Elsevier

Journal of Hepatology

Volume 33, Issue 3, September 2000, Pages 430-439
Journal of Hepatology

Rapid detection of genotypes and mutations in the pre-core promoter and the pre-core region of hepatitis B virus genome: correlation with viral persistence and disease severity

https://doi.org/10.1016/S0168-8278(00)80279-2Get rights and content

Abstract

Background/Aims: We aimed to clarify the clinical relevance of hepatitis B virus pre-core mutant detection in patients with chronic hepatitis B using a newly developed assay.

Methods: Viral genotypes and pre-core mutations were studied in relation to viral persistence and liver disease severity using INNO-LiPA methodology. The study group included 151 patients with chronic hepatitis B, 85 positive for HBeAg (group I) and 66 positive for anti-HBe (group II).

Results: The prevalence of viral genotypes in group I was: 64% A, 1% B, 15% C, 19% D, 0% E, 0% F and in group II: 39% A, 0% B, 2% C, 56% D, 2% E, 2% F (p<0.001). The prevalence of mutations at pre-core codon 28 (M2) was lower in group I (5%) than in group II (64%)(p<0.001). The prevalence of pre-core promoter mutations was also lower in group I (21%) than in group II (61%)(p<0.001). M2 mutations were more frequently detected in genotype D than in genotype A (p<0.001), while the other mutations were not influenced by viral genotype. Serum HBV DNA levels were significantly lower in group II versus group I (p<0.001), and in patients with any of the pre-core mutations versus wild-type sequence (p<0.01). Although cirrhosis was more frequent in group II (37%) versus group I (22%) and in patients with either one of the pre-core mutation (31%) versus wild-type sequence (25%), there was no statistical difference in liver severity assessed by ALT levels and Knodell score.

Conclusion: Pre-core mutants, whose molecular pattern is strongly dependent on viral genotypes, are associated with viral persistence in anti-HBe positive patients with ongoing chronic hepatitis B. The availability of this rapid assay should allow a precise monitoring of viral pre-core mutants during the course of chronic hepatitis B.

Section snippets

Patients

We studied a cohort of 151 consecutive French patients who were referred to our liver department (Hôtel-Dieu Hospital, Lyon, France) for the management of compensated chronic hepatitis B from 1994 to 1997. All patients had liver biopsy-proven chronic hepatitis B. At the time of referral, none of the patients had clinical manifestation of decompensation of the liver disease, such as jaundice, ascites, variceal bleeding, encephalopathy, or liver carcinoma. None of the patients received

Epidemiological characteristics of the patients

The 151 patients were classified into two groups according to the results of HBeAg/anti-HBe serology. Eighty-five patients were positive for HBeAg and 66 patients were positive for anti-HBe. The demographic characteristics of the patients are presented in detail in Table 1. HBeAg positive patients were younger than those who were anti-HBe positive (p<0.001). There was no statistical difference between the two groups in terms of sex ratio, but a difference was observed in terms of mode of

Discussion

In this study of a large cohort of 151 French patients with ongoing chronic hepatitis B, we found that HBV genotyping can be performed on a large scale using a new post-PCR hybridization assay. This line probe assay was previously set up for HCV genotyping (40) and was applied only very recently to HBV genome detection 33., 36.. This assay was first evaluated blindly with our in-house tests 15., 20., 31. and viral genome sequence analysis that demonstrated its reliability for the rapid

Acknowledgements

We thank Dr Frano̧ise Huisse (Chiron diagnostics, France) for providing the branched DNA assay kits. This work was supported by grants form the INSERM and the“Hospices Civils de Lyon”.

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