Epidemiology and Genotype Distribution of Hepatitis C Virus in Russia

The hepatitis C virus (HCV) causes both acute and chronic infection of the liver that can lead to liver cirrhosis, cancer, and liver failure. HCV is characterized by high genetic diversity and substantial variations in the prevalence of specific HCV genotypes throughout the world. Many effective regimens of direct-acting antivirals (DAAs), including pan-genotypic, can successfully treat HCV infection. Additionally, genotype-specific treatments for HCV are being actively employed in national plans for eliminating HCV infection around the world. The evaluation of HCV genotype prevalence in a given country is necessary for the successful implementation of the HCV elimination plans and for allocating financial resources to the DAAs which are the most effective against those specific HCV genotypes prevalent in a given country. Here, we analyzed HCV genotypes, subgenotypes, and recombinants in 10,107 serum samples collected in 2015-2017 from patients with chronic HCV infection living in all federal districts of Russia. This is the first and largest evaluation of HCV genotypes performed on samples from all territories of Russia, from its Central federal district to the Far East. Moreover, we have updated retrospective epidemiological analysis of chronic and acute HCV infection in Russia from 2001 to 2021. We demonstrate that the incidence of acute HCV (AHC) infection in Russia decreased from 16.7 cases per 100,000 people in 2001 to 0.6/100,000 in 2021. The number of cases of chronic HCV (CHC) infection also decreased from 29.5 to 16.4 per 100,000 people during this period. The HCV genotype analysis indicated that HCV genotype 1 dominates in Russia (53.6%), while genotypes 3 and 2 were detected in 35.4% and 7.8% of patients, respectively. These proportions are virtually identical in all regions of Russia except for the Far East, where HCV genotype 2 was detected in only 1% of the samples. HCV genotypes 1 and 2 are more widespread in women, and HCV genotype 3 in men. Genotype 3 was the most prevalent in 31-40-year-olds (44.9%), and genotype 1 was most prevalent in those over 70 years of age (72.2%). HCV genotype 2 was predominant among HCV-infected persons older than 40 years. Discriminating between HCV genotype 2 and recombinant RF1_2k/1b, which are frequently misclassified, is important for successful antiviral treatment. For the first time, we demonstrate, here, countrywide prevalence of HCV RF1_2k/1b in different regions of Russia. HCV RF1_2k/1b makes up 3.2% of HCV genotypes, reaching 30% among samples classified as genotype 2 by some commercial genotyping tests. The highest proportion of HCV RF1_2k/1b was detected in the North-West (60%), Southern (41.6%), and Central (31.6%) federal districts; its frequency in the Far Eastern and North Caucasus districts was ~14.3%. HCV RF1_2k/1b, and it was not detected in the Volga, Ural, or Siberian districts. To conclude, this is the first and most complete evaluation of HCV epidemiology and genotype/subgenotype distribution in Russia.