Hepatitis B Surface Antigen(HBsAg) Loss in Chronic Hepatitis B Patients With Low Viral Load
Condition: Chronic Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic
Study type: Interventional

Summary: 
      Rationale:

      Worldwide, approximately 400 million people are chronically infected with hepatitis B virus
      (HBV). Chronic HBV infection increases the risk of developing cirrhosis, hepatic
      decompensation and hepatocellular carcinoma (HCC). The risk of developing hepatocellular
      carcinoma is highest in HBeAg positive patients with high HBV DNA levels, but still the
      relative risk remains 10 for HBeAg negative patients. Furthermore it has been shown that when
      HBsAg is cleared before cirrhosis has developed, the prognosis is excellent. Recently the
      investigators have shown that HBeAg negative patients with high HBV-DNA load and low baseline
      HBsAg levels had a significantly higher HBsAg clearance (positive predictive value of 85%)
      after combination therapy with peginterferon alfa2a (Peg-IFN) and adefovir.

      Based on these results, a trial was designed to investigate whether combination of a
      nucleos(t)ide analogue combined with PegIFN, could also provoke a high rate of HBsAg
      clearance in chronic hepatitis B patients with low (HBV DNA <20,000 IU/mL) viral load.

      Study design:

      This is a three arm open-label prospective randomized controlled trial. 150 patients will be
      enrolled into the study after assessment of eligibility. All patients must have documented
      HBsAg positivity for longer than 6 months, HBeAg negativity, anti-HBe positivity, HBV DNA <
      20,000 IU/mL and ALT < 5 * upper limit of normal. Patients with a Child Pugh class B or C
      will be excluded. Group 1 will consist of patients treated with Peg-IFN and adefovir, group 2
      will consist of patients treated with Peg-IFN and tenofovir and group 3 will consist of
      untreated controls. Patients in group 1 and 2 will receive medication for the period of one
      year. For enrolment into the study a liverbiopsy at time of enrolment is compulsory and is
      advisable at end of treatment (week 48).

      Study population: The study population will consist of 150 patients chronically infected with
      hepatitis B virus with low viral load and HBeAg negativity.

      Main study parameters/endpoints:

      The aim of this study is to investigate what proportion of HBeAg negative, inactive carriers
      of the hepatitis B virus with low (< 20,000 IU/mL) load will lose HBsAg when treated with
      nucleot(s)ide analogue/Peg-IFN combination therapy.

      In this study the investigators hypothesize that both treatment with peg-interferon and ADF
      or Peg-IFN and TDF in HBeAg negative chronic hepatitis B patients with low HBV DNA viral load
      will induce a high rate of HBsAg loss, comparable to that in patients with high viral load
      after treatment with ADF and Peg-IFN.
    


Intervention name(s): Peg-Interferon alfa 2a + Adefovir dipivoxil, Peg-Interferon alfa 2a + Tenofovir disoproxil fumarate
Intervention type(s): Drug
Intervention description(s): Peg-Interferon alfa 2a 180ug/week + Adefovir dipivoxil 10mg/day, Peg-Interferon alfa 2a 180ug/week + Tenofovir disoproxil fumarate 245mg/day
Other intervention name(s): Pegsys®; Hepsera®; Viread®
Intervention MeSH terms: Interferons; Tenofovir; Interferon-alpha; Interferon alpha-2; Adefovir; Adefovir dipivoxil; Peginterferon alfa-2a
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: HBsAg loss; HBsAg seroconversion; chronic hepatitis B; low viral load; inactive carrier hepatitis B