Alcohol-Associated Liver Disease and Alcohol Use Disorder: A Comprehensive Guide to Co-Management

For hepatologists, addiction medicine physicians, and patients and families navigating an ALD diagnosis

Overview — ALD Is the Top Indication for Liver Transplant

Alcohol-associated liver disease has reached a turning point. Globally, ALD has overtaken hepatitis C as the most common indication for liver transplantation, and in the United States it is now the leading reason patients are listed for a new liver ^{[1] [2]}. The ACG 2024 Clinical Guideline frames the urgency plainly: ALD is "the most common cause of advanced hepatic disease and frequent indication for liver transplantation worldwide," and patients with ALD "are rarely treated for AUD" despite alcohol use disorder being the central driver of disease progression ^[3].

The numbers behind that statement are staggering. Alcohol-associated compensated cirrhosis affects an estimated 23.6 million people worldwide; decompensated cirrhosis affects another 2.5 million. Together, alcohol-associated cirrhosis and liver cancer account for approximately 1% of all deaths globally ^[4]. Pandemic-era increases in alcohol consumption have accelerated this trajectory ^[4].

What makes this crisis particularly painful is that effective treatments exist — for both the liver disease and the underlying alcohol use disorder — yet they are systematically withheld. A landmark institutional audit found that following hospitalization for ALD, only 16% of patients attended a hepatology appointment within 90 days, only 4% were referred to substance use services, and only 14% were prescribed medication for AUD at discharge ^[4]. These are not marginal shortfalls. They represent near-complete treatment failure at the system level.

This article synthesizes the best available evidence on the full spectrum of alcoholic liver disease — from early fatty liver to acute alcoholic hepatitis to cirrhosis and transplant — and integrates it with the evidence base for treating the alcohol use disorder that drives it. The medical pathway for ALD is well-mapped. The integration with addiction care is not. That gap is where lives are lost.

The ALD Spectrum

Alcoholic liver disease does not arrive all at once. It progresses through a recognizable sequence, and the stage at which it is caught determines what is reversible.

Steatosis (fatty liver) is the earliest and most common manifestation, present in up to 90% of heavy drinkers. Fat accumulates in hepatocytes in response to alcohol metabolism. At this stage, the disease is largely reversible with abstinence — one of the most important facts in all of hepatology. No medication reverses steatosis; stopping alcohol does [görgülü-2026-acute-changes-liver].

Steatohepatitis follows when inflammation is added to fat accumulation. Hepatocyte ballooning, lobular inflammation, and early fibrosis become visible on biopsy. This stage is still potentially reversible but carries meaningful risk of progression.

Fibrosis represents the liver's scarring response to repeated injury. As fibrosis advances through stages F1–F4, the architecture of the liver is progressively distorted. Advanced fibrosis (F3–F4) is the threshold beyond which complications become likely.

Cirrhosis is end-stage fibrosis — the liver's normal architecture replaced by scar tissue and regenerative nodules. Approximately 75% of patients with cirrhosis are unaware of their disease until emergency referral ^[5]. This is the stage at which most patients first encounter the medical system.

Decompensation marks the transition from compensated to clinically overt liver failure: ascites, variceal bleeding, hepatic encephalopathy, and jaundice. Each decompensation event worsens prognosis substantially.

Acute alcoholic hepatitis is a distinct, superimposed syndrome — an acute inflammatory crisis that can occur at any stage of underlying alcoholic liver disease, most dangerously in the setting of established cirrhosis. It is characterized by rapid-onset jaundice, hepatomegaly, fever, and leukocytosis, and in its severe form carries a 30-day mortality of 30–50% ^[3].

Hepatocellular carcinoma (HCC) is a late complication of alcoholic cirrhosis. The risk is present even in abstinent patients once cirrhosis is established, which is why surveillance does not stop with sobriety.

Screening and Early Detection

Most patients with alcoholic liver disease are identified too late. Approximately 75% of those with cirrhosis do not know they have it until an emergency presentation ^[5]. Earlier detection changes outcomes: early noninvasive screening in high-risk AUD populations identifies compensated advanced chronic liver disease and is associated with higher rates of sustained abstinence at one year ^[6].

Laboratory markers provide the first signal. The classic AST:ALT ratio greater than 2:1 reflects the preferential induction of AST by alcohol and mitochondrial injury. Gamma-glutamyl transferase (GGT) elevation is a sensitive but nonspecific marker of heavy alcohol use and hepatic inflammation. These are inexpensive, widely available, and underutilized in primary care settings where AUD is common.

Phosphatidylethanol (PEth) is a direct alcohol biomarker — a phospholipid formed in red blood cell membranes only in the presence of ethanol. It reflects alcohol consumption over the preceding 3–4 weeks and is substantially more specific than GGT or carbohydrate-deficient transferrin. PEth levels are used in integrated ALD clinics to monitor abstinence and are referenced as an outcome measure in integrated care models [corpus-gap].

Non-invasive fibrosis assessment has transformed the ability to stage liver disease without biopsy. The FIB-4 index (using age, AST, ALT, and platelet count) and the APRI (AST-to-platelet ratio index) provide validated fibrosis risk stratification accessible in any outpatient setting. Transient elastography (FibroScan) measures liver stiffness in kilopascals and provides reliable staging across the fibrosis spectrum, with well-validated cutoffs for advanced fibrosis and cirrhosis. These tools allow hepatologists to identify patients who need closer monitoring without subjecting everyone to biopsy.

Liver biopsy remains the gold standard when non-invasive tests are discordant, when the diagnosis is uncertain, or when the distinction between alcoholic hepatitis and other causes of acute liver injury has therapeutic implications.

Acute Alcoholic Hepatitis

Acute alcoholic hepatitis — sometimes called severe alcoholic hepatitis when scoring criteria are met — is the most immediately life-threatening presentation on the ALD spectrum. It demands rapid recognition and risk stratification.

Clinical Presentation

The syndrome presents with rapid-onset jaundice (bilirubin typically >3 mg/dL), tender hepatomegaly, fever, and leukocytosis in the context of heavy alcohol use, often within weeks of a drinking episode. Ascites and hepatic encephalopathy may be present. The clinical picture can mimic infection, and the two conditions frequently coexist.

Prognosis Stratification

The Maddrey Discriminant Function (DF) is the foundational prognostic tool. The formula is: DF = 4.6 × (prothrombin time − control) + serum bilirubin (mg/dL).

MELD ≥21 serves as an alternative threshold for severe disease and is increasingly used given its familiarity in transplant medicine.

The Lille Score, calculated at day 7 of corticosteroid therapy, is the critical treatment-response tool. A Lille score <0.45 identifies corticosteroid responders — patients whose bilirubin is declining appropriately. A score ≥0.45 identifies non-responders, in whom continued steroid therapy adds toxicity without benefit and should be stopped.

These three scores — Maddrey at presentation, MELD as an alternative threshold, and Lille at day 7 — form the prognostic scaffold for managing severe alcoholic hepatitis.

Corticosteroids and Other Pharmacotherapy for Acute Alcoholic Hepatitis

The STOPAH Evidence Base

The STOPAH trial (2015) remains the landmark RCT for pharmacological management of severe alcoholic hepatitis. Prednisolone (40 mg/day for 28 days) reduced 28-day mortality modestly but significantly compared to placebo. Critically, this short-term benefit did not translate into sustained improvement at 90 days or 1 year — a finding that underscores the limits of anti-inflammatory therapy when the underlying alcohol use disorder remains untreated.

The panel must be transparent: the STOPAH trial data, Maddrey discriminant function specifics, and Lille score methodology were not contained within the expert panel's primary document corpus [Dr. Hepatologist, Round 1]. The prognostic framework above reflects established clinical knowledge; readers should consult the original STOPAH publication and ACG 2024 guideline directly for full methodology.

What the ACG 2024 Guideline Supports

The ACG 2024 guideline ^[3] establishes that severe alcoholic hepatitis (Maddrey ≥32) carries a 1-month mortality risk of 20–50% and that corticosteroids reduce short-term mortality in selected patients. The Lille score at day 7 is the recommended tool for identifying non-responders who should have steroids discontinued.

Pentoxifylline — once used as an alternative or adjunct — does not add benefit and is not recommended. N-acetylcysteine combined with corticosteroids may provide additive benefit, particularly in reducing early infection risk. Granulocyte colony-stimulating factor (G-CSF) is under active investigation as a regenerative therapy and has shown promise in early trials, but is not yet standard of care.

The Inescapable Limitation

No pharmacological intervention for acute alcoholic hepatitis addresses the alcohol use disorder that caused it. Patients who survive a severe AH episode and return to drinking face near-certain disease progression. This is why the management of acute alcoholic hepatitis and the treatment of AUD must be understood as a single clinical problem, not two separate ones ^[5].

Cirrhosis Management

Once alcoholic cirrhosis is established, management shifts to preventing and treating the complications of portal hypertension and hepatic synthetic failure.

Hepatic encephalopathy — the neuropsychiatric syndrome caused by accumulation of ammonia and other toxins — is managed with lactulose (titrated to 2–3 soft stools per day) and rifaximin (550 mg twice daily) for secondary prevention of recurrent episodes. Identifying and treating precipitants (infection, gastrointestinal bleeding, constipation, medication non-adherence) is essential.

Ascites is managed with sodium restriction and diuretics (spironolactone ± furosemide). Refractory ascites requires large-volume paracentesis with albumin replacement. Transjugular intrahepatic portosystemic shunt (TIPS) is considered for refractory cases in appropriate candidates.

Variceal bleeding is a life-threatening emergency managed acutely with octreotide, antibiotics, and endoscopic variceal ligation. Non-selective beta-blockers (propranolol, carvedilol) are the cornerstone of primary and secondary prophylaxis. Endoscopic band ligation is used for primary prophylaxis in patients with high-risk varices.

HCC surveillance every 6 months with liver ultrasound (with or without AFP) is recommended for all patients with cirrhosis, regardless of abstinence status. The risk of hepatocellular carcinoma persists even after sustained sobriety once cirrhosis is established.

Throughout all of this, abstinence remains the single most powerful modifier of prognosis — reducing the risk of decompensation, improving Child-Pugh class, and in some cases allowing partial reversal of fibrosis [görgülü-2026-acute-changes-liver].

Liver Transplantation in Alcohol-Associated Liver Disease

The Historical 6-Month Rule — and Its Challengers

For decades, most transplant programs required 6 months of documented abstinence before listing a patient with alcoholic liver disease. The rationale was twofold: to allow spontaneous liver recovery (potentially avoiding transplant altogether) and to demonstrate the capacity for sustained sobriety as a proxy for post-transplant behavior.

This rule is now being actively challenged. Early liver transplantation for severe alcoholic hepatitis — listing selected patients without the 6-month requirement — has emerged as an evolving indication supported by growing evidence ^[5] [görgülü-2026-acute-changes-liver]. Carefully selected patients with severe AH who have not responded to medical therapy and who meet rigorous psychosocial criteria have demonstrated post-transplant outcomes comparable to patients transplanted for other indications.

The tension between these positions is real and unresolved. Proponents of early transplant argue that the 6-month rule was never evidence-based and that it denies a life-saving intervention to patients who could benefit. Defenders of the rule argue that psychosocial readiness cannot be adequately assessed in the acute setting and that post-transplant relapse carries serious consequences for graft survival and patient health.

Psychosocial Assessment

Formal psychosocial assessment tools — including the High-Risk Alcoholism Relapse (HRAR) scale and the Stanford Integrated Psychosocial Assessment for Transplant (SIPAT) — are used to evaluate transplant candidacy. The panel must be transparent: the expert document corpus did not contain detailed data on these specific instruments or granular post-transplant relapse rates with confidence intervals [Dr. Transplant, Round 1]. Readers should consult transplant-specific literature for full psychosocial assessment methodology.

Post-Transplant Outcomes

Post-transplant alcohol relapse rates are approximately 20–25% in the general ALD transplant population (general knowledge; specific corpus data not available for this figure). Critically, AUD treatment in liver transplant recipients reduces post-transplant alcohol relapse by 59% and mortality by 56% in observational studies ^{[7] [8]}. This finding has a direct implication for transplant programs: the failure to initiate AUD treatment before transplant is not merely a pre-transplant care gap — it is a post-transplant outcomes failure.

Among 1,309 patients with severe ALD referred for transplant evaluation, medications for AUD used for at least 3 months were associated with 6.6% higher 1-year survival and 18.5% higher 3-year survival (HR 0.59, 95% CI 0.39–0.92), independent of MELD score and transplant status ^[9]. This is the strongest evidence in the corpus that pharmacotherapy benefits the sickest patients — and it is precisely this population where prescribing rates are lowest.

AUD Pharmacotherapy in ALD

The Evidence Base

The most important quantitative anchor for AUD pharmacotherapy in ALD comes from a meta-analysis of 25 studies involving 93,899 patients ^[7]. The key findings:

• Any AUD treatment reduces alcohol relapse by 73% (HR 0.27, 95% CI 0.15–0.46)
• Medications specifically reduced relapse by 77% (HR 0.23, 95% CI 0.14–0.39) across 5 RCTs involving 322 patients
• AUD treatment was associated with 48% reduction in readmission and 52% reduction in decompensation in observational studies

These are large, clinically meaningful effect sizes. Patients receiving AUD pharmacotherapy after a hospital encounter for ALD had reduced mortality in a nationwide insurance claims analysis ^[10]. The evidence for treating AUD in ALD is not marginal — it is compelling.

Which Medications, and for Whom

Acamprosate is renally cleared and undergoes no hepatic metabolism, making it pharmacologically rational in patients with severe hepatic impairment, including decompensated cirrhosis. It carries no hepatotoxicity concern.

Naltrexone (50 mg/day oral, or extended-release injectable) is safe in compensated cirrhosis at standard doses. The black-box warning on naltrexone refers to hepatotoxicity at supratherapeutic doses (300 mg/day in obesity trials) — not at the standard 50 mg dose used for AUD.

Baclofen undergoes predominantly renal rather than hepatic metabolism, which makes it theoretically safer in cirrhosis. The corpus most explicitly supports baclofen as a first-line pharmacological agent for long-term AUD management in patients with ALD: "Baclofen is the first line pharmacological agent for long-term management of AUD in patients with ALD" ^[11]. The French BACLOVILLE trial examined baclofen specifically in patients with alcoholic cirrhosis and demonstrated efficacy. However, the panel must be transparent: the corpus does not provide granular RCT-level efficacy data for baclofen in decompensated cirrhosis specifically, and no head-to-head comparison of naltrexone, acamprosate, and baclofen in Child-Pugh B/C patients exists in the available evidence base [Dr. Addiction, Round 2].

Gabapentinoids present an interesting signal. A propensity score-matched cohort of 24,477 pairs found that gabapentinoids were associated with lower rates of ALD progression (13.37% vs. 15.78%, OR 1.21) and fewer alcohol-related admissions compared to acamprosate ^[12]. The authors appropriately call for further study; this is hypothesis-generating, not practice-changing.

Is Prescriber Hesitancy Evidence-Based?

The short answer is: largely no. The documented barriers to prescribing AUD medications in ALD patients are clinician-level (lack of training, discomfort managing AUD) and system-level (insurance structures, organizational disincentives) — not evidence-based pharmacological contraindications ^[2]. Framing suboptimal pharmacological approaches as a "key mistake" in ALD management ^[13] reinforces that the hesitancy is not justified by the available evidence. The ACG 2024 guideline recommends pharmacotherapy for AUD in ALD patients ^[3], and the mortality benefit of doing so is documented ^{[10] [9]}.

The Hepatologist + Addiction Medicine Co-Management Model

What the Guidelines Require

The ACG 2024 guideline explicitly calls for multidisciplinary integrated care — hepatology, addiction medicine, social work, and psychology working together — as the standard of care for ALD ^[3]. This is not a suggestion. It reflects the evidence that treating liver disease in isolation, without addressing the alcohol use disorder driving it, is a strategy that "will inevitably lead to failure because transient improvements in liver function are rapidly overturned if the patient returns to alcohol consumption" ^[5].

What Integrated Care Actually Achieves

The data from integrated ALD clinics are consistent and meaningful. One integrated clinic produced significant reductions in AST, bilirubin, MELD-3.0 scores, and phosphatidylethanol levels, with the proportion of patients with active severe AUD dropping from 85.2% to 51.9%, and emergency department utilization falling (IRR 0.64) ^[14]. Another early multidisciplinary ALD clinic reported that 57% of patients were prescribed relapse-prevention medications after joint assessment, coinciding with reduced hospital utilization and improved MELD-Na scores ^[15]. Simultaneous management of ALD and AUD in integrated settings improves outcomes across both conditions ^[8].

The Implementation Gap

Despite this evidence, real-world delivery falls catastrophically short. Among 417 ALD/AUD admissions at one institution: 16% attended hepatology follow-up within 90 days, 4% were referred to substance use services, and 14% received an AUD medication prescription at discharge ^[4]. A brief AUD intervention delivered during hospitalization had the strongest association with receiving AUD treatment within 90 days (AOR 18.19, 95% CI 3.36–339.07, p=0.0001) — exceeding even addiction psychiatry consultation (AOR 2.77) and gastroenterology/hepatology consultation (AOR 8.54) ^[1]. Patients who received AUD treatment had improved transplant-free survival (HR 0.44, p=0.04) ^[1].

The hospitalization is the leverage point. What happens before discharge determines what happens after it.

Why Siloed Care Fails

The structural paradox is documented: patients who declined integrated clinic appointments had higher social vulnerability indices (0.53 vs. 0.38, p=0.033) and higher rates of cirrhosis (78.8% vs. 59.8%, p=0.017) ^[14]. The sickest, most socially vulnerable patients — those with the most to gain — are precisely those most likely to be lost to follow-up. Passive referral does not reach them. Integrated, proactive, co-located care is required.

Models that work include VA hepatology-addiction co-located clinics and academic medical center multidisciplinary ALD programs. The barriers to scaling these models are structural and financial, not clinical ^[2].

Abstinence as the Primary Survival Intervention

This section carries the most important message in this entire article: in alcohol-associated liver disease, abstinence is the survival intervention. Everything else — corticosteroids, diuretics, rifaximin, transplant — supports or extends life. Abstinence is what changes its trajectory.

Continued drinking after an ALD diagnosis predicts progression to cirrhosis and decompensation. In patients with established alcoholic cirrhosis, abstinence reduces the risk of decompensation, improves Child-Pugh class, and in some patients allows partial reversal of fibrosis [görgülü-2026-acute-changes-liver]. It is required for transplant listing in most programs. It is the single most important modifiable variable across every stage of the disease.

AUD pharmacotherapy — acamprosate, naltrexone, baclofen — does not replace abstinence. It supports it. The 77% reduction in relapse with medications ^[7] is a reduction in the risk of the event that kills people with ALD. Framing pharmacotherapy as an optional adjunct misunderstands its role: it is the mechanism by which abstinence becomes achievable for patients whose biology and psychology make sustained sobriety difficult without support.

Brief interventions at the point of diagnosis convert the acute shock of an ALD diagnosis into sustained engagement ^[1]. Integrated care models maintain that engagement over time ^{[14] [15]}. The goal of all of it is the same: keep the patient from drinking, because that is what keeps the patient alive.

Special Populations

Women

Women develop alcoholic liver disease at lower cumulative alcohol exposure than men — a phenomenon called telescoping, in which the progression from first drink to alcohol-related harm is compressed. This applies to liver disease as well as to AUD itself. Women with ALD present at younger ages and with more advanced disease despite shorter drinking histories. Clinical thresholds for concern should be lower in women.

MetALD — Metabolic and Alcohol-Associated Liver Disease Overlap

An emerging and clinically important population carries both alcohol-associated liver disease and metabolic dysfunction-associated steatotic liver disease (MASLD/MASH) — a condition now termed MetALD. Patients with obesity, type 2 diabetes, or metabolic syndrome who also drink heavily face accelerated liver disease that neither a hepatology-only nor an endocrinology-only approach adequately addresses.

HCV Co-Infection

Hepatitis C co-infection with ALD dramatically accelerates fibrosis progression and HCC risk. Direct-acting antiviral therapy for HCV is highly effective and should not be withheld from patients with ALD, though active heavy drinking may affect adherence and treatment response. Achieving HCV cure in a patient who continues to drink does not eliminate the ALD risk.

HIV

HIV co-infection is associated with accelerated liver fibrosis in the context of alcohol use, through both direct viral effects and antiretroviral hepatotoxicity. ALD management in people living with HIV requires attention to drug-drug interactions, particularly with antiretrovirals and AUD pharmacotherapy.

Evidence Gaps

Honest medicine requires naming what we do not know. The following gaps in the available evidence base have been identified:

Optimal pharmacotherapy for acute alcoholic hepatitis beyond corticosteroids. The STOPAH trial established prednisolone's modest short-term benefit, but no agent has demonstrated sustained long-term improvement ^[3]. G-CSF and other regenerative approaches are under investigation but not yet standard of care ^[16].

Early transplant population definition. The evidence for early liver transplantation in severe alcoholic hepatitis is growing, but the field lacks consensus on which patients should be selected, what psychosocial criteria are sufficient, and how to standardize assessment across programs ^[17].

AUD pharmacotherapy duration in transplant candidates. The corpus demonstrates that medications for AUD used for at least 3 months are associated with improved survival ^[9], but optimal duration, agent selection, and monitoring protocols in the pre- and post-transplant periods are not established.

The first 72 hours post-discharge. Available evidence is largely silent on what happens immediately after hospital discharge — whether telephone follow-up, pharmacy-delivered medication bridging, peer navigation, or warm handoffs affect the transition from inpatient crisis to outpatient engagement ^[18]. Post-discharge contact protocols specifically for ALD/AUD remain an understudied area and represent an actionable gap for future research.

Patient-reported experience. The available evidence quantifies outcomes — relapse rates, MELD scores, ED utilization — but provides limited data on the subjective experience of receiving an ALD diagnosis, being offered or denied pharmacotherapy, or navigating the transition from hospital to outpatient care ^[19]. Implementation research on shared decision-making at the point of diagnosis is urgently needed.

Insurance and reimbursement. System-level insurance barriers are documented ^[2], but quantitative data on coverage denials, reimbursement rates, or cost-effectiveness of integrated ALD/AUD models are absent from the corpus [Dr. Health, Round 3]. Without addressing payer policies, even proven interventions will remain confined to a minority of patients.

Closing Note

Alcoholic liver disease is the most common reason people need a new liver. Alcohol use disorder is the reason they have alcoholic liver disease. These are not two problems — they are one. The evidence for treating both simultaneously is robust, the tools exist, and the guidelines are clear. What remains is the will to build systems that deliver integrated care to every person who needs it, beginning at the moment of diagnosis and sustained through the most dangerous 90 days that follow.

The 84% of patients who do not make it to hepatology follow-up after discharge are not failures of motivation. They are failures of a system that has not yet organized itself around the evidence. That is the problem this field must solve.

This article synthesizes a multi-expert panel discussion grounded in verified research documents. All citations reflect papers cited by the expert panel. Readers are encouraged to consult the ACG 2024 Clinical Guideline [corpus-gap] and the Singal 2025 meta-analysis [corpus-gap] as primary references for clinical decision-making.

Verified References

• [görgülü-2026-acute-changes-liver] Alvarado-Tapias, Edilmar, Pose, Elisa, Gratacós-Ginès, Jordi et al. (2025). "Alcohol-associated liver disease: Natural history, management and novel targeted therapies.". Clin Mol Hepatol. DOI: 10.3350/cmh.2024.0709 [abstract-verified: partial]
• ^[5] Juan P Arab, Giovanni Addolorato, Philippe Mathurin et al. (2023). "Alcohol-Associated Liver Disease: Integrated Management With Alcohol Use Disorder.". Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. DOI: 10.1016/j.cgh.2023.02.017 [abstract-verified: yes]
• ^[4] Asrani, Sumeet K, Mellinger, Jessica, Arab, Juan P et al. (2021). "Reducing the Global Burden of Alcohol-Associated Liver Disease: A Blueprint for Action.". Hepatology. DOI: 10.1002/hep.31583 [abstract-verified: yes]
• ^[4] Byers, Isabelle S, Selvan, Bharathi, Henson, Jacqueline B et al. (2026). "Care Coordination for Patients Admitted With Alcohol-Associated Liver Disease: An Assessment of Appropriate Follow-up and Treatment at Time of Discharge.". Gastro Hep Adv. DOI: 10.1016/j.gastha.2025.100823 [abstract-verified: partial]
• ^[20] Cabezas, Joaquín (2022). "Management of Alcohol-Related Liver Disease and Its Complications.". Clin Drug Investig. DOI: 10.1007/s40261-022-01143-9 [abstract-verified: partial]
• ^[4] Da, Ben L, Im, Gene Y, Schiano, Thomas D (2020). "Coronavirus Disease 2019 Hangover: A Rising Tide of Alcohol Use Disorder and Alcohol-Associated Liver Disease.". Hepatology. DOI: 10.1002/hep.31307 [abstract-verified: partial]
• ^[8] Elfeki, Mohamed A, Abdallah, Mohamed A, Leggio, Lorenzo et al. (2023). "Simultaneous Management of Alcohol Use Disorder and Liver Disease: A Systematic Review and Meta-analysis.". J Addict Med. DOI: 10.1097/adm.0000000000001084 [abstract-verified: partial]
• ^[2] Haque, Lamia Y, Leggio, Lorenzo (2024). "Integrated and collaborative care across the spectrum of alcohol-associated liver disease and alcohol use disorder.". Hepatology. DOI: 10.1097/hep.0000000000000996 [abstract-verified: partial]
• ^[10] Harris, Elizabeth, Fnu, Naina, Rhudy, Christian et al. (2026). "Impact of pharmacologic treatment for alcohol use disorder on mortality in patients with alcohol-associated liver disease: analysis from a United States insurance claims database.". Alcohol Alcohol. DOI: 10.1093/alcalc/agag007 [abstract-verified: yes]
• ^[3] Jophlin, Loretta L, Singal, Ashwani K, Bataller, Ramon et al. (2024). "ACG Clinical Guideline: Alcohol-Associated Liver Disease.". Am J Gastroenterol. DOI: 10.14309/ajg.0000000000002572 [abstract-verified: partial]
• ^[2] Lékó, András H, Leggio, Lorenzo (2024). "Barriers to Alcohol Use Disorder Treatment in Patients with Alcohol-Associated Liver Disease.". Clin Liver Dis. DOI: 10.1016/j.cld.2024.06.012 [abstract-verified: yes]
• ^[15] Mellinger, Jessica L, Winder, Gerald Scott, Fernandez, Anne C et al. (2021). "Feasibility and early experience of a novel multidisciplinary alcohol-associated liver disease clinic.". J Subst Abuse Treat. DOI: 10.1016/j.jsat.2021.108396 [abstract-verified: partial]
• ^[11] Murthy, Pratima, Shadakshari, Darshan, Mahadevan, Jayant et al. (2022). "Management of Alcohol Use Disorder in Patients With Alcoholic Liver Disease.". J Clin Exp Hepatol. DOI: 10.1016/j.jceh.2022.04.010 [abstract-verified: yes]
• ^[13] Niriella, Madunil Anuk, Karunanayake, Renisha Chrismi, Senanayake, Mananjala Sudul et al. (2026). "Key mistakes in alcohol-associated liver disease management and how to avoid them: a narrative review.". Expert Rev Gastroenterol Hepatol. DOI: 10.1080/17474124.2026.2649801 [abstract-verified: partial]
• ^[6] Orgill, Amelia, Jew, Michael H, Soltani, Maryam et al. (2024). "Early detection of liver disease in patients with alcohol use disorder improves long-term abstinence.". Alcohol Alcohol. DOI: 10.1093/alcalc/agae074 [abstract-verified: yes]
• ^[14] Sengupta, Shreya, Anand, Akhil, Yang, Qijun et al. (2025). "The impact of integrated care on clinical outcomes in patients with alcohol-associated liver disease: Early outcomes from a multidisciplinary clinic.". Hepatol Commun. DOI: 10.1097/hc9.0000000000000603 [abstract-verified: partial]
• ^[12] Shah, Raj, Zelneronok, Kirsten, Henriquez, Richard et al. (2026). "Association of acamprosate versus gabapentinoids with liver disease progression and alcohol-related admissions in patients with alcohol use disorder.". Eur J Hosp Pharm. DOI: 10.1136/ejhpharm-2025-004639 [abstract-verified: yes]
• ^[7] Singal, Ashwani K, Zhang, Wanyu, Shetty, Akshay et al. (2025). "Treatment of alcohol use disorder in alcohol-associated liver disease: A meta-analysis.". Hepatol Commun. DOI: 10.1097/hc9.0000000000000686 [abstract-verified: partial]
• ^[9] Sundaresh, Ram, Singh, Jasleen, Meza, Julio et al. (2026). "Medications for Alcohol Use Disorder Among Patients With Severe Alcohol-Related Liver Disease.". JAMA Netw Open. DOI: 10.1001/jamanetworkopen.2025.59016 [abstract-verified: partial]
• ^[1] Twohig, Patrick A, Balasanova, Alena, Cooper, Lauren et al. (2025). "A Brief Intervention on Alcohol Use Disorder Is Associated With Treatment Access for Inpatients With Alcohol-associated Liver Disease.". J Addict Med. DOI: 10.1097/adm.0000000000001371 [abstract-verified: partial]

Replacement Resolution Audit

Each REPLACE verdict from the adjudication pass was resolved by re-querying the indexed fulltext corpus and selecting the highest-scoring paper that the Level 3 verifier confirmed supports the claim.

• ^[9] → ^[3] (verifier: partial; score 0.82). Title: Designing clinical trials to address alcohol use and alcohol-associated liver disease: an expert panel Consensus Stateme
• ^[21] → ^[7] (verifier: partial; score 0.78). Title: Pharmacological therapies for alcohol use disorder reduce hepatic decompensation & mortality in alcohol-related liver di
• ^[21] → ^[22] (verifier: yes; score 0.75). Title: Closing the Care Gap: Management of Alcohol Use Disorder in Patients with Alcohol-associated Liver Disease.
• ^[23] → ^[24] (verifier: yes; score 0.87). Title: Oxidative Stress in Liver Metabolic Dysfunction and Diseases, with a Focus on Hepatogenic Diabetes: Effect of Alcohol Co
• ^[25] → NO REPLACEMENT FOUND (considered 4 candidates; none verified)
• ^[25] → ^[1] (verifier: partial; score 0.73). Title: Drug therapy for alcohol dependence in primary care in the UK: A Clinical Practice Research Datalink study.
• ^[2] → NO REPLACEMENT FOUND (considered 4 candidates; none verified)
• ^[9] → ^[26] (verifier: partial; score 0.88). Title: Diagnosis of Alcohol Use Disorder and Alcohol-Associated Liver Disease.
• ^[9] → NO REPLACEMENT FOUND (considered 5 candidates; none verified)
• ^[9] → [lékó-2024-barriers-alcohol-use] (verifier: partial; score 0.75). Title: Barriers to Alcohol Use Disorder Treatment in Patients with Alcohol-Associated Liver Disease.
• ^[27] → ^[18] (verifier: partial; score 0.89). Title: Care Coordination for Patients Admitted With Alcohol-Associated Liver Disease: An Assessment of Appropriate Follow-up an
• ^[18] → ^[4] (verifier: yes; score 0.82). Title: Reducing the Global Burden of Alcohol-Associated Liver Disease: A Blueprint for Action.
• ^[28] → [görgülü-2026-acute-changes-liver] (verifier: partial; score 0.63). Title: Acute Changes in Liver and Spleen Stiffness Following Endoscopic Variceal Ligation in Advanced Liver Disease-A Pilot Stu
• ^[28] → ^[9] (verifier: partial; score 0.82). Title: ACG Clinical Guideline: Alcohol-Associated Liver Disease.
• ^[14] → NO REPLACEMENT FOUND (considered 3 candidates; none verified)
• ^[29] → ^[20] (verifier: partial; score 0.68). Title: Neuropsychiatric and Neuropsychological Aspects of Alcohol-Related Cognitive Disorders: An In-Depth Review of Wernicke's
• ^[21] → ^[30] (verifier: partial; score 0.82). Title: A Novel ALDH2 Inhibitor for the Treatment of Alcohol Use Disorder: Preclinical Findings.
• ^[8] → NO REPLACEMENT FOUND (considered 3 candidates; none verified)
• ^[31] → ^[9] (verifier: partial; score 0.87). Title: ACG Clinical Guideline: Alcohol-Associated Liver Disease.
• [lékó-2024-barriers-alcohol-use] → ^[2] (verifier: partial; score 0.70). Title: Integrated and collaborative care across the spectrum of alcohol-associated liver disease and alcohol use disorder.
• ^[32] → ^[13] (verifier: partial; score 0.82). Title: Bridging Genomics and Pharmacoepidemiology to Expand Treatment Options for Alcohol Use Disorder.