Hepatitis B Surface Antigen(HBsAg) Loss in Chronic Hepatitis B Patients With Low Viral Load
Status:
Completed
Trial end date:
2019-10-01
Target enrollment:
Participant gender:
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.
Phase:
N/A
Details
Lead Sponsor:
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)