The role of the hepatologist in the alcohol-associated liver disease epidemic

INTRODUCTION Alcohol use is a major global cause of premature death. It accounts for 43% of all disability-adjusted life years in patients with cirrhosis and substantially impairs quality of life.1,2 Alcohol-associated liver disease (ALD) is also the leading indication for liver transplantation in the United States.3 However, alcohol use is frequently underreported by as much as 55% in some settings,4 making it challenging to identify patients who need counseling and targeted interventions. Hepatology consultation is crucial to support alcohol cessation and prevent long-term harm. Therefore, hepatologists must be able to identify and treat hazardous drinking and alcohol use disorder (AUD); the following sections outline practical, actionable steps clinicians can apply. DETECTION OF AUD AND LIVER FIBROSIS IN THE LIVER CLINIC AUD can be identified through self-report tools and laboratory tests. Because alcohol use often carries social stigma, these assessments should be performed with empathy and without judgment.5 The Alcohol Use Disorders Identification Test–Consumption (AUDIT-C) is a 1–2-minute, 3-item screening tool that identifies at-risk drinking. A score of ≥3 in women or ≥4 in men is considered a positive screen for hazardous drinking and might suggest a diagnosis of AUD.5 Biomarkers can objectively document alcohol exposure. Phosphatidylethanol (PEth) is a direct biomarker for recent alcohol use and has a broader detection window compared with other biomarkers (up to 3–4 wk). A PEth ≥20 ng/mL indicates alcohol use within the past 4 weeks (sensitivity 73% and specificity 96%), and ≥80 ng/mL suggests consumption ≥4 drinks/d (sensitivity 91%, specificity 77%).6 Moreover, PEth can also detect occasional binge drinking.7 Other direct alcohol biomarkers in urine and blood, including ethyl glucuronide and ethyl sulfate, are helpful but have a narrow detection window (up to 3–5 d).6 Indirect biomarkers, such as AST, the AST/ALT ratio, carbohydrate-deficient transferrin, and mean corpuscular volume, can support the diagnosis but are comparatively less specific.8 Thus, although indirect biomarkers may suggest recent alcohol exposure, direct alcohol biomarkers remain the best option for implementation in clinical practice. The use of PEth testing should be disclosed to the patient and family, and results should always be interpreted within the appropriate clinical context.9 Liver fibrosis assessment is a key component of ALD management. A practical, evidence-based approach is to begin screening with the fibrosis-4 index (FIB-4), a free and simple noninvasive test with a high negative predictive value for advanced fibrosis. A FIB-4 score below 1.3 excludes with high precision the presence of advanced fibrosis in most patients. When the FIB-4 score is ≥1.3, further assessment with a second-line test such as transient elastography is recommended.9 This latter method is well validated for assessing liver stiffness: measurements <8 kPa generally rule out advanced fibrosis, while values ≥12 kPa are strongly associated with stages F3–F4.10 Active hepatic inflammation and excessive alcohol use in the past 12 weeks may overestimate liver stiffness. Indeterminate results (ie, liver stiffness on transient elastography between 8 and 12 kPa) may require reassessment after a period of alcohol abstinence or combined with additional markers to improve diagnostic precision.6,9 Adding transient elastography to fibrosis assessment and counseling programs has been associated with short-term reductions in alcohol consumption and increased abstinence in individuals with AUD.11,12 NONPHARMACOLOGICAL INTERVENTIONS Nonpharmacologic interventions are behavioral and psychosocial approaches that help patients modify their relationship with alcohol without the use of medication. They focus on mental and emotional processes, fostering motivation and behavioral change to reduce consumption, prevent relapse, and sustain abstinence. Among these, brief intervention is considered the first-line strategy in most clinical settings, including the hepatology consultation. It involves 1 or more structured 5–20-minute sessions to discuss alcohol-associated risks, set achievable goals, and encourage behavioral change. More complex approaches, such as motivational interviewing, cognitive-behavioral therapy, Twelve-Step Facilitation, or contingency management,13 require specialized training and are typically delivered by mental health professionals. Whenever the hepatologist identifies hazardous drinking using the AUDIT-C, they should provide a brief intervention and coordinate referral to an interdisciplinary care team if moderate-to-severe AUD is present. If such a team is not available, referral to an addiction medicine specialist or a social worker should be considered. Integration between hepatology and mental health care enhances treatment adherence, reduces relapse rates, and enables a comprehensive approach to the behavioral determinants of ALD.14 MEDICATIONS FOR AUD IN THE LIVER CLINIC Pharmacotherapy for AUD should be offered to most patients with ALD, ideally in combination with behavioral treatment. Pharmacotherapy implementation should follow a structured approach. First, define the immediate clinical objective (detoxification support, reduction in heavy drinking, and/or relapse prevention) and assess liver and renal function, opioid exposure, encephalopathy risk, pregnancy status, and comorbid psychiatric illness. Finally, several non–FDA-approved agents (eg, baclofen, topiramate, gabapentin, and varenicline) might be considered on a case-by-case basis, particularly when first-line therapy is contraindicated, ineffective, or unavailable.15 In the following paragraphs, we will detail the main characteristics of the most common medications for AUD. Naltrexone reduces heavy drinking and craving and can be dosed orally (50 mg daily, with a 25 mg daily dose during the first 3 days) or as a monthly extended-release injection (380 mg).5 The principal adverse effects are gastrointestinal symptoms, insomnia, and dizziness. Concomitant opioid use is an absolute contraindication because naltrexone can precipitate withdrawal and block analgesia. Naltrexone might be more suitable for patients aiming to reduce consumption or support early abstinence with close clinical and biochemical monitoring. Acamprosate is dosed at 666 mg 3 times daily.5 It is renally cleared, and a dose reduction is required when the glomerular filtration rate (GFR) is between 30 and 50 mL/min (333 mg 3 times daily), and should not be used if the GFR is <30 mL/min. Its strongest effect is maintenance of abstinence once drinking has stopped. Acamprosate has been shown to reduce relapse and increase the number of cumulative abstinent days. All in all, acamprosate is favored when hepatic reserve is limited, when opioid therapy is required (precluding naltrexone), or when the clinical aim is relapse prevention after detoxification.7 Baclofen, a GABA-B agonist eliminated primarily by renal excretion, has been studied directly in patients with cirrhosis due to ALD, with randomized trials and observational data supporting improved abstinence rates.5 Typical dosing is 10–30 mg 3 times daily, with titration to effect; higher doses (eg, 90 mg/d) may benefit selected patients but increase adverse events. Dose needs to be adjusted in patients with a GFR <60 mL/min. Sedation and worsening hepatic encephalopathy are the key concerns, necessitating careful titration and monitoring. American guidelines endorse baclofen (off-label) as a reasonable option for AUD in ALD, particularly when naltrexone is contraindicated, and acamprosate is insufficient or not tolerated.9 In turn, gabapentin might be used in patients at risk of alcohol withdrawal or to attenuate withdrawal symptoms, although caution is warranted due to sedation.16 MODELS OF CARE AND FURTHER PERSPECTIVES Up to this point, we have discussed clinician-dependent approaches. However, there is a need to design and implement care pathways that extend beyond brief clinic encounters and coordinate detection, treatment initiation, navigation, and follow-up under shared metrics and joint governance across hepatology, addiction medicine, primary care, and other providers. For example, integrated inpatient care with active hepatology involvement, associated with higher rates of fibrosis assessment, AUD medication initiation, and hepatology consultation, has been linked to lower short-term return to alcohol use.5,15 Similarly, alcohol care teams embedded within inpatient services can develop contingency plans, facilitate behavioral interventions, support adherence to pharmacotherapy, and promote lifestyle change.14 In the outpatient setting, multidisciplinary clinic models have been associated with fewer hospital and emergency department visits.17 Notably, these models depend on strong leadership from hepatology teams and sustained institutional support for their successful and scalable implementation. Some challenges persist in the daily practice of hepatologists. Brief alcohol discussions remain underused, particularly in patients without cirrhosis, precisely where preventive interventions are most impactful.18 Also, screening-to-referral pathways are not standardized, even though their implementation should be a core quality indicator.18 In parallel, digital tools are emerging as practical enablers that strengthen the bridge between hospital and ambulatory care. In a randomized pilot among adults with ALD, a preference-tailored mobile health intervention was acceptable and feasible, increasing engagement in AUD treatment.19 Ultimately, hepatology must transition from “detect and advise” to designing and leading integrated systems that facilitate the best course of action, making it easy to follow and effective for patients, caregivers, and health care providers. CONCLUDING REMARKS In recent years, there has been an increase in ALD publications, and practical, evidence-based messages are emerging on how to approach this population. Whatever we adopt must be scalable, simple, low-cost, and easily embeddable into routine care. Many elements will be refined over the coming years; meanwhile, pragmatic step-wise algorithms, such as the one presented in the figure, offer the most sensible path for a common, high-burden problem (Figure 1).FIGURE 1: Integrated hepatology-based algorithm for fibrosis risk assessment and alcohol use evaluation in patients with suspected or confirmed chronic liver disease.