALD, hence these patients have a dual pathology whose optimal treatment requires both hepatology and addiction specialists involved in their care. However, unfortunately, a synergistic hepatology/addiction integrated management of these patients is more the exception than the rule. Indeed, there are patient-, clinician-, and organization-level barriers that prevent the effective development of hepatology/addiction multi-disciplinary integrated care approaches to treat these patients. Of note, at least some of the reasons why these barriers exist reflect the strong influence that stigma plays on AUD and addictions in our society. Therefore, it is imperative to develop multi-disciplinary integrated care approaches where both hepatology- and addiction-specialists manage together and synergistically these patients. Investments aimed at developing effective and sustainable multidisciplinary integrated approaches are much needed for patients with this dual AUD/ALD pathology.

KEY POINTS:

• Patients with alcohol-associated liver disease (ALD) have alcohol use disorder (AUD) which is the underlying reason for the development of ALD

• There are patient-, clinician-, and organization-level barriers that prevent the effective development of hepatology/addiction multi-disciplinary integrated care approaches to treat these patients with dual pathology (ALD and AUD)

• Stigma around AUD is clearly the chief challenge across all barriers summarized here; stigma affects the ability to screen, diagnose, treat, and manage AUD.

• Investments aimed at developing effective and sustainable multidisciplinary integrated approaches are much needed for patients with AUD and ALD.

CLINICS CARE POINTS.

• AUD treatment is often suboptimal or absent in individuals with ALD; however, addressing, managing and treating AUD is essential to reduce the risk of hepatic decompensation, relapse to drinking after LT, and long-term mortality;

• Integrative care models, like multidisciplinary AUD/ALD integrated clinics, reduce dramatically morbidity and mortality;

• Appropriate screening is crucial to detect which patient needs AUD treatment. AUDIT is useful for diagnosing AUD, and SALT scoring for evaluating the risk of relapse after LT;

• Underreported alcohol use can be addressed by measuring highly specific, direct biomarkers of alcohol consumption, e.g.: ethyl glucuronide, ethyl sulfate, or phosphatidylethanol;

• Reducing stigma around AUD is important to facilitate patients’ confidence and compliance, and the acceptance of AUD treatment;

• Education of the patients about alcohol-related harms and the chronic course of AUD is required to overcome popular misconceptions, which are serious barriers to AUD treatment;

• Education of clinicians can help them properly diagnose and treat AUD;

• National policies are required to increase federal and state-level funding for integrated care of AUD and ALD and for facilitating collaboration between hepatology and addiction medicine.

SYNOPSIS.

The cornerstone in managing alcohol-associated liver disease (ALD) is treatment of alcohol use disorder (AUD), yet this is often absent or suboptimal. Several barriers prevent the implementation of adequate treatment and integrated care models. There are patient-level barriers, including the lack of self-awareness of AUD and being ashamed of AUD. There are clinician-level barriers, including lack of training and discomfort in managing AUD patients. There are system-level barriers, including challenges related to insurance-based health care systems, and the general reluctance to invest in AUD by organizations focused on for-profit milestones. Therefore, it is imperative to develop multi-disciplinary hepatology/addiction integrated care approaches.