Alcohol Use Disorder
Conditions
Keywords
Alcohol, Liver, Biopsy
Brief summary
Patients with hepatic steatosis due to alcohol will be offered liver biopsies when they enter a detoxification program. The first biopsy will occur in the first week of admission and the second in the fourth week when the steatosis has resolved. The hepatic transcriptome will be compared,
Detailed description
Study Description: The liver is central to lipid metabolism, intimately involved with lipid uptake, lipoprotein synthesis and lipid synthesis. Alcohol has known effects on changing lipid composition including increases in HDL and decreases in LDL; nevertheless, the underlying mechanisms of this altered lipoprotein metabolism is not understood. Current spectroscopy data characterize the changes in lipoprotein profiles with alcohol cessation. We aim to study liver lipid metabolism by performing liver biopsies and transcriptome analysis in participants with alcohol use disorder. Objectives: Primary Objective: To understand the transcriptomics of hepatic lipid metabolism in alcohol use disorder Secondary Objective: To understand other transcriptome changes in alcohol use cessation. Tertiary Objective: To elucidate the genomics-transcriptomics-metabolomics pathway of hepatic lipid metabolism in alcohol use disorder. Endpoints: Primary Endpoints: -Transcriptome changes in lipid metabolism between week 1 and week 4. Secondary Endpoints: -Other transcriptome changes between week 1 and week 4. Tertiary Endpoints: * To make connections with existing genetics and metabolomics data with transcriptomics. * Stool microbiome studies
Interventions
DIAGNOSTIC_TESTLiver biopsy
Biopsy of the liver
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* INCLUSION CRITERIA: In order to be eligible to participate in this study, an individual must meet all of the following criteria: * Any individual \>=18 years of age who is enrolled in 14-AA-0181 and is seeking inpatient treatment. * Vibration Controlled Elastography parameters with initial CAP of \>295dB/m.
Exclusion criteria
An individual who meets any of the following criteria will be excluded from participation in this study: * Pregnancy * Existing diagnosis of hyperlipidemia or essential hypertension * Hemoglobin A1c \>= 6.5% * Waist to hip ratio: \>=0.90 in males, \>=0.85 in females * Existing use of cholesterol lowering medications including statins, fibrates, or other similar medications used for the purposes of treating hyperlipidemia. * Those with evidence of severe alcoholic hepatitis with a Maddrey s Discriminant Function \> 32 * Those with other chronic liver diseases including chronic hepatitis B (positive hepatitis B surface Ag on admission), hepatitis C (positive hepatitis C RNA), or autoimmune hepatitis (clinical diagnosis based on high titer of positive ANA and or anti smooth muscle Ab and a history of autoimmune disease) * HIV infection * Contraindication or inability to perform a liver biopsy. * Participants with coagulopathy (PT/PTT values that are prolonged (Bullet) 3 seconds from the upper limit of the normal, including treatment with oral and parenteral anticoagulants), thrombocytopenia (\< 70,000), abnormal bleeding time or platelet dysfunction. Antiplatelet agents taken for cardiovascular prevention will not exclude participants, unless they cannot be stopped safely for the performance of a liver biopsy. * Hemoglobin level \< 11 g/dL * Inability to provide informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Transcriptome changes in lipid metabolism between week 1 and week 4 of alcohol cessation. | November 2029 | Analysis of liver biopsies |
Secondary
| Measure | Time frame |
|---|---|
| Other transcriptome changes between week 1 and week 4 of alcohol cessation | November 2029 |
Countries
United States
Contacts
CONTACTSawsan Fathma, M.D.
CONTACTTheo Heller, M.D.
PRINCIPAL_INVESTIGATORTheo Heller, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Outcome results
None listed