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Effect of hepatitis B virus subgenotype on antiviral response in nucleoside-treated hepatitis B e antigen-positive patients.

Abstract

BACKGROUND

Previous studies have reported that hepatitis B virus (HBV) genotype is not a predictor of treatment response with nucleos(t)ide analogue (NUC) therapy. However, the impact of subgenotype on treatment response is unknown.

AIM

To identify the effect of HBV subgenotype on treatment response.

METHODS

In this retrospective study, the derivation dataset comprised patients from the EFFORT study (NCT00962533) telbivudine monotherapy group; patients infected with genotypes B or C from the GLOBE (NCT00057265) and 015 (NCT00131742) studies formed the validation dataset. HBV subgenotype was determined using phylogenetic analysis based on the surface or overlapping polymerase gene. Molecular modeling was used to investigate relationships between positions of the substitutions within reverse transcriptase and genotypic resistance.

RESULTS

Of the patients in the derivation dataset, 110, 24, 162, and 1 patients were classified as having HBV subgenotypes B2, C1, C2, or other, respectively, compared to 222, 146, 282, and 51 in the validation dataset. Patients infected with subgenotype C1 showed higher virologic response rate and hepatitis B e antigen (HBeAg) seroconversion rate, and lower genotypic resistance rate than those infected with subgenotypes B2 and C2. Patients with genotypic resistance to telbivudine with subgenotype C1 showed fewer secondary mutations. The crystal structure model of reverse transcriptase showed that these secondary mutations were located around the YMDD motif, which possibly influenced the chance of mutations at rtM204.

CONCLUSION

HBV subgenotype C1 is associated with better antiviral response to NUCs in HBeAg-positive patients than B2 and C2. The exact mechanism needs to be explored further.

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  • Authors+Show Affiliations

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    Department of Infectious Diseases, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.

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    Department of Infectious Diseases, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.

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    Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.

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    Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Science, Nagoya, Japan.

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    Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Science, Nagoya, Japan.

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    Department of Infectious Diseases, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.

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    Department of Infectious Diseases, Ruijin Hospital, Shanghai.

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    Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha.

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    Department of Infectious Diseases, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.

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    Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

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    Department of Infectious Diseases, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.

    Department of Infectious Diseases, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.

    Source

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    28422442