Study of High-Dose Oral Vitamin D for the Prevention of Liver Cancer

This study will be done in two phases. The first phase is being done to find the highest dose
of VD that can be tolerated, in other words taken without causing severe side effects. The
second phase is a 6 month treatment with the dose determined to be safe in the first phase,
to investigate general health benefits and the potential to reduce the development of
Hepatocellular carcinoma (HCC), also known as liver cancer. Improvement of general health
will be determined by interviews with patients, markers in the blood for response to VD, bone
remodeling, inflammation, and evidence of HCC on routine imaging.

Inclusion Criteria:

1. All subjects between the ages of 18 and 75 with cirrhosis of any etiology followed at
the Georgetown Transplant Institute, Washington, DC, will be offered entry into this
study. The diagnosis of cirrhosis will be based on clinical, imaging or histological
studies.

2. No evidence of HCC on entry imaging study ( if liver nodules are present, these should
be classified as LIRADS 1-3 only).

3. Model for End Stage Liver Disease (MELD) score under 22 (a MELD score over 22 would
predict a 3 month mortality rate of approximately 20%).

4. Not currently participating in another intervention study.

5. Not pregnant or lactating, and willing to use effective contraception during study
period.

6. Absence of any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up schedule.

7. Ability to provide written informed consent according to national/local regulations

Exclusion Criteria:

1. Any diagnosis of kidney stones

2. A diagnosis of granulomatous diseases (e.g., sarcoidosis), active chronic fungal or
mycobacterial infections (e.g., tuberculosis, histoplasmosis, coccidioidomycosis,
blastomycosis, berylliosis, or Wegener's granulomatosis) in the past 6 months

3. A diagnosis of hyperparathyroidism or other serious disturbance of calcium metabolism
in the past 5 years

4. A diagnosis of severe kidney disease, e.g., chronic renal failure, in the past 6
months

5. A diagnosis of unexplained hypercalcemia in the past 6 months

6. Any diagnosis of osteoporosis with physician recommendation for treatment of low bone
mass

7. A diagnosis of two or more low trauma fractures in the past 6 months

8. A diagnosis of a medical condition requiring treatment with VD (e.g., osteomalacia) in
the past 6 months