Advanced Search

Publications > Journals > Journal of Clinical and Translational Hepatology > Article Full Text


Integrated Multidisciplinary Management of Alcohol-associated Liver Disease

  • Malia Holbeck1,
  • Hannah Statz DeVries2,#,* and
  • Ashwani K. Singal3,#,* 
 Author information
Journal of Clinical and Translational Hepatology   2023;11(6):1404-1412

doi: 10.14218/JCTH.2023.00002


Alcohol-associated liver disease (ALD) is one of the most common liver diseases and indications for liver transplantation (LT). Alcohol use disorder (AUD), a frequent accompaniment in ALD patients, may also be associated with psychiatric comorbidities such as depression and anxiety. Identification of ALD at an earlier stage, and treatment of AUD may help prevent progression to advanced stage of ALD such as cirrhosis and alcoholic hepatitis. Screening for alcohol use and AUD treatment in ALD patients is often not performed due to several barriers at the level of patients, clinicians, and administrative levels. This review details the integrated multidisciplinary care model especially on the specific role of the hepatologist, psychiatrist, addiction counselor, and social worker in providing complete management for the dual pathology of liver disease and of AUD. Laboratory assessment, pharmacological and behavioral therapies, and recommended assessments for follow-up care by the respective specialists is outlined. We provide perspective along with the literature support, with the goal of providing team based comprehensive care of patients with ALD.

Graphical Abstract


Alcohol, Cirrhosis, Liver transplant, Depression, Anxiety, Multidisciplinary


Alcohol-associated liver disease (ALD) is one of the most common liver diseases worldwide. There were over 2 million cases of alcohol-associated cirrhosis in 2017, which contributed to 48% of cirrhosis related hospitalizations and 27% of deaths, with over $23 billion spent on direct patient care in the US.1,2 Alcoholic hepatitis (AH) contributes significantly to the ALD related disease burden, with a risk of up to 60–80% mortality in short-term at 90 days especially in those with severe forms of acute on chronic liver failure.3,4 During the coronavirus 2019 (COVID-19) pandemic, over 60% of individuals increased alcohol consumption5 with an accelerated increase in ALD related healthcare burden.6–8 Further, this disease burden is increasing in young individuals including prevalence of alcohol use disorder (AUD), hospitalizations, liver transplant (LT) need, and patient mortality.9–11

Approximately 10–20% of patients with ALD develop cirrhosis, with the highest risk and progression of fibrosis in those with AH.2,12 Patients with ALD present at an advanced spectrum of liver disease of cirrhosis, AH, and complications compared to liver diseases other than ALD.13,14 Further, the progression of liver disease is much faster to more advanced forms and complications in ALD patients.2 This becomes even more relevant given lack of effective medical therapies for ALD.2,15 Although, LT is an effective destination therapy for ALD cirrhosis, only 4% of LT were reported to be performed for AH in the US from regions with most LT performed for this indication.6 Due to lack of uniform objective criteria for candidate selection for early liver transplantation (eLT) in severe AH, it is used heterogeneously across providers and transplant centers,6 with some centers not performing LT for AH and some centers performing up to 4% of all LT for a diagnosis of AH.

AUD and addiction to alcohol is a chronic relapsing condition characterized by inability to abstain, impairment in behavioral control, cravings, diminished recognition of problems with one’s behaviors and interpersonal relationships, and a dysfunctional emotional response. A total of 10.2% of individuals ≥ 12 years old in the USA had a diagnosis of AUD in 2020.5 Diagnosis of AUD is made using the Diagnostic Statistical Manual fifth edition (DSM-5) criteria, with at least two criteria met of 11 focusing on alcohol use in spite of harms or negative effects, craving, tolerance, or withdrawal. The number of positive criteria increases with severity, with 4–5 indicating moderate, and six or more criteria defines severe AUD.

Clearly, individuals with harmful alcohol use who are at risk of developing ALD should be identified early at any opportunity of medical encounters so that they can be engaged in focused counseling aiming to reduce alcohol use and prevent development of cirrhosis and its complications.16 In a retrospective cohort study using the Danish database, 5% of women and 6% of men developed cirrhosis during a follow-up between 1998 and 2002. The majority of individuals who developed cirrhosis had one or more medical encounters during their follow-up, with missed opportunities to identify those with exposure to harmful alcohol use, and prevent advanced ALD. Controlling the risk factor of cessation of alcohol use is also the single most important determinant of liver related readmission to the hospital and long-term patient survival in patients with AUD and decompensated cirrhosis and those with AH.17–19 In prospective studies, among patients who survived an episode of severe AH, the risk of long-term mortality was over two-fold higher in those reducing their alcohol intake below the recommended harmful limits compared with those completely abstaining from alcohol use.17,20 It clearly remains to be seen if there is a safe limit of alcohol use that can be allowed in these patients with advanced liver disease. Although complete abstinence is ideal, but is difficult to achieve in a majority of these patients.21 Further, AUD treatment including behavioral and/or pharmacological therapies are rarely used in ALD patients including those with cirrhosis.18,19,22,23 For example, in a retrospective cohort of over 35,682 veterans with ALD cirrhosis and a diagnosis of AUD, only less than 14% were treated for the AUD within 6 months from diagnosis, with only 0.4% receiving some pharmacotherapy.22

Barriers to AUD treatment

Patients with liver disease aggravated by alcohol suffer from a dual pathology of AUD and liver disease. Educating patients with ALD and AUD on the need for complete abstinence is not enough and may require management by hepatology specialists for liver disease and by an addiction team for managing the dual pathology. That is preferably achieved within an integrated multidisciplinary care model.23,24 This care model has shown to reduce alcohol relapse both within and outside LT settings.19,25–27 However, the implementation of such models in clinical practice is challenging.22–24 Although national and international organizations have proposed integrated care models to manage ALD patients,4,28 widespread adoption of these recommendations is poor.22 Barriers at the level of patients, clinicians, and systems may be encountered in treating patients with ALD and AUD (Table 1).23,24,29

Table 1

Barriers limiting implementation of managing alcohol use disorder and establishing integrated multidisciplinary care model in routine clinical practice

BarrierPossible solution
Clinician level barriers
  Clinician trainingHepatology training curriculum, ECHO model
  Time for screening for AUDEducation, AUDIT-C shorter version
Patient level barriers
  Awareness and lack of insightEducation and Brief Intervention
  Lack of accepting diagnosis and/or treatmentNonjudgmental approach, avoid stigma
  Too sick for treatmentDigital monitoring and telemedicine
System and administration level barriers
  Financial and insuranceFunding and social work support
  Resources and manpowerCollaborative billing models
  Protocol in monitoringProtocol on biomarkers use and alcohol relapse definition

Integrated multidisciplinary care model

Several disciplines working in an integrated team has been proposed as a model to for comprehensive care for the dual pathology of AUD and of ALD.24,26,30 An integrated care model overcomes several but not all of the barriers limiting AUD treatment in ALD patients. Specifically, an integrated care model is successful in overcoming the barrier of insufficient physician training to treat AUD, and increasing the comfort level of hepatologists in addressing AUD and of addiction team in prescribing medications in ALD patients.24 However, this model may not completely overcome stigma attached to the diagnosis of ALD26 and uncertainty on where to seek treatment, described by Szerman et al.30 as the “wrong door syndrome.” Moreover, organizational and logistical barriers because of limited resources allocated to mental health and addiction care limit the establishment and implementation of an ideal integrated care model and overcoming siloed practices of the two different specialties.24,26 Hepatologists, psychiatrists, addiction counselors, and social workers see patients at the same location under the same roof in an ideal integrated multidisciplinary care model, with a goal of providing comprehensive patient care to manage both AUD as well as liver disease. AUD treatment in an integrated care model compared with siloed treatment of AUD and of ALD results in reduced risk of relapse to alcohol with improved liver related outcomes, especially among LT recipients. For example, in a recent systematic review, pooled data from six studies on 649 LT recipients, AUD treatment using an integrated care model reduced alcohol relapse by 44% and patient mortality by 71% with and odds ratios (ORs) and 95% confidence intervals (CIs) of 0.56 (0.36–0.87) and 0.29 (0.08–0.99).20

Assessment of liver disease

It should be recognized that patents with AUD may have liver disease with causes other than alcohol, such as nonalcoholic fatty liver disease caused by metabolic syndrome and obesity, chronic viral (hepatitis B, hepatitis C, or human immunodeficiency virus) infections, and other rare diseases including alpha-1 antitrypsin deficiency, autoimmune diseases, and drug induced liver injury.31 A thorough assessment of liver disease (Fig. 1) other than diagnosis of the underlying liver disease includes determination of liver fibrosis in those without cirrhosis, complications of liver disease in those with cirrhosis (ascites, hepatic encephalopathy, varices, and portal hypertension, malnutrition, and hepatocellular carcinoma), model for end-stage liver disease score, need for LT, graft function as evaluated with liver chemistry in LT recipients, and if abnormal further evaluation that may include a doppler ultrasound examination for hepatic vasculature, cholangiogram for biliary abnormalities, serological work-up for opportunistic infections, and a liver biopsy for acute or chronic rejection. Use of noninvasive serological and radiological markers for fibrosis assessment is limited by overestimation of fibrosis in patients who are actively drinking alcohol. In these patients, liver stiffness and fibrosis assessment should be adjusted for serum bilirubin and AST values or tests repeated after at least 2 weeks of abstinence.32 The sequence and extent of these tests varies from patient to patient depending on clinical scenario, availability, and provider / patient choice. It is recommended to provide an adequate nutrition intake for cirrhosis patients with 30–35 kcal/kg/d and 1.0–1.5 gm/k/d protein intake, with vegetable and not animal sources of protein, especially in patients with hepatic encephalopathy.33 Patients are advised to take small frequent meals and include a nighttime snack before going to bed to maintain nutritional status and avoid muscle loss.33 It is recommended to include a dietician as a part of the multidisciplinary care model, especially for patients who are unable to take adequate nutrition. For patients with a caloric intake below 21.5 kcal/k/d, nutritional supplementation should be used, preferably by the enteral route.34

Assessment by liver specialist on patients with alcohol use disorder and liver disease.
Fig. 1  Assessment by liver specialist on patients with alcohol use disorder and liver disease.

Decompensation includes one or more of ascites, hepatic encephalopathy, variceal bleeding, hepatocellular carcinoma; enhanced liver fibrosis (ELF) score incorporating an algorithm using special laboratory evaluation for serum hyaluronic acid, tissue inhibitor of metalloproteinase, and procollagen III amino terminal peptide. AH, alcoholic hepatitis; ALT, alanine aminotransferase; AST, aspartate aminotransferase; FIB-4, fibrosis-4 score (patient’s age, AST, ALT, platelet count); HTN, hypertension; LT, liver transplant; MRE, magnetic resonance elastography; MELD-Na, model for end-stage liver disease-sodium score (algorithm including serum total bilirubin, serum creatinine, institutional normalized ratio, and serum sodium); USG, ultrasonography.

Assessment of AUD

The addiction counselor determines the severity of AUD (Fig. 2), identifies barriers that may impact access to treatment and assesses motivation to change, and assists in making recommendations on the level of care needed (see later section on behavioral therapies), recovery specific resources, and relapse prevention planning.35 Biomarkers may be used to complement self-reported alcohol use for better accuracy in determining active ongoing alcohol consumption.36 Several biomarkers measure direct damage of end organs from alcohol like aspartate amino transferase, alanine amino transferase, carbohydrate deficient transferrin, gamma-glutamyl transpeptidase, mean corpuscular volume, or products of alcohol metabolism like ethyl glucuronide, ethyl sulfate, and phosphatidylethanol. The first group of biomarkers related to end-organ damage are limited by low sensitivity and specificity. Of the biomarkers measuring alcohol metabolites, phosphatidylethanol is used most often in clinical practice as it is most accurate, not confounded by endogenous alcohol exposure, and can detect alcohol use within the previous up to 3 weeks from the last drink.36,37

Definition of an alcohol-containing drink.
Fig. 2  Definition of an alcohol-containing drink.

Source: https://www.niaaa.nih.gov/sites/default/files/standard-Drink-June2022.jpeg .

If an addiction counselor is unavailable, a social worker can fill in this role, which is mainly to assess the biological, psychological, and social assessment of the patient to provide a holistic approach to patient care, and improve patient outcomes.5 The social worker emphasizes the importance of self-determination and assists patients to develop meaningful goals that support their overall health. Additionally, the addiction counselor provides resources to empower and guide patients to overcome barriers and achieve these goals.38

Assessment of psychiatric status and comorbidities

The psychiatric assessment begins with the Patient Health Questionnaire-9 to assess depression and the Generalized Anxiety Disorder-7 questionnaire to assess anxiety (Supplementary Tables 1 and 2). The psychiatrist also complements addiction counselors and social workers to provide clarification on the diagnosis and treatment of AUD and of other recreational substance use, monitor alcohol use on follow-up as the diagnosis of AUD is often evolving, provide pharmacotherapy for AUD and for psychiatric comorbidities (see later section on pharmacotherapies), and identify post-acute withdrawal syndrome, which can overlap with psychiatric comorbidities (depression, anxiety, insomnia), and can last from months for up to 2 years after the cessation of alcohol.39

Management of AUD

This can be achieved by behavioral and/or pharmacological therapies.

Behavioral Therapies

These therapies are effective in motivating patients to change their behavior, and virtual options may allow easier access for individuals seeking help. Person-centered approaches are used to formulate an approach that the individual can carry out successfully. Facilitated by licensed professionals, evidenced-based therapies such as cognitive behavioral therapy, which helps patients identify and modify behavior by adjusting their thought patterns and motivational interviewing, that utilizes techniques to help patients gain motivation by resolving their ambivalences about changing behavior have been shown to be effective.40,41 Therapies can be delivered in the form of group, individual and family therapy with the goal to control alcohol use and transition the patients into self-management of their addiction.40

The determination of level of care requires comprehensive evaluation of AUD using the American Society of Addiction Medicine criteria developed in the 1980s by an interdisciplinary group. This includes an assessment of six dimensions, with each of these dimensions scaled for severity from 1 to 4 (Table 2). The total severity score determines the level of care recommendation, and ongoing assessment helps transition the patient on the continuum of care (Table 3).42,43

Table 2

Assessing alcohol use disorder on six dimensions as per American Society of Addiction Medicine (ASAM) criteria

1. Acute intoxication and/or withdrawal potentialSignificant risk of severe withdrawal symptoms or seizures
2. Biomedical conditions and complicationsAny acute or chronic medical illness that might interfere with the current treatment
3. Emotional, behavioral, or cognitive conditions and complicationsAny psychiatric issues, including behavioral or emotional problems that might impede the treatment process
4. Readiness to changePatient’s openness to treatment, acceptance of addiction, readiness for change, and motivation for compliance
5. Relapse, continued use or problem potentialPatient’s ability to cope with cravings, comprehension of triggers, and ability to abstain
6. Recovering/living environmentCurrent living situation, adequacy of social support network, and financial resources
Table 3

Level of care continuum as per American Society of Addiction Medicine

Level of treatmentDescription
I: Outpatient treatmentOrganized nonresidential services or office practices with designated addiction treatment personnel who provide professionally directed evaluation, treatment, and recovery services to addicted patients. The services are provided in regularly scheduled sessions of usually fewer than 9 h per week.
II: Intensive outpatient and partial hospitalization treatmentAn organized service with designated addiction personnel provides a planned treatment regimen consisting of regularly scheduled sessions of at least 9 h per week within a structured program. This level of care affords patients the opportunity to interact with the real-world environment while still benefiting from a programmatically structured therapeutic milieu.
III: Medically monitored inpatient (residential) treatmentOffered in permanent facilities with inpatient beds, includes a planned regimen of round-the-clock professionally directed evaluation, care, and treatment for addicted patients provided by designated addiction personnel. The treatment is specific to addiction and does not require the full resources of an acute care general hospital.
IV: Medically managed inpatient treatmentDesignated addiction professionals provide a round-the-clock planned regimen of medically directed evaluation, care, and treatment for addicted patients in an acute care inpatient setting. A multidisciplinary staff and the full resources of a general hospital are available to provide treatment for patients with severe acute problems necessitating primary medical and nursing services. Treatment is specific to addiction, although the available support services allow concurrent treatment of coexisting acute biomedical and emotional conditions.

Outpatient treatment

Outpatient treatments include individual therapy and/or group therapy. Individual therapy is appropriate for individuals that are stable in their recovery or can also be given as an adjunct to group therapy. It provides a confidential space to the participant to focus on individual areas of concerns. Group therapy including education, skill building, cognitive restructuring, and interpersonal processing focuses on identifying and processing the underlying factors that contributed to addiction. It is an effective modality due to its advantages of peer support, reducing isolation, observing the success of others, structure, accountability, and feedback.40 Recovery community groups are popular, as they are offered at no cost to attend have an accommodating time schedule, offer autonomy in deciding the amount of information to share, and are offered either in-person or virtually.44 Alcoholics Anonymous, founded in 1935, is the most well-known recovery community group which has continued to grow to a global level.45 Additional support groups have been developed over the years with varying philosophies to recovery which offers diverse treatment opportunities for patients.40

Intensive outpatient treatment

Intensive outpatient treatment is a highly utilized treatment program, and is offered by 46% of treatment facilities in the US.46 It can be administered as the primary treatment, a step down from residential treatment, or a step up from a less intensive treatment. Benefits include flexible timing, developing and practicing recovery skills, and incorporating community support to help with transition into self-management.46,47

Inpatient treatment

Inpatient treatment in an acute care setting is supplemented by the facilities of the hospital itself to manage associated medical issues. This is the best example of integrated multidisciplinary comprehensive care of patients by professionals for the medical and addiction issues in an acute care setting (Table 3). Completing inpatient therapy is usually transitioned to outpatient treatment sessions.

Pharmacological therapy

Therapies for AUD

We recommend a clear discussion with patients that medications are not the sole treatment for their AUD, and behavioral treatments are the cornerstone which provides accountability, structure, and a support network. This network in particular not only assists with ongoing recovery efforts, but tends to have a positive and lasting impact on patient mental health. There are three FDA-approved medications for AUD; naltrexone, acamprosate, and disulfiram. Data on these drugs for AUD in ALD patients are limited, as randomized controlled trials in AUD typically exclude patients with ALD because AUD treatments are rarely used in ALD patients. On clinicaltrials.gov there is a study in which 12 patients with ALD were given acamprosate to evaluate its safety in the context of liver disease (https://clinicaltrials.gov/ct2/show/results/NCT04287920 ). As acamprosate has no hepatic metabolism, it is considered to be safe for use in ALD patients. However, caution should be taken in those with renal impairment as advanced ALD patients with decompensated cirrhosis and AH may have renal dysfunction due to hepatorenal syndrome, with this agent not recommended in patients with creatinine clearance below 30 mL/min. Disulfiram and naltrexone carry a risk for hepatotoxicity especially if administered to patients with liver disease. There are no studies of disulfiram specific to ALD patients. However, there is a recent retrospective study published in 2022 of 100 patients prescribed naltrexone with concurrent ALD; it evaluated hepatic safety by monitoring liver enzyme changes during naltrexone treatment and follow-up. The results were an overall decrease in AST and ALT, indicating safety in patients with liver disease, including those with compensated cirrhosis.48 The study is promising in that, if replicated, it may significantly alter clinical practice for the better; however, the study does call for more safety data for those with decompensated cirrhosis. More often, off-label treatments for AUD are used in ALD patients which include varenicline, topiramate, gabapentin, baclofen and ondansetron (Table 4).26,27,49

Table 4

Pharmacological therapies for AUD

DrugMechanism of actionAccepted dose rangeAUD patients with hepatic impairmentTarget outcomeNotes:
FDA-approved medications for AUD
  NaltrexoneMu opioid receptor antagonist50 mg orally daily
380 mg monthly intramuscular
Use with caution, regular monitoring and limit in advanced liver diseaseAchieve and maintain abstinence and reduce drinkingStart at 25 mg orally with food, and increase to 50 mg dose if needed and tolerated.
  AcamprosateModulates glutamate activity, NMDA receptor agonist666 mg orally three times a dayNo hepatic metabolismAchieve and maintain abstinenceNumber of pills, three times a day dosing and flatus may limit compliance.
  DisulfiramInhibits aldehyde dehydrogenase250–500 mg orally dailyHepatically metabolized; caution or avoid useAchieve and maintain abstinenceCaution in patients with history of psychosis.
Off-label treatments for AUD
  VareniclineNicotinic acetylcholine receptor agonistUp to 1 mg orally twice dailySafe, minimal hepatic metabolismReduce drinking (particularly useful for smokers)EAGLES trial removed black box warning for serious neuropsychiatric events such as suicidality. Can cause vivid dreams.
  TopiramateInhibits glutamate and increases GABA activityUp to 300 mg/d orally in divided doses (lower doses better tolerated)Partial hepatic metabolism by glucuronidationAchieve abstinence reduce drinking, and craving outcomesDose dependent cognitive side effects may mimic hepatic encephalopathy. Consider lower dosing + psychotherapy.
  GabapentinModulates GABA-ergic transmissionTypically 900 mg orally twice daily; may need higher doses up to 1,200 mg three times a dayNo hepatic metabolismAchieve abstinence and reduce drinkingCaution with comorbid opioid use disorder, risk for misuse or abuse.
  BaclofenGABAB agonistTypically 10–20 mg orally three times a day, not to exceed 80 mg per daySafe, minimal hepatic metabolismAchieve and maintain abstinenceMixed results with higher dosing (upwards of 200 mg per day), and optimal dose remains debatable.
  Ondansetron5-HT3 receptor antagonist1–16 mcg/kg twice dailyOverall safe, but caution due to reports of liver toxicityAchieve abstinence and reduce drinkingParticularly useful in combination with naltrexone. Unclear clinical relevance of proposed dosing.

Though baclofen is not FDA approved for AUD, there is some data to support its use. A randomized controlled trial demonstrated the efficacy and safety of baclofen in patients with AUD and cirrhosis. In this study on 84 patients with alcohol-associated cirrhosis (42 assigned to placebo), abstinence was higher in the baclofen arm (71 vs. 29%, p < 0.05). There was also improvement in liver function including serum albumin and international normalized ratio.50 A post hoc analysis of this study explored baclofen’s effect in a subgroup of 24 patients (12 received placebo) with concomitant hepatitis C virus infection.51

Therapies for concomitant psychiatric comorbidities

It is crucial that providers managing ALD patients recognize coexisting associated psychiatric comorbidities like depression, anxiety, and insomnia.26 For example, AUD as many as 50% of patients may have psychiatric comorbidities and 5–10% use recreational substances other than nicotine or marijuana.52,53 Similar to management of AUD, there are no randomized studies on the use of psychotropics in ALD patients with mental health conditions. In a meta-analysis for treatment of depression in patients with AUD, a modest beneficial effect for patients with dual diagnoses was noted, but also suggested that concurrent counseling targeting the addiction is also indicated. The current practice is based on the safety profile of the medication in the context of liver impairment or ongoing alcohol use (Table 5). Primary health and anxiety questionnaires are completed on follow-up visits, which helps guide psychotropic medication management.

Table 5

Pharmacotherapies for management of coexistent psychosomatic comorbidities in patients with alcohol use disorder (AUD)

ClassAcceptable in hepatic impairmentGenerally avoid or notable clinical concerns
SSRISertraline – generally safe, consider decreased dose with hepatic impairment, large dose range 25–200 mg is useful clinicallyFluoxetine – no absolute contraindication. Reduce dose, as half-life may triple with hepatic impairment, drug-drug and 2D6 interactions
Escitalopram (s-enantiomer of citalopram) – do not exceed 10 mg/d due to increased risk of QTc prolongation as concentrations may increase by 50% or more with cirrhosisParoxetine – Most frequently associated with liver toxicity. Short half-life requires strict compliance due to withdrawal symptoms of this SSRI
Citalopram – do not exceed 20 mg/d due to increased risk of QTc prolongation, potential for doubling of half-lifeCaution or minimize co-administration with antiplatelet or NSAIDs due to increased risk of bleeding
SNRIDesvenlafaxine (metabolite of venlafaxine) - generally preferable to venlafaxineDuloxetine – do not use in hepatic impairment, up to 85% reduction in clearance
Venlafaxine – no absolute contraindication; dose reduction up to 50% with liver impairment, more so with cirrhosis
Levomilnacipran – no dose adjustment necessary
NDRIBupropion – generally safe; no significant concerns with CTP A r B class, but consider lowered dose or frequency with CTP class CNot an absolute contraindication but caution if patient is actively consuming alcohol or with history of withdrawal seizures as it lowers threshold for seizures. Also avoid with history of an eating disorder
AntipsychoticPaliperidone (metabolite of risperidone) – excreted by kidneys, generally safe, no adjustments in CTP A or B, limited data in CTP class CRisperidone – undergoes hepatic biotransformation; free drug increased up to 35% in CTP class C
Olanzapine – generally safe, half-life may be increased, consider starting dose of 2.5 to 5mg and slower titration
Quetiapine – half-life may be increased but generally safe particularly at lower dosing; start at 25 mg can titrate by 25–50 mg/dayUse haloperidol (first generation) with caution, lower dosing and careful titrations after discussion with pharmacist, generally avoid with active alcohol use
Ziprasidone – no dose adjustment necessary, avoid with prolonged QTc
BenzodiazepinesLorazepam, Oxazepam, Temazepam – generally safe but recommend lower dosingFor anxiety or insomnia, prefer hydroxyzine or gabapentin (minimal liver dependence or clearance) due to benzodiazepine addiction potential
OtherTrazodone – generally safe; may require dose adjustment based on severity of impairment but minimal data; avoid in hepatic encephalopathy due to sedationAvoid TCA due to lowered seizure threshold, bleeding risk especially when used with antiplatelet or NSAIDs, confusion and sedation. If used, keep the dose 50% of normal
Mirtazapine – generally safe; decreased clearance by up to a third of normal, careful titration
Vortioxetine – no adjustment for CTP A/B; not studied in CTP C

Monitoring alcohol use and AUD treatment

Successful treatment of AUD varies for the individual based on treatment goals. For example, it will differ if the goal is harm reduction versus abstinence. Over a short period of time, alcohol use can be monitored with the use of the alcohol timeline follow back tool (https://www.nova.edu/timeline/index.html ), which includes self-report of amounts, frequency, and patterns of use over a given period of time, up to 12 months. TLFB for alcohol use aids in identifying correlations between calendar dates and patterns of use. Feedback on alcohol use assists patients in identifying patterns of relapse which in turn increases their motivation to change.54 As mentioned earlier, biomarkers can be used for better accuracy of determining alcohol use and defining success of treatment outcomes. Reduction in alcohol use can be gauged from baseline based on five levels of drinking as defined in grams by the World Health Organization. One alcohol-containing drink is equivalent to 14 gm, and the five World Health Organization levels are defined as abstinent (0 gm in both men and women), low risk (1–40 gm in men and 1–20 gm in women), medium risk (41–60 gm in men and 21–40 gm in women), high risk (61–100 gm in men and 41–60 gm in women), and very high risk (> 100 gm in men and > 60 gm in women). Reduction of alcohol use by two or more levels is usually considered a successful treatment outcome. However, whether that outcome is clinically relevant in ALD patients remains to be defined, and currently abstinence is considered the gold standard for improved long-term outcomes, especially in those with advanced ALD including cirrhosis and AH. As far as successful treatment for AUD is considered over the long-term, early remission is defined as not meeting AUD criteria other than craving for over 3 months but less than 12 months, and sustained remission is not meeting AUD criteria other than craving for over 12 months.


ALD contributes significantly to healthcare and economic burden. Screening for alcohol use should be performed at every healthcare encounter and those at risk should be further screened for presence and to determine severity of liver disease. To improve long-term outcomes of patients with ALD, an integrated multidisciplinary care model involving a hepatologist, psychiatrist, addiction counselor, and social worker should be promoted to provide comprehensive care for the dual pathology of AUD and of liver disease.

Supporting information

Supplementary Table 1

Patient health questionnaire-9.


Supplementary Table 2

Generalized anxiety disorder-7.




Alcohol-Associated Liver Disease


Alcoholic Hepatitis


Alcohol Use Disorder


Liver Transplant



None to declare.

Conflict of interest

ASK has been an associate editor of Journal of Clinical and Translational Hepatology since 2021. The other authors have no conflict of interests related to this publication.

Authors’ contributions

Conception and design of the study (AKS) and drafting the original version of the article (MH, HSDV, AKS). All the authors participated in writing, review, and approving the final version of the manuscript.


  1. GBD 2017 Cirrhosis Collaborators. The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol 2020;5(3):245-266 View Article PubMed/NCBI
  2. Singal AK, Mathurin P. Diagnosis and Treatment of Alcohol-Associated Liver Disease: A Review. JAMA 2021;326(2):165-176 View Article PubMed/NCBI
  3. Singal AK, Louvet A, Shah VH, Kamath PS. Grand Rounds: Alcoholic Hepatitis. J Hepatol 2018;69(2):534-543 View Article PubMed/NCBI
  4. Singal AK, Bataller R, Ahn J, Kamath PS, Shah VH. ACG Clinical Guideline: Alcoholic Liver Disease. Am J Gastroenterol 2018;113(2):175-194 View Article PubMed/NCBI
  5. Papadimitriou G. The “Biopsychosocial Model”: 40 years of application in Psychiatry. Psychiatriki 2017;28(2):107-110 View Article PubMed/NCBI
  6. Wong RJ, Singal AK. Trends in Liver Disease Etiology Among Adults Awaiting Liver Transplantation in the United States, 2014-2019. JAMA Netw Open 2020;3(2):e1920294 View Article PubMed/NCBI
  7. Cotter TG, Sandıkçı B, Paul S, Gampa A, Wang J, Te H, et al. Liver transplantation for alcoholic hepatitis in the United States: Excellent outcomes with profound temporal and geographic variation in frequency. Am J Transplant 2021;21(3):1039-1055 View Article PubMed/NCBI
  8. Moon AM, Curtis B, Mandrekar P, Singal AK, Verna EC, Fix OK. Alcohol-Associated Liver Disease Before and After COVID-19-An Overview and Call for Ongoing Investigation. Hepatol Commun 2021;5(9):1616-1621 View Article PubMed/NCBI
  9. Tapper EB, Parikh ND. Mortality due to cirrhosis and liver cancer in the United States, 1999-2016: observational study. BMJ 2018;362:k2817 View Article PubMed/NCBI
  10. Singal AK, Arsalan A, Dunn W, Arab JP, Wong RJ, Kuo YF, et al. Alcohol-associated liver disease in the United States is associated with severe forms of disease among young, females and Hispanics. Aliment Pharmacol Ther 2021;54(4):451-461 View Article PubMed/NCBI
  11. Singal AK, Arora S, Wong RJ, Satapathy SK, Shah VH, Kuo YF, et al. Increasing Burden of Acute-On-Chronic Liver Failure Among Alcohol-Associated Liver Disease in the Young Population in the United States. Am J Gastroenterol 2020;115(1):88-95 View Article PubMed/NCBI
  12. Gao B, Bataller R. Alcoholic liver disease: pathogenesis and new therapeutic targets. Gastroenterology 2011;141(5):1572-1585 View Article PubMed/NCBI
  13. Shoreibah M, Raff E, Bloomer J, Kakati D, Rasheed K, Kuo YF, et al. Alcoholic liver disease presents at advanced stage and progresses faster compared to non-alcoholic fatty liver diseas. Ann Hepatol 2016;15(2):183-189 View Article PubMed/NCBI
  14. Shah ND, Ventura-Cots M, Abraldes JG, Alboraie M, Alfadhli A, Argemi J, et al. Alcohol-Related Liver Disease Is Rarely Detected at Early Stages Compared With Liver Diseases of Other Etiologies Worldwide. Clin Gastroenterol Hepatol 2019;17(11):2320-2329.e12 View Article PubMed/NCBI
  15. Arora SS, Axley P, Ahmed Z, Satapathy SK, Wong R, Kuo YF, et al. Decreasing frequency and improved outcomes of hepatitis C-related liver transplantation in the era of direct-acting antivirals - a retrospective cohort study. Transpl Int 2019;32(8):854-864 View Article PubMed/NCBI
  16. Askgaard G, Leon DA, Kjaer MS, Deleuran T, Gerds TA, Tolstrup JS. Risk for alcoholic liver cirrhosis after an initial hospital contact with alcohol problems: A nationwide prospective cohort study. Hepatology 2017;65(3):929-937 View Article PubMed/NCBI
  17. Louvet A, Labreuche J, Artru F, Bouthors A, Rolland B, Saffers P, et al. Main drivers of outcome differ between short term and long term in severe alcoholic hepatitis: A prospective study. Hepatology 2017;66(5):1464-1473 View Article PubMed/NCBI
  18. Singal AK, DiMartini A, Leggio L, Arab JP, Kuo YF, Shah VH. Identifying Alcohol Use Disorder in Patients With Cirrhosis Reduces 30-Days Readmission Rate. Alcohol Alcohol 2022;57(5):576-580 View Article PubMed/NCBI
  19. Elfeki MA, Abdallah MA, Leggio L, Singal AK. Simultaneous Management of Alcohol Use Disorder and Liver Disease: A Systematic Review and Meta-analysis. J Addict Med 2023;17(2):e119-e128 View Article PubMed/NCBI
  20. Thursz MR, Richardson P, Allison M, Austin A, Bowers M, Day CP, et al. Prednisolone or pentoxifylline for alcoholic hepatitis. N Engl J Med 2015;372(17):1619-1628 View Article PubMed/NCBI
  21. Mathurin P, Lucey MR. Liver transplantation in patients with alcohol-related liver disease: current status and future directions. Lancet Gastroenterol Hepatol 2020;5(5):507-514 View Article PubMed/NCBI
  22. Rogal S, Youk A, Zhang H, Gellad WF, Fine MJ, Good CB, et al. Impact of Alcohol Use Disorder Treatment on Clinical Outcomes Among Patients With Cirrhosis. Hepatology 2020;71(6):2080-2092 View Article PubMed/NCBI
  23. DiMartini AF, Leggio L, Singal AK. Barriers to the management of alcohol use disorder and alcohol-associated liver disease: strategies to implement integrated care models. Lancet Gastroenterol Hepatol 2022;7(2):186-195 View Article PubMed/NCBI
  24. Mellinger JL, Scott Winder G, DeJonckheere M, Fontana RJ, Volk ML, Lok ASF, et al. Misconceptions, preferences and barriers to alcohol use disorder treatment in alcohol-related cirrhosis. J Subst Abuse Treat 2018;91:20-27 View Article PubMed/NCBI
  25. Lucey MR, Singal AK. Integrated Treatment of Alcohol Use Disorder in Patients With Alcohol-Associated Liver Disease: An Evolving Story. Hepatology 2020;71(6):1891-1893 View Article PubMed/NCBI
  26. Leggio L, Lee MR. Treatment of Alcohol Use Disorder in Patients with Alcoholic Liver Disease. Am J Med 2017;130(2):124-134 View Article PubMed/NCBI
  27. Caputo F, Domenicali M, Bernardi M. Diagnosis and Treatment of Alcohol Use Disorder in Patients With End-Stage Alcoholic Liver Disease. Hepatology 2019;70(1):410-417 View Article PubMed/NCBI
  28. Lucey MR, Im GY, Mellinger JL, Szabo G, Crabb DW. Introducing the 2019 American Association for the Study of Liver Diseases Guidance on Alcohol-Associated Liver Disease. Liver Transpl 2020;26(1):14-16 View Article PubMed/NCBI
  29. Im GY, Mellinger JL, Winters A, Aby ES, Lominadze Z, Rice J, et al. Provider Attitudes and Practices for Alcohol Screening, Treatment, and Education in Patients With Liver Disease: A Survey From the American Association for the Study of Liver Diseases Alcohol-Associated Liver Disease Special Interest Group. Clin Gastroenterol Hepatol 2021;19(11):2407-2416.e8 View Article PubMed/NCBI
  30. Szerman N, Torrens M, Maldonado R, Balhara YPS, Salom C, Maremmani I, et al. Addictive and other mental disorders: a call for a standardized definition of dual disorders. Transl Psychiatry 2022;12(1):446 View Article PubMed/NCBI
  31. Russ KB, Chen NW, Kamath PS, Shah VH, Kuo YF, Singal AK. Alcohol Use after Liver Transplantation is Independent of Liver Disease Etiology. Alcohol Alcohol 2016;51(6):698-701 View Article PubMed/NCBI
  32. Moreno C, Mueller S, Szabo G. Non-invasive diagnosis and biomarkers in alcohol-related liver disease. J Hepatol 2019;70(2):273-283 View Article PubMed/NCBI
  33. Nartey YA, Asem M, Agyei-Nkansah A, Awuku YA, Setorglo J, Duah A, et al. Nutritional management of cirrhosis patients: A qualitative study exploring perceptions of patients and health workers in Ghana. Clin Nutr ESPEN 2019;34:18-22 View Article PubMed/NCBI
  34. Moreno C, Deltenre P, Senterre C, Louvet A, Gustot T, Bastens B, et al. Intensive Enteral Nutrition Is Ineffective for Patients With Severe Alcoholic Hepatitis Treated With Corticosteroids. Gastroenterology 2016;150(4):903-10.e8 View Article PubMed/NCBI
  35. Ford HB. What is an addiction counselor? Available from: https://www.hazeldenbettyford.org/graduate-school-addiction-studies/what-are-addiction-counselors
  36. Woźniak MK, Wiergowski M, Namieśnik J, Biziuk M. Biomarkers of Alcohol Consumption in Body Fluids - Possibilities and Limitations of Application in Toxicological Analysis. Curr Med Chem 2019;26(1):177-196 View Article PubMed/NCBI
  37. Singal AK, Kwo P. Blood phosphatidylethanol testing and liver transplant eligibility selection: A step closer. Alcohol Clin Exp Res 2022;46(5):702-704 View Article PubMed/NCBI
  38. Saxe Zerden L, Lombardi BM, Jones A. Social workers in integrated health care: Improving care throughout the life course. Soc Work Health Care 2019;58(1):142-149 View Article PubMed/NCBI
  39. Ford HB. Post-acute withdrawal syndrome. 2019 Available from: https://www.hazeldenbettyford.org/articles/post-acute-withdrawal-syndrome
  40. Miller WR, Forcehimes AA, Zweben A. Treating Addiction: A Guide for Professionals 2nd ed. NY: The Guilford Press; 2019
  41. McHugh RK, Hearon BA, Otto MW. Cognitive behavioral therapy for substance use disorders. Psychiatr Clin North Am 2010;33(3):511-525 View Article PubMed/NCBI
  42. Morey LC. Patient Placement Criteria: Linking Typologies to Managed Care. Alcohol Health Res World 1996;20(1):36-44 PubMed/NCBI
  43. Chuang E, Wells R, Alexander JA, Friedmann PD, Lee IH. Factors Associated With Use of ASAM Criteria and Service Provision in a National Sample of Outpatient Substance Abuse Treatment Units. J Addict Med 2009;3(3):139-150 View Article PubMed/NCBI
  44. Parikh ND, Schlansky B. Comparative Effectiveness of Medical Therapies for Severe Alcoholic Hepatitis: Guidance at Last?. Gastroenterology 2015;149(4):857-859 View Article PubMed/NCBI
  45. Gross M. Alcoholics Anonymous: still sober after 75 years. 1935. Am J Public Health 2010;100(12):2361-2363 View Article PubMed/NCBI
  46. Center for Substance Abuse Treatment. PubMed/NCBI
  47. McCarty D, Braude L, Lyman DR, Dougherty RH, Daniels AS, Ghose SS, et al. Substance abuse intensive outpatient programs: assessing the evidence. Psychiatr Serv 2014;65(6):718-726 View Article PubMed/NCBI
  48. Ayyala D, Bottyan T, Tien C, Pimienta M, Yoo J, Stager K, et al. Naltrexone for alcohol use disorder: Hepatic safety in patients with and without liver disease. Hepatol Commun 2022;6(12):3433-3442 View Article PubMed/NCBI
  49. Burnette EM, Nieto SJ, Grodin EN, Meredith LR, Hurley B, Miotto K, et al. Novel Agents for the Pharmacological Treatment of Alcohol Use Disorder. Drugs 2022;82(3):251-274 View Article PubMed/NCBI
  50. Addolorato G, Leggio L, Ferrulli A, Cardone S, Vonghia L, Mirijello A, et al. Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: randomised, double-blind controlled study. Lancet 2007;370(9603):1915-1922 View Article PubMed/NCBI
  51. Leggio L, Ferrulli A, Zambon A, Caputo F, Kenna GA, Swift RM, et al. Baclofen promotes alcohol abstinence in alcohol dependent cirrhotic patients with hepatitis C virus (HCV) infection. Addict Behav 2012;37(4):561-564 View Article PubMed/NCBI
  52. Grant BF, Goldstein RB, Saha TD, Chou SP, Jung J, Zhang H, et al. Epidemiology of DSM-5 Alcohol Use Disorder: Results From the National Epidemiologic Survey on Alcohol and Related Conditions III. JAMA Psychiatry 2015;72(8):757-766 View Article PubMed/NCBI
  53. Stinson FS, Grant BF, Dawson DA, Ruan WJ, Huang B, Saha T. Comorbidity between DSM-IV alcohol and specific drug use disorders in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Drug Alcohol Depend 2005;80(1):105-116 View Article PubMed/NCBI
  54. Sobell LC, Sobell MB. Timeline Follow-Back. Totowa, NJ: Humana Press 1992
  • Journal of Clinical and Translational Hepatology
  • pISSN 2225-0719
  • eISSN 2310-8819
Back to Top

Integrated Multidisciplinary Management of Alcohol-associated Liver Disease

Malia Holbeck, Hannah Statz DeVries, Ashwani K. Singal
  • Reset Zoom
  • Download TIFF