Epidemic spread of hepatitis C virus genotype 3a and relation to high incidence of hepatocellular carcinoma in Pakistan

Abstract

Studies conducted in different populations worldwide revealed an association between HCV genotype 1 and the development of hepatocellular carcinoma (HCC) than in infection with other HCV genotypes. There are reports which reveal the association of HCV genotype 3a (HCV-3a) with hepatic steatosis and fibrosis but its relation with the development of HCC has not been investigated. In Pakistan, where the incidence of HCC is increasing, 189 patients with chronic liver disease including 82 with HCC were enrolled. HCV genotypes were determined by phylogeny in the NS5B region and the epidemic history of HCV-3a was examined using coalescent theory based methods. HCV-3a was the predominant genotype (81.4%) in the cohort studied, followed by 3b (9.3%), 3k (2.3%), 1a (1.5%), 1c (1.5%), 1b (0.8%), and 2a (0.8%) where 76% of HCC and 86% of non-HCC were infected with HCV-3a. The significant factors associated with HCC were older age (mean +/- SD) 55.8 (+/-9.9) (P < 0.0001), and male gender (P < 0.001). HCV RNA was significantly higher in patients with HCC and chronic hepatitis than in liver cirrhosis (P < 0.0001). Molecular evolutionary analysis revealed a distinct phylogenetic cluster of HCV-3a in Pakistan and an estimation of the effective number of HCV infections indicated the appearance of HCV-3a in this region around 1920s and a rapid exponential growth in the 1950s. This indicates that the epidemic spread of HCV-3a occurred earlier in Pakistan than in other countries in which this genotype has been reported. HCV-3a which spread earlier in Pakistan may be associated with an increasing incidence of HCC.

Spatiotemporal Reconstruction of the Introduction of Hepatitis C Virus into Scotland and Its Subsequent Regional Transmission

“…As short sequences can adversely affect the calculation of important parameters in MCMC analyses, they were not included in this analysis. The evolutionary rate of the Gt3a sequences from the global data set was 1.65 ϫ 10 Ϫ3 s/s/y which is slightly higher than previously noted (1.3 ϫ 10 Ϫ3 s/s/y [20] [22]), but another study has estimated that extant global Gt3a sequences coalesced much earlier, approximately 300 years ago (20). In the latter study, however, three sequences from Pakistan formed a distinct cluster which was phylogenetically distant from the remainder of the Pakistani sequences and sequences from other countries; without this outlying cluster, the remaining global Gt3a pool coalesces approximately 80 years ago, supporting our findings.…”

“…The second peak of Gt3a lineage expansion (1951 to 1975) suggests that migration from the Indian subcontinent may be the source of currently circulating Gt3a sequences in Scotland. Approximately 1% of the Scottish population originates from Pakistan, where epidemic Gt3a transmission has been shown to have occurred earlier than in any other country (22). Extant Gt3a strains in the United Kingdom are considered to originate from the Indian subcontinent where HCV is endemic (23) via migration which peaked in the 1950s and 1960s, and subsequently, these sequences pro-…”

Molecular Epidemiology and Genetic History of Hepatitis C Virus Subtype 3a Infection in Thailand

“…Genotypes 1, 2 and 3 are distributed worldwide and contribute to the majority of HCV infection. Subtypes 1a and 1b are most common in Europe, the USA and Japan, and subtypes 2a and 2b are predominant in Japan, North America and Europe, while subtype 3a is most prevalent in the Indian subcontinent and Thailand [11,12,13]. On the other hand, the less common genotypes 4, 5 and 6 are restricted to certain geographic areas.…”

“…Previous studies have demonstrated that the initial spread time of HCV infection is associated with the prevailing socioeconomic conditions, reflecting the present incidence as well as predicting the future development of HCC [11,27,28,29,30]. Because HCC is associated directly with the incubation period of HCV infection and HCV subtype 3a is the predominant genotype [11,30], the initial spread of HCV subtype 3a among the Thai population may occur later than in other countries. …”

Vírus da Hepatite C e Células Mononucleares do Sangue Periférico

“…Portanto, o rastreamento da transmissão é fundamental para o controle do VHC e da Hepatite C (Khudyakov, 2012). A história da epidemia de Hepatite C é muito dinâmica e em meados do século passado, houve um rápido aumento no número total de infecções, sendo os subtipos 1a e 1b prevalentes mundialmente (Magiorkinis GE, et al, 2009;Iles JC, et al, 2013), o genótipo 2 e o subtipo 5a encontrados na África (Tanaka Y, et al 2006;Markov PV, et al 2009) e subtipo 3a localizado no Paquistão e Ásia Central (Tanaka Y, et al 2006;Khan A, et al 2009). Posteriormente, durante a década de 1980 e início de 1990, observou-se um rápido declínio no número casos de Hepatite C aguda nos EUA (Williams LT, et al 2011).…”