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Updated: Feb 25, 2026
A Mouse Model of Chronic Liver Fibrosis for the Study of Biliary Atresia
Published on: February 3, 2023
CXCL9-11 polymorphisms are associated with liver fibrosis in patients with chronic hepatitis C: a cross-sectional
María Ángeles Jiménez-Sousa1, Ana Zaida Gómez-Moreno2, Daniel Pineda-Tenor3
1Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera Majadahonda- Pozuelo, Km 2.2, 28220, Majadahonda, Madrid, Spain.
Insights
Certain genetic variations in CXCL9-11 chemokines are linked to liver fibrosis in patients with Hepatitis C virus (HCV) infection. These findings suggest polymorphisms may influence chronic hepatitis C progression and guide therapy choices.
Area of Science:
- Immunogenetics
- Hepatology
- Virology
Background:
- Chemokine (C-X-C motif) ligand (CXCL) 9-11 polymorphisms are associated with various infectious diseases.
- Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and fibrosis.
- The role of CXCL9-11 gene variations in the development and progression of liver fibrosis in HCV patients remains to be fully elucidated.
Purpose of the Study:
- To investigate the association between specific CXCL9, CXCL10, and CXCL11 gene polymorphisms and the presence and severity of liver fibrosis in patients with HCV infection.
- To determine if certain genotypes of CXCL9-11 are protective or risk factors for liver fibrosis progression in HCV patients.
Main Methods:
- A cross-sectional study was conducted involving 389 patients with HCV infection.
- Genotyping for CXCL9 (rs10336), CXCL10 (rs3921), and CXCL11 (rs4619915) polymorphisms was performed using MassARRAY.
- Liver stiffness measurement (LSM) was used to assess liver fibrosis, with defined cut-offs for significant, advanced fibrosis, and cirrhosis.
Main Results:
- The overdominant inheritance model best fit the data, with heterozygous genotypes (e.g., CXCL9 rs10336 AG) associated with lower LSM and reduced odds of significant, advanced fibrosis, and cirrhosis.
- Conversely, the recessive model showed that homozygous genotypes (e.g., CXCL9 rs10336 AA) were linked to higher LSM and increased odds of significant and advanced fibrosis.
- Both heterozygous and homozygous genotypes for the studied CXCL9-11 polymorphisms demonstrated a significant association with liver stiffness and fibrosis severity.
Conclusions:
- CXCL9-11 polymorphisms are significantly associated with the likelihood and severity of liver fibrosis in patients with HCV infection.
- Specific heterozygous genotypes of CXCL9-11 appear to be protective against liver fibrosis progression.
- These findings suggest that CXCL9-11 polymorphisms could serve as potential biomarkers for predicting fibrosis progression and guiding the prioritization of antiviral therapy in chronic hepatitis C.
Background And Aims:
CXCL9-11 polymorphisms are related to various infectious diseases, including hepatitis C virus (HCV) infection. In this study, we analyzed the association between CXCL9-11 polymorphisms and liver fibrosis in HCV-infected patients.
Methods:
We performed a cross-sectional study in 389 patients who were genotyped for CXCL9-11 polymorphisms (CXCL9 rs10336, CXCL10 rs3921, and CXCL11 rs4619915) using the Sequenom's MassARRAY platform. The primary outcome variable was the liver stiffness measurement (LSM). We established three cut-offs of LSM: LSM ≥ 7.1 kPa (F ≥ 2-significant fibrosis), LSM ≥ 9.5 kPa (F ≥ 3-advanced fibrosis), and LSM ≥ 12.5 kPa (F4-cirrhosis).
Results:
Recessive, overdominant and codominant models of inheritance showed significant values, but the overdominant model was the best fitting our data. In this case, CXCL9 rs10336 AG, CXCL10 rs3921 CG and CXCL11 rs4619915 AG were mainly associated with lower values of LSM [(adjusted GMR (aGMR) = 0.85 (p = 0.005), aGMR = 0.84 (p = 0.003), and aGMR = 0.84 (p = 0.003), respectively]. Patients with CXCL9 rs10336 AG genotype had lower odds of significant fibrosis (LSM ≥ 7.1 kPa) [adjusted OR (aOR) = 0.59 (p = 0.016)], advanced fibrosis (LSM ≥ 9.5 kPa) [aOR = 0.54 (p = 0.010)], and cirrhosis (LSM ≥ 12.5 kPa) [aOR = 0.56 (p = 0.043)]. Patients with CXCL10 rs3921 CG or CXCL11 rs4619915 AG genotypes had lower odds of significant fibrosis (LSM ≥ 7.1 kPa) [adjusted OR (aOR) = 0.56 (p = 0.008)], advanced fibrosis (LSM ≥ 9.5 kPa) [aOR = 0.55 (p = 0.013)], and cirrhosis (LSM ≥ 12.5 kPa) [aOR = 0.57 (p = 0.051)]. Additionally, CXCL9-11 polymorphisms were related to lower liver stiffness under a codominant model of inheritance, being the heterozygous genotypes also protective against hepatic fibrosis. In the recessive inheritance model, the CXCL9 rs10336 AA, CXCL10 rs3921 CC and CXCL11 rs4619915 AA were associated with higher LSM values [(adjusted GMR (aGMR) = 1.19 (p = 0.030), aGMR = 1.21 (p = 0.023), and aGMR = 1.21 (p = 0.023), respectively]. Moreover, patients with CXCL9 rs10336 AA genotype had higher odds of significant fibrosis (LSM ≥ 7.1 kPa) [adjusted OR (aOR) = 1.83 (p = 0.044)] and advanced fibrosis (LSM ≥ 9.5 kPa) [aOR = 1.85 (p = 0.045)]. Furthermore, patients with CXCL10 rs3921 CC or CXCL11 rs4619915 AA genotypes had higher odds of advanced fibrosis (LSM ≥ 9.5 kPa) [aOR = 1.89 (p = 0.038)].
Conclusions:
CXCL9-11 polymorphisms were related to likelihood of having liver fibrosis in HCV-infected patients. Our data suggest that CXCL9-11 polymorphisms may play a significant role against the progression of CHC and could help prioritize antiviral therapy.
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