The Curative Effect of Entecavir Combined Resveratrol on HBV patients-a Multi-center, Random, Open Clinical Trial
Condition: Hepatitis
MeSH terms: Hepatitis A; Hepatitis
Study type: Interventional

Summary: 
      The purpose of this study is to use entecavir combined with other drug such as resveratrol
      and thymosin to treat patients with hepatitis B, which may provide a novel therapy target
      hepatitis B.
    

Detailed description: 
      Hepatitis B virus (HBV) infections continue to be a major public health problem worldwide.
      More than 400 million people worldwide are currently infected with hepatitis B virus.
      Approximately 20% of HBV patients will develop chronic hepatitis, and are at significant risk
      of developing cirrhosis or liver hepatocarcinoma. HBV is the prototype of hepadnaviridae, a
      family of small enveloped hepatotropic DNA viruses that can infect the liver of human.

      In recent years, researches on antiviral treatment of chronic hepatitis B has made remarkable
      progress, interferon and nucleoside analogues which are the synthetic reverse transcriptase
      inhibitors can attenuate liver inflammation and fibrosis. However, HBsAg and HBeAg
      seroconversion ratio is merely 7% and 21%, respectively. To completely clear HBsAg is very
      difficult, the main reason is that HBV cccDNA (a covalently closed circular form of the viral
      genome through DNA repair of the relaxed circular replicative HBV DNA inside the nuclei of
      hepatocytes in the HBV life cycle), the template for viral and pregenomic messenger RNA
      cannot be eliminated, lead to the continuous replication of the virus. Apart from that, none
      of these therapies are completely safe and effective. Although direct antiviral therapy could
      efficiently control chronic active hepatitis B, drug resistance or renal toxicity could
      develop progressively several months after the initiation of therapy. It is thus still
      urgently required to identify effective anti-HBV agents.

      Pegylated IFN-α (pegIFN-α) is effective in achieving sustained virologic response, defined as
      HBeAg seroconversion and/or hepatitis B virus (HBV) DNA levels below 20,000 copies/mL at 6
      months after completion of the therapy, in only 30% of hepatitis e antigen (HBeAg)-positive
      and 40% of HBeAg-negative cases. However, the pegIFN-α therapy does promote HBsAg clearance
      or seroconversion in a small, but significant fraction of treated patients. Hence, we should
      develop feasible antiviral therapeutics target cccDNA in liver cells to cure chronic
      hepatitis B.

      Resveratrol, a grape polyphenol, is representative of a group of diet-derived putative cancer
      chemopreventive agents encompassing, among others, curcumin, tea polyphenols and apigenin,
      which have attracted a lot of interest in the cancer chemoprevention community. It has shown
      considerable promise as a therapeutic agent in the treatment of liver ailments. Recent study
      found that SITR1 activators can inhibit cccDNA, and resceratrol is a member of SIRT1
      activator family. Apart from that, several studies have highlighted the hepatoprotective
      properties of resveratrol. Resveratrol has been shown to prevent hepatic damage because of
      free radicals and inflammatory cytokines, induce antioxidant enzymes and elevate glutathione
      content. Resveratrol has also been shown to modulate varied signal transduction pathways
      implicated in liver diseases. For instance, resveratrol can inhibit Th17 proliferation and
      function, and many researches found that increasing Th17 in patients with hepatitis B.
      Importantly, in vitro, we found that resveratrol can significantly reduce both HBsAg and
      HBeAg in a dose-depend manner.

      Nowadays, increasing studies focus on natural materials in the application of the treatment,
      and there are many health care products used resveratrol as main ingredient. Report on trial
      of resveratrol in healthy volunteers after daily doses of up to 5g per day administered for
      29 days suggests that it is safe, as borne out by the lack of serious adverse reactions
      detected by clinical, biochemical or hematological analyses during the study and study
      follow-up. Besides, in our country, the traditional Chinese medicine also used giant knotweed
      (main ingredients is resveratrol) to treat viral hepatitis and autoimmune hepatitis.

      Therefore, We aim to use entecavir combined with other drug such as resveratrol and
      peg-interferon to treat patients with hepatitis B, which may provide a novel therapy target
      hepatitis B.
    

Intervention name(s): entecavir+resveratrol; Entecavir; entecavir+thymosin α1
Intervention type(s): Drug; Drug; Drug
Intervention description(s): entecavir+resveratrol; Entecavir; entecavir+thymosin α1
Intervention MeSH terms: Entecavir; Resveratrol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: entecavir; resveratrol; thymosin; hepatitis B