owering viral load with nucleos(t)ide analogues prior to peg-interferon alfa-2b treatment to increase sustained response in HBeAg-positive chronic hepatitis B (PADD-study)

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 30

Inclusion Criteria

· Chronic hepatitis B (HBsAg positive > 6 months)
· HBeAg positive, anti-HBe negative within one month prior to initiation of peg-interferon alfa-2b
· HBV DNA < 2000 IU/ml during nucleos(t)ide analogue treatment within one month prior to initiation of peg-interferon alfa-2b
· Compensated liver disease
· Age > 18 years
· Written informed consent

Exclusion Criteria

· Treatment with any investigational drug within 30 days of entry to this protocol
· Severe hepatitis activity as documented by ALT>10 x ULN
· History of decompensated cirrhosis (defined as jaundice in the presence of cirrhosis, ascites, bleeding gastric or esophageal varices or encephalopathy)
· Pre-existent neutropenia (neutrophils <1,800/mm3) or thrombocytopenia (platelets <90,000/mm3)
· Co-infection with hepatitis C virus, hepatitis D virus or human immunodeficiency virus (HIV)
· Other acquired or inherited causes of liver disease: alcoholic liver disease, obesity induced liver disease, drug related liver disease, auto-immune hepatitis, hemochromatosis, Wilson*s disease or alpha-1 antitrypsin deficiency
· Alpha fetoprotein > 50 ng/ml
· Hyper- or hypothyroidism (subjects requiring medication to maintain TSH levels in the normal range are eligible if all other inclusion/exclusion criteria are met)
· Immune suppressive treatment within the previous 6 months
· Contra-indications for alfa-interferon therapy like suspected hypersensitivity to interferon or PEG-interferon or any known pre-existing medical condition that could interfere with the patient's participation in and completion of the study.
· Pregnancy, breast-feeding
· Other significant medical illness that might interfere with this study: significant pulmonary dysfunction in the previous 6 months, malignancy other than skin basocellular carcinoma in previous 5 years, immunodeficiency syndromes (e.g. HIV positivity, auto-immune diseases, organ transplants other than cornea and hair transplant)
· Any medical condition requiring, or likely to require chronic systemic administration of steroids, during the course of the study
· Substance abuse, such as alcohol (>80 g/day), I.V. drugs and inhaled drugs in the past 2 years.
· Any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in and completing the study

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Sustained response defined as HBV DNA level < 200 IU/ml and HBeAg loss at week<br /><br>72<br /><br>Frequency, phenotype and function of NK cells, Tregs and DCs.<br /><br>Determination of HBV-specific T cell response<br /><br>Determination of HBV and proteins in/on NK cells</p><br>

Secondary Outcome Measures