Nucleos(t)ide Analogue Treatment for Patients With Hepatitis B Virus (HBV) e Antigen–Positive Chronic HBV Genotype C Infection: A Nationwide, Multicenter, Retrospective Study

ABSTRACT We aimed to identify genomic markers in hepatitis B virus (HBV) that are associated with hepatocellular carcinoma (HCC) development by comparing the complete genomic sequences of HBVs among patients with HCC and those without. One hundred patients with HBV-related HCC and 100 age-matched HBV-infected non-HCC patients (controls) were studied. HBV DNA from serum was directly sequenced to study the whole viral genome. Data mining and rule learning were employed to develop diagnostic algorithms. An independent cohort of 132 cases (43 HCC and 89 non-HCC) was used to validate the accuracy of these algorithms. Among the 100 cases of HCC, 37 had genotype B (all subgenotype Ba) and 63 had genotype C (16 subgenotype Ce and 47 subgenotype Cs) HBV infection. In the control group, 51 had genotype B and 49 had genotype C (10 subgenotype Ce and 39 subgenotype Cs) HBV infection. Genomic algorithms associated with HCC were derived based on genotype/subgenotype-specific mutations. In genotype B HBV, mutations C1165T, A1762T and G1764A, T2712C/A/G, and A/T2525C were associated with HCC. HCC-related mutations T31C, T53C, and A1499G were associated with HBV subgenotype Ce, and mutations G1613A, G1899A, T2170C/G, and T2441C were associated with HBV subgenotype Cs. Amino acid changes caused by these mutations were found in the X, envelope, and precore/core regions in association with HBV genotype B, Ce, and Cs, respectively. In conclusion, infections with different genotypes of HBV (B, Ce, and Cs) carry different genomic markers for HCC at different parts of the HBV genome. Different HBV genotypes may have different virologic mechanisms of hepatocarcinogenesis.

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Geographic distribution of hepatitis B virus (HBV) genotype in patients with chronic HBV infection in Japan

Hepatology ◽

10.1053/jhep.2001.27221 ◽

2001 ◽

Vol 34 (3) ◽

pp. 590-594 ◽

Cited By ~ 293

Author(s):

E Orito

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Geographic Distribution ◽

Hbv Infection ◽

Hbv Genotype ◽

Chronic Hbv Infection ◽

B Virus ◽

Chronic Hbv

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Hepatitis B virus pre-existing drug resistant mutation is related to the genotype and disease progression

The Journal of Infection in Developing Countries ◽

10.3855/jidc.9021 ◽

2017 ◽

Vol 11 (09) ◽

pp. 727-732 ◽

Cited By ~ 1

Author(s):

Liping Wang ◽

Fangzheng Han ◽

Hualing Duan ◽

Fang Ji ◽

Xuebing Yan ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Hbv Infection ◽

Drug Resistant ◽

Resistance Mutations ◽

Hbv Genotype ◽

B Virus ◽

Drug Resistant Mutation ◽

Genotype C ◽

Resistant Mutation

Introduction: Previous studies have indicated that the drug-resistant mutations of hepatitis B virus (HBV) are a major obstacle to antiviral therapy. However, it is still unclear whether there are pre-existent resistance mutations in patients with HBV infection and the relationship between drug-resistant mutation, genotypes, and progression of hepatitis B disease. Methodology: A total of 357 treatment-naïve patients with HBV infection were involved in this retrospective study. The drug-resistant mutations of HBV reverse transcriptase domain were screened by direct gene sequencing. Results: Lamivudine (LAM) resistance was detected in 8 patients (3.7%) with chronic hepatitis B (CHB), 13 (11.7%) patients with liver cirrhosis (LC), and 6 (21.4%) patients with hepatocellular carcinoma (HCC). Adefovir(ADV)-resistant mutations were detected in 10 (4.6%) patients with CHB, 15 (13.5%) patients with LC and 4 (14.5%) patients with HCC. Both LAM and ADV resistant mutations were detected in 2 patients (0.9%) with CHB, 1 patient (0.9%) with LC and 1 patient (3.6%) with HCC. Significant differences (p <0.01) were observed in the drug-resistance rates among patients with CHB, LC and HCC. Meanwhile, all the drug-resistant mutations were found in patients with HBV genotype C. Conclusions: This study demonstrated higher risk of pre-existing drug-resistant mutations in patients with HBV genotype C comparing to patients with HBV genotype B. Likewise, increasing prevalence of pre-existing drug-resistant mutations was shown, alongside with the progression of the disease.

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The Global Hepatitis B Virus Genotype Distribution Approximated from Available Genotyping Data

Genes ◽

10.3390/genes9100495 ◽

2018 ◽

Vol 9 (10) ◽

pp. 495 ◽

Cited By ~ 13

Author(s):

Stoyan Velkov ◽

Jördis Ott ◽

Ulrike Protzer ◽

Thomas Michler

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Treatment Strategies ◽

Population Data ◽

Genotype Distribution ◽

Virus Genotype ◽

Hbv Genotype ◽

B Virus ◽

Chronic Hbv ◽

The Individual

Hepatitis B virus (HBV) is divided into nine genotypes, A to I. Currently, it remains unclear how the individual genotypes contribute to the estimated 250 million chronic HBV infections. We performed a literature search on HBV genotyping data throughout the world. Over 900 publications were assessed and data were extracted from 213 records covering 125 countries. Using previously published HBV prevalence, and population data, we approximated the number of infections with each HBV genotype per country and the genotype distribution among global chronic HBV infections. We estimated that 96% of chronic HBV infections worldwide are caused by five of the nine genotypes: genotype C is most common (26%), followed by genotype D (22%), E (18%), A (17%) and B (14%). Genotypes F to I together cause less than 2% of global chronic HBV infections. Our work provides an up-to-date analysis of global HBV genotyping data and an initial approach to estimate how genotypes contribute to the global burden of chronic HBV infection. Results highlight the need to provide HBV cell culture and animal models that cover at least genotypes A to E and represent the vast majority of global HBV infections to test novel treatment strategies.

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Genotype C of hepatitis B virus can be classified into at least two subgroups

Journal of General Virology ◽

10.1099/vir.0.19633-0 ◽

2004 ◽

Vol 85 (2) ◽

pp. 283-292 ◽

Cited By ~ 83

Author(s):

Tran Thien-Tuan Huy ◽

Hiroshi Ushijima ◽

Vo Xuan Quang ◽

Khin Maung Win ◽

Pairoj Luengrojanakul ◽

...

Keyword(s):

Amino Acids ◽

Phylogenetic Analysis ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Far East ◽

Full Length ◽

Hbv Genotype ◽

B Virus ◽

Protein Amino Acids ◽

Genotype C

A genomic characterization of hepatitis B virus (HBV) was done for 56 pre-S1/pre-S2 genes and 10 full-length HBV genotype C isolates from five Asian countries. Phylogenetic analysis of the pre-S1/pre-S2 genes revealed two major groups within genotype C: one for isolates from southeast Asia including Vietnam, Myanmar and Thailand (named HBV/C1) and the other for isolates from Far East Asia including Japan, Korea and China (named HBV/C2). This finding was confirmed by phylogenetic analysis based on the full-length sequence of 32 HBV genotype C isolates, including 22 from database entries. Two isolates from Okinawa, the island off the southern end of Japan, formed a different branch. Specific amino acid sequence changes were identified in the large S protein (amino acids 51, 54, 60, 62 and 73) and P protein (amino acids 231, 233, 236, 248, 252 and 304). Our results indicate that genotype C of HBV can be classified into at least two subgroups.

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Progress of research on the immune tolerance of chronic HBV infection

Infection International ◽

10.2478/ii-2018-0026 ◽

2018 ◽

Vol 7 (3) ◽

pp. 88-93

Author(s):

Xuemei Li ◽

Xiaoxia Li

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Immune Tolerance ◽

The Body ◽

Hbv Infection ◽

Research Progress ◽

Hbv Genotype ◽

Chronic Hbv Infection ◽

B Virus ◽

Chronic Hbv

Abstract Immune tolerance is a specific lack or negative response of T and B lymphocytes to antigen. According to different formation periods, immune tolerance can be divided into central and peripheral tolerances. The immune tolerance of the body to hepatitis B virus (HBV) after infection is the main cause of chronic HBV infection. In this paper, the functional defects of hepatitis B virus e antigen and dendritic cells, hyporesponsiveness of cytotoxic T lymphocyte, variation of helper T lymphocytes and cytokines, HBV genotype and genome, and the role of host gene polymorphism in the formation of immune tolerance in chronic HBV infection and its related research progress are introduced briefly.

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High Viral Load and Hepatitis B Virus Subgenotype Ce Are Associated With Increased Risk of Hepatocellular Carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2007.13.2043 ◽

2008 ◽

Vol 26 (2) ◽

pp. 177-182 ◽

Cited By ~ 200

Author(s):

Henry Lik-Yuen Chan ◽

Chi-Hang Tse ◽

Frankie Mo ◽

Jane Koh ◽

Vincent Wai-Sun Wong ◽

...

Keyword(s):

Risk Factors ◽

Hepatocellular Carcinoma ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Hbv Dna ◽

Hazard Ratio ◽

Hbv Genotype ◽

Hbv Genotypes ◽

B Virus ◽

Genotype C

Purpose We aimed to investigate the impact of hepatitis B virus (HBV) DNA and HBV genotypes/subgenotypes on the risk of hepatocellular carcinoma (HCC). Patients and Methods A prospective cohort of patients infected with chronic HBV in a surveillance program for HCC since 1997 was studied. Ultrasound and alpha-fetoprotein evaluation were regularly performed to detect HCC. Risk factors for HCC and the relationship between HBV DNA and HBV genotypes were determined. Results Among 1,006 patients with a median follow-up of 7.7 years, 86 patients (8.5%) developed HCC. With reference to the low HBV DNA stratum (log HBV DNA ≤ 4.5 copies/mL), the hazard ratio for HCC of the intermediate HBV DNA stratum (log HBV DNA > 4.5 to 6.5 copies/mL) was 1.62 (95% CI, 1.05 to 2.48; P = .027) and that of the high HBV DNA stratum (log HBV DNA > 6.5 copies/mL) was 2.73 (95% CI, 1.76 to 4.25; P < .001). Among patients with genotyping results, 330 patients had HBV genotype B and 439 patients had HBV genotype C (94 subgenotype Ce and 345 subgenotype Cs). With reference to HBV genotype B, HBV subgenotype Ce has the highest risk of HCC (hazard ratio = 2.75; 95% CI, 1.66 to 4.56; P < .0001) and HBV subgenotype Cs has intermediate risk (hazard ratio = 1.70; 95% CI, 1.09 to 2.64; P = .020). On multivariate analysis, HBV DNA, HBV genotypes, liver cirrhosis, male sex, older age, and lower serum albumin were independent risk factors of HCC. Conclusion High HBV DNA level and HBV genotype C, particularly subgenotype Ce, increased the risk of HCC in chronic hepatitis B.

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A new intertype recombinant between genotypes C and D of hepatitis B virus identified in China

Journal of General Virology ◽

10.1099/vir.0.80771-0 ◽

2005 ◽

Vol 86 (4) ◽

pp. 985-990 ◽

Cited By ~ 53

Author(s):

Zhanhui Wang ◽

Zhihua Liu ◽

Guobing Zeng ◽

Shujuan Wen ◽

Yipeng Qi ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Phylogenetic Trees ◽

Phylogenetic Analyses ◽

Open Reading Frames ◽

Polymorphism Analysis ◽

Hbv Genotypes ◽

B Virus ◽

Genotype C ◽

Chronic Hbv

Hepatitis B virus (HBV) genotypes have a characteristic geographical distribution. More than 90 % of chronic HBV patients in China are infected with genotypes B or C. Here, eight HBV isolates that were initially classified as genotype D by PCR-restriction fragment length polymorphism analysis were analysed in detail. The complete HBV genome was sequenced and compared with 32 sequences retrieved from GenBank, representing HBV genotypes A–G. Phylogenetic analysis of the S gene (nt 10–800) classified all eight isolates as genotype D. However, phylogenetic analyses of nt 800–10 and the open reading frames (ORFs) of the precore/core and X genes classified all eight isolates as genotype C. This discordance between phylogenetic trees reconstructed on different ORFs suggested that intertype recombination has occurred in all eight isolates. By using the simplot program, the site of recombination with genotype D was located in the preS2/S region, spanning nt 10–799 in seven of eight isolates and nt 10–1499 in the other isolate. These results demonstrate that intertype recombination should be considered as a type of variation that increases the genetic diversity of HBV. Hybrids of different HBV genotypes might exhibit specific virological properties and their significance in the diagnosis and management of chronic hepatitis B deserves further investigation.

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Complete Genome Sequence of a Circulating Hepatitis B Virus Genotype C Strain Isolated from a Chronically Infected Patient Identified at an Outdoor Hospital in Bangladesh

Genome Announcements ◽

10.1128/genomea.01601-17 ◽

2018 ◽

Vol 6 (9) ◽

pp. e01601-17 ◽

Cited By ~ 4

Author(s):

Modhusudon Shaha ◽

Keshob Chandra Das ◽

M. Saddam Hossain ◽

Munira Jahan ◽

Abu Hashem ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Genome Sequence ◽

Complete Genome Sequence ◽

Complete Genome ◽

Virus Genotype ◽

Hbv Genotype ◽

B Virus ◽

Genotype C ◽

Potential Vaccine

ABSTRACT Hepatitis B virus (HBV) causes significant global health problems despite the presence of a potential vaccine. HBV chronic cases are increasing rapidly in developing countries like Bangladesh. Here, we report the complete genome sequence of an HBV genotype C strain isolated from a chronic patient identified at an outdoor hospital section.

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Possible role of tocopherols in the modulation of host microRNA with potential antiviral activity in patients with hepatitis B virus-related persistent infection: a systematic review

British Journal Of Nutrition ◽

10.1017/s0007114514002839 ◽

2014 ◽

Vol 112 (11) ◽

pp. 1751-1768 ◽

Cited By ~ 10

Author(s):

S. Fiorino ◽

L. Bacchi-Reggiani ◽

S. Sabbatani ◽

F. Grizzi ◽

L. di Tommaso ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Antiviral Activity ◽

Hbv Infection ◽

Cochrane Library ◽

Viral Pathogen ◽

Increased Risk ◽

B Virus ◽

Chronic Hbv

Hepatitis B virus (HBV) infection represents a serious global health problem and persistent HBV infection is associated with an increased risk of cirrhosis, hepatocellular carcinoma and liver failure. Recently, the study of the role of microRNA (miRNA) in the pathogenesis of HBV has gained considerable interest as well as new treatments against this pathogen have been approved. A few studies have investigated the antiviral activity of vitamin E (VE) in chronic HBV carriers. Herein, we review the possible role of tocopherols in the modulation of host miRNA with potential anti-HBV activity. A systematic research of the scientific literature was performed by searching the MEDLINE, Cochrane Library and EMBASE databases. The keywords used were ‘HBV therapy’, ‘HBV treatment’, ‘VE antiviral effects’, ‘tocopherol antiviral activity’, ‘miRNA antiviral activity’ and ‘VE microRNA’. Reports describing the role of miRNA in the regulation of HBV life cycle,in vitroandin vivoavailable studies reporting the effects of VE on miRNA expression profiles and epigenetic networks, and clinical trials reporting the use of VE in patients with HBV-related chronic hepatitis were identified and examined. Based on the clinical results obtained in VE-treated chronic HBV carriers, we provide a reliable hypothesis for the possible role of this vitamin in the modulation of host miRNA profiles perturbed by this viral pathogen and in the regulation of some cellular miRNA with a suggested potential anti-HBV activity. This approach may contribute to the improvement of our understanding of pathogenetic mechanisms involved in HBV infection and increase the possibility of its management and treatment.

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