lowering viral load with nucleos(t)ide analogues prior to peginterferon treatment to ncrease sustained response in chb

Conditions: Chronic Hepatitis B

Summary: treatment with a nucleoside analogue and subsequent viral decline has shown to partially restore immune hyporesponsiveness in chronic hepatitis b patients. recent pilot studies investigating whether the effect of lowering viral load with nucleoside analogue therapy prior to the initiation of peginterferon results in higher sustained off-treatment responses showed contradictory findings. the aim of this study is to investigate sustained off-treatment response to peginterferon alfa-2b in chronic hbeag-positive hepatitis b patients who are pretreated with nucleos(t)ide analogues, thereby lowering viral load


Eligibility criteria:
inclusion criteria: * chronic hepatitis b (hbsag positive \> 6 months) * hbeag positive, anti-hbe negative within 4 weeks prior to initiation of peginterferon alfa-2b * hbv dna \< 2000 iu/ml within one month prior to initiation of peginterferon alfa-2b after a minimum of 12 months treatment with either entecavir (one of all 3 brands) or tenofovir * alt \< 5x uln * compensated liver disease * age ≥ 18 years and ≤ 70 years * written informed consent exclusion criteria: * treatment with any investigational drug within 30 days of entry to this protocol * treatment with telbivudine * severe hepatitis activity as documented by alt \> 5 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 \< 1,500/mm3) or thrombocytopenia (platelets \< 90,000/mm3) * co-infection with hepatitis c 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 peginterferon 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

Keywords: hepatitis b sustained response peginterferon nucleos(t)ide analogues