Distribution of Hepatitis C Virus Genotypes among Chronic HCV Patients in Greece from 2004 to 2019: Association of Genotypes and Viral Load with Gender and Age

Review Article

J Hepat Res. 2022; 7(1): 1048.

Distribution of Hepatitis C Virus Genotypes among Chronic HCV Patients in Greece from 2004 to 2019: Association of Genotypes and Viral Load with Gender and Age

Martinez-Gonzalez B1, Mpekoulis G2, Karatapanis S3, Lagou D2, Horefti E4, Papatheodoridis G5, Koskinas J6, Sgouras DN1, Mentis A4, Vassilaki N2* and Angelakis E4,7

1Laboratory of Medical Microbiology, Hellenic Pasteur Institute, Greece

2Laboratory of Molecular Virology, Hellenic Pasteur Institute, Greece

3First Department of Internal Medicine, General Hospital of Rhodes, Greece

4Diagnostic Department and Public Health Laboratories, Hellenic Pasteur Institute, Greece

5Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens “Laiko”, Greece

6Second Department of Internal Medicine, “Hippokratio” General Hospital, Greece

7Aix Marseille Université, IRD, APHM, VITROME, IHUMéditerranée Infection, France

*Corresponding author: Vassilaki N, Laboratory of Molecular Virology, Hellenic Pasteur Institute, Athens, Greece

Received: October 11, 2022; Accepted: November 08, 2022; Published: November 15, 2022


Identification of Hepatitis C Virus (HCV) genotypes and viral load are considered critical factors for the selection of the appropriate antiviral treatment regimens. In Greece, it is estimated that approximately 0.8% to 1.8% of the general population has been chronically infected with HCV. We aimed to evaluate the HCV genotype distribution trends and viral load levels in Greece from 2004 to 2019, according to gender and age, and to estimate the association of HCV genotypes with the viral load. A total of 6,824 serum samples from chronic HCV patients (4,614 males; average age of 47 ± 14.2), were assayed for HCV RNA and HCV genotyping. HCV genotype 3 was the most prevalent (42.4%) followed by genotype 1 (37.4%), genotype 4 (13.5%), genotype 2 (6.2%) and genotype 5 (0.3%). Genotype 6 was detected only in one Asian immigrant in 2012. The predominant subtypes were 3a (41.3%) and 1b (23.4%). HCV genotype distribution differed significantly (p < 0.001) between genders, with genotype 1 being more frequent in females, whereas genotype 3 was more common in males. The highest percentage of HCV infections was at the age-group 40-59 (44.8% of 6,097) and the lowest one at the age-group < 18 (0.6% of 6,097). Genotype 3 was highly represented in younger patients (19-39 age- group), while genotype 1 was more common in older ones (> 60 age-group). The distribution pattern of HCV genotypes during the 16-yearperiod study revealed a decreasing trend in the proportion of genotype 3 and a gradually increasing trend of genotype 1. HCV viral load was significantly lower (p < 0.001) in genotype 4 compared to genotypes 1, 2 and 3. Moreover, it was associated with gender, with elevated viral load in male individuals, and was positively correlated with age.

Keywords: Hepatitis C Virus; HCV Genotypes; Greece; Gender; Age; Viral load


The Hepatitis C Virus (HCV) infection is a global health problem with an estimated prevalence rate of 1.1 % (range 0.9-1.4%) in the general population, corresponding to approximately 1.4% when considering those over 15 years of age [1]. The virus can cause both acute and chronic hepatitis. Acute HCV infection is usually asymptomatic or causes mild to moderate acute hepatitis, but it progresses to chronicity in the majority of cases. Chronic HCV infection can result in serious, even life-threatening health problems like cirrhosis, Hepatocellular Carcinoma (HCC), non-Hodgkin’s lymphomas, mixed cryoglobulinemia and liver-related death [2- 4]. Until recently, end-stage liver disease caused by chronic HCV infection is one of the most common reasons for liver transplantation in developed countries [5,6]. According to the World Health Organization (WHO), 58 million people have chronic HCV infection, with about 1.5 million infections occurring per year. In 2019, approximately 290,000 people died from HCV infection, mostly from cirrhosis and HCC [7]. The ultimate goal of the WHO is to reduce the global incidence of HCV infection to a negligible amount of less than 0.9 million chronic cases by the year 2030 [8].

Greece has made significant efforts towards HCV elimination over the recent years. The Hellenic National Plan for Hepatitis C is in alignment with the WHO goal to achieve eradication of HCV infection by 2030 [9]. Epidemiological studies in Greece demonstrate that the current prevalence of HCV chronically infected patients in the general population is estimated to range from 0.8% to 1.8% and between 1% to 1.9% in high-risk patient groups [9-11]. These data suggest that approximately 134,000 adults in the general population have chronic hepatitis C [9].

The HCV is an RNA virus, member of the Flaviviridae family, characterized by high genetic variability [12]. On the basis of phylogenetic analysis, there are 8 major genotypes (HCV 1-8), which comprise over 86 confirmed different subtypes of HCV [13-15]. HCV genotypes and subtypes information plays an important role in the pre-treatment evaluation of patients, as it is considered crucial for the selection of appropriate treatment regimens [13,16,17]. Despite HCV genotypes, HCV viral load assessment is an important tool particularly useful before initiating antiviral therapy, counting as a surrogate marker of antiviral response. The management of patients with HCV infection has changed substantially with the introduction of the highly effective oral Direct-Acting Antiviral Agents (DAAs), providing eradication rates higher than 95% [7], including populations that have been difficult to treat in the past [18,19]. Although pangenotypic DAAs have revolutionized HCV treatments, their high cost remains a major barrier to access in many countries [20]. So far, unless pangenotypic DAAs are made widely available, the initiation of a standard HCV treatment needs the determination of HCV genotype and subtype and the measurement of viral load level in order to improve treatment outcomes [13,16,17]. Moreover, HCV genotyping is essential for the evaluation of regional/national epidemiological status, as HCV genotypes are associated with the different transmission routes of HCV infection and have different geographical distribution [13]. However, the evidence of a correlation between HCV genotype and viral load remains controversial [21-23].

The aim of this study was to analyze the distribution pattern of HCV genotypes in chronically infected patients in a large sample size and over a sixteen-year period (2004-2019) according to gender and age, and to address the association with HCV viral load.

Materials and Methods

A retrospective study was carried out on HCV-positive patients who were successfully genotyped during the time period 2004-2019. Serum samples were collected from confirmed chronic HCV patients attending hospitals and clinical laboratories situated in different cities, from different geographical regions of Greece (Table 1). We tested HCV patients with long-term inflammation of the liver for at least six months, with positive HCV antibody and positive HCV RNA test. Written informed consent was requested from each patient at collection centers. Samples were sent to the Diagnostic Department at the Hellenic Pasteur Institute (HPI) at 2-8°C, if they were referred from hospitals located in the Capital City of Greece (Athens) and its metropolitan area or were shipped on dry ice when specimens were coming from other geographical regions of the country. Specimens were immediately stored at -80°C for further analysis at the Diagnostic Department of the HPI.