The current Genome Wide Association Study (GWAS) identified genetic variants that are associated with both short- and long-term responses to pegylated interferon (Peg IFN) in patients with chronic hepatitis B (CHB), according to study results published in Clinical Infectious Diseases.1

Peg IFN is used to reduce viral load and hepatic necroinflammation in patients with CHB infection, thus decreasing the risk for hepatocellular carcinoma and the complications of cirrhosis.2-4 However, in addition to considerable adverse effects, only 20% to 30% of treated patients have a sustained response to treatment.5-8 Therefore, researchers sought to determine host genetic determinants of response in order to reduce the costs and side effects of treatment by analyzing 1058 patients with CHB treated with Peg IFN for at least 12 weeks with or without nucleos (t)ide analogues from 21 centers in Europe, Asia, and North America.1

Response at 24 weeks after Peg IFN treatment was defined as combined HBeAg-loss with HBVDNA <2000 IU/mL, or an HBVDNA <2000 IU/mL in patients who are HBeAg-negative. They found that 282 (31%) patients achieved the response and 4% HBsAg-loss. Single-nucleotide polymorphisms PRELI domain containing 2 gene, PRELID2 and G3BP stress granule assembly factor 2 gene, G3BP2 were associated with both short- and long-term responses to Peg IFN in patients with CHB who were HBeAg-positive and HBeAg-negative, respectively.

This was the first and largest GWAS study about patients with CHB who were treated with PegIFN to date.1 The investigators concluded that, “Although no genome-wide significant hits were found, the current GWAS identified genetic variants associated with PegIFN response in CHB.” In addition, “The current findings could pave the way for gene polymorphism-guided clinical counselling, both in the setting of (Peg)IFN and the natural history, and possibly for new immune-modulating therapies.”

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References

  1. Brouwer WP, Chan HLY, Lampertico P, et al. Genome wide association study identifies genetic variants associated with early and sustained response to (Peg)Interferon in chronic hepatitis B patients: the GIANT-B study [published on February 2, 2019]. Clin Infect Dis. doi: 10.1093/cid/ciz084
  2. Wong VW, Wong GL, Chim AM, et al. Surrogate end points and long-term outcome in patients with chronic hepatitis B. Clin Gastroenterol Hepatol. 2009;7:1113-1120.
  3. Sung JJ, Tsoi KK, Wong VW, Li KC, Chan HL. Meta-analysis: treatment of hepatitis B infection reduces risk of hepatocellular carcinoma. Aliment Pharmacol Ther. 2008;28:1067-1077.
  4. Liaw YF, Sung JJ, Chow WC, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004;351:1521-1531.
  5. Janssen HL, van Zonneveld M, Senturk H, et al. Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial. Lancet. 2005;365:123-129.
  6. Marcellin P, Lau GK, Bonino F, et al. Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. N Engl J Med. 2004;351:1206-1217.
  7. Chan HL, Leung NW, Hui AY, et al. A randomized, controlled trial of combination therapy for chronic hepatitis B: comparing pegylated interferonalpha2b and lamivudine with lamivudine alone. Ann Intern Med. 2005;142:240-250.
  8. Lau GK, Piratvisuth T, Luo KX, et al. Peginterferon alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med. 2005;352:2682-2695.