Non-alcoholic Fatty Liver Disease (NAFLD) in HIV: The Role of Nutritional Interventions

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of a one-year nutritional intervention with either betaine or vitamin E supplementation, or a weight reducing diet and exercise program on liver steatosis and steatohepatitis.

Official Title
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Non-alcoholic Fatty Liver Disease (NAFLD) in HIV: The Role of Nutritional Interventions

Conditions
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HIV Infections, Fatty Liver

Intervention / Treatment
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* Drug: antioxidant vitamin E
* Behavioral: weight reduction and exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Baseline liver biopsy with macrovesicular fatty degeneration with inflammation (lobular or portal), with or without Mallory bodies, hepatocyte damage, and/or fibrosis diagnostic of NAFLD Convincing evidence of negligible alcohol consumption (< 20 grams of ethanol per day) obtained from a detailed history, confirmed by at least one close relative If hyperlipidemia or diabetes, stable drug regimen required for the 6 months prior to and during the study Willingness to maintain stable weight and normal exercise program for the duration of the study, if randomized to vitamin E or betaine Exclusion Criteria: Liver disease of other etiology diagnosed as per routine medical investigation (e.g., chronic viral hepatitis, auto-immune chronic hepatitis, primary biliary cirrhosis or genetic liver disease such as Wilson's disease, hemochromatosis, alpha-1 antitrypsin deficiency, or biliary obstruction) Complications of liver disease such as recurrent variceal bleeding, resistant ascites, spontaneous portosystemic encephalopathy, or bacterial peritonitis Concurrent medical illness contra-indicating a liver biopsy, history of unexplained bleeding, hemophilia or abnormal coagulation results as per routine laboratory work-up or other reason judged by the hepatologist to contra-indicate a percutaneous liver biopsy Medications known to precipitate steatohepatitis (corticosteroids, high dose estrogens, methotrexate, amiodarone, calcium channel blockers, spironolactone, sulfasalazine, naproxen, oxacillin or ampinovire) in the 6 months prior to entry Antioxidant vitamin supplementation, ursodeoxycholic acid, or any other experimental drug 6 months prior to study entry Pregnant or lactating

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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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin E<br>alpha-tocoperol, capsules, 2 per day | Drug: antioxidant vitamin E<br>* Vitamin E 800IU per day for 12 months<br>Behavioral: weight reduction and exercise<br>* Patients will be asked to consume a self-selected, low fat, low-calorie diet of approximately 1200 kcal/d, which is consistent with American Heart Association guidelines for healthy weight reduction. Subjects will be provided with a videotape involving a structured 20 min aerobic exercise to be performed 3x/week.<br>* Other names: a high drop-out rate was observed in the weigh-loss arm;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in grading of inflammation assessed by liver biopsy from month 0 to month 12 of the study |  | month 0 and month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver histology for steatosis and fibrosis staging |  | month 0 and month 12 | 
| Liver immuno-histochemistry for adducts of MDA: a product of LP |  | month 0 and month 12 | 
| Alpha-smooth muscle actin (alpha-SMA): a marker of hepatic stellate cell activation |  | month 0 and month 12 | 
| Transforming growth factor (TGF-beta): a pro-fibrogenic cytokine involved in fibrogenesis |  | month 0 and month 12 | 
| Liver lipid peroxides and TNP-alpha | For oxidative stress and inflammation in the liver | month 0, month 6 and month 12 | 
| Liver steatosis and volume will be assessed by ultrasound |  | month 0 and month 12 | 
| Liver enzymes and IR (HOMA and QUICKY) will also be measured |  | month 0, month 6 and month 12 | 
| Lipid peroxides, TNF-alpha, vitamin E and C in plasma | Parameters for oxidative stress and antioxidant capacity | month 0, month 6 and month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, non-alcoholic fatty liver disease