Analysis of HBV genotype, drug resistant mutations, and pre‐core/basal core promoter mutations in Korean patients with acute hepatitis B

Lee, Jong Ho; Hong, Sun; Jang, Eun Sun; Park, Sang Jong; Hwang, Seong Gyu; Kang, Sook-Kyoung; Jeong, Sook‐Hyang

doi:10.1002/jmv.24148

Cited by 7 publications

(3 citation statements)

References 25 publications

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“…Our data showed there was no significant difference between strains of the 3 clades with respect to frequency of the preC/C mutation (G1896A; Figure 5 ). However, for BCP double mutations A1762T and G1764A, strains belonging to C2(2) or C2(3) exhibited significantly higher frequency compared with C2(1), despite no significant difference between C2(2) and C2(3), consistent with the previous finding of higher frequency of BCP mutation in chronic HBV infection patients in South Korea ( Lee et al, 2015 ). The frequency of the rtL269I polymorphism associated with the development of liver disease was significantly higher in clade C2(2) than in C2(1) and C2(3).…”

Section: Resultssupporting

confidence: 89%

Global prevalence and molecular characteristics of three clades within hepatitis B virus subgenotype C2: Predominance of the C2(3) clade in South Korea

et al. 2023

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Hepatitis B Virus (HBV) genotypes reflect geographic, ethical or clinical traits and are currently divided into 10 genotypes (A–J). Of these, genotype C is mainly distributed in Asia, is the largest group and comprises more than seven subgenotypes (C1–C7). Subgenotype C2 is divided into three phylogenetically distinct clades, C2(1), C2(2), and C2(3), and is responsible for most genotype C infections in three East Asian nations, including China, Japan, and South Korea, which are major HBV endemic areas. However, despite the significance of subgenotype C2 with regard to clinical or epidemiologic aspects, its global distribution and molecular characteristics remain largely unknown. Here, we analyze the global prevalence and molecular characteristics between 3 clades within subgenotype C2 using 1,315 full genome sequences of HBV genotype C retrieved from public databases. Our data show that almost all HBV strains from South Korean patients infected with genotype C belong to clade C2(3) within subgenotype C2 [96.3%] but that HBV strains from Chinese or Japanese patients belong to diverse subgenotypes or clades within genotype C, suggesting clonal expansion of a specific HBV type, C2(3), among the Korean population. Our genome sequence analysis indicated a total of 21 signature sequences specific to the respective clades C2(1), C2(2), and C2(3). Of note, two types of four nonsynonymous C2(3) signature sequences, sV184A in HBsAg and xT36P in the X region, were detected in 78.9 and 82.9% of HBV C2(3) strains, respectively. In particular, HBV strains C2(3) versus C2(1) and C2(2) show a higher frequency of reverse transcriptase mutations related to nucleot(s)ide analog (NA) resistance, including rtM204I and rtL180M, suggesting an increased possibility of C2(3) infection in those with NA treatment failure. In conclusion, our data show that HBV subgenotype C2(3) is extremely prevalent in Korean patients with chronic HBV infection, which is distinct from two other East Asian nations, China and Japan, where diverse subgenotypes or clades within genotype C coexist. This epidemiologic trait might affect distinct virological and clinical traits in chronic HBV patients in Korea, where exclusively C2(3) infection is predominant.

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Section: Resultssupporting

confidence: 89%

Global prevalence and molecular characteristics of three clades within hepatitis B virus subgenotype C2: Predominance of the C2(3) clade in South Korea

et al. 2023

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“…The problem posed by pre-C and BCP mutations would call into question the algorithm (HBeAg/ALAT score) [1,9] for identifying people to be put on antiviral treatment proposed by the WHO, particularly in countries with a high prevalence of HBV. The literature suggests that BCP mutants (A1762T/G1764A) increase viral replication [21,26]. Although the clinical implication of pre-core and BCP mutants remains to be elucidated, several studies on the subject tend to link these mutants with the risk of developing cirrhosis or HCC [20,27,28].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Diagnostic Performances of the SD-Bioline®HBeAg Rapid Test Used Routinely for the Management of HBV-Infected Individuals in Burkina Faso

Dera,

Sanou,

Ouattara

et al. 2023

Diagnostics

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Hepatitis B e antigen (HBeAg) is a marker of wild-type hepatitis B virus replication. In resource-limited countries where access to enzyme-linked immunosorbent assay (ELISA) remains a challenge, rapid diagnostic tests (RDT) constitute a good alternative. The HBeAg status is employed to evaluate eligibility for antiviral therapy and to prevent the transmission of hepatitis B from mother to child (PMTCT). The objective of this study was to assess the diagnostic performance of the SD-Bioline®HBeAg RDT commonly used for detecting HBeAg in laboratories in Burkina Faso. The sample panel used was collected from HBsAg-positive patients received in the laboratory for the detection of HBeAg with the rapid test. The samples were retested for HBeAg using the VIDAS HBe/Anti-HBe enzyme-linked fluorescent assay (ELFA) (Gold standard). Then, the viral load (VL) of HBV DNA was determined using the GENERIC HBV CHARGE VIRLAE kit (GHBV-CV). The diagnostic performances of the SD-Bioline®HBeAg and its agreement with the gold standard were calculated with their 95% confidence intervals. Overall, 340 sera obtained from HBsAg-positive patients were included in this evaluation Compared to the VIDAS HBe/Anti-HBe ELFA test, the sensitivity (Se) and specificity (Sp) of the SD-Bioline®HBeAg test were 33.3% and 97.9%, respectively. The concordance between the two tests was 0.42. Depending on the viral load, the Se and Sp varied from 8.8% and 98.3% for a VL < 2000 IU/mL to 35.5% and 98.4% for a VL > 2,000,000 IU/mL. The results showed a low sensibility of the SD-Bioline®HBeAg RDT test, indicating that its use is inappropriate for the clinical management of HBV-infected patients. They also highlight the urgent need to develop HBeAg rapid tests with better sensitivities.

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“…We report a dominance of HBV/D in acute patients which is in concordance with some earlier reports from the western world like the US and Italy [ 3 , 24 ]. However, in some Asian countries, such as China and Korea, genotype C predominates among acute HBV patients [ 5 , 25 ]. On the other hand, in the present study, HBV/C was significantly higher in chronic when compared to acute, thus affirming that HBV/C is more associated with chronic infection in India as compared to HBV/A and HBV/D, the other two genotypes circulating among patients from India.…”

Section: Discussionmentioning

confidence: 99%

Virological Characteristics of Acute Hepatitis B in Eastern India: Critical Differences with Chronic Infection

Sarkar¹,

Pal²,

Das³

et al. 2015

PLoS ONE

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Hepatitis B Virus (HBV) manifests high genetic variability and is classifiable into ten genotypes (A-J). HBV infection can lead to variable clinical outcomes, ranging from self-limiting acute hepatitis to active chronic hepatitis, cirrhosis and hepatocellular carcinoma. The present study characterizes HBV strains circulating among patients with acute (AHB) and chronic HBV infection (CHB). Among a total of 653 HBsAg positive cases, 40 manifested acute infection. After sequencing the surface(S), basal core promoter/pre-core(BCP/PC) and the X gene regions, phylogenetic tree was constructed using MEGA4 by neighbor-joining method. Statistical robustness was established with bootstrap analysis. Nucleotide diversity was determined by Shannon entropy per site using the Entropy program of the Los Alamos National Laboratories. Analyses of acute patients revealed that HBV/D2 is the major circulating sub-genotype and commonly associated with sexual promiscuity and the age group between15-30 years. Comparison of AHB and CHB patients revealed that HBeAg positivity, ALT levels and genotype D were significantly high in AHB, whereas CHB patients were predominantly male, had a high viral load, and were commonly associated with genotype C. The frequencies of mutations in the S, BCP/PC, and X gene were low in AHB as compared to CHB. Drug resistant mutations were not detectable in the polymerase gene of AHB. Average nucleotide diversity in AHB was considerably low as compared to CHB. Further, the highest average ΔH (average difference in entropy between chronic and acute infection) was observed in the BCP/PC region implying that this region was most vulnerable to mutations upon HBV persistence, especially in case of genotype C. Additionally, among all substitutions, the A1762T and G1764A BCP mutations were the strongest indicators of chronicity. In conclusion, the study exhibits a general portrait of HBV strains circulating among acute hepatitis B patients in Eastern India and their intricate differences with chronic patients which should be useful from the clinical point of view.

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Analysis of HBV genotype, drug resistant mutations, and pre‐core/basal core promoter mutations in Korean patients with acute hepatitis B

Cited by 7 publications

References 25 publications

Global prevalence and molecular characteristics of three clades within hepatitis B virus subgenotype C2: Predominance of the C2(3) clade in South Korea

Global prevalence and molecular characteristics of three clades within hepatitis B virus subgenotype C2: Predominance of the C2(3) clade in South Korea

Evaluation of the Diagnostic Performances of the SD-Bioline®HBeAg Rapid Test Used Routinely for the Management of HBV-Infected Individuals in Burkina Faso

Virological Characteristics of Acute Hepatitis B in Eastern India: Critical Differences with Chronic Infection

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