Clinical research Genotype distribution of hepatitis C virus in 952 cases from 2014 to 2016 in Hunan Province, China Jian-Hua Lei, Xing Gong, Xin-Qiang Xiao, Zi Chen, Feng Peng Department of Infectious Diseases, Second Xiangya Hospital, Central South Corresponding author: University, Changsha, China Prof. Jian-Hua Lei Department of Infectious Submitted: 24 August 2017 Diseases Accepted: 17 September 2017 Second Xiangya Hospital Central South University Arch Med Sci 2018; 14, 5: 1055–1060 139 Middle DOI: https://doi.org/10.5114/aoms.2017.70664 Renmin Road Copyright © 2017 Termedia & Banach 410011 Changsha Hunan 410011, China Phone: +86 731 85292105 Abstract E-mail: leijianhua73@163. com Introduction: Few large-scale investigations on genotype (GT) distribution of hepatitis C virus (HCV) in Hunan Province, China, are reported. Material and methods: We recruited all of the 952 patients in the cen- sus register of Hunan Province who were first diagnosed with HCV infection in the Second Xiangya Hospital, Central South University in 2014–2016. HCV genotypes were surveyed. The genotype distribution pattern was compared with those of the neighboring regions in China. Results: Among the 952 patients, genotype 1 (GT1) (69.9%) was the most common HCV genotype, followed by GT6 (19.0%), GT3 (8.4%), and GT2 (2.6%). GT4 and GT5 were not found. One case had mixed infection of GT3 and GT6. Predominance of GT1 HCV was more evident in the patients aged ≥ 40 years than in those aged < 40 years (79.5% vs. 47.9%, c2 = 95.993, p < 0.001). HCV genotype distribution had gender difference (c2 = 44.695, p < 0.001), with GT3 and GT6 more prevalent in males than in females (36.2% vs. 18.2%, c2 = 39.088, p < 0.001) while GT1 more prevalent in females than in males (80.1% vs. 60.3%, c2 = 44.276, p < 0.001). Though Hunan Province is located in cen- tral China, its HCV genotype priority was similar with the change trend in south and southwest China, while distinguished from those of other regions, in particular from the neighboring central province, Hubei Province. Conclusions: HCV GT1 was the most predominant HCV genotype in Hunan Province, and GT6 and GT3 accounted for a significant percentage, especial- ly in young patients. The HCV distribution pattern was more similar to those of the regions in south China. Key words: epidemiology, hepatitis C virus, genotype. Introduction Hepatitis C is a global pandemic disease. About 185 million people are infected or have previously been infected with hepatitis C virus (HCV), most of whom are progressing or have developed into the chronic stage. Moreover, new infections are emerging [1, 2]. Hepatitis C is moderate- ly prevalent in East Asia including China, with an estimated prevalence rate of 0.29–3.2% in the general population [2–5]. Most HCV-infected patients are unaware that they are at higher risk for life-threatening dis- eases such as liver cirrhosis and hepatocellular carcinoma (HCC), whose incidences are predicted to rise in the coming decade [1, 2]. Epidemiological studies have confirmed that the prevalence of HCV has regional characteristics, and the HCV genotypes prevailing in differ- ent regions are widely divergent [5–7]. Knowing the distribution pattern Jian-Hua Lei, Xing Gong, Xin-Qiang Xiao, Zi Chen, Feng Peng of virus genotypes is conducive to the control and consent was obtained from the 341 participants prevention of the epidemic of HCV infection, and enrolled in 2016. genotyping of the virus before anti-HCV treatment is essential for adjustment of the therapeutic reg- Diagnosis of HCV infection and genotyping imen [4, 5, 8–10]. of HCV Prevailing patterns of HCV are evolving in China Serum anti-HCV was assessed by an enzyme- due to changes in transmission modes and other linked immunosorbent assay diagnostic kit (Zhuhai influencing factors such as immigration and global Livzon Diagnostics Inc., China) according to the man- travel [3, 4, 11, 12]. For example, HCV genotype 2 ufacturer’s instructions. Quantitation of plasma HCV (HCV GT2), the second predominant HCV strain RNA was assessed in a 7500 real-time polymerase following HCV GT1 in north and central China, is chain reaction (PCR) system (Applied Biosystems prevalent in the southern and western provinces Inc., USA) using a HCV RNA quantitative fluores- of China at a relatively lower level, while HCV GT6 cence diagnostic kit (Sansure biotech Inc. Ltd, Chi- is increasingly prevalent in Guangdong Province in na), and the lower detection limit was 25 IU/ml. south China, and HCV GT3 is thriving in Yunnan A multiplex one-step real-time fluorescent RT- Province in southwest China [13, 14]. HCV GT6 has PCR assay based on the analysis of the conserved recently migrated from Guangdong Province to sequence of the HCV genome was carried out in other provinces in the southern half of China [13]. an SLAN-96P real-time fluorescence quantitative Although patients from Hunan Province have PCR instrument (Hongshi Medical Technology Co., been recruited in several large-size national-wide Ltd, Shanghai, China) using a hepatitis C virus surveys on HCV infection in China, the number of genotype diagnostic kit (PCR-fluorescence prob- the participants was limited, and no independent ing) (Sansure biotech Inc. Ltd, Hunan, China). This survey in Hunan Province was available [11, 12]. protocol could discern HCV genotypes 1–6 and de- To our knowledge, there are few large reports on termine subtype 1b [15, 16]. It could detect mixed the distribution pattern of HCV genotypes in Hu- HCV infections of multiple genotypes on the basis nan Province in the authoritative literature about of fluorescent signals. HCV infection and epidemiology. Here we docu- mented the HCV genotype distribution pattern of Statistical analysis 952 patients with a first-time confirmed diagnosis in Hunan Province in 2014–2016. All statistical analyses were performed with IBM SPSS Statistics version 20.0, using descriptive sta- Material and methods tistical indexes such as median, the 25th or the 75th centile, etc. The one-sample Kolmogorov-Smirnov Study participants test was used to verify the normal distribution of 2 We recruited 952 patients (494 males and 458 fe- data sets. The c test and Kruskal-Wallis H test were males) from the census register of Hunan Province performed for comparison of ratios or medians. The who were confirmed for the first time to be infect- Levene test was used to verify the homogeneity of ed with HCV by seropositive anti-HCV antibody variance. For all these tests, a p-value less than 0.05 and simultaneously detectable plasma HCV ribo- was considered statistically significant. nucleic acid (RNA) in the Second Xiangya Hospi- tal, Central South University in Hunan Province in Results 2014–2016. HCV was genotyped. In order to fully Distribution of HCV genotypes and reveal the local HCV infection status, ethnicities subtypes and occupations of the patients, as well as their serum liver function indexes and complications HCV genotypic diversity was observed (Table I). Genotype distribution patterns from 2014 to 2016 such as liver cirrhosis, HCC and other diseases, are relatively stable (Pearson c2 = 10.038, p = were not considered in the exclusion criteria. 0.262). GT1 was the most common HCV genotype Collection of all the demographic data, clini- across Hunan Province, comprising 69.9% of the cal features and biological samples including the overall first-time confirmed HCV infected patients, peripheral blood of the research objects fulfilled followed by GT6 (19.0%) and GT3 (8.4%). GT2 was the requirements of medical ethics. The ethical re- rare (2.6%). GT4 and GT5 were not found. One pa- view committees of the Second Xiangya Hospital tient had mixed infections of genotypes 3 and 6. of Central South University approved this study. Guidelines of the Declaration of Helsinki set by Agewise distribution of the HCV infected the committees were strictly followed. Due to the patients with different virus genotypes retrospective nature of the study, the written in- formed consent of the 611 participants enrolled The age of the 952 patients recruited took in 2014 or 2015 was exempted. Written informed an abnormal distribution (Kolmogorov-Smirnov 1056 Arch Med Sci 5, August / 2018 Genotype distribution of hepatitis C virus in 952 cases from 2014 to 2016 in Hunan Province, China Table I. Distribution of HCV genotypes in 952 HCV cases in Hunan Province, China, 2014–2016 Year N HCV genotype, n (%) 1 2 3 6 3 + 6 2014 200 133 (66.5) 9 (4.5) 20 (10.0) 37 (18.5) 1 (0.5) 2015 411 286 (69.6) 7 (1.7) 34 (8.3) 84 (20.4) 0 (0.0) 2016 341 246 (72.1) 9 (2.6) 26 (7.6) 60 (17.6) 0 (0.0) Total 952 665 (69.9) 25 (2.6) 80 (8.4) 181 (19.0) 1 (0.1) Pearson c2 = 10.038, p = 0.262. test, Z = 1.586, p = 0.013), with the peak at age 80 37–53 years (Figure 1, Table II). Patients infect- ed with HCV of different genotypes had specific age distribution features. Seventy-five percent of 60 the HCV GT1 infected patients were older than 42 and the median was 49 years old, while GT3 40 and GT6 were more prevalent in younger patients (IQR, interquartile range from the 25th to the 75th Age [year] centile, 33–45 and 33–43 years old, respectively). 20 HCV GT2 was detected in fewer cases, manifest- ing a sporadic distribution (Figure 1, Table II). The participants were grouped into 3–39 and 40–79 0 years age groups. For the patients aged 40 years 1 2 3 6 3 + 6 and above, the predominance of HCV GT1 was HCV genotype more evident than the patients younger than Figure 1.