ATHN 11: Liver Transplantation Outcomes Study

Study Overview
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Brief Summary
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This study is designed as a multi-center, observational cohort study of participants with hemophilia A and B who have and have not undergone liver transplantation. Participants will be asked to complete health related quality of life questionnaires and provide medical history.

Detailed Description
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At a time when gene therapy is becoming a reality for individuals with hemophilia A and B, little is known about long-term cures. Yet, there are few data to provide real life testing of the impact of long-term cures. Specifically, little is known about the relationship between factor level achieved with gene therapy and clinical outcomes or quality of life. The analogy to liver transplant is clear. There has been no systematic method to collect and analyze the long-term outcomes of liver transplantation in individuals with hemophilia. Previous efforts to access data through the United Network for Organ Sharing national database have been complicated by lack of identification of those with hemophilia. As most of the individuals with hemophilia who undergo liver transplantation receive care at a hemophilia treatment center (HTC), ATHN proposes to leverage its existing relationship with the HTCs to support HTC execution of this study. ATHN, in collaboration with US Hemophilia Treatment Centers (HTCs), can provide the infrastructure and organization to support a longitudinal cohort study of subjects with congenital hemophilia who have and have not undergone liver transplantation. This cohort study will compare quality of life outcomes between cases that have undergone liver transplantation and controls that have not undergone liver transplantation. The study will determine if factor levels attained post-transplantation correlate with or predict improvement in quality of life measures. The existence of ATHN and the ATHN System for clinical care and research provides an opportunity to observe a cohort of subjects after liver transplantation with facility. During the study period, it is predicted that sustained normalization in factor VIII or IX levels following liver transplantation improves clinical functioning and quality of life in adults with hemophilia A and B. All study related contact will be timed to coincide with routine, scheduled care whenever possible. The study schedule will include: Study enrollment - Study activities will begin after participant consent. Activities include the documentation of relevant medical history and the administration of quality of life (QoL) questionnaires. Participants will be asked to complete health related (QoL) questionnaires and provide medical history. These questionnaires include: Hemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL): A quality of life questionnaire designed to asses health-related quality of life in adult patients with hemophilia. Domains include physical health, feelings, view of self, sports and leisure, work and school, dealing with hemophilia, treatment, future, family planning, and partnership and sexuality. Patient Reported Outcomes Measurement Information System (PROMIS-29): A quality of life questionnaire designed to assess physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles and activities, pain interference, and pain intensity. Hemophilia Orthotopic Liver Transplantation QoL Questionnaire (HOT): A quality of life questionnaire, adapted from a cancer survivorship tool, designed to assess adults with hemophilia who have received a liver transplant. Domains include physical well-being, psychological well-being, stress, anxiety, fear, work, family, relationships, and spiritual well-being.

Official Title
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An Observational Cohort Study of Long-Term Outcomes of Orthotopic Liver Transplantation in People With Hemophilia

Conditions
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Hemophilia A and B, Liver Transplantation

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Participants who meet the following inclusion criteria are eligible for enrollment into the study: Congenital hemophilia A or B of any severity, who have and have not undergone a liver transplant; Age > 18; and Sex assigned at birth was male Exclusion Criteria Participants who fall into any of the following exclusion criteria at the time of screening are not eligible for enrollment into the study: 1. Age <18.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Hemophilia A and B Cases<br>No intervention. Only patients that have undergone a liver transplant per study eligibility are in this cohort. | |
| Hemophilia A and B Controls<br>No intervention. Comparable patients to those in Case cohort will be put in this cohort. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life (Haem-A-QoL) | Health related quality of life questionnaire Hemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL): Domains include physical health, feelings, view of self, sports and leisure, work and school, dealing with hemophilia, treatment, future, family planning, and partnership and sexuality. For comparing questionnaire scores between two cohorts, we could use a combined score of PROMIS-29, Haem-A-QoL, and HOT questionnaires rescaled in 0-100 or use each separate survey. | 1 year | 
| Quality of life (PROMIS-29) | Health related Quality of Life measured by the Patient Reported Outcome Measurement Information System (PROMIS-29) Profile measure physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles and activities, pain interference, and pain intensity. | 1 year | 
| Quality of Life (HOT) | Hemophilia Orthotopic Liver Transplantation QoL Questionnaire (HOT) Domains include physical well-being, psychological well-being, stress, anxiety, fear, work, family, relationships and spiritual well-being. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clotting factor protein | impact of sustained increase in clotting factor proteins (FVIII and FIX) levels after liver transplantation. The medical record will be accessed to record baseline hemophilia history including primary factor diagnosis and baseline factor level used to access disease severity, post-transplant factor levels and genotype. | 1year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemophilia A, Hemophilia B, Liver Transplantation, Quality of Life, Hemophilia Treatment Centers (HTCs)