Virological and clinical implication of core promoter C1752/V1753 and T1764/G1766 mutations in hepatitis B virus genotype D infection in Mongolia

Elkady, Abeer; Tanaka, Yasuhito; Kurbanov, Fuat; Oynsuren, Tsendsuren; Mizokami, Masashi

doi:10.1111/j.1440-1746.2008.05321.x

Cited by 32 publications

(30 citation statements)

References 47 publications

(98 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In Mongolia and Inner Mongolia, which are located in the north of Gansu and Ningxia provinces, genotype D is the most prevalent HBV strain, and ‘CD1’ recombinant was observed with a very low prevalence [24], [25], [26]. In contrast, we found that ‘CD2’ exists at a slight higher prevalence than ‘CD1’ in Tibet, contradicting a previous prediction that all C/D hybrids were ‘CD2’ recombinant in this region [16].…”

Section: Discussioncontrasting

confidence: 99%

Geographical and Ethnic Distribution of the HBV C/D Recombinant on the Qinghai-Tibet Plateau

et al. 2011

View full text Add to dashboard Cite

Two forms of hepatitis B virus (HBV) C/D recombinant have been identified in western China, but little is known about their geographical and ethnic distributions, and particularly the clinical significance and specific mutations in the pre-core region. To address these questions, a total of 624 chronic HBV carriers from four ethnic populations representing five provinces in western China were enrolled in this study. Genotypes were firstly determined by restriction fragment length polymorphism, and then confirmed by full or partial genome nucleotide sequencing. The distribution of HBV genotypes was as follows: HBV/B: 40 (6.4%); HBV/C: 221 (35.4%); HBV/D: 39 (6.3%); HBV/CD: 324 (51.9%). In the 324 HBV C/D recombinant infections, 244 (75.3%) were infected with the “CD1” and 80 (24.7%) were infected with the “CD2.” The distribution of HBV genotypes exhibited distinct patterns in different regions and ethnic populations. Geographically, the C/D recombinant was the most prevalent HBV strain on the Qinghai-Tibet Plateau. Ethnically, the C/D recombinant had a higher prevalence in Tibetan patients than in other populations. Clinically, patients with HBV/CD1 showed significantly lower levels of serum total bilirubin than patients with HBV/C2. The prevalence of HBeAg was comparable between patients with HBV/CD1 and HBV/C2 (63.3% vs 50.0%, P = 0.118) whether patients were taken together or stratified by age into three groups (65.6% vs 58.8% in <30 years, P = 0.758; 61.9% vs 48.0% in 30–50 years, P = 0.244; 64.3% vs 33.3%, P = 0.336). Virologically HBV/CD1 had a significantly lower frequency of G1896A than HBV/C2. In conclusion, the HBV C/D recombinant is restricted to the Qinghai-Tibet Plateau in western China and is found predominantly in Tibetans. The predominance of the premature pre-core stop mutation G1896A in patients with the HBV C/D recombinant may account for the higher prevalence of HBeAg in these patients.

show abstract

Section: Discussioncontrasting

confidence: 99%

Geographical and Ethnic Distribution of the HBV C/D Recombinant on the Qinghai-Tibet Plateau

et al. 2011

View full text Add to dashboard Cite

show abstract

“…In the present study, 93.2% of genotype D strains had pre-C stop codon G1896A mutation, whereas only four genotype A2 strains had this mutation. This result was consistent with previous data showing that G1896A mutation was the strongest factor of HBeAg clearance in HBV/D-infected individuals [38], [39]. The basis of the relation between G1896A mutation and HBV genotypes is due to the base pairing of the stem loop structure of the encapsidation signal (ε), essential for viral replication.…”

Section: Discussionsupporting

confidence: 92%

“…Thus, the relationship between this mutation and severity of liver disease is not mediated by an increase in HBV replication but probably to direct pathogenic or oncogenic effects of this mutation. The T1753V mutation had earlier been associated with HCC development among Mongolian patients with genotype D [39]. Regarding the biological aspects, it was suggested that T1753V lead to the enhancement of transactivation and antiproliferation activity of HBx protein by altering HBx aa 127 (I127T/N/S) and enhancement of virus replication leading to persistent infection and higher frequency of HBV-DNA integration events into the human genome [52].…”

Section: Discussionmentioning

confidence: 99%

Variability in the Precore and Core Promoter Regions of HBV Strains in Morocco: Characterization and Impact on Liver Disease Progression

et al. 2012

View full text Add to dashboard Cite

BackgroundHepatitis B virus (HBV) is one of the most common human pathogens that cause aggressive hepatitis and advanced liver disease (AdLD), including liver cirrhosis and Hepatocellular Carcinoma. The persistence of active HBV replication and liver damage after the loss of hepatitis B e antigen (HBeAg) has been frequently associated with mutations in the pre-core (pre-C) and core promoter (CP) regions of HBV genome that abolish or reduce HBeAg expression. The purpose of this study was to assess the prevalence of pre-C and CP mutations and their impact on the subsequent course of liver disease in Morocco.Methods/Principal FindingsA cohort of 186 patients with HBeAg-negative chronic HBV infection was studied (81 inactive carriers, 69 with active chronic hepatitis, 36 with AdLD). Pre-C and CP mutations were analyzed by PCR-direct sequencing method. The pre-C stop codon G1896A mutation was the most frequent (83.9%) and was associated with a lower risk of AdLD development (OR, 0.4; 95% CI, 0.15–1.04; p = 0.04). HBV-DNA levels in patients with G1896A were not significantly different from the other patients carrying wild-type strains (p = 0.84). CP mutations C1653T, T1753V, A1762T/G1764A, and C1766T/T1768A were associated with higher HBV-DNA level and increased liver disease severity. Multiple logistic regression analysis showed that older age (≥40 years), male sex, high viral load (>4.3 log10 IU/mL) and CP mutations C1653T, T1753V, A1762T/G1764A, and C1766T/T1768A were independent risk factors for AdLD development. Combination of these mutations was significantly associated with AdLD (OR, 7.52; 95% CI, 4.8–8; p<0.0001).ConclusionsThis study shows for the first time the association of HBV viral load and CP mutations with the severity of liver disease in Moroccan HBV chronic carriers. The examination of CP mutations alone or in combination could be helpful for prediction of the clinical outcome.

show abstract

“…1 HBsAg endemicity in 1990-2013 and geographic distribution of HBV genotypes in Asia. The prevalence data are retrieved from a systematic review [1]; this map is prepared according to the literature [1,6,15,[17][18][19][20][21][22][23][24][25][26][27][28][29][30] HBV genotypes and response to antiviral therapy in Asia HBV genotypes and response to interferon (IFN)-based therapies HBV genotypes are significantly associated with sustained response to IFN-based therapies. In general, for HBeAgpositive patients, the probability of sustained response is in a descending order from genotype A-D [50].…”

Section: Hbv Genotypes and Clinical Manifestation In Asiamentioning

confidence: 99%

Hepatitis B virus genotypes: epidemiological and clinical relevance in Asia

Tian

Jia

2016

Hepatol Int

View full text Add to dashboard Cite

Hepatitis B virus (HBV) is characterized by a high genetic heterogeneity since it replicates via a reverse transcriptase that lacks proofreading ability. Up to now, ten genotypes (A-J) have been described, with genotype A and D being ubiquitous but most prevalent in Europe and Africa, genotype B and C being confined to Asia and Oceania. Infections with other genotypes such as E, F, G and H are also occasionally observed in Asia. Genotype I is rare and can be found in Laos, Vietnam, India and China, whereas genotype J has been described in Japan and Ryukyu. Novel variants generated by recombination and co-infection with other genotypes have gradually gotten worldwide attention and may be correlated with certain clinical features. There are substantial differences in HBV infection regarding prevalence, clinical manifestation, disease progression and response to antiviral therapy. Due to the complex interplay among viral, host and environmental factors, the relationship between HBV genotypes and clinical profiles remains incompletely revealed. In general, genotype A is associated with better response to interferon therapy; genotype C, and to lesser extent B, usually represent a risk factor for perinatal infection and are associated with advanced liver diseases such as cirrhosis and hepatocellular carcinoma; genotype D may be linked with poor response to interferon therapy. Future studies with better design and larger sample size are warranted to further clarify the controversial issues and guide the day-to-day clinical practice.

show abstract

Virological and clinical implication of core promoter C1752/V1753 and T1764/G1766 mutations in hepatitis B virus genotype D infection in Mongolia

Abstract: In Mongolians infected with HBV/D, C1752 and/or V1753 mutation was associated with HCC.

Cited by 32 publications

References 47 publications

Geographical and Ethnic Distribution of the HBV C/D Recombinant on the Qinghai-Tibet Plateau

Geographical and Ethnic Distribution of the HBV C/D Recombinant on the Qinghai-Tibet Plateau

Variability in the Precore and Core Promoter Regions of HBV Strains in Morocco: Characterization and Impact on Liver Disease Progression

Hepatitis B virus genotypes: epidemiological and clinical relevance in Asia

Contact Info

Product

Resources

About