Sex-differences in the association of interleukin-10 and interleukin-12 variants with the progression of hepatitis B virus infection in Caucasians

Janett Fischer; Eleni Koukoulioti; Tobias Müller; Renate Heyne; Mohammed Eslam; Jacob George; Fabian Finkelmeier; Oliver Waidmann; Thomas Berg; Florian van Bömmel

doi:10.1111/hepr.13952

Sex-differences in the association of interleukin-10 and interleukin-12 variants with the progression of hepatitis B virus infection in Caucasians

Hepatol Res. 2023 Dec;53(12):1156-1168. doi: 10.1111/hepr.13952. Epub 2023 Aug 24.

Authors

Affiliations

¹ Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Laboratory for Clinical and Experimental Hepatology, Leipzig, Germany.
² Hepatogastroenterology Unit, Second Department of Internal Medicine - Propaedeutic, Research Institute and Diabetes Center, Medical School, National and Kapodistrian University of Athens, "Attikon" University General Hospital, Athens, Greece.
³ Department of Hepatology and Gastroenterology, University Hospital Charité, Berlin, Germany.
⁴ Liver and Study Center Checkpoint, Berlin, Germany.
⁵ Storr Liver Center, Westmead Hospital and Westmead Millennium Institute for Medical Research, University Sydney, Sydney, New South Wales, Australia.
⁶ Department of Gastroenterology, Hepatology and Endocrinology, University Hospital Frankfurt, Frankfurt, Germany.
⁷ Centrum for Hematology and Oncology Bethanien, Frankfurt, Germany.

PMID: 37565510
DOI: 10.1111/hepr.13952

Abstract

Aim: Interleukin (IL)-10 and IL-12 contribute to immune responses against hepatitis B virus (HBV) infection. Polymorphisms in the IL-10 and IL-12A genes might affect the clinical outcome of HBV infection. We evaluated the association of IL-10 rs1800896 and rs3024490, and IL-12A rs568408 and rs2243115 with the progression of HBV infection and development of severe liver disease stages in a white European population.

Method: A total of 636 white European patients with chronic HBV infection, 239 individuals with spontaneous HBV surface antigen seroclearance, and 254 healthy controls were enrolled. The chronic HBV infection group included patients with hepatitis B envelope antigen (HBeAg) negative chronic hepatitis B (n = 255), with HBeAg positive chronic hepatitis B (n = 99) and with HBeAg negative HBV infection (n = 228). A total of 104 chronically infected patients were diagnosed with liver cirrhosis. Serum levels of cytokines were measured in patients with HBV infection (n = 195) and in healthy controls (n = 160).

Results: In adjusted multivariate analysis, the IL-10 rs1800896 AG/GG genotypes were significantly associated with an increased probability of HBV surface antigen seroclearance (OR = 1.75, 95% CI 1.04-2.94, p = 0.034), with an increased likelihood of HBeAg negative chronic infection (OR = 1.93, 95% CI 1.05-3.54, p = 0.034) and with increased serum cytokines levels in female patients. In contrast, the IL-12A rs568408 AG/AA genotypes were independently associated with an increased risk to develop liver cirrhosis, with an OR of 1.90 (95% CI 1.07-3.39, p = 0.029) in male patients.

Conclusion: The current study shows a sex-related association of the IL-10 single-nucleotide polymorphism rs1800896 and IL-12A single-nucleotide polymorphism rs568408 with different stages of HBV infection and with HBV-related liver cirrhosis in white European patients.

Keywords: HBsAg seroclearance; cytokines; liver cirrhosis; sex disparity.

Grants and funding

Gilead Sciences