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Harmful alcohol use is a common cause of hospital admissions and the leading cause of liver cirrhosis. Timely detection of liver disease is crucial to prevent liver disease progression and reduce alcohol-related harms. 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. The study will recruit 500 patients at risk of alcohol-related liver disease who are admitted for inpatient care for any reason. Recruitment will be done at 8 Norwegian hospitals over an 18-month period. Participants will be randomized to liver elastography (liver stiffness measurement) and personalized alcohol counselling, or to usual care. After discharge, participants will be followed with study visits after 3, 6 and 12 months. Assessments during follow-up include self-reported alcohol use, the alcohol biomarker PEth and health-related quality of life. The primary outcome is the number of emergency hospital admissions for any reason within 2 years, collected from the Norwegian Patient Registry. The study has very low risk for the participants, with no invasive procedures or risks associated with the intervention. The potential benefit is considerably greater, with opportunities for improved health, prognosis, and quality of life for a large patient group for whom effective interventions are largely lacking. The study has very low risk for the participants, with no invasive procedures or risks associated with the intervention. The potential benefit is considerably greater, with opportunities for improved health, prognosis, and quality of life for a large patient group for whom effective interventions are largely lacking.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Usual care | No Intervention | Participants randomized to the usual care arm will recieve standard clinical care as provided during routine hospital practice for inpatients with signs of harmful alcohol use. | |
| Elastography-based brief alcohol intervention | Active Comparator | Participants randomized to the elastography-based brief alcohol intervention groupe, will, in addition to usual care, recieve liver stifness measurements (LSM) and brief alcohol intervention. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Elastography-based brief alcohol intervention | Behavioral | Participants randomized to elastography-based BAI will receive elastography assessment during first hospitalization. Elastography is a widely validated ultrasound-based technique that measures liver stiffness as a surrogate marker of liver fibrosis. The BAI will be delivered according to the FRAMES model, a structured, evidence-based framework for brief motivational interventions targeting harmful alcohol use. The intervention is patient-centered, non-confrontational, and based on principles of motivational interviewing. Both the elastography and the BAI will last approximately 10-15 minutes and will be delivered by trained study personnel directly following elastography assessment. At 3 months, participants will receive BAI by telephone. Follow-up reinforcement of elastography-based BAI will subsequently be provided during scheduled visits at 6 and 12 months. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of all-cause emergency hospitalizations | What is the effect of elastography-based BAI on new all-cause emergency hospital admissions in hospitalized patients at risk of ALD receiving elastography-based BAI compared with usual care, regardless of adherence to study intervention and while at risk of an emergency hospitalization? The primary outcome will be measured as any emergency inpatient emergency admission within 24 months after randomization, as registred in The Norwegian Patient Registry (NPR). | 24 months after randomization. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in phosphatidylethanol (PEth) | What is the effect of elastography-based BAI on alcohol consumption as measured by PEth? This will be measured as change in PETh from baseline to 12 months. | Baseline, 6 and 12 months after randomization. |
| Reduction in phosphatidylethanol (PEth) |
| Measure | Description | Time Frame |
|---|---|---|
| Predictive value of the Enhanced Liver Fibrosis (ELF) score for liver-related events | Can baseline ELF score predict subsequent liver-related events? Liver related events is defined as variceal bleeding, ascites, overt hepatic encephalopathy, severe alcoholic hepatitis, heptaocellular carcinoma, liver transplantation and liver-related death, as registred in The Norwegian Patient Registry (NPR) and Norwegian cause of death registry (CDR). |
Inclusion Criteria:
Exclusion Criteria:
Decompensated liver disease that impedes intervention delivery, defined as one or more of the following:
Acute hepatitis of any aetiology, defined as ALT or AST >5 x upper limit of normal (ULN)
Unable to participate for any reason in the opinion of the investigator
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Håvard Midgard, Professor | Contact | +47 908 30 071 | havardmi@gmail.com | |
| Caroline Rootwelt | Contact | +47 928 37 796 | carroo@ous-hf.no |
| Name | Affiliation | Role |
|---|---|---|
| Mette Vesterhus | Haraldsplass Deaconess Hospital, Bergen, Norway | Principal Investigator |
| Håvard Midgard | Oslo University Hospital, Oslo, Norway | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Haraldsplass Deaconess Hospital | Bergen | Norway |
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| ID | Term |
|---|---|
| D008108 | Liver Diseases, Alcoholic |
| D000437 | Alcoholism |
| D008103 | Liver Cirrhosis |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D020751 | Alcohol-Induced Disorders |
| D019973 | Alcohol-Related Disorders |
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| ID | Term |
|---|---|
| D000431 | Ethanol |
| D008722 | Methods |
| ID | Term |
|---|---|
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D008919 | Investigative Techniques |
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The study statistician will, to the best ability, perform the analysis as if the study was blinded.
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|
What is the effect of elastography-based BAI on alcohol consumption as measured by PEth? This will be measured as whether or not PEth at 12 months is <0.30 μmol/L. |
| Baseline and 12 months after randomization. |
| Change in The Alcohol Use Disorders Identification Test (AUDIT) score | What is the effect of elastography-based BAI on alcohol-related symptoms and risk as measured by AUDIT score? This outcome will be defined as the change in AUDIT score (range 0-40) from baseline to 12 months. | Baseline, 6 and 12 months after randomization. |
| Reduction in The Alcohol Use Disorders Identification Test (AUDIT) score | What is the effect of elastography-based BAI on alcohol-related symptoms and risk? This outcome will be defined as whether or not AUDIT score at 12 months is <8 points. | Baseline and 12 months after randomization. |
| Change in weekly alcohol units | What is the effect of elastography-based BAI on weekly alcohol consumption? This will be assessed as change in weekly alcohol intake (units per week) over the past month from baseline to 12 months, measured using the Timeline Follow-Back questionnaire (TLFB-28). | Baseline, 6 and 12 months after randomization. |
| Change in proportion of drinking days | What is the effect of elastography-based BAI on the proportion of drinking days? The outcome will be defined as the change in the proportion of drinking days from baseline to 12 months, measured using the Timeline Follow-Back questionnaire (TLFB-28). | Baseline, 6 and 12 months after randomization. |
| Change in proportion of heavy drinking days | What is the effect of elastography-based BAI on change in proportion of heavy drinking days (≥5 units per day for men and ≥4 units per day for women) from baseline to 12 months? This will be measured using the Timeline Follow-Back questionnaire (TLFB-28). | Baseline, 6 and 12 months after randomization. |
| Achieving stringent alcohol reduction | What is the effect of elastography-based BAI on achieving stringent alcohol reduction? This will be measured as whether or not AUDIT score is <8 points at 12 months AND at least 2-point AUDIT reduction at 12 months AND any reduction in PEth from baseline to 12 months. | Baseline, 6 and 12 months after randomization. |
| Change in health-related quality of life EuroQol 5-Dimension 5-Level (EQ-5D-5L) | What is the effect of elastography-based BAI on health-related quality of life? The outcome will be defined as the change in EQ-5D-5L index score (range 0-1) from baseline to 12 months. | Baseline, 6 and 12 months after randomization. |
| Improvement in health-related quality of life measured by EuroQol 5-Dimension 5-Level (EQ-5D-5L) | What is the effect of elastography-based BAI on health-related quality of life? This will be assessed as whether or not EQ-5D-5L index score has increased by ≥0.05 from baseline to 12 months. | Baseline, 6 and 12 months after randomization |
| Change in health-related quality of life measured in Euro-Qol Visual Analogue Scale (EQ-VAS) | What is the effect of elastography-based BAI on health-related quality of life? This will be assessed as change in EQ-VAS (0-100) from baseline to 12 months. | Baseline, 6 and 12 months after randomization |
| Change in anxiety and depression measured by EQ-5D-5L anxiety/depression dimension score | What is the effect of elastography-based BAI on reducing anxiety and depression? This will be measured as change in EQ-5D-5L anxiety/depression dimension score from baseline to 12 months. | Baseline, 6 and 12 months after randomization. |
| Reduction in anxiety and depression measured by EQ-5D-5L anxiety/depression dimension score | What is the effect of elastography-based BAI on reducing anxiety and depression? This will be measured as whether or not EQ-5D-5L anxiety/depression score is reduced by ≥1 level from baseline to 12 months. | Baseline, 6 and 12 months after randomization. |
| Improving cost-effectiveness | What is the effect of elastography-based BAI on improving cost-effectiveness? The outcome will be incremental cost-effectiveness ratios (ICERs), estimated using quality-adjusted life years (QALYs) as the measure of health effects from EQ-5D-5L utility scores, and total health care costs derived from health care utilization derived from the Norwegian Patient Registry (number of hospitalizations, bed days, outpatients visit, procedures). | 24 months after randomization. |
| Reduction in re-hospitalizations | What is the effect of elastography-based BAI on reducing re-hospitalizations? The outcome will be measured as whether or not a participant is rehospitalized for any reason at least once within 24 months after randomization. | 24 months after randomization. |
| Reduction in liver-related hospitalizations | What is the effect of elastography-based BAI in reducing liver-related hospitalizations? Three estimands are defined for this endpoint:
The endpoints will be measured as number of liver-related hospitalizations, as registred in The Norwegian Patient Registry (NPR). | 24, 60 and 120 months after randomization. |
| Reduction in alcohol-related hospitalizations | What is the effect of elastography-based BAI in reducing alcohol-related hospitalizations? Three estimands are defined for this endpoint:
The endpoints will be measured as number of alcohol-related hospitalizations, as registred in The Norwegian Patient Registry (NPR). | 24, 60 and 120 months after randomization. |
| Reduction in liver-related mortality | What is the effect of elastography-based BAI in reducing liver-related mortality? Three estimands are defined for this endpoint:
The endpoints will be measured as number of liver-related deaths as registred in The Norwegian Patient Registry (NPR) and Norwegian cause of death registry (CDR). | 24, 60 and 12 months after randomization. |
| Reduction in all-cause mortality | What is the effect of elastography-based BAI in reducing all-cause mortality? Three estimands are defined for this endpoint:
The endpoints will be measured as number of all-cause deaths as registred in The Norwegian Patient Registry (NPR) and Norwegian cause of death registry (CDR). | 24, 60 and 120 months after randomization. |
| Reduction in liver related events | What is the effect of elastography-based BAI on reducing number of liver-related events? Three estimands are defined for this endpoint:
The endpoints will be measured as number of liver related events defined as variceal bleeding, ascites, overt hepatic encephalopathy, severe alcoholic hepatitis, heptaocellular carcinoma, liver transplantation and liver-related death, as registered from inpatient admissions or outpatient consultations in NPR, the Nordic Liver Transplant Registry and the Norwegian Cancer Registry. | 24, 60 and 120 months after randomization. |
| Time to first liver-related event | What is the effect of elastography-based BAI on time to first liver-related event? The endpoint will be measured as time to first liver related event, defined as variceal bleeding, ascites, overt hepatic encephalopathy, severe alcoholic hepatitis, heptaocellular carcinoma, liver transplantation and liver-related death, as registered from inpatient admissions or outpatient consultations in NPR, the Nordic Liver Transplant Registry and the Norwegian Cancer Registry. | 24, 60 and 120 months after randomization. |
| 24, 60 and 120 months after randomization. |
| Predictive value of baseline level of heat shock protein 47 and subsequent liver-related events | Can baseline levels of heat shock protein 47 predict subsequent liver-related events? Liver related events is defined as variceal bleeding, ascites, overt hepatic encephalopathy, severe alcoholic hepatitis, heptaocellular carcinoma, liver transplantation and liver-related death. | 24, 60 and 120 months after randomization. |
| Relative change in Enhanced Liver Fibrosis (ELF) score from baseline to 12 months | Is there a difference in the relative change in ELF score from baseline to 12 months between the intervention arms? | Baseline, 6 and 12 months after randomization. |
| Change in liver stiffness measured by transient elastography | Does liver stiffness measurements, measured by transient elastography, change in the intervention arm? | Baseline, 6 and 12 months after randomization. |
| Associations between self-rated effects of alcohol and concentration of magnesium, calcium and phosphate | Are there associations between self-reported effects of alcohol, as measured by the Self-Rating of the Effects of Alcohol (SRE) questionnaire, and concentrations of the biochemical markers magnesium, calcium, and phosphate? | Baseline, 6 and 12 months after randomization. |
| Associations between self-rated effects of alochol and liver- and alcohol-related events | Are there associations between self-rated effects of alcohol at baseline, 6, and 12 months, as measured by the Self-Rating of the Effects of Alcohol (SRE) questionnaire, and number of liver- and alcohol-related events within 24 months? | Baseline, 6, 12 and 24 months after randomization. |
| Prevalence of genetic polymorphisms linked to susceptibility and disease progression in alcohol-related liver disease | What is the prevalence of the following genetic polymorphisms?
| Baseline |
| Vestre Viken Bærum Hospital | Drammen | Norway |
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| Sykehuset Nord-Trøndelag Levanger | Levanger | Norway |
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| Sykehuset Innlandet Lillehammer | Lillehammer | Norway |
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| Akershus University Hospital | Lørenskog | Norway |
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| Diakonhjemmet Hospital | Oslo | Norway |
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| Lovisenberg Diaconal Hospital | Oslo | Norway |
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| Oslo University Hospital | Oslo | Norway |
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| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
| D005355 | Fibrosis |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |