Hepatitis C virus (HCV) infection is a worldwide health problem that causes chronic life-threatening diseases, such as liver cirrhosis and hepatocellular carcinoma.1,2 HCV is an RNA virus member of the Hepacivirus genus and Flaviviridae family that is divided into seven phylogenetically distinct GTs (GT1-GT7) and a vast series of subtypes (67 subtypes).3 Molecular epidemiology and phylodynamic analyses have revealed that HCV genomic types and subtypes have distinctive patterns of geographical distribution,1–3 which may be related to different transmission networks and transitional shifting of RFs.4–6 Moreover, the dominant GT in a given population may reflect an outbreak in a particular high-risk group, city or geographic region, which later continues to spread by means of related RFs.5,7

The Latin American region has nearly the lowest HCV prevalence worldwide with 1.5% of anti-HCV antibodies.8,9 In this region, updated studies on the molecular epidemiology of HCV infection are scarce. Nonetheless, HCV GT1 is the most frequent, followed by either GT2 or GT3,8,10 whereas the other GTs (GT 4-7) are less common.10 However, both the prevalence of HCV infection and circulating HCV GTs may not be homogenous throughout Latin America or within regions of the same country.7,11,12 In Mexico, HCV infection is the second cause of clinical hepatitis in adults and children.13,14 The overall HCV seroprevalence is 0.4-1.6% among asymptomatic patients15,16 with local variations,17 yet some risk populations have a higher seroprevalence.18,19 Several cross-sectional studies have been performed to ascertain the geographical distribution of HCV genotypes throughout the country. These studies have shown that the dominant GT1 has a dissimilar geographical subtype distribution. While GT1a accessed by line probe assay (Lipa), and DNA sequencing is more prevalent in West Mexico,7,20 GT1b prevails in Northern-Central Mexico.21,22 In regards to GT2, subtype 2b is frequent in southern Mexico,22 whereas subtype 3a prevails mainly in northern Mexico and in less proportion in the southern region.23,24 Despite proactive blood bank screening, recent studies indicate that HCV infection is an emerging health problem25 which may due to the underestimation of the associated RFs involved in the transmission of HCV. On the other hand, the dynamic process of evolving patterns of HCV GTs distribution, RFs and HCV prevalence over time has not been clearly defined. Herein, we assess the temporal trend of HCV GTs and related RFs that prevail among different age groups of Mexican HCV-infected patients from two distinct geographical regions (CW and NE regions of Mexico) in order to improve information about evolution and trends of HCV disease.

In this study, the overall HCV genotypic distribution (GT1 > GT2 > GT3) among the studied population was consistent with previous data from Mexico,7,21–24,33–35 but contrasting with the epidemiology of HCV infection (GT1 > GT3 > GT2) reported from Western countries and Australia.36–38 While the prevalence of GT1a remained stable in the CW region, the prevalence of GT3 significantly increased in the total group and the NE region, and GT1b decreased only in the entire group. Likewise, the overall RF pattern was similar to that observed in earlier studies among Mexican CHC patients,7,17,22,33,34 given that in this study, BTb1992 (56%) and surgeries (56%) were highly prevalent, followed by tattooing (18%), and IDU (16%) and other less frequent RFs.

However, marked differences in age-specific pattern of HCV GT and RFs were observed in this study as it has been reported in other countries.1,37,38 In this study, GT3 tended to prevail among youths rather than in older adults (21 vs. 3%; p < 0.001), whereas, GT1b was more commonly seen as older were the patients (16 vs. 31%; p = 0.006). Similar results involving these two GTs have been reported in Europe,37 Canada,37 USA39 and Australia.40 Unlike patients from Lahore, Pakistan,41 blood transfusion is a risk factor rarely seen in Mexican patients with GT3 reported here. This finding is consistent with earlier cross-sectional HCV prevalence studies that have not reported cases of GT3 among blood donors.17,42 However, if the upward trend of GT3 further continues, this may effectually shift the current association of GT1b with chronic liver disease found in this study. Thus, awareness of a potential epidemiological transition of HCV GTs is an essential factor in order to avoid chronic liver disease among distinct risk groups.

As expected, BTb1992 (~70%) and surgeries (~55%) emerged as a relevant RF for HCV infection in patients born before 1959 and 1974, respectively (p < 0.001). However, IDU (≥ 14%), SP (≥ 22%) and tattooing (≥ 18%) emerged as a major RF for patients born upon 1959 (p < 0.001) (Table 2). Moreover, in this study, RFs were also seen to cluster SP, IDU and tattooing positive correlations with males born in 1959 onwards, whereas, BTb1992 and surgeries correlated positively with females born before 1959.

Additionally, a particular transmission route does not always equal a specific GT. In this study, there was a significant association between a high prevalence of BTb1992 (56%) and GT1 (71%) that contrasts to what has been reported in Canada and France. In these countries, a low prevalence of BTb1992 (10%, 32%, respectively) and a high prevalence of GT1 (64%, 57%, respectively) was reported.37 Additionally, both GT1a and GT3 have been significantly associated with IDU in another series of studies.37,39,43 Contrarily, in this study IDU did not stand as an independent RF neither for GT3 alone nor alongside G1a- infected patients. However, in the case of Mexico, HCV GT1 infection may have been introduced by professional blood donors coming from the Unites States.13 Before 1992, routine HCV screening had not been implemented in the country.7,13 Thus, iatrogenic transmission of HCV GT1 could have spread by contaminated blood transfusion, either through obstetric/gynecological surgery in women44 or by general surgery among both genders.7,13

On the other hand, IDUs were uncommon before 1990 in Mexico.13 However, it has been recently suggested that in younger patients, IDUs could currently account for a primary HCV transmission route in Mexico (67%),23 similarly to the United States cases (27-93%).45 Moreover, migration or deportation histories are related determinants that currently have been linked to both new drug trends and risky behaviors. These trends may not only affect the distribution of HCV GTs, but also the continued transmission of HCV infection among returning or deported Mexican migrants46,47 and IDUs along the United States-Mexico border.48

Mathematical estimations have projected that HCV prevalence in Mexico will continue to increase during the next decades, mainly due to low diagnostic and treatment rates,11,49 along with a lack of awareness and education of the disease. Given the historial CHC seroprevalence (2000), the Mexican bimodal pattern25 resembles the ones present in France, Germany, Czech Republic and Switzerland, but with thrice their seroprevalence (1.4% (6), 0.3%, 0.3%, 0.4% and 0.4%, respectively).36,50 Interestingly, they also share the same GT transition found in the present study, being GT3 more prevalent among youths, but not GT1b.36 Additionally, results found here and elsewhere11,46 suggest that Mexican GT1 patients are commonly found with higher VL whereas GT3 patients with a lower one. However, this remains to be confirmed. Noteworthy, advanced liver disease burden is also expected to continue to increase in almost all countries,36,50 whether or not they have a relatively stable chronic HCV prevalence.

Also, this study suggests that cirrhotic patients could be profiled as patients ≥ 50 years old, are infected with GT1 and already exposed to AT. However, further probabilistic sample-size studies are needed to evaluate this possibility, because the patients characteristics might account for the significant treatment rate found across studied DOB (~36%) that could influence the prevalence of cirrhosis found herein (40%).

Finally, the associations observed in the current study provide a descriptive glimpse of the epidemiological data regarding the distribution of HCV GTs in two distinct geographical regions of Mexico. However, further studies are warranted to elucidate the underlying mechanisms explaining the above-mentioned epidemiological data from these regions and nationwide. Prevention and treatment strategies are also required to avoid the incidence and spread of new cases of HCV among distinct risk groups based on regional surveillance data. Likewise, molecular epidemiology studies, that rely on DNA sequencing, evolutionary (molecular clock) and phylogeographic analyses of HCV sequences are warranted. Such updated information may provide the actual source of infection and routes of dissemination of the HCV infection in Mexico, as well as a better understanding of the evolving genetic variability and distribution of the HCV subtypes.

In conclusion, GT1a prevalence in CW Mexico remained stable throughout the studied period, whereas GT3 increased as GT1b decreased in younger patients from CW and NE regions, along with associated RFs. The data shown in this present study can help to understand the transitional epidemiological shifting of HCV GT and related RFs among HCV-infected patients in Mexico.

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  AT: antiviral therapy.

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  BTb1992: blood transfusion before 1992.

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  CHC: chronic hepatitis C.

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  CW: Central West.

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  DOB: date of birth.

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  DP: dental procedures.

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  GT(s): genotype(s).

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  HCV: hepatitis C virus.

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  IDU(s): injection drug user(s).

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  Lipa: line probe assay.

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  NE: North-East.

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  RF(s): risk factor(s).

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  SP: sexual promiscuity.

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  VL: viral load.

This work was partially supported by grants: 1) CONACyT (SALUD-2010-C01-139085) to SR, 2) CONACYT (CB2010-01155082) and the Universidad Autónoma de Nuevo León (PAICYT-SA1161-05) to AMRE, and 3) CONACYT-GRANT 162077 to LEME. LEME, AP and MCGR are representative recipients for the sponsorship given to the “Red Temática de Colaboración Académica en Fisiopatología de las Enfermedades Hepáticas, SEP-Promep, Mexico”.

We are especially grateful to the medical and technical staff of the Liver Unit at the Internal Medicine Department, Hospital Universitario de la Universidad Autónoma de Nuevo León (UANL) and Hospital Civil de Guadalajara, Fray Antonio Alcalde.