1. Introduction

Chronic viral hepatitis C (CVHC) is a widespread infectious disease worldwide and in Uzbekistan, causing significant social and economic burden. According to the World Health Organization, a large proportion of individuals infected with the hepatitis C virus (HCV) progress to a chronic form, which over 10–20 years may lead to liver cirrhosis, hepatocellular carcinoma, and severe hepatic dysfunction. In addition, HCV infection has long-term effects on patients’ health and results in socio-economic consequences such as loss of work capacity, increased costs of medications, and expenses related to inpatient treatment. The clinical course of CVHC and the development of its complications are not limited to virological factors alone but are also closely associated with the patient’s immune response and genetic characteristics. In particular, genetic polymorphisms regulating cytokine synthesis play an important role in determining the activity of inflammation, the rate of fibrosis progression, and disease prognosis. In this regard, IL-10 (G108A) and TNF-α (G308A) gene polymorphisms are considered key genetic markers of scientific and practical significance in the pathogenesis of chronic hepatitis C [1,3,4]. Studies by Powell et al. (2000) demonstrated that the TNF-α (G308A) gene polymorphism is associated with higher inflammatory activity and accelerated development of fibrosis in liver tissue. The authors emphasized that patients carrying the A allele of the TNF-α gene have a more severe disease course and a higher risk of complications. In CVHC, cytokines such as IL-10 and TNF-α play a central role in regulating immune responses. IL-10 is an anti-inflammatory cytokine that suppresses intercellular inflammation and immune reactions. The G108A polymorphism of the IL-10 gene may influence IL-10 production and its functional activity. The G308A polymorphism of the TNF-α gene can affect cytokine levels and the intensity of inflammation, thereby increasing the risk of liver tissue damage, fibrosis, and progression to cirrhosis. In clinical practice, the diagnosis of chronic hepatitis C is most often based on clinical findings and standard laboratory parameters, which limits the possibilities for early detection of the disease and prediction of complications. In contrast, the assessment of genetic polymorphisms makes it possible to identify the underlying mechanisms influencing the clinical course of the disease, to detect high-risk patients at an early stage, and to implement individualized monitoring strategies [2,5]. Taking these aspects into account, the aim of the present study is to evaluate the key genetic polymorphisms that determine the clinical course and progression of chronic hepatitis C in affected patients, to identify their associations with laboratory and clinical parameters, and, based on the obtained data, to improve early diagnosis and disease prognosis.

2. Materials and Methods

In this study, the associations of genetic polymorphisms (IL-10 (G108A) and TNF-α (G308A)) with clinical, laboratory, and virological parameters were evaluated. The main group included 105 patients with a confirmed diagnosis of chronic hepatitis C, of whom 58 were male and 47 were female. The patients’ ages ranged from 25 to 76 years, with a mean age of 49.6 ± 1.2 years. The control group consisted of 60 healthy individuals with no history of hepatitis C infection. They were matched to the main group by sex and age: 32 males and 28 females, aged 20–63 years (mean age 41.9 ± 1.1 years). The study was conducted with approval from the Ethics Committee of Bukhara Medical Institute. Genetic analysis. DNA was extracted from peripheral blood using standard methods. IL-10 (G108A) and TNF-α (G308A) polymorphisms were determined using the PCR–RFLP method. Genotypes were classified as GG, GA, and AA variants. Comparative analysis of qualitative variables was performed using the χ² (chi-square) test or Fisher’s exact test. Genotype and allele frequency distributions were calculated, and odds ratios (OR) and relative risks (RR) with 95% confidence intervals were determined. Associations between genetic polymorphisms, clinical features, and laboratory parameters were assessed using Spearman’s or Pearson’s correlation coefficients. Logistic regression analysis was performed to predict complications of chronic hepatitis C. Statistical significance was defined as p < 0.05.

3. Results and Analysis

Genetic analyses were performed on DNA samples isolated from peripheral blood. IL-10 (G108A) and TNF-α (G308A) gene polymorphisms were identified using the PCR–RFLP method. Genotypes were classified into GG, GA, and AA variants. The distribution of genotypes was evaluated for compliance with Hardy–Weinberg equilibrium.

Table 1. IL-10 (−1082 G/A) Gene Polymorphism: Genotype Distribution in Patients and the Control Group

This table presents the genotype distribution of the IL-10 (−1082 G/A) gene polymorphism in patients with chronic viral hepatitis C (n=105) and in a healthy control group (n=60). In the patient group, the frequency of the GG genotype was significantly lower compared to the control group (32.4% vs. 51.7%; OR = 0.44; χ² = 5.01; p < 0.05), indicating that this genotype may have a protective effect. Conversely, the AA genotype was significantly more frequent in patients than in controls (23.8% vs. 13.3%; OR = 2.10; χ² = 3.98; p < 0.05), suggesting an association with increased risk of disease development. No statistically significant difference was observed between the groups for the GA heterozygous genotype (p > 0.05).

Allele analysis showed that the frequency of the A allele was significantly higher in patients compared to controls (45.7% vs. 30.8%; OR = 1.88; χ² = 6.12; p < 0.05). At the same time, the G allele was less frequent in patients than in controls (54.3% vs. 69.2%; OR = 0.53; p < 0.05), confirming its potential protective role.

Table 2. TNF-α (−308 G/A) Gene Polymorphism: Genotype Distribution in Patients and Control Group

Analysis of the TNF-α (−308 G/A) gene polymorphism showed that the GG genotype was significantly less frequent in the patient group compared to the control group (39.0% vs. 58.3%; OR = 0.46; χ² = 5.21; p < 0.05). In contrast, the AA genotype was significantly more frequent in patients than in controls (19.1% vs. 8.4%; OR = 2.36; χ² = 4.44; p < 0.05), indicating its association with increased susceptibility to the disease. No statistically significant difference was observed between the groups for the GA genotype (p > 0.05).

Allele analysis revealed that the frequency of the A allele was significantly higher in patients than in the control group (40.0% vs. 25.0%; OR = 2.00; χ² = 6.34; p < 0.05). Conversely, the G allele was less frequent in patients compared to controls (60.0% vs. 75.0%; OR = 0.50; p < 0.05), suggesting its protective role.

Table 3. Hardy–Weinberg equilibrium (HWE)

Table 3 presents the compliance of IL-10 (−1082 G/A) and TNF-α (−308 G/A) gene polymorphisms with Hardy–Weinberg equilibrium in both patients and control groups. According to the results, the χ² (HWE) values for both gene polymorphisms did not exceed the statistically significant threshold in either group (p > 0.05). This indicates that the genotype distributions correspond to random population expectations and confirms the genetic representativeness of the study sample.

In conclusion, the results of this study demonstrate that IL-10 (−1082 G/A) and TNF-α (−308 G/A) gene polymorphisms are significantly associated with susceptibility to chronic viral hepatitis C and its progression. Analysis showed that for both genes, the AA genotype and A allele were significantly more frequent in patients than in controls, identifying them as risk factors for the development of chronic viral hepatitis C (p < 0.05). Conversely, the GG genotype and G allele were more common in the control group, confirming their protective role against the disease.

Furthermore, the genotype distributions of IL-10 and TNF-α in both patients and controls were in accordance with Hardy–Weinberg equilibrium (p > 0.05), indicating the genetic representativeness of the study sample and the reliability of the obtained results.

Assessment of IL-10 (−1082 G/A) and TNF-α (−308 G/A) gene polymorphisms plays an important role in the early diagnosis of chronic viral hepatitis C, predicting individual risk, and developing personalized treatment strategies, and represents a promising direction for implementation in clinical practice.