Variants in STAT4 Associated With Cure of Chronic HBV Infection in HBeAg-positive Patients Treated With Pegylated Interferon-alpha.

Abstract

BACKGROUND & AIMS:

Variants in STAT4 (rs7574865) have been associated with seroconversion to hepatitis B e antigen (HBeAg) and reduction in levels of hepatitis B virus (HBV) DNA in patients with chronic infection treated with interferon alpha (IFNA). We evaluated the associations among rs7574865, loss of HB surface antigen (HBsAg, a marker of functional cure of HBV infection), and response to treatment with pegylated IFNA (PegIFN) or nucleos(t)ide analogues (NUCs) in HBeAg-positive patients with chronic HBV infection.

METHODS:

We performed a retrospective analysis of 1823 HBeAg-positive patients with chronic HBV infection (954 patients treated with PegIFN and 869 patients treated with NUCs) included in 4 phase-4 multicenter randomized controlled trials. The Cochran-Armitage trend test was used to evaluate the association of rs7574865 genotype with combined response (CR, defined as HBeAg seroconversion and HBV DNA level <2000 IU/mL) and loss of HBsAg at week 72, for patients given PegIFN, or week 104, for patients given NUCs.

RESULTS:

We found a significant association between rs7574865 genotype and CR (P = .004) and loss of HBsAg (P = .037) in patients treated with PegIFN. In patients with HBV genotype B infection, 43.6% of those with rs7574865 TT achieved a CR, compared to patients with rs7574865 GG (20.5%), and 7.7% had loss of HBsAg, compared to 1.9% of patients with rs7574865 GG. However, in patients treated with NUCs, we found no association of rs7574865 genotype with CR (P = .811) or loss of HBsAg (P=.439).

CONCLUSIONS:

In a retrospective analysis of data from 4 clinical trials, we found rs7574865 in STAT4 to be associated with functional cure of chronic HBV infection by PegIFN treatment, but not NUCs treatment, in HBeAg-positive patients with HBV genotype B infection.

• Authors: Haitao Chen, Jian Sun, Bin Zhou, Qing Xie, Xier Liang, Rong Fan, Carly Conran, Jianfeng Xu, Yuan Ji, Xinxin Zhang, Li Sun, Jidong Jia, Guiqiang Wang, Jinlin Hou, De-Ke Jiang
• Journal: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (Clin Gastroenterol Hepatol) Vol. 18 Issue 1 Pg. 196-204.e8 (01 2020) ISSN: 1542-7714 [Electronic] United States
• PMID: 31042581 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antiviral Agents
• DNA, Viral
• Hepatitis B e Antigens
• Interferon-alpha
• Nucleosides
• Nucleotides
• Recombinant Proteins
• STAT4 Transcription Factor
• STAT4 protein, human
• Polyethylene Glycols

Topics

• Adult
• Antiviral Agents (therapeutic use)
• DNA, Viral (analysis)
• Female
• Genotype
• Hepatitis B e Antigens (immunology)
• Hepatitis B, Chronic (drug therapy, genetics, immunology)
• Humans
• Interferon-alpha (therapeutic use)
• Male
• Nucleosides (therapeutic use)
• Nucleotides (therapeutic use)
• Polyethylene Glycols (therapeutic use)
• Randomized Controlled Trials as Topic
• Recombinant Proteins (therapeutic use)
• Retrospective Studies
• STAT4 Transcription Factor (genetics)
• Seroconversion
• Young Adult