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Hepatitis Delta Prevalence in South America: A Systematic Review and Meta-Analysis

Abstract

Hepatitis delta virus (HDV) has been associated with acute or chronic hepatitis in Latin America, but there is no prevalence study covering South American countries. This meta-analysis aimed to estimate anti-HDV prevalence through a systematic review of published articles in English, Portuguese and Spanish until December 2017. Searches were conducted in Health Virtual Library, Capes, Lilacs, PubMed, and SciELO, according to defined criteria regarding participant selection and geographical setting. Study quality was assessed using the GRADE guidelines. Pooled anti-HDV prevalence was calculated using the DerSimonian-Laird random-effects model with Freeman-Tukey double arcsine transformation. Out of the 405 identified articles, only 31 met the eligibility criteria for inclusion in the meta-analysis. In South America, pooled anti-HDV prevalence among hepatitis B virus carriers was 22.37% (95% confidence interval: 13.72-32.26), though it appeared less frequently in some countries and populations, according to the data collection date. The findings indicated significant successive reductions in anti-HDV prevalence over thirty years. However, there was a scarcity of HDV epidemiological studies outside the Amazon Basin, notably in the Southwest continent and absence of target population standardization. There was a high HDV prevalence in South American countries, despite differences in methodological characteristics and outcomes, highlighting a drastic decline in the last decades. Future studies should identify HDV prevalence estimates in other regions of the continent and identify risk factors.

Keywords:
Hepatitis delta virus; Anti-HDV; Prevalence; South America; Epidemiology

INTRODUCTION

Hepatitis delta virus (HDV) infection can cause acute or chronic hepatitis. HDV is a defective virus capable of multiplying only in hepatitis B virus (HBV) infected hepatocytes, requiring HBV surface antigen (HBsAg) as its envelope protein11. Rizzetto M. Hepatitis D Virus: Introduction and Epidemiology. Cold Spring Harb Perspect Med. 2015;5(7):a021576.. Diagnostic assays using antibodies against HDV antigen (anti-HD) performed on HBsAg carriers are reliable sources of information on HDV epidemiology and molecular tests (HDV-RNA) are indicated for active infection confirmation. It is estimated that 18 million HBsAg carriers around the world also have anti-HDV antibody, representing 5% of HBV infected individuals. However, this estimate presents a range of substantial uncertainty since not all are tested for HDV infection11. Rizzetto M. Hepatitis D Virus: Introduction and Epidemiology. Cold Spring Harb Perspect Med. 2015;5(7):a021576.,22. Botelho-Souza LF, Vasconcelos MPA, Santos AO, Salcedo JMV, Vieira DS. Hepatitis delta: virological and clinical aspects. Virol J. 2017;14(1):177..

HDV infection is ubiquitous worldwide, but its distribution pattern is not uniform 11. Rizzetto M. Hepatitis D Virus: Introduction and Epidemiology. Cold Spring Harb Perspect Med. 2015;5(7):a021576.

2. Botelho-Souza LF, Vasconcelos MPA, Santos AO, Salcedo JMV, Vieira DS. Hepatitis delta: virological and clinical aspects. Virol J. 2017;14(1):177.

3. Abbas Z, Jafri W, Raza S. Hepatitis D: Scenario in the Asia-Pacific region. World J Gastroenterol. 2010;16(5):554-62.

4. Amini N, Alavian SM, Kabir A, Hosseini SYS, Andabili SHA. Clinical Features and Seroepidemiology of Anti-HDV Antibody in patients With Chronic Hepatitis B Virus Infection in Iran: A Meta-Analysis. Hepat Mon. 2011;11(12):960-7.

5. Amini N, Alavian SM, Kabir A, Aalaei-Andabili SH, Hosseini SYS, Rizzetto M. Prevalence of hepatitis d in the eastern mediterranean region: systematic review and meta analysis. Hepat Mon . 2013;13(1):e8210.

6. Değertekin H, Yalçin K, Yakut M, Yurdaydin C. Seropositivity for delta hepatitis in patients with chronic hepatitis B and liver cirrhosis in Turkey: a meta-analysis. Liver Int. 2008;28(4):494-8.

7. Elzouki AN, Bashir SM, Elahmer O, Elzouki I, Alkhattali F. Prevalence and risk factors of hepatitis D virus infection in patients with chronic hepatitis B infection attending the three main tertiary hospitals in Libya. Arab J Gastroenterol. 2017;18(4):216-219.

8. Gaeta GB, Stroffolini T, Chiaramonte M, Ascione T, Stornaiuolo G, Lobello S, et al. Chronic hepatitis D: a vanishing Disease? An Italian multicenter study. Hepatology. 2000;32(4 Pt 1):824-7.

9. Gish RG, Yi DH, Kane S, Clark M, Mangahas M, Baqai S, et al. Coinfection with hepatitis B and D: epidemiology, prevalence and disease in patients in Northern California. J Gastroenterol Hepatol. 2013;28(9):1521-5.

10. Sagnelli E, Sagnelli C, Pisaturo M, Macera M, Coppola N. Epidemiology of acute and chronic hepatitis B and delta over the last 5 decades in Italy. World J Gastroenterol . 2014;20(24):7635-43.

11. Sanou AM, Benkirane K, Tinto B, Cissé A, Sagna T, Ilboudo AK, et al. Prevalence of Hepatitis B virus and Hepatitis D virus Coinfection in Western Burkina Faso and molecular characterization of the detected virus strains. Int J Infect Dis. 2018;70:15-19.
-1212. Stockdale AJ, Chaponda M, Beloukas A, Phillips RO, Matthews PC, Papadimitropoulos A, et al. Prevalence of hepatitis D virus infection in sub-Saharan Africa: a systematic review and meta-analysis. Lancet Glob Health. 2017;5(10):e992-e1003.. Even in endemic areas, anti-HDV prevalence differs greatly depending on geographical region, such as in the Eastern Mediterranean55. Amini N, Alavian SM, Kabir A, Aalaei-Andabili SH, Hosseini SYS, Rizzetto M. Prevalence of hepatitis d in the eastern mediterranean region: systematic review and meta analysis. Hepat Mon . 2013;13(1):e8210., sub-Saharan Africa1212. Stockdale AJ, Chaponda M, Beloukas A, Phillips RO, Matthews PC, Papadimitropoulos A, et al. Prevalence of hepatitis D virus infection in sub-Saharan Africa: a systematic review and meta-analysis. Lancet Glob Health. 2017;5(10):e992-e1003., Iran44. Amini N, Alavian SM, Kabir A, Hosseini SYS, Andabili SHA. Clinical Features and Seroepidemiology of Anti-HDV Antibody in patients With Chronic Hepatitis B Virus Infection in Iran: A Meta-Analysis. Hepat Mon. 2011;11(12):960-7., and Turkey66. Değertekin H, Yalçin K, Yakut M, Yurdaydin C. Seropositivity for delta hepatitis in patients with chronic hepatitis B and liver cirrhosis in Turkey: a meta-analysis. Liver Int. 2008;28(4):494-8.. In Latin America, HDV has been associated with acute and chronic infection, particularly severe and fulminant hepatitis. The study area was based on articles already reporting high HDV endemicity in South America, since the 1980s1313. Ljunggren KE, Patarroyo ME, Engle R, Purcell RH, Gerin JL. Viral hepatitis in Colombia: a study of the "hepatitis of the Sierra Nevada de Santa Marta". Hepatology. 1985;5(2):299-304.

14. da Fonseca JCF, Ferreira LCL, Brasil LM, Castinho MC, MossI R, Barone M. Fulminant Labrea hepatitis--the role of hepatitis A (HAV), B (HBV), C (HCV), and D (HDV) infection. (Preliminary report). Rev Inst Med Trop Sao Paulo. 1992;34(6):609-12.

15. Fonseca JC, Simonetti SR, Schatzmayr HG, Castejón MJ, Cesário AL, Simonetti JP. Prevalence of infection with hepatitis delta virus (HDV) among carriers of hepatitis B surface antigen in Amazonas State, Brazil. Trans R Soc Trop Med Hyg. 1988;82(3):469-71.

16. Hadler SC, Alcala de Monzon M, Rivero D, Perez M, Bracho A, Fields H. Epidemiology and long-term consequences of hepatitis delta virus infection in the Yucpa Indians of Venezuela. Am J Epidemiol. 1992;136(12):1507-16.

17. Soares MCP, Bensabath G. Indian tribes of East Amazonia as risk population for hepatitis D (delta) (letter). Rev. Inst. Med. Trop. São Paulo. 1991;33(3):241-2

18. Torres JR, Mondolfi A. Protracted outbreak of severe delta hepatitis: experience in an isolated Amerindian population of the Upper Orinoco basin. Rev Infect Dis. 1991;13(1):52-5.
-1919. Indacochea S, Gotuzzo E, De la Fuente J, Phillips I. High prevalence of hepatitis B and Delta markers in the interandean valley of Abancay. Rev. Méd. Hered. 1991;2(4):168-7.. There are relatively few data on HDV prevalence in South American countries and most of them are regional cross-sectional studies11. Rizzetto M. Hepatitis D Virus: Introduction and Epidemiology. Cold Spring Harb Perspect Med. 2015;5(7):a021576.,22. Botelho-Souza LF, Vasconcelos MPA, Santos AO, Salcedo JMV, Vieira DS. Hepatitis delta: virological and clinical aspects. Virol J. 2017;14(1):177.,2020. Arboleda M, Castilho MC, Fonseca JCF, Albuquerque BC, Saboia RC, Yoshida CFT. Epidemiological aspects of hepatitis B and D virus infection in the northern region of Amazonas, Brazil. Trans R Soc Trop Med Hyg . 1995;89(5):481-3.

21. Azevedo RA, Silva AE, Ferraz ML, Marcopito LF, Baruzzi RG. Prevalence of serologic markers of hepatitis B and D viruses in children of the Caiabi and Txucarramãe tribes from the Indian Reservation of Xingu, central Brazil. Rev Soc Bras Med Trop. 1996;29(5):431-9.
-2222. Soares MC, Menezes RC, Martins SJ, Bensabath G. Epidemiology of hepatitis B, C and D viruses among indigenous Parakanã tribe in the Eastern Brazilian Amazon Region. Bol Oficina Sanit Panam. 1994;117(2):124-35.. To date, there has been no HDV infection prevalence estimate for South America. Therefore, a systematic review with meta-analysis was planned to provide a clearer and more comprehensive presentation of published data on HDV prevalence among HBsAg carriers in South American countries.

METHODS

Study design

All methods of this systematic review and meta-analysis were conducted according to the MOOSE (Meta-analyses of Observational Studies in Epidemiology) guidelines and reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist2323. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283(15):2008-12.,2424. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097..

Study area

South America extends across 17,819,100 km² (12% terrestrial surface) and comprises 6% of the world population. It encompasses the following countries: Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Guyana, Paraguay, Peru, Suriname, Uruguay, and Venezuela. Also, the following independent territories are part of the continent: French Guiana, Falkland Island and South Georgia and the South Sandwich Islands.

Relevant article search strategy

An algorithm was developed to search for articles containing the topic of interest by combining the following key descriptors and medical terms (MeSH); "hepatitis D" OR "HDV" OR "hepatitis Delta virus" OR "anti-HD" and "prevalence" OR "seroprevalence" OR "epidemiology". This was adapted to predefined electronic databases (PubMed, SciELO, Lilacs, Capes, and Virtual Health Library). Each country/independent territory name was added individually. The time frame included all published articles until 31st December 2017 and searches were conducted for articles published in English, Portuguese and Spanish.

In addition, a limited manual search of cross-references was conducted to identify all published articles on HDV prevalence. Thus, identified articles were selected first by their titles and abstracts, according to inclusion and exclusion criteria by five researchers independently and duplicates removed. Relevant articles were read in full.

Inclusion criteria

  • Any study reporting HDV prevalence.

  • Clearly stated information about number of HBV-infected people and HDV diagnosis based on anti-HDV antibody presence or molecular tests.

  • Case series, cross-sectional, case control, or cohort appropriated studies.

  • People residing in any South American country and no criteria regarding size, gender or age.

  • Published data in five electronic databases.

Exclusion criteria

  • Studies conducted in populations residing outside South America.

  • Studies designed as case reports, reviews, comments, and editorials.

  • Studies with no primary data and/or explicit description of laboratory methods.

  • Studies about HDV genotyping.

Quality assessment and data extraction of studies

Each paper was quality assessed according to the GRADE approach2525. Atkins D, Best D, Briss PA, Eccles M, Falck-Ytter Y, Flottorp S, et al. Grading quality of evidence and strength of recommendations. BMJ. 2004;328(7454):1490. and a scoring system was established considering: study design, population group, sampling method, HDV diagnostic method, anti-HDV prevalence outcome, endemic region and relative risk measure or reported odds ratios. Points ranged from 0 to 2 points on evaluation by two researchers individually, with a partial blinding process. Consensus was used to resolve misunderstandings in appraisals by investigators. Quality level was arbitrarily categorized as very low (0-2.5), low (2.6-5.0), moderate (5.1-7.5), and high (7.6-9.5). A five-point minimum score was established for an article to be included in the meta-analysis.

General information (authors, year, country), primary data (study design, target population, positive HBsAg, and anti-HDV case number) were extracted from each included article in the meta-analysis (met the eligibility criteria). One researcher checked all extracted data for accuracy.

Statistical analysis

Data analysis was performed using the “metan” and “metaprop” packages in Stata version 11.0 (StataCorp LLC, College Station, TX, USA) 2626. Nyaga VN, Arbyn M, Aerts M. Metaprop: a Stata command to perform meta-analysis of binomial data. Arch Public Health. 2014;72(1):39.,2727. Harris RJ, Bardburn M, Deeks JJ, Harbord RM, Altman DG, Sterne JAC. Metan: fixed- and random-effects meta-analysis. Stata J. 2008;8(1):3-28.. Study primary data were computed to establish individual HDV prevalence and confidence intervals (95%CI) were calculated using the Wilson method. Publication bias was verified through a funnel plot and Egger’s test. Study heterogeneity was evaluated using the chi-squared test based on the Q statistic and calculated by I 2. Pooled anti-HDV prevalence was calculated using DerSimonian-Laird’s random-effects model with Freeman-Tukey’s double arcsine transformation, based on the heterogeneity test result. Forest plot and descriptive tables were used to display the main results.

Meta-regression was performed using the residual maximum-likelihood model to examine for heterogeneity sources related to study country or design, selected population, specific geographic area, data collection decade, anti-HDV diagnostic method, HDV/HBV infection risk, and quality assessment. Methodological and clinical heterogeneity due to groups and potentially non-representative samples were investigated with sensitivity analysis with Tau22. Botelho-Souza LF, Vasconcelos MPA, Santos AO, Salcedo JMV, Vieira DS. Hepatitis delta: virological and clinical aspects. Virol J. 2017;14(1):177. showing variation between subgroups.

RESULTS

Search outcomes

A total of 405 records were found in the searched databases, but only 171 of them were retained after duplicates were removed. Further evaluation excluded 91 titles because they were not related to anti-HDV prevalence in South American countries. Twenty four articles were not made available by the authors. Fifty-five articles were selected based on inclusion and exclusion criteria after full text reading. Two very low-quality studies (4.5 score) were excluded1515. Fonseca JC, Simonetti SR, Schatzmayr HG, Castejón MJ, Cesário AL, Simonetti JP. Prevalence of infection with hepatitis delta virus (HDV) among carriers of hepatitis B surface antigen in Amazonas State, Brazil. Trans R Soc Trop Med Hyg. 1988;82(3):469-71.,1919. Indacochea S, Gotuzzo E, De la Fuente J, Phillips I. High prevalence of hepatitis B and Delta markers in the interandean valley of Abancay. Rev. Méd. Hered. 1991;2(4):168-7.. Therefore, only 31 of 33 eligible articles with 71,733 participants were included in the final phase for quantitative analysis (meta-analysis) as shown by the flowchart (Figure 1) and Table 1.

FIGURE 1:
Systematic flow for article selection for inclusion in review and meta-analysis on HDV prevalence in South America

TABLE 1:
Data of articles included in the meta-analysis on the prevalence of HDV infection in South America (1985-2015).

Characteristics of included articles

Of the thirty one studies included in the meta-analysis, nine different population groups were described in seven out of the 12 South American countries during a period spanning from 1985 to 2015 (Figure 2). Participants were recruited in various epidemiological contexts: through specific or general community surveys, blood bank, during testing of health professionals, in HIV clinics, drug treatment centers and in university hospitals (patients with liver disease). No studies on HDV infection prevalence were found in Chile, Guyana, Suriname, Paraguay, Uruguay, French Guiana, Falkland Island and South Georgia, and the South Sandwich Islands published until 2017.

FIGURE 2:
Geographic distribution of anti-HDV prevalence in several populations and South America countries, by study and year of publication.

Overall, the quality of reviewed studies showed a moderate score (median: 6.0, range from 4.5 to 8.5). Most studies (17/31; 54.84%) published data from “convenience samples” such as native indigenous or rural communities, hospitalized or HIV-infected patients and health-care workers. These selected participants had not been representative of regional populations and no country in the study was sampled nationally. A summary of articles included in the systematic review and meta-analysis with quality score is shown in Table 1.

Studies included in the meta-analysis suggested a trend towards publication bias by funnel plot, with evidence confirmed by linear regression (Egger's test, p<0.001), whereas Begg’s test yielded p=0.024. This was depicted graphically by funnel plot which incorporated the trim and fill method, and showed asymmetry of reported anti-HDV prevalence by various studies. Some studies also indicated presence of high heterogeneity (p<0.001); thus, the random-effect meta-analysis model was therefore adopted.

Overall pooled HDV infection prevalence

Although 71,733 participants were included in this meta-analysis, only 2.56% of them exhibited HBsAg-positive marker (target population of this study). Anti-HDV marker positivity rate ranged from 0.45% to 54.00% for the analyzed studies (Table 2). Pooled anti-HDV prevalence at 22.37% (95%CI: 13.72-32.26) among 1,835 HBsAg carriers (in South American) was estimated by the random effects meta-analysis model, in which individual study variances had been stabilized by Freeman-Tukey’s double-arc transformation method. There was significantly high heterogeneity among the included studies (I 2=94.79%; Cochran's Q=575.94; p< 0.001).

TABLE 2:
Summary meta-analysis of studies on HDV prevalence in South American region (1985-2015), using random effects model and Freeman-Tukey transformations.

Source of heterogeneity and subgroup analysis

The influence of multiple factors on studies’ heterogeneity was analyzed by meta-regression analysis, suggesting that there was a strong association between HDV infection prevalence with collected data decade (coefficient 0.53, 95%CI: 0.19-1.07, p=0.019), geographic area (coefficient -1.10, 95%CI: -1.84 to -0.22, p=0.008) and study quality (coefficient -0.89; 95%CI: -1.81 to -0.29, p=0.023). Publication bias was found for all group analyses, except for the HDV/HBV infection risk group (p=0.447).

HDV prevalence rate was 3.70% for six articles categorized in the low-quality group, while at the opposite extreme this was 51.53% for three classified as high quality, which constituted a significant variation among studies (p<0.001) (Figure 3A). Meanwhile, anti-HDV prevalence in the moderate quality group, which consisted of a significant number of articles (22/31, 70.97%), was estimated to be 25.34% among HBsAg positive patients, close to the group estimated prevalence (22.37%).

The four oldest studies had their data collected in the 1980s1414. da Fonseca JCF, Ferreira LCL, Brasil LM, Castinho MC, MossI R, Barone M. Fulminant Labrea hepatitis--the role of hepatitis A (HAV), B (HBV), C (HCV), and D (HDV) infection. (Preliminary report). Rev Inst Med Trop Sao Paulo. 1992;34(6):609-12.,1616. Hadler SC, Alcala de Monzon M, Rivero D, Perez M, Bracho A, Fields H. Epidemiology and long-term consequences of hepatitis delta virus infection in the Yucpa Indians of Venezuela. Am J Epidemiol. 1992;136(12):1507-16.

17. Soares MCP, Bensabath G. Indian tribes of East Amazonia as risk population for hepatitis D (delta) (letter). Rev. Inst. Med. Trop. São Paulo. 1991;33(3):241-2
-1818. Torres JR, Mondolfi A. Protracted outbreak of severe delta hepatitis: experience in an isolated Amerindian population of the Upper Orinoco basin. Rev Infect Dis. 1991;13(1):52-5. and had the highest HDV infection prevalence in the meta-analysis (Figure 3B), contributing to overestimated pooled HDV infection prevalence; however, a cumulative meta-analysis could confirm that the epidemiological profile of this virus has undergone significant changes (p<0.001), with successive reductions since 1990s.

FIGURE 3:
Forest plot of prevalence of HDV infection among HBsAg-positive carriers in South America region (1985-2015) by different subgroups: (A) quality assessment score and (B) decade of data for each study

Nearly all analyzed studies reported cross-sectional observational design (27/31; 87.10%), although the presence of other designs had been observed (cohort, case control and case series). Anti-HDV prevalence also varied considerably by HDV screening method, suggesting one probable methodological heterogeneity cause among studies (p<0.001). In addition, many studies had not clearly identified how many cases were positive for anti-HDV in serologic screening, nor did they include HDV infection confirmation by antibody retesting or HDV-RNA detection. Eight studies detected HDV-RNA presence in 60 seropositive participants (10.29% with active infection).

Anti-HDV marker seroprevalence varied significantly between South American countries (p=0.035) as shown in Figure 4A. A single study conducted in native indigenous communities of Ecuador also estimated a high HDV infection prevalence (31.91%) in 20002727. Harris RJ, Bardburn M, Deeks JJ, Harbord RM, Altman DG, Sterne JAC. Metan: fixed- and random-effects meta-analysis. Stata J. 2008;8(1):3-28.. Most of the studies (15/31, 48.39%) were conducted in Brazil, covering the largest number of participants (998), although HDV prevalence was estimated at 17.26% (95%CI: 6.10-31.89). The findings showed about three times higher HDV infection prevalence for a specific geographic area (31.12% in the Amazon Basin) compared to 11.27% in other studied areas (Figure 4B).

FIGURE 4:
Forest plot of HDV infection prevalence among HBsAg-positive carriers (1985-2015) by different subgroups: (A) study country and (B) geographic area in South America region

The target populations (HBsAg positive) were significantly associated with HDV seroprevalence (p<0.001). Five articles revealed high anti-HDV rate (49.99%) in the general population; in contrast, a very low rate (0.92%) was observed in another study conducted among blood donors. The pooled HDV prevalence was 22.20% among native indigenous communities from 14 studies in five countries. Among three studies in which patient HIV status was reported, the HDV seroprevalence was 3.30%. Surprisingly, no HDV infection case was reported in one study with injecting drug users from Rio de Janeiro, Brazil2828. Casey JL, Niro GA, Engle RE, Vega A, Gomez H, McCarthy M, et al. Hepatitis B virus (HBV)/hepatitis D virus (HDV) coinfection in outbreaks of acute hepatitis in the Peruvian Amazon basin: the roles of HDV genotype III and HBV genotype F. J Infect Dis. 1996;174(5):920-6., whereas in another study conducted in a school community in Peru, the anti-HDV prevalence was 16.67%2929. Chang J, Zavaletta A, Philips I. Seroepidemiology for hepatitis B in four communities in the peruvian central jungle. Rev. Med. Exp. 1997;14(1):34-39..

DISCUSSION

This is the first systematic review to perform a meta-analysis on HDV infection prevalence in several populations, whose focus was on South America. Only a large regional epidemiological study could estimate with precision overall HDV infection prevalence in South America. This review is important for the better understanding of current HDV-infection geographical distribution between South American countries, notably, in highly endemic areas and with acute and chronic cases recorded over a 30-year period11. Rizzetto M. Hepatitis D Virus: Introduction and Epidemiology. Cold Spring Harb Perspect Med. 2015;5(7):a021576.,22. Botelho-Souza LF, Vasconcelos MPA, Santos AO, Salcedo JMV, Vieira DS. Hepatitis delta: virological and clinical aspects. Virol J. 2017;14(1):177.,4949. Navascués CA, Rodríguez M, Sotorrío NG, Sala P, Linares A, Suárez A, et al. Epidemiology of hepatitis D virus infection: changes in the last 14 years. Am J Gastroenterol. 1995;90(11):1981-4.,5050. Romeo R, Perbellini R. Hepatitis delta virus: Making the point from virus isolation up to 2014. World J Hepatol. 2015;7(22):2389-95..

The study area was based on evidence that HDV is widespread throughout the world, with its prevalence rate varying widely in different geographic regions, which does not exactly match the HBV infection rate11. Rizzetto M. Hepatitis D Virus: Introduction and Epidemiology. Cold Spring Harb Perspect Med. 2015;5(7):a021576.,22. Botelho-Souza LF, Vasconcelos MPA, Santos AO, Salcedo JMV, Vieira DS. Hepatitis delta: virological and clinical aspects. Virol J. 2017;14(1):177.. This is confirmed with cross-sectional studies conducted since 1980, evidencing a large difference in HDV prevalence in America under several epidemiological contexts99. Gish RG, Yi DH, Kane S, Clark M, Mangahas M, Baqai S, et al. Coinfection with hepatitis B and D: epidemiology, prevalence and disease in patients in Northern California. J Gastroenterol Hepatol. 2013;28(9):1521-5.,1313. Ljunggren KE, Patarroyo ME, Engle R, Purcell RH, Gerin JL. Viral hepatitis in Colombia: a study of the "hepatitis of the Sierra Nevada de Santa Marta". Hepatology. 1985;5(2):299-304.,1515. Fonseca JC, Simonetti SR, Schatzmayr HG, Castejón MJ, Cesário AL, Simonetti JP. Prevalence of infection with hepatitis delta virus (HDV) among carriers of hepatitis B surface antigen in Amazonas State, Brazil. Trans R Soc Trop Med Hyg. 1988;82(3):469-71.,4545. Braga WSM, Castilho MC, Borges FG, Leão JRDT, Martinho ACS, Rodrigues IS, et al. Hepatitis D virus infection in the Western Brazilian Amazon - far from a vanishing disease. Rev Soc Bras Med Trop . 2012;45(6):691-5.,5151. Kucirka LM, Farzadegan H, Feld JJ, Mehta SH, Winters M, Glenn JS, et al. Prevalence, correlates, and viral dynamics of hepatitis delta among injection drug users. J Infect Dis . 2010;202(6):845-52.. However, this review sought to estimate an overall prevalence encompassing all South American countries, which has demonstrated high rates of HDV infection within this subcontinent, according to other previous studies1010. Sagnelli E, Sagnelli C, Pisaturo M, Macera M, Coppola N. Epidemiology of acute and chronic hepatitis B and delta over the last 5 decades in Italy. World J Gastroenterol . 2014;20(24):7635-43.,1717. Soares MCP, Bensabath G. Indian tribes of East Amazonia as risk population for hepatitis D (delta) (letter). Rev. Inst. Med. Trop. São Paulo. 1991;33(3):241-2

18. Torres JR, Mondolfi A. Protracted outbreak of severe delta hepatitis: experience in an isolated Amerindian population of the Upper Orinoco basin. Rev Infect Dis. 1991;13(1):52-5.
-1919. Indacochea S, Gotuzzo E, De la Fuente J, Phillips I. High prevalence of hepatitis B and Delta markers in the interandean valley of Abancay. Rev. Méd. Hered. 1991;2(4):168-7.,2828. Casey JL, Niro GA, Engle RE, Vega A, Gomez H, McCarthy M, et al. Hepatitis B virus (HBV)/hepatitis D virus (HDV) coinfection in outbreaks of acute hepatitis in the Peruvian Amazon basin: the roles of HDV genotype III and HBV genotype F. J Infect Dis. 1996;174(5):920-6.,3434. Paula VS, Arruda ME, Vitral CL, Gaspar AMC. Seroprevalence of viral hepatitis in riverine communities from the Western Region of the Brazilian Amazon Basin. Mem Inst Oswaldo Cruz. 2001;96(8):1123-8..

This review found a heterogeneous anti-HDV positive geographical distribution in South America, with low and high antibody prevalence differing between areas even within the same country1313. Ljunggren KE, Patarroyo ME, Engle R, Purcell RH, Gerin JL. Viral hepatitis in Colombia: a study of the "hepatitis of the Sierra Nevada de Santa Marta". Hepatology. 1985;5(2):299-304.,1818. Torres JR, Mondolfi A. Protracted outbreak of severe delta hepatitis: experience in an isolated Amerindian population of the Upper Orinoco basin. Rev Infect Dis. 1991;13(1):52-5.,2828. Casey JL, Niro GA, Engle RE, Vega A, Gomez H, McCarthy M, et al. Hepatitis B virus (HBV)/hepatitis D virus (HDV) coinfection in outbreaks of acute hepatitis in the Peruvian Amazon basin: the roles of HDV genotype III and HBV genotype F. J Infect Dis. 1996;174(5):920-6.,2929. Chang J, Zavaletta A, Philips I. Seroepidemiology for hepatitis B in four communities in the peruvian central jungle. Rev. Med. Exp. 1997;14(1):34-39.,3434. Paula VS, Arruda ME, Vitral CL, Gaspar AMC. Seroprevalence of viral hepatitis in riverine communities from the Western Region of the Brazilian Amazon Basin. Mem Inst Oswaldo Cruz. 2001;96(8):1123-8.,3535. Braga WSM, Brasil LM, Souza RAB, Castilho MC, Fonseca JC. The occurrence of hepatitis B and delta virus infection within seven Amerindian ethnic groups in the Brazilian western Amazon. Rev Soc Bras Med Trop . 2001;34(4):349-55.,4040. Duarte MC, Cardona N, Poblete F, González K, García M, Pacheco M, et al. A comparative epidemiological study of hepatitis B and hepatitis D virus infections in Yanomami and Piaroa Amerindians of Amazonas State, Venezuela. Trop Med Int Health. 2010;15(8):924-33.,4848. Villa DF, Cortes-Mancera F, Payares E, Montes N, Hoz F, Arbelaez MP, et al. Hepatitis D virus and hepatitis B virus infection in Amerindian communities of the Amazonas state, Colombia. Virol J . 2015;12:172.. One reason for these variations may be limited sample size in some studies, without previous sample calculation. Another explanation would be different criteria established for participant inclusion11. Rizzetto M. Hepatitis D Virus: Introduction and Epidemiology. Cold Spring Harb Perspect Med. 2015;5(7):a021576..

These review findings indicate that most of the studies were directed to a specific area of South America, the Amazon Basin1010. Sagnelli E, Sagnelli C, Pisaturo M, Macera M, Coppola N. Epidemiology of acute and chronic hepatitis B and delta over the last 5 decades in Italy. World J Gastroenterol . 2014;20(24):7635-43.. Recent studies suggest that high HDV infection cases in the Amazon Basin occurred due to geographic isolation, disseminating through restricted interaction to individuals and tribes5252. Cicero MF, Pena NM, Santana LC, Arnold R, Azevedo RG, Leal ES, et al. Is Hepatitis Delta infections important in Brazil? BMC Infect Dis. 2016;16(1):525.. Argentina was the only country identified by this review that does not belong to the Amazon Basin3131. Fainboim H, González J, Fassio E, Martínez A, Otegui L, Eposto M, et al. Prevalence of hepatitis viruses in an anti-human immunodeficiency virus-positive population from Argentina. A multicentre study. J Viral Hepat. 1999;6(1):53-7.,4444. Delfino CM, Eirin ME, Berini C, Malan R, Gentile E, Castillo A, et al. HDAg-L variants in covert hepatitis D and HBV occult infection among Amerindians of Argentina: new insights. J Clin Virol. 2012;54(3):223-8.,4646. Delfino CM, Gentile EA, Castillo AI, Cuestas ML, Pataccini G, Cánepa C, et al. Hepatitis B virus and hepatitis D virus in blood donors from Argentina: circulation of HBsAg and reverse transcriptase mutants. Arch Virol. 2014;159(5):1109-17.. This systematic review shows that there were more than twice as many Brazilian articles compared to other countries22. Botelho-Souza LF, Vasconcelos MPA, Santos AO, Salcedo JMV, Vieira DS. Hepatitis delta: virological and clinical aspects. Virol J. 2017;14(1):177.,44. Amini N, Alavian SM, Kabir A, Hosseini SYS, Andabili SHA. Clinical Features and Seroepidemiology of Anti-HDV Antibody in patients With Chronic Hepatitis B Virus Infection in Iran: A Meta-Analysis. Hepat Mon. 2011;11(12):960-7.,77. Elzouki AN, Bashir SM, Elahmer O, Elzouki I, Alkhattali F. Prevalence and risk factors of hepatitis D virus infection in patients with chronic hepatitis B infection attending the three main tertiary hospitals in Libya. Arab J Gastroenterol. 2017;18(4):216-219.

8. Gaeta GB, Stroffolini T, Chiaramonte M, Ascione T, Stornaiuolo G, Lobello S, et al. Chronic hepatitis D: a vanishing Disease? An Italian multicenter study. Hepatology. 2000;32(4 Pt 1):824-7.

9. Gish RG, Yi DH, Kane S, Clark M, Mangahas M, Baqai S, et al. Coinfection with hepatitis B and D: epidemiology, prevalence and disease in patients in Northern California. J Gastroenterol Hepatol. 2013;28(9):1521-5.
-1010. Sagnelli E, Sagnelli C, Pisaturo M, Macera M, Coppola N. Epidemiology of acute and chronic hepatitis B and delta over the last 5 decades in Italy. World J Gastroenterol . 2014;20(24):7635-43.,1313. Ljunggren KE, Patarroyo ME, Engle R, Purcell RH, Gerin JL. Viral hepatitis in Colombia: a study of the "hepatitis of the Sierra Nevada de Santa Marta". Hepatology. 1985;5(2):299-304.,1717. Soares MCP, Bensabath G. Indian tribes of East Amazonia as risk population for hepatitis D (delta) (letter). Rev. Inst. Med. Trop. São Paulo. 1991;33(3):241-2,1818. Torres JR, Mondolfi A. Protracted outbreak of severe delta hepatitis: experience in an isolated Amerindian population of the Upper Orinoco basin. Rev Infect Dis. 1991;13(1):52-5.,2020. Arboleda M, Castilho MC, Fonseca JCF, Albuquerque BC, Saboia RC, Yoshida CFT. Epidemiological aspects of hepatitis B and D virus infection in the northern region of Amazonas, Brazil. Trans R Soc Trop Med Hyg . 1995;89(5):481-3.,2222. Soares MC, Menezes RC, Martins SJ, Bensabath G. Epidemiology of hepatitis B, C and D viruses among indigenous Parakanã tribe in the Eastern Brazilian Amazon Region. Bol Oficina Sanit Panam. 1994;117(2):124-35.,2424. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097.,2525. Atkins D, Best D, Briss PA, Eccles M, Falck-Ytter Y, Flottorp S, et al. Grading quality of evidence and strength of recommendations. BMJ. 2004;328(7454):1490.,2828. Casey JL, Niro GA, Engle RE, Vega A, Gomez H, McCarthy M, et al. Hepatitis B virus (HBV)/hepatitis D virus (HDV) coinfection in outbreaks of acute hepatitis in the Peruvian Amazon basin: the roles of HDV genotype III and HBV genotype F. J Infect Dis. 1996;174(5):920-6.,3030. Oliveira MLA, Bastos FI, Telles PR, Yoshida CFT, Schatzmayr HG, Paetzold U, et al. Prevalence and risk factors for HBV, HCV and HDV infections among injecting drug users from Rio de Janeiro, Brazil. Braz J Med Biol Res. 1999;32(9):1107-14.. On the other hand, all eligible articles pointed to local studies, so they were not representative of any of these countries’ populations.

The pooled HDV prevalence estimate was 22.37% (95%CI: 13.72-32.26) in South America by meta-analysis1313. Ljunggren KE, Patarroyo ME, Engle R, Purcell RH, Gerin JL. Viral hepatitis in Colombia: a study of the "hepatitis of the Sierra Nevada de Santa Marta". Hepatology. 1985;5(2):299-304.

14. da Fonseca JCF, Ferreira LCL, Brasil LM, Castinho MC, MossI R, Barone M. Fulminant Labrea hepatitis--the role of hepatitis A (HAV), B (HBV), C (HCV), and D (HDV) infection. (Preliminary report). Rev Inst Med Trop Sao Paulo. 1992;34(6):609-12.

15. Fonseca JC, Simonetti SR, Schatzmayr HG, Castejón MJ, Cesário AL, Simonetti JP. Prevalence of infection with hepatitis delta virus (HDV) among carriers of hepatitis B surface antigen in Amazonas State, Brazil. Trans R Soc Trop Med Hyg. 1988;82(3):469-71.

16. Hadler SC, Alcala de Monzon M, Rivero D, Perez M, Bracho A, Fields H. Epidemiology and long-term consequences of hepatitis delta virus infection in the Yucpa Indians of Venezuela. Am J Epidemiol. 1992;136(12):1507-16.

17. Soares MCP, Bensabath G. Indian tribes of East Amazonia as risk population for hepatitis D (delta) (letter). Rev. Inst. Med. Trop. São Paulo. 1991;33(3):241-2

18. Torres JR, Mondolfi A. Protracted outbreak of severe delta hepatitis: experience in an isolated Amerindian population of the Upper Orinoco basin. Rev Infect Dis. 1991;13(1):52-5.

19. Indacochea S, Gotuzzo E, De la Fuente J, Phillips I. High prevalence of hepatitis B and Delta markers in the interandean valley of Abancay. Rev. Méd. Hered. 1991;2(4):168-7.

20. Arboleda M, Castilho MC, Fonseca JCF, Albuquerque BC, Saboia RC, Yoshida CFT. Epidemiological aspects of hepatitis B and D virus infection in the northern region of Amazonas, Brazil. Trans R Soc Trop Med Hyg . 1995;89(5):481-3.

21. Azevedo RA, Silva AE, Ferraz ML, Marcopito LF, Baruzzi RG. Prevalence of serologic markers of hepatitis B and D viruses in children of the Caiabi and Txucarramãe tribes from the Indian Reservation of Xingu, central Brazil. Rev Soc Bras Med Trop. 1996;29(5):431-9.
-2222. Soares MC, Menezes RC, Martins SJ, Bensabath G. Epidemiology of hepatitis B, C and D viruses among indigenous Parakanã tribe in the Eastern Brazilian Amazon Region. Bol Oficina Sanit Panam. 1994;117(2):124-35.,2828. Casey JL, Niro GA, Engle RE, Vega A, Gomez H, McCarthy M, et al. Hepatitis B virus (HBV)/hepatitis D virus (HDV) coinfection in outbreaks of acute hepatitis in the Peruvian Amazon basin: the roles of HDV genotype III and HBV genotype F. J Infect Dis. 1996;174(5):920-6.

29. Chang J, Zavaletta A, Philips I. Seroepidemiology for hepatitis B in four communities in the peruvian central jungle. Rev. Med. Exp. 1997;14(1):34-39.

30. Oliveira MLA, Bastos FI, Telles PR, Yoshida CFT, Schatzmayr HG, Paetzold U, et al. Prevalence and risk factors for HBV, HCV and HDV infections among injecting drug users from Rio de Janeiro, Brazil. Braz J Med Biol Res. 1999;32(9):1107-14.

31. Fainboim H, González J, Fassio E, Martínez A, Otegui L, Eposto M, et al. Prevalence of hepatitis viruses in an anti-human immunodeficiency virus-positive population from Argentina. A multicentre study. J Viral Hepat. 1999;6(1):53-7.

32. León P, Venegas E, Bengoechea L, Rojas E, López JA, Elola C, et al. Prevalence of infections by hepatitis B, C, D and E viruses in Bolivia. Rev Panam Salud Publica. 1999;5(3):144-51.

33. Manock SR, Kelley PM, Hyams KC, Douce R, Smalligan RD, Watts DM, et al. An outbreak of fulminant hepatitis delta in the Waorani, an indigenous people of the Amazon basin of Ecuador. Am J Trop Med Hyg. 2000;63(3-4):209-13.

34. Paula VS, Arruda ME, Vitral CL, Gaspar AMC. Seroprevalence of viral hepatitis in riverine communities from the Western Region of the Brazilian Amazon Basin. Mem Inst Oswaldo Cruz. 2001;96(8):1123-8.

35. Braga WSM, Brasil LM, Souza RAB, Castilho MC, Fonseca JC. The occurrence of hepatitis B and delta virus infection within seven Amerindian ethnic groups in the Brazilian western Amazon. Rev Soc Bras Med Trop . 2001;34(4):349-55.

36. Segovia MG, Galvan K, Garcia VA, Huamani L, Gotuzzo EH. Prevalencia de marcadores serológicos para hepatitis B y delta e infección intrafamiliar en el valle del río Pampas, Perú¹. Rev Peru Med Exp Salud Publica. 2002;19(2):57-62.

37. Viana S, Paraná R, Moreira RC, Compri AP, Macedo V. High prevalence of hepatitis B virus and hepatitis D virus in the western Brazilian Amazon. Am J Trop Med Hyg . 2005; 73(4):808-14.

38. Cabezas CS, Suárez MJ, Romero GC, Carrillo CP, García MP, Reátegui JS. Hiperendemicidad de Hepatitis viral B y Delta en pueblos indìgenas de la Amazonía Peruana. Rev. Perú. Med. Exp. Salud Publica. 2006;23(2):114-122.

39. Nunes HM, Monteiro MR, Soares MC. Prevalence of hepatitis B and D serological markers in the Parakanã, Apyterewa Indian Reservation, Pará State, Brazil. Cad Saude Publica. 2007;23(11):2756-66.

40. Duarte MC, Cardona N, Poblete F, González K, García M, Pacheco M, et al. A comparative epidemiological study of hepatitis B and hepatitis D virus infections in Yanomami and Piaroa Amerindians of Amazonas State, Venezuela. Trop Med Int Health. 2010;15(8):924-33.

41. Mendes-Correa MC, Gomes-Gouvêa MS, Alvarado-Mora MV, Da Silva MH, Lázari C, Cavalcanti NC, et al. Hepatitis delta in HIV/HBV co-infected patients in Brazil: is it important? Int J Infect Dis . 2011;15(12):e828-32.

42. Barros LM, Gomes-Gouvêa MS, Pinho JR, Alvarado-Mora MV, Dos Santos A, Mendes-Corrêa MC, et al. Hepatitis Delta virus genotype 8 infection in Northeast Brazil: inheritance from African slaves? Virus Res. 2011;160(1-2):333-9.

43. Alvarado-Mora MV, Fernandez MF, Gomes-Gouvêa MS, de Azevedo Neto RS, Carrilho FJ, Pinho JR. Hepatitis B (HBV), hepatitis C (HCV) and hepatitis delta (HDV) viruses in the Colombian population--how is the epidemiological situation? PLoS One. 2011;6(4):e18888.

44. Delfino CM, Eirin ME, Berini C, Malan R, Gentile E, Castillo A, et al. HDAg-L variants in covert hepatitis D and HBV occult infection among Amerindians of Argentina: new insights. J Clin Virol. 2012;54(3):223-8.

45. Braga WSM, Castilho MC, Borges FG, Leão JRDT, Martinho ACS, Rodrigues IS, et al. Hepatitis D virus infection in the Western Brazilian Amazon - far from a vanishing disease. Rev Soc Bras Med Trop . 2012;45(6):691-5.

46. Delfino CM, Gentile EA, Castillo AI, Cuestas ML, Pataccini G, Cánepa C, et al. Hepatitis B virus and hepatitis D virus in blood donors from Argentina: circulation of HBsAg and reverse transcriptase mutants. Arch Virol. 2014;159(5):1109-17.

47. Freitas SZ, Soares CC, Tanaka TS, Lindenberg AS, Teles SA, Torres MS, et al. Prevalence, risk factors and genotypes of hepatitis B infection among HIV-infected patients in the State of MS, Central Brazil. BrazJ Infect Dis . 2014;18(5):473-80.
-4848. Villa DF, Cortes-Mancera F, Payares E, Montes N, Hoz F, Arbelaez MP, et al. Hepatitis D virus and hepatitis B virus infection in Amerindian communities of the Amazonas state, Colombia. Virol J . 2015;12:172.. This geographical region is traditionally recognized as endemic for hepatitis delta and a higher frequency for this virus was previously expected22. Botelho-Souza LF, Vasconcelos MPA, Santos AO, Salcedo JMV, Vieira DS. Hepatitis delta: virological and clinical aspects. Virol J. 2017;14(1):177.. Extreme caution should be exercised regarding the interpretation of the estimated prevalence for South America, due to selection biases observed during study review. These biases have been caused by the absence of information from several countries located far from the Amazon basin, as well as the use of data collected by studies conducted in the 1980s11. Rizzetto M. Hepatitis D Virus: Introduction and Epidemiology. Cold Spring Harb Perspect Med. 2015;5(7):a021576.,22. Botelho-Souza LF, Vasconcelos MPA, Santos AO, Salcedo JMV, Vieira DS. Hepatitis delta: virological and clinical aspects. Virol J. 2017;14(1):177.,55. Amini N, Alavian SM, Kabir A, Aalaei-Andabili SH, Hosseini SYS, Rizzetto M. Prevalence of hepatitis d in the eastern mediterranean region: systematic review and meta analysis. Hepat Mon . 2013;13(1):e8210.,66. Değertekin H, Yalçin K, Yakut M, Yurdaydin C. Seropositivity for delta hepatitis in patients with chronic hepatitis B and liver cirrhosis in Turkey: a meta-analysis. Liver Int. 2008;28(4):494-8. and 1990s33. Abbas Z, Jafri W, Raza S. Hepatitis D: Scenario in the Asia-Pacific region. World J Gastroenterol. 2010;16(5):554-62.,44. Amini N, Alavian SM, Kabir A, Hosseini SYS, Andabili SHA. Clinical Features and Seroepidemiology of Anti-HDV Antibody in patients With Chronic Hepatitis B Virus Infection in Iran: A Meta-Analysis. Hepat Mon. 2011;11(12):960-7.,77. Elzouki AN, Bashir SM, Elahmer O, Elzouki I, Alkhattali F. Prevalence and risk factors of hepatitis D virus infection in patients with chronic hepatitis B infection attending the three main tertiary hospitals in Libya. Arab J Gastroenterol. 2017;18(4):216-219.

8. Gaeta GB, Stroffolini T, Chiaramonte M, Ascione T, Stornaiuolo G, Lobello S, et al. Chronic hepatitis D: a vanishing Disease? An Italian multicenter study. Hepatology. 2000;32(4 Pt 1):824-7.

9. Gish RG, Yi DH, Kane S, Clark M, Mangahas M, Baqai S, et al. Coinfection with hepatitis B and D: epidemiology, prevalence and disease in patients in Northern California. J Gastroenterol Hepatol. 2013;28(9):1521-5.

10. Sagnelli E, Sagnelli C, Pisaturo M, Macera M, Coppola N. Epidemiology of acute and chronic hepatitis B and delta over the last 5 decades in Italy. World J Gastroenterol . 2014;20(24):7635-43.

11. Sanou AM, Benkirane K, Tinto B, Cissé A, Sagna T, Ilboudo AK, et al. Prevalence of Hepatitis B virus and Hepatitis D virus Coinfection in Western Burkina Faso and molecular characterization of the detected virus strains. Int J Infect Dis. 2018;70:15-19.

12. Stockdale AJ, Chaponda M, Beloukas A, Phillips RO, Matthews PC, Papadimitropoulos A, et al. Prevalence of hepatitis D virus infection in sub-Saharan Africa: a systematic review and meta-analysis. Lancet Glob Health. 2017;5(10):e992-e1003.

13. Ljunggren KE, Patarroyo ME, Engle R, Purcell RH, Gerin JL. Viral hepatitis in Colombia: a study of the "hepatitis of the Sierra Nevada de Santa Marta". Hepatology. 1985;5(2):299-304.

14. da Fonseca JCF, Ferreira LCL, Brasil LM, Castinho MC, MossI R, Barone M. Fulminant Labrea hepatitis--the role of hepatitis A (HAV), B (HBV), C (HCV), and D (HDV) infection. (Preliminary report). Rev Inst Med Trop Sao Paulo. 1992;34(6):609-12.

15. Fonseca JC, Simonetti SR, Schatzmayr HG, Castejón MJ, Cesário AL, Simonetti JP. Prevalence of infection with hepatitis delta virus (HDV) among carriers of hepatitis B surface antigen in Amazonas State, Brazil. Trans R Soc Trop Med Hyg. 1988;82(3):469-71.

16. Hadler SC, Alcala de Monzon M, Rivero D, Perez M, Bracho A, Fields H. Epidemiology and long-term consequences of hepatitis delta virus infection in the Yucpa Indians of Venezuela. Am J Epidemiol. 1992;136(12):1507-16.
-1717. Soares MCP, Bensabath G. Indian tribes of East Amazonia as risk population for hepatitis D (delta) (letter). Rev. Inst. Med. Trop. São Paulo. 1991;33(3):241-2,2121. Azevedo RA, Silva AE, Ferraz ML, Marcopito LF, Baruzzi RG. Prevalence of serologic markers of hepatitis B and D viruses in children of the Caiabi and Txucarramãe tribes from the Indian Reservation of Xingu, central Brazil. Rev Soc Bras Med Trop. 1996;29(5):431-9., which led to an overestimation of HDV infection cases in the studied area.

Pooled HDV infection prevalence found in South America have similar rates described in recent meta-analyses for other regions with high endemicity, as well as the Eastern Mediterranean Region (15% and 28% among asymptomatic HBsAg positive carriers and chronic hepatitis patients, respectively)55. Amini N, Alavian SM, Kabir A, Aalaei-Andabili SH, Hosseini SYS, Rizzetto M. Prevalence of hepatitis d in the eastern mediterranean region: systematic review and meta analysis. Hepat Mon . 2013;13(1):e8210. and in sub-Saharan Africa (7% in western Africa and 26% in central Africa)1212. Stockdale AJ, Chaponda M, Beloukas A, Phillips RO, Matthews PC, Papadimitropoulos A, et al. Prevalence of hepatitis D virus infection in sub-Saharan Africa: a systematic review and meta-analysis. Lancet Glob Health. 2017;5(10):e992-e1003., but it exceeds Southeast Asia (8% in Iran)44. Amini N, Alavian SM, Kabir A, Hosseini SYS, Andabili SHA. Clinical Features and Seroepidemiology of Anti-HDV Antibody in patients With Chronic Hepatitis B Virus Infection in Iran: A Meta-Analysis. Hepat Mon. 2011;11(12):960-7.. In South America, the estimated prevalence is closest to the mean of HDV prevalence reported in Turkey (27%)66. Değertekin H, Yalçin K, Yakut M, Yurdaydin C. Seropositivity for delta hepatitis in patients with chronic hepatitis B and liver cirrhosis in Turkey: a meta-analysis. Liver Int. 2008;28(4):494-8. and Mauritania (up to 30%) in West Africa5353. Lunel-Fabiani F, Mansour W, Amar AO, Aye M, Le Gal F, Malick FZ, et al. Impact of hepatitis B and delta virus co-infection on liver disease in Mauritania: a cross sectional study. J Infect. 2013;67(5):448-57..

The present study confirms a high pooled HDV infection prevalence in South America over more than three decades. HDV prevalence has demonstrated successive reductions over time, as seen in different areas of the world, currently close to the expected global rate at 5 to 10% among HBsAg carriers33. Abbas Z, Jafri W, Raza S. Hepatitis D: Scenario in the Asia-Pacific region. World J Gastroenterol. 2010;16(5):554-62.,88. Gaeta GB, Stroffolini T, Chiaramonte M, Ascione T, Stornaiuolo G, Lobello S, et al. Chronic hepatitis D: a vanishing Disease? An Italian multicenter study. Hepatology. 2000;32(4 Pt 1):824-7.,1010. Sagnelli E, Sagnelli C, Pisaturo M, Macera M, Coppola N. Epidemiology of acute and chronic hepatitis B and delta over the last 5 decades in Italy. World J Gastroenterol . 2014;20(24):7635-43.,4949. Navascués CA, Rodríguez M, Sotorrío NG, Sala P, Linares A, Suárez A, et al. Epidemiology of hepatitis D virus infection: changes in the last 14 years. Am J Gastroenterol. 1995;90(11):1981-4.,5454. Huo TI, Wu JC, Lin RY, Sheng WY, Chang FY, Lee SD. Decreasing hepatitis D virus infection in Taiwan: an analysis of contributory factors. J Gastroenterol Hepatol . 1997;12(11):747-51.. Stratified study analysis revealed a trend of successive reductions in pooled HDV prevalence over time in South America, from hyperendemic regions in the 80's and 90's (40.29% and 28.01%, respectively), to moderate endemic level in 2000 (13.58%), reaching values (6.97%) close to worldwide rates in 201011. Rizzetto M. Hepatitis D Virus: Introduction and Epidemiology. Cold Spring Harb Perspect Med. 2015;5(7):a021576.. This change in HDV infection epidemiological profile was probably due to the vaccination policy against HBV initiated cross campaign form for Amazonas Brazilian state in 1989 and obligatory screening of blood and blood products for serum HBV markers22. Botelho-Souza LF, Vasconcelos MPA, Santos AO, Salcedo JMV, Vieira DS. Hepatitis delta: virological and clinical aspects. Virol J. 2017;14(1):177.. The observed decline in prevalence rates is consistent with a recent review in which HDV infection prevalence decreased from 24% (1990) to 8.5% in Italy (2006).

Most of the studies included in this meta-analysis presented moderate methodological quality in relation to established criteria quality11. Rizzetto M. Hepatitis D Virus: Introduction and Epidemiology. Cold Spring Harb Perspect Med. 2015;5(7):a021576.,22. Botelho-Souza LF, Vasconcelos MPA, Santos AO, Salcedo JMV, Vieira DS. Hepatitis delta: virological and clinical aspects. Virol J. 2017;14(1):177.,44. Amini N, Alavian SM, Kabir A, Hosseini SYS, Andabili SHA. Clinical Features and Seroepidemiology of Anti-HDV Antibody in patients With Chronic Hepatitis B Virus Infection in Iran: A Meta-Analysis. Hepat Mon. 2011;11(12):960-7.

5. Amini N, Alavian SM, Kabir A, Aalaei-Andabili SH, Hosseini SYS, Rizzetto M. Prevalence of hepatitis d in the eastern mediterranean region: systematic review and meta analysis. Hepat Mon . 2013;13(1):e8210.

6. Değertekin H, Yalçin K, Yakut M, Yurdaydin C. Seropositivity for delta hepatitis in patients with chronic hepatitis B and liver cirrhosis in Turkey: a meta-analysis. Liver Int. 2008;28(4):494-8.
-77. Elzouki AN, Bashir SM, Elahmer O, Elzouki I, Alkhattali F. Prevalence and risk factors of hepatitis D virus infection in patients with chronic hepatitis B infection attending the three main tertiary hospitals in Libya. Arab J Gastroenterol. 2017;18(4):216-219.,99. Gish RG, Yi DH, Kane S, Clark M, Mangahas M, Baqai S, et al. Coinfection with hepatitis B and D: epidemiology, prevalence and disease in patients in Northern California. J Gastroenterol Hepatol. 2013;28(9):1521-5.,1212. Stockdale AJ, Chaponda M, Beloukas A, Phillips RO, Matthews PC, Papadimitropoulos A, et al. Prevalence of hepatitis D virus infection in sub-Saharan Africa: a systematic review and meta-analysis. Lancet Glob Health. 2017;5(10):e992-e1003.

13. Ljunggren KE, Patarroyo ME, Engle R, Purcell RH, Gerin JL. Viral hepatitis in Colombia: a study of the "hepatitis of the Sierra Nevada de Santa Marta". Hepatology. 1985;5(2):299-304.

14. da Fonseca JCF, Ferreira LCL, Brasil LM, Castinho MC, MossI R, Barone M. Fulminant Labrea hepatitis--the role of hepatitis A (HAV), B (HBV), C (HCV), and D (HDV) infection. (Preliminary report). Rev Inst Med Trop Sao Paulo. 1992;34(6):609-12.

15. Fonseca JC, Simonetti SR, Schatzmayr HG, Castejón MJ, Cesário AL, Simonetti JP. Prevalence of infection with hepatitis delta virus (HDV) among carriers of hepatitis B surface antigen in Amazonas State, Brazil. Trans R Soc Trop Med Hyg. 1988;82(3):469-71.

16. Hadler SC, Alcala de Monzon M, Rivero D, Perez M, Bracho A, Fields H. Epidemiology and long-term consequences of hepatitis delta virus infection in the Yucpa Indians of Venezuela. Am J Epidemiol. 1992;136(12):1507-16.

17. Soares MCP, Bensabath G. Indian tribes of East Amazonia as risk population for hepatitis D (delta) (letter). Rev. Inst. Med. Trop. São Paulo. 1991;33(3):241-2

18. Torres JR, Mondolfi A. Protracted outbreak of severe delta hepatitis: experience in an isolated Amerindian population of the Upper Orinoco basin. Rev Infect Dis. 1991;13(1):52-5.

19. Indacochea S, Gotuzzo E, De la Fuente J, Phillips I. High prevalence of hepatitis B and Delta markers in the interandean valley of Abancay. Rev. Méd. Hered. 1991;2(4):168-7.
-2020. Arboleda M, Castilho MC, Fonseca JCF, Albuquerque BC, Saboia RC, Yoshida CFT. Epidemiological aspects of hepatitis B and D virus infection in the northern region of Amazonas, Brazil. Trans R Soc Trop Med Hyg . 1995;89(5):481-3.,2323. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283(15):2008-12.,2626. Nyaga VN, Arbyn M, Aerts M. Metaprop: a Stata command to perform meta-analysis of binomial data. Arch Public Health. 2014;72(1):39.

27. Harris RJ, Bardburn M, Deeks JJ, Harbord RM, Altman DG, Sterne JAC. Metan: fixed- and random-effects meta-analysis. Stata J. 2008;8(1):3-28.

28. Casey JL, Niro GA, Engle RE, Vega A, Gomez H, McCarthy M, et al. Hepatitis B virus (HBV)/hepatitis D virus (HDV) coinfection in outbreaks of acute hepatitis in the Peruvian Amazon basin: the roles of HDV genotype III and HBV genotype F. J Infect Dis. 1996;174(5):920-6.

29. Chang J, Zavaletta A, Philips I. Seroepidemiology for hepatitis B in four communities in the peruvian central jungle. Rev. Med. Exp. 1997;14(1):34-39.
-3030. Oliveira MLA, Bastos FI, Telles PR, Yoshida CFT, Schatzmayr HG, Paetzold U, et al. Prevalence and risk factors for HBV, HCV and HDV infections among injecting drug users from Rio de Janeiro, Brazil. Braz J Med Biol Res. 1999;32(9):1107-14.. The information provided in this review revealed that almost all studies had cross-sectional designs22. Botelho-Souza LF, Vasconcelos MPA, Santos AO, Salcedo JMV, Vieira DS. Hepatitis delta: virological and clinical aspects. Virol J. 2017;14(1):177.

3. Abbas Z, Jafri W, Raza S. Hepatitis D: Scenario in the Asia-Pacific region. World J Gastroenterol. 2010;16(5):554-62.

4. Amini N, Alavian SM, Kabir A, Hosseini SYS, Andabili SHA. Clinical Features and Seroepidemiology of Anti-HDV Antibody in patients With Chronic Hepatitis B Virus Infection in Iran: A Meta-Analysis. Hepat Mon. 2011;11(12):960-7.
-55. Amini N, Alavian SM, Kabir A, Aalaei-Andabili SH, Hosseini SYS, Rizzetto M. Prevalence of hepatitis d in the eastern mediterranean region: systematic review and meta analysis. Hepat Mon . 2013;13(1):e8210.,88. Gaeta GB, Stroffolini T, Chiaramonte M, Ascione T, Stornaiuolo G, Lobello S, et al. Chronic hepatitis D: a vanishing Disease? An Italian multicenter study. Hepatology. 2000;32(4 Pt 1):824-7.

9. Gish RG, Yi DH, Kane S, Clark M, Mangahas M, Baqai S, et al. Coinfection with hepatitis B and D: epidemiology, prevalence and disease in patients in Northern California. J Gastroenterol Hepatol. 2013;28(9):1521-5.

10. Sagnelli E, Sagnelli C, Pisaturo M, Macera M, Coppola N. Epidemiology of acute and chronic hepatitis B and delta over the last 5 decades in Italy. World J Gastroenterol . 2014;20(24):7635-43.

11. Sanou AM, Benkirane K, Tinto B, Cissé A, Sagna T, Ilboudo AK, et al. Prevalence of Hepatitis B virus and Hepatitis D virus Coinfection in Western Burkina Faso and molecular characterization of the detected virus strains. Int J Infect Dis. 2018;70:15-19.

12. Stockdale AJ, Chaponda M, Beloukas A, Phillips RO, Matthews PC, Papadimitropoulos A, et al. Prevalence of hepatitis D virus infection in sub-Saharan Africa: a systematic review and meta-analysis. Lancet Glob Health. 2017;5(10):e992-e1003.
-1313. Ljunggren KE, Patarroyo ME, Engle R, Purcell RH, Gerin JL. Viral hepatitis in Colombia: a study of the "hepatitis of the Sierra Nevada de Santa Marta". Hepatology. 1985;5(2):299-304.,1515. Fonseca JC, Simonetti SR, Schatzmayr HG, Castejón MJ, Cesário AL, Simonetti JP. Prevalence of infection with hepatitis delta virus (HDV) among carriers of hepatitis B surface antigen in Amazonas State, Brazil. Trans R Soc Trop Med Hyg. 1988;82(3):469-71.

16. Hadler SC, Alcala de Monzon M, Rivero D, Perez M, Bracho A, Fields H. Epidemiology and long-term consequences of hepatitis delta virus infection in the Yucpa Indians of Venezuela. Am J Epidemiol. 1992;136(12):1507-16.

17. Soares MCP, Bensabath G. Indian tribes of East Amazonia as risk population for hepatitis D (delta) (letter). Rev. Inst. Med. Trop. São Paulo. 1991;33(3):241-2

18. Torres JR, Mondolfi A. Protracted outbreak of severe delta hepatitis: experience in an isolated Amerindian population of the Upper Orinoco basin. Rev Infect Dis. 1991;13(1):52-5.

19. Indacochea S, Gotuzzo E, De la Fuente J, Phillips I. High prevalence of hepatitis B and Delta markers in the interandean valley of Abancay. Rev. Méd. Hered. 1991;2(4):168-7.

20. Arboleda M, Castilho MC, Fonseca JCF, Albuquerque BC, Saboia RC, Yoshida CFT. Epidemiological aspects of hepatitis B and D virus infection in the northern region of Amazonas, Brazil. Trans R Soc Trop Med Hyg . 1995;89(5):481-3.

21. Azevedo RA, Silva AE, Ferraz ML, Marcopito LF, Baruzzi RG. Prevalence of serologic markers of hepatitis B and D viruses in children of the Caiabi and Txucarramãe tribes from the Indian Reservation of Xingu, central Brazil. Rev Soc Bras Med Trop. 1996;29(5):431-9.

22. Soares MC, Menezes RC, Martins SJ, Bensabath G. Epidemiology of hepatitis B, C and D viruses among indigenous Parakanã tribe in the Eastern Brazilian Amazon Region. Bol Oficina Sanit Panam. 1994;117(2):124-35.

23. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283(15):2008-12.

24. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097.

25. Atkins D, Best D, Briss PA, Eccles M, Falck-Ytter Y, Flottorp S, et al. Grading quality of evidence and strength of recommendations. BMJ. 2004;328(7454):1490.

26. Nyaga VN, Arbyn M, Aerts M. Metaprop: a Stata command to perform meta-analysis of binomial data. Arch Public Health. 2014;72(1):39.

27. Harris RJ, Bardburn M, Deeks JJ, Harbord RM, Altman DG, Sterne JAC. Metan: fixed- and random-effects meta-analysis. Stata J. 2008;8(1):3-28.

28. Casey JL, Niro GA, Engle RE, Vega A, Gomez H, McCarthy M, et al. Hepatitis B virus (HBV)/hepatitis D virus (HDV) coinfection in outbreaks of acute hepatitis in the Peruvian Amazon basin: the roles of HDV genotype III and HBV genotype F. J Infect Dis. 1996;174(5):920-6.

29. Chang J, Zavaletta A, Philips I. Seroepidemiology for hepatitis B in four communities in the peruvian central jungle. Rev. Med. Exp. 1997;14(1):34-39.

30. Oliveira MLA, Bastos FI, Telles PR, Yoshida CFT, Schatzmayr HG, Paetzold U, et al. Prevalence and risk factors for HBV, HCV and HDV infections among injecting drug users from Rio de Janeiro, Brazil. Braz J Med Biol Res. 1999;32(9):1107-14.
-3131. Fainboim H, González J, Fassio E, Martínez A, Otegui L, Eposto M, et al. Prevalence of hepatitis viruses in an anti-human immunodeficiency virus-positive population from Argentina. A multicentre study. J Viral Hepat. 1999;6(1):53-7. as they fit prevalence studies; therefore, they did not provide information on relative time of exposure and outcome. A strength of this review is that participant selection focused on HBV-infected individuals, notably positive HBsAg carriers because they were the target population who were more adequate and susceptible to HDV infection. This was chosen in consistency with previous studies showing that HDV requires obligatory HBV presence for its propagation to hepatocytes11. Rizzetto M. Hepatitis D Virus: Introduction and Epidemiology. Cold Spring Harb Perspect Med. 2015;5(7):a021576.,22. Botelho-Souza LF, Vasconcelos MPA, Santos AO, Salcedo JMV, Vieira DS. Hepatitis delta: virological and clinical aspects. Virol J. 2017;14(1):177..

It is possible that the HDV prevalence reported in this evaluation may be overestimated, since the studies included in the meta-analysis were conducted with more vulnerable populations such as HIV-infected patients, hospitalized patients, health-care workers, injecting drug users and indigenous communities11. Rizzetto M. Hepatitis D Virus: Introduction and Epidemiology. Cold Spring Harb Perspect Med. 2015;5(7):a021576.,22. Botelho-Souza LF, Vasconcelos MPA, Santos AO, Salcedo JMV, Vieira DS. Hepatitis delta: virological and clinical aspects. Virol J. 2017;14(1):177.,44. Amini N, Alavian SM, Kabir A, Hosseini SYS, Andabili SHA. Clinical Features and Seroepidemiology of Anti-HDV Antibody in patients With Chronic Hepatitis B Virus Infection in Iran: A Meta-Analysis. Hepat Mon. 2011;11(12):960-7.

5. Amini N, Alavian SM, Kabir A, Aalaei-Andabili SH, Hosseini SYS, Rizzetto M. Prevalence of hepatitis d in the eastern mediterranean region: systematic review and meta analysis. Hepat Mon . 2013;13(1):e8210.

6. Değertekin H, Yalçin K, Yakut M, Yurdaydin C. Seropositivity for delta hepatitis in patients with chronic hepatitis B and liver cirrhosis in Turkey: a meta-analysis. Liver Int. 2008;28(4):494-8.

7. Elzouki AN, Bashir SM, Elahmer O, Elzouki I, Alkhattali F. Prevalence and risk factors of hepatitis D virus infection in patients with chronic hepatitis B infection attending the three main tertiary hospitals in Libya. Arab J Gastroenterol. 2017;18(4):216-219.
-88. Gaeta GB, Stroffolini T, Chiaramonte M, Ascione T, Stornaiuolo G, Lobello S, et al. Chronic hepatitis D: a vanishing Disease? An Italian multicenter study. Hepatology. 2000;32(4 Pt 1):824-7.,1010. Sagnelli E, Sagnelli C, Pisaturo M, Macera M, Coppola N. Epidemiology of acute and chronic hepatitis B and delta over the last 5 decades in Italy. World J Gastroenterol . 2014;20(24):7635-43.,1111. Sanou AM, Benkirane K, Tinto B, Cissé A, Sagna T, Ilboudo AK, et al. Prevalence of Hepatitis B virus and Hepatitis D virus Coinfection in Western Burkina Faso and molecular characterization of the detected virus strains. Int J Infect Dis. 2018;70:15-19.,1313. Ljunggren KE, Patarroyo ME, Engle R, Purcell RH, Gerin JL. Viral hepatitis in Colombia: a study of the "hepatitis of the Sierra Nevada de Santa Marta". Hepatology. 1985;5(2):299-304.

14. da Fonseca JCF, Ferreira LCL, Brasil LM, Castinho MC, MossI R, Barone M. Fulminant Labrea hepatitis--the role of hepatitis A (HAV), B (HBV), C (HCV), and D (HDV) infection. (Preliminary report). Rev Inst Med Trop Sao Paulo. 1992;34(6):609-12.

15. Fonseca JC, Simonetti SR, Schatzmayr HG, Castejón MJ, Cesário AL, Simonetti JP. Prevalence of infection with hepatitis delta virus (HDV) among carriers of hepatitis B surface antigen in Amazonas State, Brazil. Trans R Soc Trop Med Hyg. 1988;82(3):469-71.

16. Hadler SC, Alcala de Monzon M, Rivero D, Perez M, Bracho A, Fields H. Epidemiology and long-term consequences of hepatitis delta virus infection in the Yucpa Indians of Venezuela. Am J Epidemiol. 1992;136(12):1507-16.

17. Soares MCP, Bensabath G. Indian tribes of East Amazonia as risk population for hepatitis D (delta) (letter). Rev. Inst. Med. Trop. São Paulo. 1991;33(3):241-2
-1818. Torres JR, Mondolfi A. Protracted outbreak of severe delta hepatitis: experience in an isolated Amerindian population of the Upper Orinoco basin. Rev Infect Dis. 1991;13(1):52-5.,2121. Azevedo RA, Silva AE, Ferraz ML, Marcopito LF, Baruzzi RG. Prevalence of serologic markers of hepatitis B and D viruses in children of the Caiabi and Txucarramãe tribes from the Indian Reservation of Xingu, central Brazil. Rev Soc Bras Med Trop. 1996;29(5):431-9.

22. Soares MC, Menezes RC, Martins SJ, Bensabath G. Epidemiology of hepatitis B, C and D viruses among indigenous Parakanã tribe in the Eastern Brazilian Amazon Region. Bol Oficina Sanit Panam. 1994;117(2):124-35.

23. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283(15):2008-12.

24. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097.

25. Atkins D, Best D, Briss PA, Eccles M, Falck-Ytter Y, Flottorp S, et al. Grading quality of evidence and strength of recommendations. BMJ. 2004;328(7454):1490.

26. Nyaga VN, Arbyn M, Aerts M. Metaprop: a Stata command to perform meta-analysis of binomial data. Arch Public Health. 2014;72(1):39.
-2727. Harris RJ, Bardburn M, Deeks JJ, Harbord RM, Altman DG, Sterne JAC. Metan: fixed- and random-effects meta-analysis. Stata J. 2008;8(1):3-28.,3030. Oliveira MLA, Bastos FI, Telles PR, Yoshida CFT, Schatzmayr HG, Paetzold U, et al. Prevalence and risk factors for HBV, HCV and HDV infections among injecting drug users from Rio de Janeiro, Brazil. Braz J Med Biol Res. 1999;32(9):1107-14.,3131. Fainboim H, González J, Fassio E, Martínez A, Otegui L, Eposto M, et al. Prevalence of hepatitis viruses in an anti-human immunodeficiency virus-positive population from Argentina. A multicentre study. J Viral Hepat. 1999;6(1):53-7.. Discrepancies reported in the global epidemiology for HDV infection prevalence may be related to erroneous participant selection, generally not representative of general population or involving blood donors11. Rizzetto M. Hepatitis D Virus: Introduction and Epidemiology. Cold Spring Harb Perspect Med. 2015;5(7):a021576., reinforcing once again that this estimated HDV infection prevalence in meta-analysis is restricted to the populations studied.

This review had still others limitations. The estimate of pooled HDV infection prevalence in South America did not include unpublished data or official data sources. Additionally, there were no data available from seven countries (mainly outside Amazon Basin), and there was an absence of population-based studies. These reasons may directly interfere in pooled HDV infection prevalence calculations. The lack of standardized criteria for participant selection or even failure to report the gross number of HBV infected individuals in studies may induce inaccurate estimates or study exclusion. This fact constitutes further limitation to the inference drawn. In contrast, the search for articles reported in both English as in other native languages of the region (Portuguese and Spanish), increased the number of selected articles. Furthermore, the pooled HDV infection prevalence estimated for South America was accurate due to strong and reliable methodology (sample size of 1,835 HBV-infected included in random effects model) and statistical procedures used.

CONCLUSION

This systematic review provides evidence that hepatitis delta remains neglected in some South American areas, notably outside the Amazon Basin. The pooled anti-HDV prevalence was 22.37% covering several populations of seven South American countries through meta-analysis. In addition, the findings highlight a drastic decline in HDV prevalence over the last decades. In future studies, we plan to identify risk factors and evaluate HDV infection control measures.

Acknowledgements

The authors would like to thank the statistical assistance provided by Jean Joel R. Bigna, and the English grammatical review provided by Michael Hardman.

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    Amini N, Alavian SM, Kabir A, Hosseini SYS, Andabili SHA. Clinical Features and Seroepidemiology of Anti-HDV Antibody in patients With Chronic Hepatitis B Virus Infection in Iran: A Meta-Analysis. Hepat Mon. 2011;11(12):960-7.
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  • Erratum

    Revista da Sociedade Brasileira de Medicina Tropical/Journal of the Brazilian Society of Tropical Medicine
    Title: Hepatitis Delta Prevalence in South America: A Systematic Review and Meta-Analysis
    Vol.:52:e20180289: 2019 - doi: 10.1590/0037-8682-0289-2018 - Table 1
    2011 Mendes-Correa MC, et al. Prevalence HDV/HBsAg = 11.16
    Should read:
    2011 Mendes-Correa MC, et al. Prevalence HDV/HBsAg = 1.16
    2011 Barros LM, et al. - Prevalence HDV/HBsAg = 33.76
    Should read:
    2011 Barros LM, et al. - Prevalence HDV/HBsAg = 3.76

Publication Dates

  • Publication in this collection
    24 Jan 2019
  • Date of issue
    2019

History

  • Received
    09 Aug 2018
  • Accepted
    18 Dec 2018
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