Chronic Hepatitis B, HBeAg Negative
Conditions
Brief summary
All patients with chronic HBeAg negative hepatitis B treated with nucleos(t)ide analogues, who discontinue treatment based in the criteria outlined in the EASL hepatitis B guidelines shall be included in the present study. The aim is to evaluate the clinical outcome (virological relapse, HBsAg decline) and associated virological and immunological parameters.
Interventions
None listed
Sponsors
German Center for Infection Research
Hannover Medical School
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male and female patients with chronic hepatitis B virus infection documented by detectable HBsAg. 2. Age \> 18 years 3. Ongoing antiviral therapy with Entecavir or Tenofovir (TDF) 4. At least 3 years HBV-DNA \< 20 IU/ml (=100 copies/ml) 5. HBeAg negative 6. Willingness to give written informed consent and willingness to participate and to comply with the protocol.
Exclusion criteria
1. HIV infection, persistent HDV-infection, persistent HCV infection 2. History or other evidence of a medical condition associated with chronic liver disease other than HBV associated (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposures). 3. History or other evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease 4. Patients with advanced liver fibrosis and liver cirrhosis (fibroscan \>10.0 kPa) 5. Patients with hepatocellular carcinoma 6. History of major organ transplantation or other immunosuppressive conditions 7. History or other evidence of severe illness, malignancy or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study 8. History of any systemic anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) 12 months prior to cessation of antiviral therapy or the expectation that such treatment will be needed at any time during the study \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HBsAg | 48 weeks | HBsAg Change \> 1 log 48 weeks after stopping NA |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Biochemical relapse | at every visit up to 96 weeks | ALT \> 2 x upper limit of normal |
| Retreatment | at every visit up to 48 weeks | Retreatment until week 48 according to current EASL guidelines |
| Negativity for HBsAg | at every visit up to 96 weeks | HBsAg negative until week 96 of follow-up |
| timepoint of relapse | at every visit up to 96 weeks | timepoint of relapse |
| Virological relapse | at every visit up to 96 weeks | HBV DNA \> 2,000 IU/ml |
| Cytokine response | at every visit up to 96 weeks | \> 3x change of cytokines from baseline measured by ELISA and Multiplex assay |
| Chance in HBcrAg | at every visit up to 96 weeks | Chance in HBcrAg (U/mL) |
| Change in HBV RNA | at every visit up to 96 weeks | Chance in HBV RNA (U/mL) |
| T cell response | at every visit up to 96 weeks | \> 3x change of T cell responses from baseline after in vitro culture with HBV specific peptides |
Countries
Germany
Contacts
Primary ContactMarkus Cornberg, MD, Prof
Backup ContactChristoph Höner zu Siederdissen, MD
Outcome results
None listed