HBV DNA was analyzed in an Amerindian population exhibiting moderate prevalence of infection (17% anti-HBc), compared to other Venezuelan Amerindian populations, such as that of the Yanomami (58% anti-HBc). As described previously, this community showed a lower rate of acquisition of anti-HBc antibodies (1.4% in individuals less than 15 years old), compared to the Yanomami for example (38% in individuals less than 15 years old) . The lower prevalence of HBV exposure and infection in this Amerindian community may be due to its geographic location, since being located near the main urban centre of the state, it is closer to health services. In addition, a more frequent contact with other civilizations may have modified some socio-cultural practices, leading to a reduction in HBV transmission, together with more effective accomplishment of vaccination programs. Despite the lower rate of HBV acquisition, this community still exhibited a 17% prevalence of anti-HBc antibodies, with a low prevalence of HBsAg positivity. OBI was shown in this Piaroa population, both in individuals with HBV serological markers and, with less frequency, in individuals with silent exposure to infection. Follow-up analysis in 15 individuals confirmed the presence of OBI, since HBV DNA could be detected in an intermittent form. The frequency of OBI in this community is higher than that found previously in blood donors from Caracas (4.3%) , and in Mexican and North American Amerindians (14.2% and 9.7% respectively) [7, 10], although the methods used to determine OBI are somehow different between these reports. OBI is common among immunosuppressed individuals, due either to HIV [11, 12], or to other causes . It is important to note that Amerindians may be immunologically compromised due to multiple parasitic and bacterial infections, to add to the high prevalence of HBV exposure . As expected, the prevalence of OBI infection was also higher when HBV serological markers of previous exposure (anti-HBc and/or anti-anti-HBs) were present. In addition, this Piaroa population exhibited a good response to vaccination as evidenced by the high frequency of seroconversion observed in 2009, after vaccination.
As anticipated, phylogenetic analysis showed the presence of the HBV genotype F3, and no particular strain was shown to be associated with OBI pattern, since the isolates were closely related to HBV isolates circulating in other Piaroa and Yanomami Venezuelan individuals . In a previous study of Venezuelan blood donors, OBI was significantly associated with a higher prevalence of genotypes A and D (70%), while genotype F was predominant in overt cases (76%) . The present study shows that OBI can also be very frequent among individuals exclusively exposed to HBV genotype F. OBI has been described recently in Nahuas and Huichol native populations from Mexico, and HBV genotype H was found in several cases . Three studies have reported a predominance of genotype A and particularly D in cases of OBI [15–17], while in other studies, genotype A was present at a similar prevalence in overt and OBI infections . Altogether, these studies suggest that OBI appears not to be restricted to a particular genotype. In our study, one subject was infected by a wild type virus with variants coding for core defective proteins, a situation already described in Venezuelan blood donors with OBI . Most of the subjects with OBI were related, suggesting than familiar transmission might have played a role in this situation. However, the number of samples analyzed and the short genomic sequence available for study did not allow testing of this hypothesis.
There is accumulating evidence of a pathogenic role for OBI . OBI may contribute to the progression of liver fibrosis and HCC development , thus the potential benefits of antiviral treatment is in debate [6, 21]. As shown in this study and in others, vaccination of those populations at risk for OBI should be undertaken as it may bring some benefits to these communities .