Oral Vitamin D Treatment for the Prevention of Hepatocellular Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to determine whether vitamin D is effective in the prevention of hepatocellular carcinoma in those patients with chronic hepatitis B.

Detailed Description
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Potential participants will be identified from the follow-up cohort of chronic hepatitis B in the third Affiliated Hospital of Sun Yat-sen University (3rd SYSU). The hepatologists at the 3rd SYSU's Infectious Disease Institute will ask each potential participant if she/he is interested in participating. If the patient expresses an interest in the study, one of the researchers will meet with the patient when he/she is at the 3rd SYSU for a regular appointment and will describe the study to the potential participant. If a patient continues to be interested in participating, she/he will be given a copy of the review board approved consent document to read. The consent document will be used as a guide for explaining the study in detail to the patient. The participant allocated to the experimental group will be contacted by one of the investigators on the research team and instructed to begin taking 2 tablets per day (800 IU total) of vitamin D3 besides their regular anti-virus treatment. Those patients allocated in the control group will be informed that they are not to take any vitamin D3 and they will be followed as controls for this study. The researcher will investigate general treatment benefits and the potential to reduce the development of Hepatocellular carcinoma (HCC), also known as liver cancer. Improvement of treatment benefits will be determined by interviews with patients, the level of HBsAg and HBeAg, the development of liver fibrosis and evidence of HCC on routine imaging.

Official Title
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Study of Oral Vitamin D Treatment for the Prevention of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B

Conditions
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Hepatitis B, Carcinoma, Hepatocellular

Intervention / Treatment
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* Drug: Vitamin D3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All subjects between the ages of 18 and 70 with chronic hepatitis B and under the oral anti-virus treatment followed at the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, will be offered entry into this study. The diagnosis of chronic Hepatitis B will be based on that they had been positive for hepatitis B surface antigen (HBsAg) for at least six months, and were positive for HBeAg or negative for HBeAg with detectable HBV DNA at screening. No evidence of HCC on entry imaging study. 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%). Not currently participating in another intervention study. Not pregnant or lactating, and willing to use effective contraception during study period. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. Ability to provide written informed consent according to national/local regulations. Exclusion Criteria: evidence of hepatocellular carcinoma within 6 months after enrollment, a serum alanine aminotransferase level more than 10 times the upper limit of normal, an elevated serum creatinine level, any diagnosis of kidney stones, a diagnosis of hyperparathyroidism or other serious disturbance of calcium metabolism in the past 5 years, any evidence of autoimmune hepatitis, coinfection with hepatitis C or D virus or human immunodeficiency virus, other serious concurrent illness (e.g., alcoholism, uncontrolled diabetes, or cancer), treatment with immunomodulatory within the 6 months before screening, treatment with any investigational drug within the 30 days before the study began.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D<br>Drug: Vitamin D3 800 IU daily besides the anti-virus treatment with nucleos(t)ide medicine | Drug: Vitamin D3<br>* Participants with chronic hepatitis B will take 800 IU of vitamin D3 per day by mouth besides the anti-virus treatment with nucleos(t)ide medicine<br>|
| No Intervention: Control<br>chronic hepatitis B patients with long term anti-virus therapy | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum levels of 25-hydroxy vitamin D | Change in serum levels of 25-hydroxyvitamin D at 6 months and 12 months compared to baseline | at baseline, and at 6 and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum creatinine | Change in serum creatinine at 6 months and at 12 months compared to baseline | at baseline, and at 6 and 12 months | 
| Change in fibrosis score | Change in fibrosis score at 6 months and at 12 months compared to baseline. The investigators use Fibroscan to get the score of fibrosis. | at baseline, and at 6 and 12 months | 
| Number of participants on Vitamin D treatment with adverse events |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vitamin D treatment, chronic hepatitis B