Researchers in the Tomsk Region of Western Siberia have characterized the molecular epidemiology of hepatitis C virus (HCV) among patients with confirmed tuberculosis. The study, published in the Egyptian Liver Journal, analyzed 308 serum samples from individuals with co-infection to determine the prevalence of specific HCV subtypes and the presence of baseline resistance-associated substitutions (RAS). These genetic variants can reduce the efficacy of modern direct-acting antiviral (DAA) therapies, which are the current standard of care for eradicating the virus. The findings provide a detailed snapshot of the viral landscape in a region where data on HCV molecular epidemiology and resistance has previously been limited.
The investigation focused on a cross-sectional cohort of tuberculosis patients residing in the Tomsk Region. The sample included 241 men and 67 women, with a median age of 44 years. All participants had a verified diagnosis of tuberculosis and tested positive for HCV RNA. The researchers excluded individuals who had previously received DAA or interferon-ribavirin therapy, ensuring that the detected genetic variants represented baseline resistance rather than acquired resistance from prior treatment. This design allowed for an assessment of the circulating viral diversity and the intrinsic resistance profile of the HCV isolates in this specific population.
Phylogenetic analysis of the core and NS5B gene regions identified five distinct genetic variants among the 308 patients. Subtype 1b was the most prevalent, accounting for 43.5% of the isolates, followed closely by subtype 3a at 42.2%. Subtype 1a was detected in 12.3% of the cases, while subtypes 2a and the recombinant form 2k/1b were each present in 1.0% of the samples. This distribution reflects a stable HCV subtype profile characteristic of the Siberian Federal District, which has persisted for several decades and is consistent with epidemiological patterns observed in other parts of Russia and Eastern Europe.
The detection of the 2k/1b recombinant form, although rare at 1.0%, is notable for its implications in clinical diagnostics. The study confirmed the association of the subtype 2k core-region fragment with this recombinant form through NS5B sequencing. The authors note that commercial test systems may incorrectly classify this recombinant as genotype 2, underscoring the need for expanded molecular analysis during genotyping. The precise location of the recombination breakpoint was not determined, and the isolate is characterized as compatible with the 2k/1b form rather than definitively confirmed, due to the limited number of such isolates and the reliance on short-read sequencing.
To assess resistance, the researchers performed next-generation sequencing on a subset of 29 subtype 1b and 57 subtype 3a isolates. These subtypes were selected for in-depth analysis because they were the most prevalent in the cohort. The sequencing targeted the NS3, NS5A, and NS5B genes, which encode the non-structural proteins targeted by DAA medications. The analysis identified several baseline RAS, which are amino acid substitutions that can confer resistance to specific antiviral drugs. The presence of these variants at baseline is significant because it may influence the choice of initial treatment regimen and the likelihood of achieving a sustained virological response.
In the NS3 protein, the RAS A166S/T was detected in 21.1% of subtype 3a isolates. This substitution is associated with resistance to glecaprevir and paritaprevir and is the most common RAS in patients who experience virologic failure on the glecaprevir/pibrentasvir regimen. Among subtype 1b isolates, Y56F and S122G were each found in 10.3% of cases, while V170I was present in 13.8%. Y56F confers resistance to grazoprevir and voxilaprevir, whereas V170I is presumed to have no effect on most modern NS3/4A inhibitors except for those two specific drugs. The prevalence of these variants in the Tomsk cohort aligns with data from other regions, such as China and Europe, where similar frequencies have been reported.
Analysis of the NS5A protein revealed distinct resistance patterns between the two major subtypes. In subtype 3a isolates, Q/S62L was the most common RAS, detected in 12.3% of cases, followed by A30K/S in 5.3% and Y93H in 1.8%. A30K/S is associated with resistance to daclatasvir and velpatasvir. Among subtype 1b isolates, R30Q, L31M, P58S, and Y93H were each detected in 3.4% of the samples. The low frequency of Y93H in this cohort is consistent with published data indicating its relatively low prevalence in Russia. The detection of these variants provides a baseline for monitoring the evolution of resistance in the region, particularly as new DAA regimens are deployed.
The NS5B region, which is the target of nucleotide analog inhibitors like sofosbuvir, showed high frequencies of specific RAS in both subtypes. Among subtype 3a isolates, A150V was detected in 40.4% of cases and K206E in 22.8%. According to the literature, each of these substitutions individually reduces sensitivity to sofosbuvir by 7 to 8-fold, while their combination results in a 35-fold reduction. In subtype 1b isolates, C316N was the most prevalent RAS, found in 48.3% of the samples. This variant is associated with resistance to dasabuvir and reduced susceptibility to sofosbuvir. The high frequency of C316N in this cohort warrants attention, as comparable prevalence rates have been reported in Europe, but it is notably higher than in the United States.
The study also examined the co-occurrence of multiple RAS, which is associated with a more significant decrease in treatment effectiveness than single substitutions. For subtype 1b, the combination of L159F and C316N in the NS5B protein was found in 27.6% of isolates. A triple combination of L159F, C316N, and S556G was identified in 6.9% of the subtype 1b isolates. For subtype 3a, the pair A150V and K206E was detected in 12.3% of cases.
The distribution of HCV subtypes showed a significant difference by gender for subtype 1a, which was detected more frequently in men than in women. The authors suggest that this may be related to the association of subtype 1a with injection drug use, a risk factor that predominates in males. However, because data on infection routes were not collected in this study, no direct causal association can be established. The age distribution of infected patients did not show statistically significant patterns, with the largest proportion of cases occurring among middle-aged individuals between 35 and 54 years. This demographic profile is consistent with the broader epidemiology of HCV in Russia, where genotype 1 and 3 are the predominant strains.
Several limitations must be considered when interpreting these results. The cross-sectional design of the study, with a single sample collection, did not allow for the assessment of RAS evolution over time or the direct impact of these variants on antiviral therapy outcomes. The sample size for the in-depth RAS analysis was limited to 86 isolates, which may result in wide confidence intervals for rare substitutions. Furthermore, the study lacked systematic clinical data on the severity of tuberculosis, liver fibrosis status, and specific anti-tuberculosis regimens, which limits the ability to assess potential drug-drug interactions between DAA and anti-tuberculosis medications.
The authors emphasize that the data on baseline RAS prevalence should be viewed primarily as a tool for molecular epidemiological surveillance rather than a direct basis for individual patient treatment decisions. While the results are valuable for monitoring resistance trends and planning future research, they do not replace individual clinical assessment. Decisions regarding treatment strategy must be made by attending physicians in accordance with current clinical guidelines, taking into account the patient’s specific comorbidities and potential drug interactions. The study highlights the importance of regular regional molecular monitoring to ensure the timely detection of emerging RAS and to support the optimization of HCV treatment in co-infected populations.
Subject of Research: Molecular epidemiology of hepatitis C virus and resistance to direct-acting antivirals in tuberculosis patients of Western Siberia (Tomsk Region)
Article Title: Molecular epidemiology of hepatitis C virus and resistance to direct-acting antivirals in tuberculosis patients of Western Siberia (Tomsk Region)
Article References: Svirin, K. A., Polovkova, O. G., Fedorova, E. S., Gracheva, A. S., & Kartashov, M. Y. (2026). Molecular epidemiology of hepatitis C virus and resistance to direct-acting antivirals in tuberculosis patients of Western Siberia (Tomsk Region). Egyptian Liver Journal, 16(1), Article 84. https://doi.org/10.1186/s43066-026-00573-w
Image Credits: AI Generated
DOI: 10.1186/s43066-026-00573-w
Keywords: Molecular, epidemiology, hepatitis, virus, resistance, direct-acting, antivirals, tuberculosis, patients, Western, Siberia, Tomsk
News Source: Kristina Jarvis. (November 7, 2026). Hepatitis C Resistance Patterns in Siberian Tuberculosis Patients. Scienmag.
