Abstract
The Duffy antigen receptor for chemokines (DARC) rs12075 polymorphism regulates leukocyte trafficking and proinflammatory chemokine homeostasis. Hepatitis C virus (HCV)-mediated liver fibrosis is associated with an uncontrolled inflammatory response. In this study, we evaluate the association between the DARC rs12075 polymorphism and liver stiffness progression in HCV-infected patients. We carried out a retrospective cohort study (repeated measures design) in 208 noncirrhotic patients with chronic hepatitis C (CHC) who had at least two liver stiffness measurements (LSM) with a separation of at least 12 months. We used generalized linear models to analyze the association between DARC rs12075 polymorphism and outcome variables. During a follow-up of 46.6 months, the percentage of patients with stages of fibrosis F0/F1 decreased (p < 0.001), while LSM values and the percentage of patients with cirrhosis increased (p < 0.001). This pattern of changes was maintained in each of the groups of patients analyzed according to their rs12075 genotypes (AA or AG/GG). However, the variations in liver stiffness characteristics were lower in patients with the rs12075 AG/GG genotype (AG/GG versus AA). Thereby, in the adjusted analysis, patients with the rs12075 AG/GG genotype had a lower risk of an increased value of LSM2/LSM1 arithmetic mean ratio (AMR = 0.83; p = 0.001) and of an increase in LSM ≥ 5 kPa (odds ratio (OR) = 0.28; p = 0.009). Besides, patients with rs12075 AG/GG had a lower risk of cirrhosis progression (OR = 0.24; p = 0.009). No significant associations were found for an increase in LSM ≥ 10 kPa. We found an association between the DARC rs12075 single nucleotide polymorphism (SNP) and CHC progression. Specifically, patients with the DARC rs12075 AG/GG genotype had a lower risk of liver fibrosis progression and development of cirrhosis.
Highlights
Chronic hepatitis C (CHC) is a clinically relevant human infectious disease with a significant impact on the health system
Our objective was to explore the association between the Duffy antigen receptor for chemokines (DARC) rs12075 single nucleotide polymorphism (SNP) and liver fibrosis progression, evaluated by liver stiffness measurement (LSM), in patients infected with hepatitis C virus (HCV)
The percentage of patients with cirrhosis increased in the analyzed DARC rs12075 genotypes (AG/GG versus AA) during the study, the variations in liver stiffness were lower in patients with the rs12075 AG/GG genotype, resulting in lower risk of cirrhosis progression
Summary
Chronic hepatitis C (CHC) is a clinically relevant human infectious disease with a significant impact on the health system. The World Health Organization estimated that 71 million people are chronically infected with hepatitis C virus (HCV) [1] These individuals frequently develop serious hepatic complications such as cirrhosis and hepatocellular carcinoma [2,3], even after successful treatment with direct-acting antivirals (DAAs), patients with advanced fibrosis and cirrhosis [4,5]. This evolution depends, among other factors, on the individual’s genetic background, as several single nucleotide polymorphisms (SNPs) have been associated with liver disease progression [6,7]. The severity of liver fibrosis is mostly evaluated by noninvasive elastography techniques, the evaluation of liver stiffness measurement (LSM), which gives us quantitative data about liver stiffness [11,12]
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