Hepatitis C virus genotypes and subtypes circulating in Mainland China

Ying Chen, Changshun Yu, Xueru Yin, Xiaolei Guo, Shangwei Wu, Jinlin Hou, Ying Chen, Changshun Yu, Xueru Yin, Xiaolei Guo, Shangwei Wu, Jinlin Hou

Abstract

The hepatitis C virus (HCV) exhibits global genotypic diversity. HCV genotyping plays an important role in epidemiological studies and clinical management. Herein, we report the results of HCV genotype and subtype detection in a large number of clinical samples, as performed by an independent laboratory in China. In total, four HCV genotypes and 18 subtypes were identified among 32 030 patients from 29 provinces and municipalities in China. Five dominant subtypes were detected from 98.84% of the samples: 1b (n=16 713, 52.18%), 2a (n=9188, 28.69%), 3b (n=2261, 7.06%), 6a (n=2052, 6.41%) and 3a (n=1479, 4.62%). Twelve rare subtypes were detected, of which four (that is, 6b, 6j, 6q and 6r) are reported for the first time in the Chinese population. Genotypes 4, 5 and 7 were not detected. Mixed infections of the dominant subtypes were found in a small portion of samples (n=65, 0.203%), in the following combinations: 1b-2a, 1b-3b, 1b-6a, 3a-3b, 1b-3a and 2a-6a. No mixed infections with rare subtypes were found. Males, compared with females, showed higher HCV subtype diversity, a lower percentage of HCV1b and 2a and a higher percentage of rare subtypes and mixed infections. Our analyses revealed the comprehensive distribution patterns of HCV genotypes in the general population of mainland China. HCV genotypic patterns were differentially distributed on the basis of geography, sex and age.

Figures

Figure 1
Figure 1
Heatmap of hepatitis C virus (HCV) subtype percentages in 29 provinces. This heatmap was generated using R3.2.1 software. The maximum method was used in clustering analysis.
Figure 2
Figure 2
Hepatitis C virus (HCV) subtype distribution of males and females. Minor—minor subtypes; Mixed—mixed infections. The number of male carriers was much greater than females in this study, and male carriers showed a higher level of diversity. The Simpson’s diversity index of male and female carriers was 0.6688 and 0.5892 (P=1.23E−234), respectively.
Figure 3
Figure 3
Composition of HCV genotype 1, 2, 3, 6 in Mainland China. (A) The distribution of HCV 1 in Mainland China. (B) The distribution of HCV 2 in Mainland China. (C) The distribution of HCV 3 in Mainland China. (D) The distribution of HCV 6 in mainland China. Data for three provinces were not shown because of the lack of positive cases (Xinjiang, Tibet, Beijing).

References

    1. Mohd Hanafiah K, Groeger J, Flaxman AD et al. Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology 2013; 57: 1333–1342.
    1. Cui Y, Jia J. Update on epidemiology of hepatitis B and C in China. J Gastroenterol Hepatol 2013; 28 (Suppl 1): 7–10.
    1. Messina JP, Humphreys I, Flaxman A et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology 2015; 61: 77–87.
    1. Aceijas C, Rhodes T. Global estimates of prevalence of HCV infection among injecting drug users. Int J Drug Policy 2007; 18: 352–358.
    1. Cuypers L, Ceccherini-Silberstein F, Van Laethem K et al. Impact of HCV genotype on treatment regimens and drug resistance: a snapshot in time. Rev Med Virol 2016; 26: 408–434.
    1. Chinese Society of Hepatology CSoID. [Guidelines for prevention and therapy for hepatitis C]. Chin J Exp Clin Infect Dis 2015; 9: 590–607.
    1. Fu Y, Wang Y, Xia W et al. New trends of HCV infection in China revealed by genetic analysis of viral sequences determined from first-time volunteer blood donors. J Viral Hepat 2011; 18: 42–52.
    1. Murphy DG, Sablon E, Chamberland J et al. Hepatitis C virus genotype 7, a new genotype originating from central Africa. J Clin Microbiol 2015; 53: 967–972.
    1. Yan Z, Fan K, Wang Y et al. Changing pattern of clinical epidemiology on hepatitis C virus infection in southwest china. Hepat Mon 2012; 12: 196–204.
    1. Bao YP, Liu ZM, Lian Z et al. Prevalence and correlates of HIV and HCV infection among amphetamine-type stimulant users in 6 provinces in China. J Acquir Immune Defic Syndr 2012; 60: 438–446.
    1. Rao H, Wei L, Lopez-Talavera JC et al. Distribution and clinical correlates of viral and host genotypes in Chinese patients with chronic hepatitis C virus infection. J Gastroenterol Hepatol 2014; 29: 545–553.
    1. Ray SC, Mao Q, Lanford RE et al. Hypervariable region 1 sequence stability during hepatitis C virus replication in chimpanzees. J Virol 2000; 74: 3058–3066.
    1. Ray SC, Arthur RR, Carella A et al. Genetic epidemiology of hepatitis C virus throughout egypt. J Infect Dis 2000; 182: 698–707.
    1. Li Q, Yao Y, Shen Y et al. Assessment of HCV genotypes in Yunnan Province of Southwest China. Virus genes 2017; 53: 190–196.
    1. Westbrook RH, Dusheiko G. Natural history of hepatitis C. J Hepatol 2014; 61 (1 Suppl): S58–S68.
    1. Gower E, Estes C, Blach S et al. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol 2014; 61 (1 Suppl): S45–S57.
    1. Mao XR, Zhang LT, Jiang N et al. [Distribution of HCV genotypes in Chinese Han population with chronic hepatitis C]. Zhejiang Da Xue Xue Bao Yi Xue Ban 2015; 44: 417–422.
    1. Doi H, Apichartpiyakul C, Ohba KI et al. Hepatitis C virus (HCV) subtype prevalence in Chiang Mai, Thailand, and identification of novel subtypes of HCV major type 6. J Clin Microbiol 1996; 34: 569–574.
    1. Ruta S, Cernescu C. Injecting drug use: A vector for the introduction of new hepatitis C virus genotypes. World J Gastroenterol 2015; 21: 10811–10823.
    1. Ju W, Yang S, Feng S et al. Hepatitis C virus genotype and subtype distribution in Chinese chronic hepatitis C patients: nationwide spread of HCV genotypes 3 and 6. Virol J 2015; 12: 109.
    1. Li C, Barnes E, Newton PN et al. An expanded taxonomy of hepatitis C virus genotype 6: Characterization of 22 new full-length viral genomes. Virology 2015; 476: 355–363.
    1. Dashan Hu WZ, Xue R, Li H. [Analysis on genotype and route of infection for 215 Hepatitis C cases in Nanjing and Guangdong areas]. Jiangsu Med J 2014; 40: 597–598.
    1. Gammal RS, Spooner LM, Abraham GM. Failed triple therapy in a treatment-experienced patient with genotype 6 hepatitis C infection. Am J Health Syst Pharm 2014; 71: 204–208.
    1. Cai Q, Zhao Z, Liu Y et al. Comparison of three different HCV genotyping methods: core, NS5B sequence analysis and line probe assay. Int J Mol Med 2013; 31: 347–352.
    1. Tao Wu HL, Xiong L, Wang J et al. [Application of PCR fluorescent probe in identifying genotypes of HCV]. Chinese Journal of Clinical Infectious Diseases 2017; 10: 37–42.
    1. European Association for Study of L. EASL Recommendations on Treatment of Hepatitis C 2015. J Hepatol 2015; 63: 199–236.
    1. Wedemeyer H, Duberg AS, Buti M et al. Strategies to manage hepatitis C virus (HCV) disease burden. J Viral Hepat 2014; 21 (Suppl 1): 60–89.
    1. Zeuzem S, Jacobson IM, Baykal T et al. Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med 2014; 370: 1604–1614.
    1. Feld JJ, Kowdley KV, Coakley E et al. Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med 2014; 370: 1594–1603.
    1. Hezode C, Asselah T, Reddy KR et al. Ombitasvir plus paritaprevir plus ritonavir with or without ribavirin in treatment-naive and treatment-experienced patients with genotype 4 chronic hepatitis C virus infection (PEARL-I): a randomised, open-label trial. Lancet 2015; 385: 2502–2509.
    1. Hsu CS. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med 2013; 369: 678.
    1. Zeuzem S, Dusheiko GM, Salupere R et al. Sofosbuvir and ribavirin in HCV genotypes 2 and 3. N Engl J Med 2014; 370: 1993–2001.
    1. Gane EJ, Hyland RH, An D et al. Efficacy of ledipasvir and sofosbuvir, with or without ribavirin, for 12 weeks in patients with HCV genotype 3 or 6 infection. Gastroenterology 2015; 149: 1454–1461. e1451.

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