Elastography-based Brief Alcohol Intervention in Hospitalized Individuals

Harmful alcohol consumption constitutes a major contributor to global morbidity, being associated with many diseases and injury outcomes; it is the leading cause of liver cirrhosis and represents a significant cause of hospital admissions. Alcohol-related liver disease (ALD) is characterized by slow progression from a healthy liver to steatohepatitis, progressive fibrosis, cirrhosis, and life-threatening liver decompensation. The risk of progression is related to the volume and pattern of drinking. Because disease progression is usually asymptomatic with subtle biochemical or imaging abnormalities, liver disease may remain undiagnosed for decades and often present with end-stage complications at a point where survival is poor. At all stages of ALD, substantial reversibility and improved prognosis can be achieved if alcohol intake is stopped or reduced.

Brief alcohol intervention (BAI) is a time-limited structured motivational intervention targeting harmful alcohol use. Meta-analyses have shown that BAI can lead to modest but clinically meaningful reductions in alcohol intake, alcohol-related harm and mortality in primary care and hospital settings.

Elastography is an ultrasound-based technique that provides liver stiffness measurements (LSM) as a surrogate marker of liver fibrosis and portal hypertension. A unique feature of elastography is that it provides immediate disease staging following a quick bedside examination with ample opportunities for biofeedback, tailored BAI, and linkage to further hepatology and addiction care as needed. There is increasing evidence that such personalized healthcare communications involving biofeedback based on markers of liver injury may have more impact on drinking behavior than BAI alone.

There is an unmet need for interventions to promote case-finding, timely liver fibrosis detection, and reduction of alcohol-related harms among people at risk of ALD. Hospitalization presents a unique opportunity for intervention, as patients may be more receptive to behavioral change during acute illness. Hospital admission may therefore represent a 'teachable moment' that may enhance intervention impact.

This study will investigate the efficacy of proactive elastography-based liver disease assessment and structured counseling according to BAI principles in emergency hospitalized individuals at risk of ALD. The hypothesis is that proactive assessment of liver health during hospitalization may motivate reductions in alcohol use and thereby prevent disease complications and recurrent admissions more effectively than usual care.

This is a Norweigan multicenter study that will include patients at risk of ALD admitted for inpatient care for any reason. Approximately 500 patients will be included from 8 hospitals over a period of 18 months. Patients will be screened for harmful alcohol use (AUDIT-C) and for liver fibrosis (FIB-4) during admission/hospitalization, and will be assigned 1:1 to recieve elastography-based BAI in addition to usual care, or usual care alone, according to standard clinical practice.

Elastography-based BAI will be delivered during hospitalization. After discharge, patients will be followed up with study visits after 3, 6 and 12 months. Assessment during follow-up includes questionnaires on health related quality of life, alcohol consumption and effects of alcohol, clinical investigation, and blood test including the alcohol biomarker PEth. Long-term follow up are registry data extraction after 2, 5 and 10 years.

The primary objective is to demonstrate whether elastography-based BAI is superior to usual care in reducing hospital admissions for any reason within 2 years. Key secondary objectives are to demonstrate whether elastography-based BAI is superior to usual care in reduce harmful alcohol consumption as measured by PEth, AUDIT and weekly alcohol units. The study also aims to evaluate cost-effectiveness of the intervention, health-related quality of life, self-reported alcohol effects, prognostic serum biomarkers, candidate genetic polymorphisms, and metabolomics.

• Change in phosphatidylethanol (PEth) [Time frame: Baseline, 6 and 12 months after randomization.]
• Reduction in phosphatidylethanol (PEth) [Time frame: Baseline and 12 months after randomization.]
• Change in The Alcohol Use Disorders Identification Test (AUDIT) score [Time frame: Baseline, 6 and 12 months after randomization.]
• Reduction in The Alcohol Use Disorders Identification Test (AUDIT) score [Time frame: Baseline and 12 months after randomization.]
• Change in weekly alcohol units [Time frame: Baseline, 6 and 12 months after randomization.]
• Change in proportion of drinking days [Time frame: Baseline, 6 and 12 months after randomization.]
• Change in proportion of heavy drinking days [Time frame: Baseline, 6 and 12 months after randomization.]
• Achieving stringent alcohol reduction [Time frame: Baseline, 6 and 12 months after randomization.]
• Change in health-related quality of life EuroQol 5-Dimension 5-Level (EQ-5D-5L) [Time frame: Baseline, 6 and 12 months after randomization.]
• Improvement in health-related quality of life measured by EuroQol 5-Dimension 5-Level (EQ-5D-5L) [Time frame: Baseline, 6 and 12 months after randomization]
• Change in health-related quality of life measured in Euro-Qol Visual Analogue Scale (EQ-VAS) [Time frame: Baseline, 6 and 12 months after randomization]
• Change in anxiety and depression measured by EQ-5D-5L anxiety/depression dimension score [Time frame: Baseline, 6 and 12 months after randomization.]