Vitamin E for NASH Treatment in HIV Infected Individuals

The investigators will conduct a proof-of-concept clinical trial to evaluate the efficacy of
vitamin E for treatment of non-alcoholic steatohepatitis (NASH) in persons living with HIV.
Hypothesis: Vitamin E will improve radiographically measured hepatic fat content and
circulating markers of liver inflammation and injury in persons living with HIV who have
NASH.

A. Perform a pilot randomized placebo controlled trial of vitamin E 800 IU/daily for 6 months
in 56 persons living with HIV with biopsy-proven NASH B. Measure change in liver fat content
by magnetic resonance proton-density fat fraction (Primary outcome) C. Determine the impact
of vitamin E treatment on noninvasive markers of hepatic and systemic inflammation, hepatic
fibrosis, and systemic oxidative stress (Secondary outcomes) D. Define baseline hepatic gene
expression signatures predictive of response to therapy.

Upon completion, the proposed clinical trial may establish vitamin E as an excellent and
inexpensive candidate for further development as a treatment for NASH in persons living with
HIV.

Inclusion Criteria:

1. males and females ≥18 years with biopsy-proven NASH within 6 months prior to
enrollment

2. histological diagnosis of NASH will be confirmed by an experienced liver pathologist
before study entry

3. HIV infection

4. stable dose of anti-diabetic agents and ART in the 3 months preceding enrollment and
expected by the physician treating diabetes and HIV to remain on stable medications
during the study

5. willingness to participate in the study

6. ability to understand and give informed consent for participation

Exclusion Criteria:

1. Presence of other chronic liver diseases (hepatitis B or C, autoimmune hepatitis,
cholestatic liver disease, Wilson disease, hemochromatosis, etc.)

2. average alcohol consumption >3 drinks/day for men or >2 drinks/day for women in the 6
months prior to enrollment.

3. Alcohol Use Disorder Identification Test (AUDIT) score of ≥8

4. evidence of cirrhosis on histology or imaging

5. ongoing use of medications known to cause hepatic steatosis (e.g., corticosteroids,
amiodarone, methotrexate, tetracycline, tamoxifen, estrogens at doses greater than
those used for birth control, anabolic steroids, or valproic acid)

6. prior bariatric surgery

7. severe co-morbidities (e.g., advanced cardiac, renal, pulmonary, or psychiatric
illness)

8. allergy to vitamin E

9. use of vitamin E or multivitamins containing vitamin E in the three months preceding
enrollment

10. use of drugs with potential effect on NASH such as ursodeoxycholic acid,
S-adenosylmethionine (SAM-e), betaine, pentoxifylline, or milk thistle in the three
months prior to enrollment.

11. changing doses of statins (simvastatin, pravastatin, atorvastatin, fluvastatin,
lovastatin, rosuvastatin) or fibrates (clofibrate, fenofibrate) in the three months
prior enrollment.

12. illicit substance abuse within the past twelve months

13. breast feeding, pregnancy, inability or unwillingness to practice contraception for
the duration of the study

14. contraindications for the MRI procedure (e.g., prostheses, severe claustrophobia)

15. poorly controlled diabetes with A1C >8.5 within in the last six months

16. use of total parenteral nutrition in the 6 months preceding liver biopsy or enrollment