Hepatitis B virus pre-S2 start codon mutations in Indonesian liver disease patients

Utama, Andi; Siburian, Marlinang Diarta; Fanany, Ismail; Intan, Mariana Destila Bayu; Dhenni, Rama; Kurniasih, Tri Shinta; Achwan, Wenny Astuti; Zubir, Nasrul; Arnelis,; Lukito, Benyamin; Yusuf, Irawan; Lesmana, Laurentius A; Sulaiman, Ali

doi:10.3748/wjg.v18.i38.5418

Cited by 10 publications

(7 citation statements)

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“…The frequencies of mutations at the pre-S2 promoters were significantly higher in the patients with HCC than in the patients without HCC (pre-S2 promoter mutation: 15.3% vs 8.9%, P=0.032) [10]. Furthermore, pre-S2 start codon mutation was associated with advanced liver disease and was the more common type of pre-S mutation in Indonesian patients regardless of the HBV genotype [15,16]. …”

Section: Discussionmentioning

confidence: 99%

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High prevalence of hepatitis B virus genotype C/C1 in the Minangkabau ethnic group in Indonesia

Siburian

Utama

Dhenni

et al. 2013

Virol J

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BackgroundThe Minangkabau is one of the major ethnic groups in Indonesia. Previous studies with a limited number of samples have shown a different prevalence of HBV/C in the Minangkabau compared to the Indonesian population in general. The aim of this study was to assess the HBV genotype distribution pattern and the prevalence of pre-S, T1753V and A1762T/G1764A mutations among the Minangkabau HBV carriers. The samples were collected from Padang, West Sumatera and from western Java. Mixed primers for specific genotypes were used to determine the HBV genotype. Pre-S or S genes were amplified, sequenced and aligned with reference sequences from GenBank to derive a phylogenetic tree for subgenotyping. Pre-S genes were also analyzed for mutations. The basal core promoter (BCP) region was amplified and directly sequenced to analyze T1753V and A1762T/G1764A mutations.ResultsThe predominant HBV genotype among the Minangkabau HBV carriers (n=117) was C (72.6%) followed by B (24.8%) and co-infection with B and C (2.6%). The prevalence of pre-S mutations, including both the pre-S deletion and pre-S2 start codon mutation, was 41.0%, and the T1753V and A1762T/G1764A mutations were found in 51.9% and 71.2% respectively. HBV/C1 was the predominant HBV subgenotype in the Minangkabau HBV carriers, and was found in 66.2%, followed by B3, B7, C8, B2, B9, C2, and C10 (18.3%, 7.0%, 2.8%, 1.4%, 1.4%, 1.4%, and 1.4% respectively). From samples that were found to be co-infected with HBV B and C, two samples were successfully cloned and subgenotyped, including one with mixed subgenotypes of B3 and C1, and another one with mixed subgenotypes of B7, C1, putative intergenotypic of B/A, and C/A. Furthermore, three samples from donors of non-Minangkabau ethnicity from Padang were found to be infected with an intragenotypic recombination form, including a putative recombinant of B8/B3 and B9/B7.ConclusionHBV/C with subgenotype C1 was the predominant HBV genotype among HBV carriers of Minangkabau ethnicity. The prevalence of pre-S, A1762T/G1764A, and T1753V mutations was higher among the Minangkabau compared to Indonesian HBV carriers in general.

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Section: Discussionmentioning

confidence: 99%

“…Mutations at the BCP region such as A1762T/G1764A and T1753V were found in high prevalence (59.5% and 40.5%, respectively) and were associated with severe liver disease [12]. In a more recent study, the prevalence of pre-S mutation in Indonesian population was also reported [15,16]. …”

Section: Introductionmentioning

confidence: 99%

High prevalence of hepatitis B virus genotype C/C1 in the Minangkabau ethnic group in Indonesia

Siburian

Utama

Dhenni

et al. 2013

Virol J

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“…The prevalence of pre-S mutations has also been reported (18,19). Nevertheless, the RT region has not been fully characterized.…”

Section: Introductionmentioning

confidence: 99%

Profile of Mutations in the Reverse Transcriptase and Overlapping Surface Genes of Hepatitis B Virus (HBV) in Treatment-Naïve Indonesian HBV Carriers

et al. 2017

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“…Of the Indonesian viruses, some mutations in the HBV genome that are associated with severe liver disease have been reported, including mutations in the basal core promoter region (e.g., A1762T/G1764A and T1753V) (19)(20)(21) and the pre-S region (22,23). Several minor drug-resistant mutations of HBV in Indonesian treatment-naive patients with chronic hepatitis were recently detected using a deep sequencing method (24).…”

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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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Hepatitis B virus pre-S2 start codon mutations in Indonesian liver disease patients

Abstract: Pre-S2 start codon mutation was higher in Indonesian patients compared to other Asian countries, and its prevalence was associated with advanced liver disease, particularly in HBeAg⁺ patients.

Cited by 10 publications

References 30 publications

High prevalence of hepatitis B virus genotype C/C1 in the Minangkabau ethnic group in Indonesia

High prevalence of hepatitis B virus genotype C/C1 in the Minangkabau ethnic group in Indonesia

Profile of Mutations in the Reverse Transcriptase and Overlapping Surface Genes of Hepatitis B Virus (HBV) in Treatment-Naïve Indonesian HBV Carriers

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

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