Hepatic Lipid Metabolism-Alcohol Use Disorder

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

• 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.