Genetic Study of Peginterferon Treatment in Hepatitis B Patients: The GIANT-B Study

NCT01401400 | Completed

• 1 other identifier: HBV10-03
• Study Type: observational
• Target: 1,350
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Hepatitis B

Outcome Measures

Primary Outcomes (1)

• Response to (PEG)IFN in relation to single-nucleotide polymorphisms identified by a GWAS

  Response: HBeAg-positive patients: HBV DNA \<2000IU/ml and HBeAg seroconversion; 24 weeks off-treatment. HBeAg-negative patients: HBV DNA \<2000IU/ml

  24 weeks off-treatment

Secondary Outcomes (1)

• Response

  24 weeks off-treatment

Study Arms (1)

(Peg) interferon

Patients who are treated for at least 12 weeks with (peg-)interferon for chronic hepatitis B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Chronic hepatitis B patients treated with (peg-)interferon

You may qualify if:

• History of chronic hepatitis B, defined as the presence of positive hepatitis B surface antigen (HBsAg) for at least 6 months.
• History of treatment (per protocol or outside studies) with standard interferon (alfa-2a or alfa-2b), peginterferon alfa-2a or peginterferon alfa-2b for at least 12 weeks.
• A follow-up duration of at least 24 weeks after the last dose of (peg)interferon.
• Use of nucleos(t)ide analogues prior to or combined with (peg)interferon treatment is allowed.
• Available HBV DNA and HBeAg status at baseline, end of treatment and end of follow-up (24 weeks after end of treatment)
• Written informed consent obtained.

You may not qualify if:

• Co-infection with hepatitis C virus, delta virus or human immunodeficiency virus.
• Use of immunosuppressants, chemotherapy or systemic corticosteroids (prednisolone 30 mg daily or equivalent for more than 7 days) during (peg)interferon treatment or the 24-week pre- and post-treatment period.

Sponsors & Collaborators

• Foundation for Liver Research: lead

Study Sites (1)

Erasmus Medical Centre

Rotterdam, South Holland, 3015 GE, Netherlands

Location

Related Publications (1)

• Brouwer WP, Chan HLY, Lampertico P, Hou J, Tangkijvanich P, Reesink HW, Zhang W, Mangia A, Tanwandee T, Montalto G, Simon K, Ormeci N, Chen L, Tabak F, Gunsar F, Flisiak R, Ferenci P, Akdogan M, Akyuz F, Hirankarn N, Jansen L, Wong VW, Soffredini R, Liang X, Chen S, Groothuismink ZMA, Santoro R, Jaroszewicz J, Ozaras R, Kozbial K, Brahmania M, Xie Q, Chotiyaputta W, Xun Q, Pazgan-Simon M, Oztas E, Verhey E, Montanari NR, Sun J, Hansen BE, Boonstra A, Janssen HLA; GIANT-B Global Consortium. Genome-wide Association Study Identifies Genetic Variants Associated With Early and Sustained Response to (Pegylated) Interferon in Chronic Hepatitis B Patients: The GIANT-B Study. Clin Infect Dis. 2019 Nov 13;69(11):1969-1979. doi: 10.1093/cid/ciz084.

  PMID: 30715261 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

whole blood samples from which DNA can be isolated

MeSH Terms

Conditions

Hepatitis B, Chronic

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Harry LA Janssen, MD PhD

  Foundation of Liver research (SLO), Rotterdam AND UHN liver clininc, Toronto Western & General Hospital

  PRINCIPAL INVESTIGATOR

• Pietro Lampertico, MD PhD

  IRCCS Ca' Granda, Ospedale Maggiore Policlinico, University of Milan

  STUDY CHAIR

• Henry Chan, MD

  The Chinese University of Hong Kong, Department of Medicine and Therapeutics

  STUDY CHAIR

• Jin-Lin Hou, MD PhD

  Nanfang Hospital, Southern Medical University, Hepatology Unit and Dept of Infectious Diseases

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2011
• First Posted: July 25, 2011
• Study Start: May 1, 2010
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: August 14, 2015

Record last verified: 2015-08

Locations

NL (1)