The Effects of Vitamin D and Calcium Supplementation to Parathyroid Hormone in CHB Patients Treated With TDF
Condition: Parathyroid Hormone; Tenofovir Disoproxil Fumarate; Chronic Hepatitis B Virus; Vitamin D
MeSH terms: Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic
Study type: Interventional
Phase: Phase 4

Summary: 
      Nucleot(s)ide is an antiviral drug that can reduce the number of viruses, reduce the risk of
      HCC, regress hepatic fibrosis and reduce death from Hepatitis B viral infection. Tenofovir
      disoproxil fumarate (TDF) is one of nucleotide analogue that is recommended to treated
      patients with Hepatitis B viral infection. However, long-term TDF therapy may have side
      effects especially nephrotoxicity and bone toxicity.

      Previous studies in human immunodeficiency virus (HIV) infected patients who treated with TDF
      containing regimen antiretroviral therapy, in vitamin D supplement group had a statistic
      significance of low parathyroid hormone level and better in bone mineral density regardless
      of initial vitamin D level. Therefore, the main objective of this study is to evaluate the
      vitamin D and calcium supplement to patients with hepatitis B who have taken TDF, in
      parathyroid hormone level, bone mineral density, renal function and renal phosphate loss
      compared to patients who have no vitamin D and calcium supplement.
    

Detailed description: 
      Hepatitis B virus is a global public health problem. This infection leads to chronic
      hepatitis, cirrhosis and liver cancer. According to past statistics, infection with hepatitis
      B virus is a common cause of hepatocellular carcinoma about 60% in East-Asia and Africa and
      about 20% in Western countries. About 350-400 million people are infected worldwide.
      Infection with hepatitis B virus is also an important factor of death in 1million patients
      per year.

      Nucleot(s)ide is an antiviral drug that can reduce the number of viruses, reduce the risk of
      HCC, regress hepatic fibrosis and reduce death from Hepatitis B viral infection. Nowadays,
      the recommendation of nucleot(s)ide prefers Tenofovir disoproxil fumarate (TDF), Tenofovir
      Alafenamide (TAF) and Entecavir (ETV) than Lamivudine, Adefovir and Telbivudine due to high
      potency and low resistance rate Tenofovir disoproxil fumarate (TDF) is one of nucleotide
      analogue that inhibits reverse transcriptase in HBV replication process. However, long-term
      TDF therapy may have side effects especially nephrotoxicity. The proposed mechanisms of
      nephrotoxicity of TDF are cumulative of TDF at proximal tubule of kidney leads to
      mitochondrial toxicity, downregulation of sodium-phosphorus cotransporter, sodium/ hydrogen
      exchanger 3 and aquaporin 2, decreased endothelial nitric oxide-synthase (eNOS) and renal
      vasoconstriction results in tubulopathy in renal proximal tubule, increase of phosphate loss
      in urine and increase od serum creatinine.

      Moreover, TDF also affects to decrease bone mineral density (BMD) that related with renal
      phosphate loss, loss of osteoblast function, high parathyroid hormone level regardless of
      vitamin D level and high fibroblast growth factor 23 (FGF23) leads to worsen in bone
      mineralization Vitamin D has a protective effect and indicate for osteoporosis treatment. The
      chronic hepatitis B infected patients with vitamin D deficiency may have a poor prognosis in
      hepatic fibrosis and high HBV DNA level. Previous studies in human immunodeficiency virus
      (HIV) infected patients who treated with TDF containing regimen antiretroviral therapy, in
      vitamin D supplement group had a statistic significance of low parathyroid hormone level and
      better in bone mineral density regardless of initial vitamin D level. Therefore, the main
      objective of this study is to evaluate the vitamin D and calcium supplement to patients with
      hepatitis B who have taken TDF, in parathyroid hormone level, bone mineral density, renal
      function and renal phosphate loss compared to patients who have no vitamin D and calcium
      supplement.
    

Intervention name(s): Ergocalciferol Capsules; Calcium carbonate
Intervention type(s): Drug; Drug
Intervention description(s): Depend on initial 25(OH) vitamin D level If <10ng/mL, 60000U of Ergocalciferol capsules per week If 10-19.9ng/mL, 40000U of Ergocalciferol capsules per week If >20 ng/mL, 20000U of Ergocalciferol capsule per week; 1000mg of Calcium carbonate daily
Intervention MeSH terms: Ergocalciferols; Vitamin D; Calcium Carbonate; Calcium
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Tenofovir disoproxil fumarate; Tenofovir; Chronic hepatitis B; Parathyroid hormone; Bone mineral density; Renal phosphate loss; Vitamin D; Calcium; TDF; PTH; CHB; HBV