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Interferon-λ rs12979860 genotype association with liver fibrosis in chronic hepatitis C (CHC) patients in the Pakistani population

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Abstract

Risk and progression of liver fibrosis and cirrhosis in chronic hepatitis C (CHC) patients is significantly influenced by host genetic factors in a polygenic manner. The rs12979860 genetic polymorphism in the interferon-λ3–interferon-λ4 (IFNL3-IFNL4) region has been found to be a major determinant of hepatic inflammatory and fibrotic progression in CHC patients of mainly Caucasian origin; however, it is not known if this association applies to other ethnicities, including Pakistani CHC patients. Here, we genotyped IFNL3-IFNL4 rs12979860 genetic variants in a sample set of 502 Pakistani patients with CHC and used logistic regression analysis to determine its association with the risk and progression of HCV-related fibrosis and cirrhosis. We demonstrate that the rs12979860 major (CC) genotype, despite not determining the risk of stage-specific hepatic fibrosis independently, is associated with a marginally significant risk of liver cirrhosis (OR: 1.64, p = 0.049) after an adjustment for age, gender, body mass index, HCV viral load, and liver enzymes. In a subgroup of CHC patients with sustained ALT levels of <60 IU/L, a more pronounced impact of the IFNL3-IFNL4 rs12979860 major (CC) genotype on advanced liver fibrosis (OR: 4.99, p = 0.017) and cirrhosis (OR: 3.34, p = 0.005) was seen. The present study suggests that IFNL3-IFNL4 rs12979860 polymorphism may also be a significant predictor of hepatic fibrosis and cirrhosis in Pakistani CHC patients, especially in those with normal or near-normal liver enzyme levels.

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Abbreviations

CHC:

Chronic hepatitis C

IFNL3-IFNL4:

Interferon-λ3–interferon-λ4

HCV:

Hepatitis C virus

ALT:

Alanine aminotransferase

GWAS:

Genome-wide association studies

NAFLD:

Non-alcoholic fatty liver disease

HDV:

Hepatitis D virus

HIV:

Human immunodeficiency virus

BMI:

Body mass index

SPSS:

Statistical Package for Social Sciences

HWE:

Hardy–Weinberg equilibrium

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Acknowledgements

We thank all of the patients and Dr. Bilal Nasir (Lahore General Hospital, Lahore, Pakistan) for organizing the collection and shipment of blood specimens. We also thank the hospital staff involved in the collection of samples.

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Authors and Affiliations

  1. Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney and Westmead Hospital, Sydney, Australia

    Bisma Rauff

  2. Institute of Biomedical and Allied Health Sciences (IBAHS), University of Health Sciences (UHS), Lahore, Pakistan

    Bisma Rauff, Shafiq Ahmad Chudhary & Saqib Mahmood

  3. Department of Human Genetics and Molecular Biology, University of Health Sciences (UHS), Lahore, Pakistan

    Ali Amar

  4. Lahore General Hospital, Lahore, Pakistan

    Ghias Un Nabi Tayyab

  5. Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, Pakistan

    Rumeza Hanif

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  1. Bisma Rauff
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Rauff, B., Amar, A., Chudhary, S.A. et al. Interferon-λ rs12979860 genotype association with liver fibrosis in chronic hepatitis C (CHC) patients in the Pakistani population. Arch Virol 166, 1047–1056 (2021). https://doi.org/10.1007/s00705-020-04901-2

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