The Danish Comorbidity in Liver Transplant Recipients Study

Study Overview
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Brief Summary
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Background: Liver transplantation is the only curative treatment for patients with end-stage liver disease. Short-term survival has improved due to improved surgical techniques and greater efficacy of immunosuppressive drugs. At present, the 10-year survival after liver transplantation is 60%, but long-term survival has not improved to the same extent the short-term survival. In addition to liver- and transplant-related causes, comorbidities such as cardiovascular, pulmonary, renal, and metabolic diseases have emerged as leading causes of morbidity and mortality in liver transplant recipients. The objective of this study is to assess the burden of comorbidities and identify both liver- and transplant-related risk factors as well as traditional risk factors that contribute to the pathogenesis of comorbidity in liver transplant recipients. Methods/design: The DACOLT study is an observational, longitudinal study. The investigators aim to include all adult liver transplant recipients in Denmark. Participants will be matched by sex and age to controls from the Copenhagen General Population Study (CGPS) and the Copenhagen City Heart Study (CCHS). Physical and biological measures including blood pressure, ancle-brachial index, spirometry, exhaled nitric oxide, electrocardiogram, transthoracic echocardiography, computed tomography (CT) angiography of the heart, unenhanced CT of chest and abdomen and blood samples will be collected using uniform protocols in participants in CGPS, CCHS and DACOLT. Blood samples will be collected and stored in a research biobank. Follow-up examinations at regular intervals up to 10 years of follow-up are planned. Discussion: There is no international consensus standard for optimal clinical care or monitoring of liver transplant recipients. The study will determine prevalence, incidence and risk factors for comorbidity in liver transplant recipients and may be used to provide evidence for guidelines on screening and long-term treatment and thereby contribute to improvement of the long-term survival.

Official Title
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The Danish Comorbidity in Liver Transplant Recipients Study (DACOLT) - a Non-interventional Prospective Observational Cohort Study

Conditions
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Liver Transplantation, Comorbidities and Coexisting Conditions

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Liver transplanted age between 16 and 100 years be able to understand the study information in either Danish or English and to be able to provide an informed consent Exclusion Criteria: none

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Liver transplant recipients<br>All liver transplant recipient in Denmark aged 18-100 years will be eligible for inclusion in the DACOLT study. Inclusion requires the individual to be able to understand the study information in either Danish or English and to be able to provide an informed consent. | |
| Control group 1_CGPS<br>The Copenhagen General Population Study (CGPS) is an ongoing observational population study with more than 110.000 participants from the greater Copenhagen area. All residents in the greater Copenhagen area > 40 years and 25% of 20-40 years old are invited to participate in the study and in follow-up examinations every decade. A random sample of 10.000 participants aged ≥ 40 years had a contrast enhanced CT of the chest including CT angiography of the heart performed. Of these, 6500 had a contrast enhanced CT of the abdomen. | |
| Control group 1_CCHS<br>The Copenhagen City Heart Study (CCHS) includes a random population sample included from the greater Copenhagen area. Health surveys have been repeated 5 times between 1976 and 2015. Almost 4000 participants were randomly selected for echocardiography. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of coronary artery disease | Assessed by coronary CT angiography | Baseline cross-sectional data | 
| Change in Coronary artery disease | Assessed by coronary CT angiography | 10 years follow-up | 
| Cardiac function | Determined by transthoracic echocardiography | Baseline cross-sectional data | 
| Change in Cardiac function | Determined by transthoracic echocardiography | 10 years follow-up | 
| Cardiac structure | Determined by transthoracic echocardiography | Baseline cross-sectional data | 
| Change in cardiac structure | Determined by transthoracic echocardiography | 10 years follow-up | 
| Cardiac structure | Assessed by cardiac computed tomography (CT) | Baseline cross-sectional data | 
| Change in Cardiac structure | Assessed by cardiac computed tomography (CT) | 10 years follow-up | 
| Cardiac function | Assessed by cardiac computed tomography (CT) | Baseline cross-sectional data | 
| Change in Cardiac function | Assessed by cardiac computed tomography (CT) | 10 years follow-up | 
| Dynamic lung function indices assessed by spirometry | FVC and FEV1 assessed by spirometry | Baseline cross-sectional data | 
| Change in Dynamic lung function indices assessed by spirometry | FVC and FEV1 assessed by spirometry | 10 years follow-up | 
| Renal function | Estimated glomerular filtration rate | Baseline cross-sectional data | 
| Change in Renal function | Estimated glomerular filtration rate | 10 years follow-up | 
| Metabolic diseases | Prevalence of Diabetes | Baseline cross-sectional data | 
| Metabolic diseases | Change in Diabetes | 10 years follow-up | 
| Metabolic diseases | Prevalence of Dyslipidaemia | Baseline cross-sectional data | 
| Metabolic diseases | Change in Dyslipidaemia | 10 years follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of Depression | Major Depression Inventory (MDI): A depression questionnaire. The questionnaire consists of the ten symptoms contained in the World Health Organization WHO's depression demarcation. The patient's completed questionnaire is scored using a scoring key. When MDI is used as a rating scale in the same way as the Hamilton scales, then the sum of the ten questions indicates the degree of depression. The theoretical score range is from 0 (no depression) to 50 (maximum depression). Mild depression: MDI total score from 21 to 25 Moderate depression: MDI total score from 26 to 30 Severe depression: MDI total score of 31 or higher | Baseline cross sectional data | 
| Change in Depression | Major Depression Inventory (MDI): A depression questionnaire. The questionnaire consists of the ten symptoms contained in the World Health Organization WHO's depression demarcation. The patient's completed questionnaire is scored using a scoring key. When MDI is used as a rating scale in the same way as the Hamilton scales, then the sum of the ten questions indicates the degree of depression. The theoretical score range is from 0 (no depression) to 50 (maximum depression). Mild depression: MDI total score from 21 to 25 Moderate depression: MDI total score from 26 to 30 Severe depression: MDI total score of 31 or higher | 10 years follow-up | 
| Fracture risk | FRAX® score. The FRAX® tool has been developed to evaluate fracture risk of patients. It is based on individual patient models that integrate the risks associated with clinical risk factors. The FRAX® algorithms give the 10-year probability of fracture. The output is a 10-year probability of hip fracture and the 10-year probability of a major osteoporotic fracture (clinical spine, forearm, hip or shoulder fracture). | Baseline cross sectional data | 
| Change in Fracture risk | FRAX® score. The FRAX® tool has been developed to evaluate fracture risk of patients. It is based on individual patient models that integrate the risks associated with clinical risk factors. The FRAX® algorithms give the 10-year probability of fracture. The output is a 10-year probability of hip fracture and the 10-year probability of a major osteoporotic fracture (clinical spine, forearm, hip or shoulder fracture). | 10 year follow-up | 
| Obstructive pulmonary disease | Nitric oxide in exhaled breath | Baseline cross sectional data | 
| Obstructive pulmonary disease | Change in Nitric oxide in exhaled breath | 10 year follow-up | 
| Prevalence of Peripheral artery disease | Ankle-brachial-index (ABI) is measured using a Doppler meter by determining the systolic pressure in the arm and ankle. | Baseline cross sectional data | 
| Change in Peripheral artery disease | Ankle-brachial-index (ABI) is measured using a Doppler meter by determining the systolic pressure in the arm and ankle. | 10 years follow-up |