Distribution of the hepatitis B surface antigen subtypes in Indonesia: implications for ethnic heterogeneityand infection control measures

Mulyanto, Mulyanto; Tsuda, Fumio; Karossi, A. T.; Soewignjo, S.; Roestamsjah,; Sumarsidi, Didacus; Trisnamurti, R. H.; Sumardi, Sumardi; Surayah,; Udin, Linar Z.; Melani-Wikanta,; Kanai, Koichi; Mishiro, Shunji

doi:10.1007/s007050050230

Cited by 22 publications

(30 citation statements)

References 8 publications

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“…These results are consistent with previous studies showing that HBV genotype B3 and subtype adw are predominant in western Indonesia (30)(31)(32)(33). Some studies have shown that HBV subtype adw correlated strongly with vaccine escape mutants in Singapore (34) and surface gene variations in young Taiwanese patients with hepatocellular carcinoma (HCC) (35).…”

Section: Discussionsupporting

confidence: 92%

Ultradeep Sequencing for Detection of Quasispecies Variants in the Major Hydrophilic Region of Hepatitis B Virus in Indonesian Patients

et al. 2015

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h Quasispecies of hepatitis B virus (HBV) with variations in the major hydrophilic region (MHR) of the HBV surface antigen (HBsAg) can evolve during infection, allowing HBV to evade neutralizing antibodies. These escape variants may contribute to chronic infections. In this study, we looked for MHR variants in HBV quasispecies using ultradeep sequencing and evaluated the relationship between these variants and clinical manifestations in infected patients. We enrolled 30 Indonesian patients with hepatitis B infection (11 with chronic hepatitis and 19 with advanced liver disease). The most common subgenotype/subtype of HBV was B3/adw (97%). The HBsAg titer was lower in patients with advanced liver disease than that in patients with chronic hepatitis. The MHR variants were grouped based on the percentage of the viral population affected: major, >20% of the total population; intermediate, 5% to <20%; and minor, 1% to <5%. The rates of MHR variation that were present in the major and intermediate viral population were significantly greater in patients with advanced liver disease than those in chronic patients. The most frequent MHR variants related to immune evasion in the major and intermediate populations were P120Q/T, T123A, P127T, Q129H/R, M133L/T, and G145R. The major population of MHR variants causing impaired of HBsAg secretion (e.g., G119R, Q129R, T140I, and G145R) was detected only in advanced liver disease patients. This is the first study to use ultradeep sequencing for the detection of MHR variants of HBV quasispecies in Indonesian patients. We found that a greater number of MHR variations was related to disease severity and reduced likelihood of HBsAg titer.T he high mutation rate of hepatitis B virus (HBV), which is attributable to the lack of a proofreading function in its polymerase and the high replication rate of the virus, induces viral diversity, referred to as viral quasispecies. Many studies have demonstrated that the identification of HBV quasispecies may help predict disease progression and therapeutic outcomes (1-3). Accordingly, HBV variants in the quasispecies pool are probably clinically relevant (4).The surface (S) region used to classify HBV strains is responsible for the expression of hepatitis B surface antigen (HBsAg). HBsAg is the major target for viral neutralization by the immune responses of the host, either naturally or by vaccine-induced antibodies. However, the major hydrophilic region (MHR) located in the central HBsAg, comprising amino acids 100 to 169, contains many discontinuous B-cell epitopes that are recognized by hepatitis B surface antibodies (anti-HBs) (5-7). The exact border of the neutralizing domain of the MHR region is still unclear, although the ␣-determinant region (amino acids 124 to 147) within the MHR has been known to be strongly involved in antibody binding (8,9). Moreover, many studies have noted that variations within the MHR can alter the antigenicity of HBsAg and are responsible for (i) the evasion of vaccine-induced antibodies, (ii) the failure of immu...

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Section: Discussionsupporting

confidence: 92%

Ultradeep Sequencing for Detection of Quasispecies Variants in the Major Hydrophilic Region of Hepatitis B Virus in Indonesian Patients

et al. 2015

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“…This is comparable with a previous observation (21), as far as Surabaya is concerned. It also was reported that in Yogyakarta, central Java, adw (74%) was most prevalent, followed by adr (11%) and other compound subtypes (8).…”

Section: Discussionsupporting

confidence: 92%

“…It also was reported that in Yogyakarta, central Java, adw (74%) was most prevalent, followed by adr (11%) and other compound subtypes (8). It should be noted, however, that the prevalence of each HBV subtype appears to markedly vary with different geographical regions in Indonesia; adr was most prevalent in Irian Jaya and some parts of Sumatra while ayw was most prevalent in Flores, Sumba and Timor (21). Indonesia is a multiethnic country with an extensive territory.…”

Section: Discussionmentioning

confidence: 94%

Genotype and Subtype Analyses of Hepatitis B Virus (HBV) and Possible Co‐Infection of HBV and Hepatitis C Virus (HCV) or Hepatitis D Virus (HDV) in Blood Donors, Patients with Chronic Liver Disease and Patients on Hemodialysis in Surabaya, Indonesia

Lusida

Surayah

Sakugawa

et al. 2003

Microbiology and Immunology

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Hepatitis B virus (HBV) infection is a worldwide health problem. The prevalence of HBV carriers varies from 0.1 to 2% in low prevalent areas to 10 to 20% in high prevalent areas. Indonesia is among the HBV high prevalent countries (16). The identification of the common determinant a and two pairs of allelic variations, d/y and w/r, has lead to the definition of the four major subtypes of hepatitis B surface antigen (HBsAg), adw, adr, ayw, and ayr (3,13,18,37). Another classification system, which is based on the sequence diversity of the HBV genome has been developed and, currently eight genotypes designated A to H have been identified (1,4,23,25,35). It has been reported that distribution of HBV subtypes and genotypes varies with different geographical areas (2,15,18,22,24,26). Also, clinical manifestations and therapeutic responses to antiviral therapy might differ with different HBV genotypes (11,12,39 Abstract: Four subtypes (adw, adr, ayw, and ayr) and eight genotypes (A to H) of the hepatitis B virus (HBV) have been identified. They appear to be associated with particular geographic distribution, ethnicity, and possibly clinical outcomes. In this study, hepatitis B surface antigen (HBsAg) subtyping and HBV genotyping were carried out on sera obtained from HBsAg-positive HBV carriers, including healthy blood donors; patients with acute hepatitis, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma; and patients on hemodialysis all located in Surabaya, Indonesia. We report here that all HBV isolates tested in Surabaya belonged to genotype B, with more than 90% of them being classified into subtype adw. Our results also revealed that prevalence of hepatitis C virus (HCV) co-infection among HBV carriers in Surabaya was approximately 10% for healthy blood donors and patients with chronic liver disease, and approximately 60% for patients on maintenance hemodialysis. Interestingly, HBsAg titers were lower in HBV carriers with HCV co-infection than in those without HCV co-infection. We also found that prevalence of hepatitis D virus (HDV) co-infection was <0.5% among HBV carriers in Surabaya.

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“…1,19 The HBsAg detection rate is not uniform across the Indonesian archipelago, with higher prevalence in the eastern than the western region. 20,21 It is worthy to note that Indonesia presents an exceptionally diverse host ethnicity backgrounds, a condition that supports the emergence of new HBV subgenotypes as well as unique HBV variants. 21,22 Ternate as one of the many uniquely located historical crossroads of human migration and trade between mainland Asia and Australia (Figure 1), 23,24 is a good example to study the effects of host heterogeneity in supporting the development of unusual serological and/or molecular HBV profiles.…”

Section: Introductionmentioning

confidence: 99%

High Prevalence of Hepatitis B Virus Infection in Young Adults in Ternate, Eastern Indonesia

Ie¹,

Turyadi²,

Sidarta³

et al. 2015

The American Journal of Tropical Medicine and Hygiene

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Abstract. The incidence of hepatitis B virus (HBV) infection has been declining thanks to the universal hepatitis B infant immunization program. Nevertheless, young adults born before the program implementation might have acquired HBV in early childhood or remain susceptible to infection. This study aimed to evaluate hepatitis B epidemiology in asymptomatic young adult population in Ternate, eastern Indonesia. Serum samples of 376 subjects (aged 17-25, mean 19.82 ± 1.69 years; male/female 138/238) were screened for HBV parameters serologically (HBV surface antigen [HBsAg]; its antibody [anti-HBs]; anti-core antigen [anti-HBc]), and molecularly (HBV DNA). HBsAg, anti-HBc, anti-HBs, and HBV DNA prevalence were 15.7%, 36.2%, 24.2%, and 27.9%, respectively, with male predominance. Of all subjects, 13.0% were HBsAg negative with detectable HBV DNA (occult hepatitis B [OHB]), and 56.4% showed negativity for all seromarkers. This population showed high hepatitis B prevalence with substantial occurrence of OHB. However, a high percentage of the population were still susceptible and at risk of HBV infection. This study emphasizes the necessity to improve prevention strategies to screen and manage HBV carriers, including the adoption of catch-up or booster vaccination targeted to young adult populations. Investigations on the roles of host-virus interactions associated with OHB and its implications are warranted.

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Distribution of the hepatitis B surface antigen subtypes in Indonesia: implications for ethnic heterogeneityand infection control measures

Cited by 22 publications

References 8 publications

Ultradeep Sequencing for Detection of Quasispecies Variants in the Major Hydrophilic Region of Hepatitis B Virus in Indonesian Patients

Ultradeep Sequencing for Detection of Quasispecies Variants in the Major Hydrophilic Region of Hepatitis B Virus in Indonesian Patients

Genotype and Subtype Analyses of Hepatitis B Virus (HBV) and Possible Co‐Infection of HBV and Hepatitis C Virus (HCV) or Hepatitis D Virus (HDV) in Blood Donors, Patients with Chronic Liver Disease and Patients on Hemodialysis in Surabaya, Indonesia

High Prevalence of Hepatitis B Virus Infection in Young Adults in Ternate, Eastern Indonesia

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