Introduction

Hepatitis B virus (HBV) infection is a health problem worldwide, with approximately 400 million chronically infected people. The endemicity of a given population is determined by the presence of HBsAg in serum and is classified as low, intermediate, and high endemicity according to the percentage of infection (2%, 2–7.9%, and ≥8%, respectively) [1–5]. However, there is limited information about the epidemiology of HBV infection in many countries of low endemicity.

Asia is a region of high endemicity [1–5] for HBV infection, whereas in America, low or intermediate endemicity is prevalent [6–8]. However, several studies have revealed the existence of high endemic areas, especially within the indigenous populations throughout the continent [9–11]. Another difference between both continents besides the genetic background of the population is the HBV genome variability and geographical distribution. Genotypes B and C predominate in Asia, whereas genotypes F and H predominate in Latin American [9–13]. Genotype H has been detected mainly in Mexico [14, 15] and is scarce in some countries of Central America and abroad [16, 17]. In contrast, genotype F appears to be predominating in most countries of Central and South America [18–20].

The association between a specific HBV genotype and native population has led to the analysis and follow-up of the transmission routes between regions, especially in this present era of global mobility, since HBV infection acquisition from one region to another has been recently reported [21].

On the other hand, further evidence revealed that HBV genotype might also be associated to the natural course of infection and response to antiviral treatment [22–24]. This association has been documented mostly from countries of high endemicity and creates the necessity in those countries with low endemicity to further investigate this association, since different treatment and prevention strategies could be required for disease control.

Furthermore, the natural course of HBV infection and complications of the disease are mainly referred from countries with high endemicity of HBV infection and specific genotypes, and such evidence is generally extended to other countries, such as Latin America, and particularly to Mexico [6, 25, 26]. However, HBV genotype H is predominant in Mexico unlike the rest of the American countries and the world. This raises the question about the number of acutely or chronically HBV-infected people in the country, the main risk factors involved in infection transmission, and the prevalence of HBV-related liver diseases and complications. To answer this question, it will be also important to understand why hepatocellular carcinoma (HCC) is rare in Mexico [27, 28] considering the fact that the main causes of liver cirrhosis are alcohol, followed by hepatitis C virus (HCV) infection, and, only in 5.2% of the cases, HBV [29]. Although obesity along its associated metabolic complications is currently a main health problem in Mexico [30], the burden of their pathophysiological states in the development of liver disease is relatively unknown.

By performing a systematic review and meta-analysis of the research literature on HBV infection, the aim of this study was to estimate the HBsAg and antibody to hepatitis B core antigen (anti-HBc) seroprevalence to analyze the course of HBV infection from 1987 to 2007 and to identify the main risk factors involved and further understand the association of HBV with HCC in Mexico.

Material and methods

Main search strategy

This study was conducted following the general methodology recommended for systematic reviews [31, 32]. The main research questions formulated to guide the study search were as follows: (1) “Is Mexico a low endemicity region for HBV infection?”; (2) “Have there been changes in the HBsAg seroprevalence from 1974 to 2007?”; (3) “Which are the main risk factors involved in HBV transmission?” and (4) “Is there an association between low prevalence of HBV infection and HCC?”

The initial approach was to electronically search for both English and Spanish publications concerning the epidemiology of HBV infection in Mexico. For English and/or Spanish language studies, the databases NLM Gateway, MEDLINE, PubMed, Artemisa, Medigrafic, IMBIOMED, and Lilacs were searched by using the following terms: “HBV,” both spelt out and abbreviated, “hepatitis B prevalence,” “epidemiology,” “risk factors,” and “HBsAg” combined with “HBV infection” and “Mexico.” As for search terms in Spanish, “VHB,” “hepatitis B” (and) “prevalencia,” “infección de la hepatitis B en Mexico,” alone and/or combined with “HBsAg,” “epidemiologia,” and “factores de riesgo” were used.

All articles were reviewed and their corresponding reference lists were revised to identify additional material that had not been initially detected, and then were later either retrieved by a new electronic search or searched manually. The period for this review was set from January 1985 up to August 2007 and also the first epidemiological study dated 1974 was considered as a reference point [33].

Eligibility criteria

First-round review criteria for the selection of full-text publications included sufficient and explicit data on the year of publication, time period, selection of study group, location of study, number of subjects studied, and number of subjects positive to HBsAg, anti-HBc, or stated crude prevalence. Information related to risk factors was also extracted.

Differences in the sensibility of the HBsAg detection assay reported in each study were examined. Our strategy was to enlist each study by the year of performance, assay used, and test generation. Only those studies that tested HBV serological markers with assays that had third-generation sensitivity were included for meta-analysis. Among the different study group categories, the three main HBsAg detection assays identified were from Abbott Laboratories (Abbott Park, IL), Auszyme Monoclonal, IMx HBsAg (V2), and AxSYM HBsAg (V2). During the time period of this review, at least 90% of the studies were performed with Auszyme Monoclonal or IMx HBsAg (V2), followed by AxSYM HBsAg. Furthermore, this preliminary analysis also revealed that a second-generation assay, counterelectrophoresis (CEP), was used in a general population study performed in 1974 and thus was not included for the next stage of meta-analysis.

In studies performed in pregnant women, three different assays were detected, Auszyme Monoclonal (Abbott Laboratories), Hepanostika HBsAg Uni-form II (Organon Tecnika, B.V., The Netherlands, currently distributed by BioMerieux, France), and Monolisa HBsAg Plus (Bio-Rad Laboratories, Marnes-la-Coquette, France). In this case, studies were not included in meta-analysis.

As for meeting eligibility criteria for the abstracts that appeared during the strategy search, these were included if the same eligibility criteria were completed and excluded if data were found published as full-text publications. Direct searches were performed within specific Web sites of several national associations of medical specialists related to HBV infection to retrieve online abstracts covering all meetings enlisted.

Data extraction, synthesis, and meta-analysis

Extracted data were synthesized in tables and figures by different criteria to analyze the information and answer research questions. Data grouped by crude prevalence followed the categories established by the World Health Organization criteria of endemicity [2] according to HBsAg prevalence, that is, low prevalence (<2%), intermediate prevalence (2–7.9%), and high prevalence (≥8%).

High-risk groups were defined according to the standard criteria of high-exposed individuals to HBV infection, such as female sex workers, healthcare workers, and hemodialyzed and institutionalized patients. The number of studies was superior to the number of publications, since in some cases, more than one population group was reported in a single article.

From the data of primary studies, 95% confidence intervals (CIs) for crude seroprevalence of each study report and different estimates on the overall seroprevalence in Mexico were calculated as previously described [34]. Briefly, the pooled prevalence (PP) was calculated as follows: PP = ∑n i /N, where n i  = number of seroreactive cases in each study and N = total number of individuals. The mean prevalence (MP) was estimated as follows: MP = ∑prev i /S, where prev i  = prevalence in each study and S = number of studies. We also calculated the weighted mean prevalence (WMP) to restrict the bias that may impose the heterogeneous nature of the reports. It was calculated as follows: WMP = ∑(ωI·prev i )/∑ωI, where ωI = 1[prev i (1 − prev i /N i ] and N i  = total number of subjects studied. Here, WMP is regarded as the most accurate method to estimate prevalence of HBV infection after considering several reports. This method has proven to be reliable when combining a number of studies with inherent heterogeneity in sample size and effects. All estimates on seroprevalence are expressed as proportions and the respective 95% CI. Chi-square statistics were used to test differences in prevalence estimates between studies.

Results

General scope of publications on HBV infection prevalence

The epidemiological evidence of HBV infection prevalence in Mexico was documented by 1 of 2 serological markers, HBsAg or anti-HBc; however, in some cases, they were not simultaneously used in the same study. A total of 50 studies collected from 47 publications for this systematic review were considered eligible for meta-analysis. The main study groups were blood donors (n = 25), followed by female sex workers or men with high-risk behavior (n = 8), healthcare workers, and students (n = 6), and to a lesser extent, patients with liver diseases (n = 4), native communities (n = 3), and hemodialysis patients (n = 2), as well as psychiatric patients and emergency department attendees (1 of each). The studies performed in general population (n = 3) and pregnant women (n = 9), not included in the meta-analysis, were examined separately for comparative purposes only.

Prevalence of HBV infection by HBsAg marker

Nationwide survey studies

Each nationwide survey was performed by different institutions, first in 1974 and later in 1997 and 2000, in which none had consecutive follow-ups [7, 33, 35] (Table 1). Three types of assays were conducted with different levels of sensitivity. The earliest study from 1974 used a CEP-based assay, whereas the following studies used third-generation assays, such as Auszyme Monoclonal and AxSYM HBsAg (V2). However, all three studies revealed a low HBV seroprevalence of less than 0.3%.

Table 1 HBV seroprevalence in nationwide general population surveys
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Blood donors

In total, 21 publications [36–56] were concerning HBsAg seroprevalence in blood donor banks that involved 1,130,485 people from 10 states and Mexico City (Table 2). The crude seroprevalence reported in each study ranged from 0.073 to 1.22%. When the results from blood donors were analyzed separately by using assays as mentioned in the “Material and methods” section, no significant differences were detected among Auszyme Monoclonal, IMx HBsAg (V2), and AxSYM HBsAg (Abbott Laboratories) (data not shown). Thus, the overall estimated MP, PP, and WMP were 0.42% (95% CI, 0.29–0.56), 0.27% (95% CI, 0.26–0.28%), and 0.61% (95% CI, 0.59–0.62), respectively.

Table 2 Mean, pooled and weighed-pooled HBsAg prevalence rates estimated in Mexican study groups
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Geographical distribution of HBV infection in Mexico

These results are in agreement with other studies conducted in Mexican blood banks [57], which revealed differences in the geographical distribution of HBsAg seroprevalence in blood donors among the states within the country (p < 0.05). Figure 1 denotes the Mexican states where the individual HBsAg seroprevalence was higher than the WMP HBsAg seroprevalence estimated for this group (≥0.6%, Table 2). Populations with a higher prevalence were located in Mexico City and surrounding states, as well as located in the northern and southern borders of the country where nonpermanent migration is common. It was interesting to note that these localities are also within or near regions where the main native Mexican groups live.

Fig. 1
figure 1

Geographical distribution of HBV infection in Mexico. Encircled areas: Regions of major native Mexican population, ٭: Blood banks that report HBsAg prevalence ≥0.6%

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Pregnant women

Nine studies of HBV prevalence in pregnant women [58–61] involved 19,246 persons, in which four studies were carried out in Mexico City and five in other states. Three HBsAg detection assays were identified with different sensitivities. Significant changes in the prevalence of HBsAg in pregnant women were observed when studies were compared with Monolisa HBsAg Plus that had been recently introduced into the country. This variability in prevalence may be caused by differences in assay sensitivity and the natural variability of HBV genotype among Mexicans. Table 3 depicts studies performed in pregnant women in which both HBsAg and anti-HBc were tested in some cases.

Table 3 Prevalence of HBsAg and anti-HBc in pregnant women using different immunoassays commercial kits
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On the other hand, HBsAg prevalence was either absent or low in infants born to HBsAg-positive mothers [58, 60], suggesting that vertical HBV transmission is not the main cause of infection.

High-risk groups

The estimates of HBsAg seroprevalence of blood donors compared with high-risk groups including healthcare workers [62–67], females sex workers [68–75], patients with liver diseases [29, 40, 76, 77], hemodialysis patients [78, 79], emergency department attendees [80], and psychiatric patients [81] are depicted in Table 2. The estimates from the native Mexican population [82–84] are also included in this group based on an HBsAg seroprevalence higher than the general population and blood donors.

Prevalence of HBV infection by anti-HBc marker

Anti-HBc determination was performed only in 23 of the 50 publications reviewed in this study in which HBsAg was also tested (Table 4). As could be expected, anti-HBc seroprevalence increased proportionally as HBsAg seroprevalence increased. However, despite the high anti-HBc seroprevalence in native Mexican groups, HBsAg prevalence was low or intermediate (Fig. 2).

Table 4 Mean, pooled and weighed-pooled anti-HBc prevalence rates estimated from Mexican study groups
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Fig. 2
figure 2

HBsAg and Anti-HBc prevalence in Mexican study groups. GP General population, BD Blood donors, HCW Health care workers, FSW Female sex workers, NM Native Mexican groups, LD Liver disease patients, ERA Emergency room attendees, PP Psychiatric patients, HEMO Hemodialysis patients, ? = Unknown

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Main risk factors for HBV infection in Mexican population

Risk factors determined by univariate or multivariate analysis and associated to anti-HBc prevalence by odds ratio (OR) were reported in general population [35], pregnant women [61], healthcare workers [66], and female sex workers [73]. The main risk factors were (i) age at first sexual intercourse above 25 years in general population and in pregnant women, with a reported OR of 3.24 (95% CI, 1.44–7.28) and 5.1 (95% CI, 1.4–19.1), respectively; and (ii) age above 33 years in female sex workers with an OR of 5.4 (2.2–13.0). Marital status denoted an OR of 1.92 (95% CI, 1.0–3.6) in single or divorced pregnant women and 7.4 (95% CI, 3.9–14.2) in widows from studies in general population. Other important risk factors related to HBV transmission were blood transfusion, residence in cities with high migration rates or near the northern or southern borders, and within the rural areas with low economic status. In these particular conditions, an OR of 4.8 (95% CI, 2.1–11.3) was reported in female sex workers with antecedents of blood transfusion and an OR of 3.2 (95% CI, 1.57–6.51) in pregnant women living in cities with high migration rates. In general population, an OR of 2.8 (95% CI, 1.4–4.4) and 1.1 (95% CI, 0.8–1.6) was reported in individuals living on the border or within the rural areas, respectively. Four or more sexual partners, promiscuity, tattooing, and antecedents of surgery were risk factors detected with a high frequency; however, ORs were neither estimated nor reported.

Age-related incidence, prevalence of HBV infection, and HCC

To have a wider scope regarding HBV infection in Mexico, data related to the annual and age-related incidence rates of acute HBV infection reported by the Mexican Health Secretariat were analyzed. An incidence of 0.83 new cases per year per 100,000 inhabitants was reported in the year 2000 [85, 86]. However, further investigations have revealed that such low incidence of HBV infection has remained less than 1% from 1990 to date. Also, in the population older than 20 years, the incidence rate was 3.5 times higher than in those younger than 20 years throughout this same time period [85].

The age-related prevalence of HBV infection by anti-HBc marker is depicted in Fig. 3. The higher increase of HBsAg prevalence in adults than in the younger population is confirmed by studies that reported the anti-HBc prevalence at different ages. In two different studies from native Mexican groups and two from the general population, an important increase in the prevalence of anti-HBc marker around the age of 15, when sexual activity initiates, and older ages was observed. Similar results were obtained in the first epidemiological study performed in 1974 [33].

Fig. 3
figure 3

Age-related prevalence of anti-HBc marker in Mexican study groups. *Ref. [84], **Ref. [83], ***Ref. [7], ****Ref. [35]

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From 1992 to 2002, the Mexican Health Secretariat registered an average of 13,688 new cases of cirrhosis per year [103], whereas in a national multicenter study, HBV infection accounted for 5.2% of all cases of liver cirrhosis [29]. Such low prevalence of HBV infection is associated with a very low incidence of HCC in Mexico City [27] and the west of the country [28], which are the main population regions.

Causes of steady HBV infection in the last 30 years

Two main factors presumably involved in the prevalence of HBV infection in Mexico is horizontal transmission as reported in young and adult Mexican populations and the fact that a low HBsAg seroprevalence has remained steady from 1974 to date. To explain this state, governmental official data [87] and estimations reported elsewhere [88] were obtained for population size and the number of people both younger than and older than 20 years was determined. Figure 4 provides a comparison of the Mexican population growth rate from 1790 to 2008 and the distribution percentage of the population both younger than and older than 20 years. The years when blood bank regulations were introduced to control HBV infection in Mexico are indicated. A switch in the age distribution in the population both younger than and older than 20 years was observed between 1950 and 1990. Therefore, if sexual activity is the main risk factor in the transmission of HBV infection, this figure appears to explain why the HBsAg seroprevalence has not changed since 1974 in spite of the introduction of sanitary regulations in 1987.

Fig. 4
figure 4

Causes of steady HBV infection in the last 30 years, 1: 1987, Prohibition of blood commercialization, 2: 1993, HCV and HBV serological detection is mandatory in blood banks, 3: 1999, Universal vaccination of HBV initiates in newborns

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Discussion

To address the questions, whether Mexico is a low endemic region for HBV infection and whether changes in the HBsAg seroprevalence have occurred from 1974 to 2007, we found a limitation not only in the number of studies performed to date but also in the methodology used in each case. The immunological tests for the detection of HBsAg serological tests have evolved since the decade of the 1970s from low specificity and sensitivity to the identification of escape mutants in specific populations as reported recently [89–93].

The first large epidemiological study performed in Mexico in 1974 by Landa [33] used a CEP-based assay, which was later considered as a second-generation methodology for the detection of HBsAg. This immunological method was characterized because of its capacity to identify two of three panels used at that time by the Food and Drug Administration, Bureau of Biologics Reference Panel [94]. However, by comparing the second- and third-generation methods, the CEP assay was shown to have 0.9% of false positives against 12.1% of false negatives [89]. Based on this information, it could be deduced that the 0.29% seroprevalence obtained at that time, even with an increase of 10% in HBV seropositives, would remain as a population of low HBV endemicity.

The epidemiological studies performed in 1997 and 2000 also showed HBsAg seroprevalence below 0.3% by using third-generation tests. Besides the methodological differences, further limitations were noticed. In the first epidemiological study, actually the largest performed to date with 19,000 people sampled, the main limitation of this study was that the population studied was younger than 50 years [33]. In the second study analyzed in 1996 [7], there was no follow-up to compare data with the former study and information for population older than 40 years was lacking. The third study appeared to be complementary to the second one, since it was performed almost at the same time and included groups with persons older than 40 years but not younger than 21 years [35].

From 1987 to 1995, Auszyme Monoclonal was the main immunological test used in blood banks throughout the country. However, the analysis of the data that used this immunological test and comparison with those performed years latter, whether IMx or AxSYM, did not show statistical significant differences (data not shown). Therefore, considering that data from blood donors are obtained only from adult population, then, at least from 1987 to date, HBsAg prevalence has also been low in this group although higher than in general population. These data are in agreement with a recent study that showed no changes in the prevalence of HBV, HCV, and HIV in national blood banks from 1999 to 2003 [57].

On the other hand, those studies performed in pregnant woman were not included in the meta-analysis either because of differences in the immunological test or because of large variability in results obtained in each study. If these results are considered as valid, then they may indicate an important variability in sensitivity and specificity of all the immunological test used to date, considering that they have been designed mainly for genotypes A and/or D [90, 92, 95–98] whereas in Mexico and Latin America, genotypes H and F predominate, both with a higher genetic variability than any of the other genotypes reported [13].

Then, if this were the case, discrepant results such as those reported in native Mexican with a high prevalence of anti-HBc but a low prevalence of HBsAg could be explained because of variability in results of the immunological test that was used. This is an area that deserves further investigation. However, data obtained to date indicate that in most of the Mexican populations, a low HBsAg seroprevalence is predominant, although an underestimation could be latent. Thus, even if more sensitive and specific immunological tests were used, it would be difficult in such populations to shift HBsAg seroprevalence from low to high endemicity.

There is limited information about the distribution of HBV infection throughout the country; however, since 1974, different studies [33, 50, 57, 82] have shown heterogeneity in HBsAg seroprevalence, which appears to be due to the native Mexican populations. More than 60 native groups with a population of more than 10 millions could have HBsAg seroprevalence ranging from intermediate to high endemicity if studies are extended and confirmed in these populations.

In 2000, the Mexican population was 97.5 million, of which 56.4% were adults [87, 88]. Therefore, if HBsAg WMP from blood banks (0.61%) is considered, then we would expect that at least 300,000 adults were HBV infected at that time. The first study preformed in 1974 by Landa [33] showed that in Mexico City more than 6% of the population studied at that time have had HBV infection. Two latter studies performed in general population indicated that 1.4 and 3.3% were anti-HBc positive, respectively, suggesting at least 2.4 million people have been infected with HBV until the year 2000.

Sexual transmission was considered as an important risk factor based on the association of the number of persons that have had the infection during the age of sexual activity and the increasing number of older infected people as confirmed by subsequent studies [7, 33, 35]. For example, in a study performed recently [35], it is emphasized that a 1:200 ratio for people between the ages of 20 and 30 years have had the infection whereas the number of persons infected increases to a 1:10 ratio in those older than 50 years. The present data analysis confirms that horizontal transmission predominates in Mexico as reported in other areas of low HBV endemicity [3].

Although vertical transmission is also observed, it is not the main route of transmission as corroborated by the low or very low HBsAg seroprevalence in children younger than 10 years [99, 100]. However, besides the sexual transmission of HBV infection in the adult population, the fact that those older than 50 years are infected in a higher proportion may be due to the fact that before the 1960s in most of the Mexican villages, it was common to use a single syringe for several patients.

Therefore, the epidemiological studies performed to date indicate that the main risk factors involved in HBV transmission in Mexico are sexual activity and the exposure to contaminated body fluids and contaminated surgical equipment. People living in low social status areas have a further risk of infection with contaminated body fluids owing to the lack or deficiency of sanitized procedures. The predominance of these risk factors besides the late introduction of blood bank regulations [101], such as prohibition of blood commercialization in 1987, the mandatory detection of HCV and HBV serological markers in 1993, and the application of the HBV vaccine in 1999 in newborns [102], appears to explain why the prevalence of HBV infection remains steady in Mexico since 1974.

The same risk factors appear to explain the high prevalence of HBsAg and anti-HBc in specific population groups such as female sexual workers, as well as those who have frequent contact with contaminated surgical equipment and biological fluids, such as healthcare workers, hemodialysis patients, and emergency department attendees. Both risk factors may also prevail simultaneously in the same group and in other groups such as prison inmates and psychiatric patients.

Although blood transfusion has also been a common antecedent in HBV-infected patients, in this present analysis, it was not the main risk factor as in HCV infection [34]. Unlike other countries, intravenous drug abuse is not common among drug addicts in Mexico, instead marijuana, inhalants, and recently, an increase in cocaine abuse are prevalent [103]. These data indicate that the frequency of risk factors among countries is variable and therefore raises the necessity to recognize them individually to establish specific strategies of HBV infection control in each country.

In spite of the fact that Mexico and other countries have a low endemicity for HBV, infected individuals can continue transmitting HBV infection. This generates the need of additional specific strategies along with blood bank regulations, such as vaccination programs in young and adult populations to avoid HBV transmission by sexual relationships, better compliance to sanitary procedures, and more effective sterilization methods in hospitals and healthcare workers’ offices, including dentists. The use of highly sensitive tests for HBV detection, such as nucleic acid testing (NAT), is also warranted. HBV vaccine, which was enforced in newborn vaccination programs in 2000, will have an important effect against the acquisition of HBV infection in the next generation within 20 or 30 years if HBV genome variability due to genotype or escape vaccine mutants does not interfere.

The natural course of HBV infection has been described in international reports on the basis of clinical observations from patients primarily from high endemic areas. Such information has been mistakenly extrapolated to predict the course of disease or its complications for patients in other countries, as in the case of the Latin American studies [6, 7]. The fact that in Mexico, HBV genotype H is predominant [14, 15] and that the HBsAg seroprevalence is low or very low in spite of the high frequency of anti-HBc in some of the studies groups may be indicative of that the natural course of liver diseases may be different from that reported in Asia and even South America where HBV genotype F predominates. Another possibility is that the diagnosis of liver disease caused by HBV infection is omitted and therefore remains underestimated mainly because NAT is not commonly performed in the country and the prevalence of occult hepatitis B in patients with liver cirrhosis is unknown to date.

On the other hand, the overall average of prevalence of cirrhosis per year reported by the Mexican Health Secretariat [85] and the low prevalence of HBV infection appear to be associated with the low incidence of HCC reported to date [27, 28]. These data are conciliatory with estimates made from the total Mexican population and the lowest percentage of HBsAg-positive patients (1%) who will present with chronic hepatitis per year (n = 3,000) and cirrhosis (20%; n = 600), and for patients with cirrhosis, only 18–30 cases would be expected (3–5%) to develop HCC per year. On the basis of these estimates, then only 0.2% of HBsAg-positive patients will develop liver cirrhosis and 0.01% HCC, data that are similar to those reported earlier [28]. These data reveal that Mexico could have the lowest incidence of HCC per 100,000 per year (0.01–0.02%) than among North America (1.8–2.0%), Europe (1.5–3.4%), South America (3.8–4.7%), and very distant Asian countries such as Japan where the incidence of HCC is estimated to be 20 per 100,000 per year [104, 105].

In Japan, HBV genotypes B and C are predominant and the reported prevalence of both HCV and HBV is 1.5% [105]. However, in the former, 80% of infected individuals become chronic carriers, whereas in the latter, only 20% develop chronic hepatitis and cirrhosis [105]. In contrast, in Mexico, a lower HBV and HCV prevalence [34] and the predominance of HBV genotype H [14, 15] may indicate that viral genotypes play an important role in the development and course of liver diseases. Therefore, further investigations regarding the variability of HBV genotype H compared with other genotypes and the genetic characteristics of the human population, as well as environmental factors, will be necessary in the future.