Genetic Study of Peginterferon Treatment in Hepatitis B Patients: The GIANT-B Study
- Conditions
- Chronic Hepatitis B
- Registration Number
- NCT01401400
- Lead Sponsor
- Foundation for Liver Research
- Brief Summary
Background and rationale Chronic hepatitis B is the most common cause of liver cirrhosis and hepatocellular carcinoma worldwide.(1) Antiviral therapy with oral nucleoside analogs and interferon can reduce viral load and hepatic necroinflammation, and may reduce the risk of hepatocellular carcinoma and cirrhotic complications. (2-4) Peginterferon has both direct antiviral and immunomodulatory effects. The advantages of this drug include a finite course of treatment and the lack of drug resistance. However, it requires subcutaneous injections and carries some side effects. Besides, only 30% to 40% of treated patients have sustained response to treatment.(5-8) To reduce the costs and side effects of treatment, it is important to predict if a patient will respond to peginterferon. Genetic host studies on peginterferon response will provide a lot of knowledge on the interaction between the host and the virus to induce immune control, also outside the setting of immune modifying therapy. Recently, genome wide association studies (GWAS) identified genetic polymorphisms of the IL28B gene that were shown to be associated with treatment response to interferon and ribavirin in patients with chronic hepatitis C.(9-12) The same polymorphisms are also associated with natural clearance of hepatitis C virus. Whether the same phenomenon applies to patients with chronic hepatitis B is unclear. Furthermore, response to conventional interferon has shown to decrease the risk of hepatocellular carcinoma and to prolong survival.(13) Virological and serological response to PEG-IFN is durable in a substantial proportion of patients through 3 years of follow-up (14), but whether treatment benefits are sustained after that period and amount to clinically meaningful results is unknown. To date, a GWAS to predict the response to peginterferon in chronic hepatitis B patients has not been performed. Polymorphisms in genes such as IL28B can be identified through a GWAS and can be used to assess the chance of response to treatment and select patients who have a high probability of response to peginterferon.
We aim to perform a GWAS in chronic hepatitis B patients previously treated with peginterferon to identify polymorphisms in genes that are associated with response to this treatment regimen.
- Detailed Description
For the GWAS stage of this study, a cohort study will be conducted comparing hepatitis B patients with a response (see definitions below) versus patients who did not achieve a response to (peg)interferon treatment. Replication of SNPs identified by the GWAS will be performed in an independent cohort of patients with similar characteristics, treated with (peg)interferon. A large independent cohort of peginterferon treated HBV patients has already been identified guaranteeing a replication cohort.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1350
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Response to (PEG)IFN in relation to single-nucleotide polymorphisms identified by a GWAS 24 weeks off-treatment Response:
HBeAg-positive patients: HBV DNA \<2000IU/ml and HBeAg seroconversion; 24 weeks off-treatment.
HBeAg-negative patients: HBV DNA \<2000IU/ml
- Secondary Outcome Measures
Name Time Method Response 24 weeks off-treatment HBV DNA \<20IU/ml for both HBeAg positives as negatives sustainability of HBeAg seroconversion or HBeAg loss(only HBeAg+ patients) HBsAg loss and seroconversion, ALT normalization, data on survival, incidence of cirrhosis, hepatocellular carcinoma and liver transplantation.
Trial Locations
- Locations (1)
Erasmus Medical Centre
🇳🇱Rotterdam, Zuid-Holland, Netherlands