Epidemiology of precore mutants of hepatitis B in the United Kingdom

Ballard, Anna; Boxall, Elizabeth

doi:10.1002/1096-9071(200012)62:4<463::aid-jmv11>3.0.co;2-0

Cited by 19 publications

(14 citation statements)

References 31 publications

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“…However, different studies have demonstrated a wide geographic distribution of this variant, which has also been reported in the United Kingdom (Ballard and Boxall, 2000) and Germany (Knoll et al, 1999).…”

Section: Discussionmentioning

confidence: 79%

The precore mutation is associated with severity of liver damage in Brazilian patients with chronic hepatitis B

Rezende

Fonseca

Ramalho

et al. 2005

Journal of Clinical Virology

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Section: Discussionmentioning

confidence: 79%

The precore mutation is associated with severity of liver damage in Brazilian patients with chronic hepatitis B

Rezende

Fonseca

Ramalho

et al. 2005

Journal of Clinical Virology

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“…7 20 That these exacerbations are equally likely to be due to wild-type virus and precore mutants has been reported by us and other groups previously. [21][22][23] Anti-HBe positive patients should be monitored as carefully as HBeAg positive patients for the development of cirrhosis related complications and HCC. In addition, the majority of patients after HBeAg seroconversion still had detectable HBV DNA levels measured by the PCR assay.…”

Section: Discussionmentioning

confidence: 99%

A large population study of spontaneous HBeAg seroconversion and acute exacerbation of chronic hepatitis B infection: implications for antiviral therapy

Yuen

Yuan²,

Hui³

et al. 2003

Gut

116

102

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Background and aim: Clinical data on spontaneous hepatitis B e antigen (HBeAg) seroconversion and acute exacerbation of chronic hepatitis B (CHB) virus infection from large population studies are lacking. In the present study we examined the clinical features and significance of HBeAg seroconversion and acute exacerbation in 3063 Chinese CHB patients. Methods: Clinical assessment, liver biochemistry, hepatitis B virus (HBV) serology and HBV DNA, time of HBeAg seroconversion, and acute exacerbation were monitored. Results: Median age at HBeAg seroconversion was 34.5 years. The cumulative HBeAg seroconversion rate significantly increased with alanine aminotransferase (ALT) levels on presentation (p<0.0001). For patients with ALT levels more than twice the upper limit of normal (ULN) on presentation, the HBeAg seroconversion rate at the fifth year of follow up was 72.4%. After HBeAg seroconversion, 65.2% (73/110) of patients had undetectable HBV DNA levels by the Digene Hybrid Capture assay. Of these, 78.1% still had HBV DNA levels detectable by the Amplicor HBV Monitor Test. We found that 37.5% antibody to HBeAg (anti-HBe) positive patients had undetectable HBV DNA levels by the Digene Hybrid Capture assay before acute exacerbation. Acute exacerbations of longer duration, with higher peak ALT, bilirubin, and α fetoprotein levels were associated with an increased HBeAg seroconversion rate (p<0.0001-0.045). Acute exacerbation with peak ALT levels more than five times the ULN carried a 46.4% chance of HBeAg seroconversion within three months. HBeAg seroreversion and mortality occurred in 2.7% and 0.7% of acute exacerbations, respectively. Conclusion: In the present study we have provided information on HBeAg seroconversion and acute exacerbation, which are important in decision making for CHB treatment and in designing clinical trials.

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“…30 Thus, precore mutants prevail in the Mediterranean where non-A genotypes, particularly D, are predominant. 17,[31][32][33][34][35] However, precore mutants have also been detected in Northern Europe, 22 United Kingdom, 36 and Canada. 37 In Asian countries, where both A and non-A genotypes exist, in addition to precore mutants, BCP mutants are found.…”

Section: Prevalencementioning

confidence: 99%

Hepatitis B e antigen-negative chronic hepatitis B

2001

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Thirty years ago, the diagnosis of chronic hepatitis B (CHB) was thought to require the presence of hepatitis B e antigen (HBeAg), as a reliable and sensitive marker of hepatitis B virus (HBV) replication. 1 Individuals positive for hepatitis B surface antigen (HBsAg) but negative for HBeAg were considered to have nonreplicative HBV infection, and if their liver enzymes were normal or nearly normal they were referred to as asymptomatic or healthy HBsAg or HBV carriers. 2 If, on the other hand, they displayed elevated serum aminotransferases and liver histology indicative of chronic hepatitis, they were generally thought to be suffering from other superimposed or complicating conditions such as hepatitis D virus infection, alcohol-induced, metabolic, autoimmune, drug-induced, or other forms of chronic liver disease. 3 In the early 1980s it became apparent that HBV could replicate in the absence of HBeAg. [4][5][6] Patients from the Mediterranean area, although negative for HBeAg and positive for antibodies to HBeAg (anti-HBe), were reported to have CHB with replicating HBV. 7 The term anti-HBe-positive or HBeAgnegative CHB was then proposed 4 and subsequently became widely accepted. In 1989 the molecular basis of this form of CHB was discovered 8,9 with the identification of HBV mutations preventing HBeAg formation from an otherwise normally replicating HBV. 10,11 With time, it became apparent that HBeAg-negative CHB, initially viewed as an atypical and rare form of CHB mainly restricted in the Mediterranean area, had a much wider geographical distribution and that its frequency was increasing. 12 Its molecular virology and immunology were found to be more complex than initially thought, 13 whereas the selection of precore HBV mutants was shown to be largely determined by the HBV genotype. 14 Mutations abolishing or diminishing HBeAg formation were identified along with changes in other parts of the HBV genome. 14 More recently, the new nucleoside analog, lamivudine, has been used to treat a sizeable number of patients with HBeAg-negative CHB, and important information on its efficacy and the development of resistance has been collected. [15][16][17][18] DEFINITION AND NOMENCLATUREThe term HBeAg-negative CHB defines the condition as disease caused by strains of HBV that are not producing HBeAg. 12 It does not specify the mutations responsible for the lack of HBeAg, i.e., a precore stop-codon mutation, 10 a double basic core promoter (BCP) mutation, or other, 14 and it says nothing about the level of HBV replication. The alternative term "precore mutant CHB," used by some investigators, also does not specify the nature of the precore mutation. In clinical practice, the term HBeAg-negative CHB is appropriate for patients with chronic HBV infection who test negative for HBeAg, are usually positive for anti-HBe, have increased alanine aminotransferase (ALT) levels and display detectable HBV DNA in serum by classical hybridization techniques. 12 Despite the fact that the identification of the underlying mutations in ...

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Epidemiology of precore mutants of hepatitis B in the United Kingdom

Cited by 19 publications

References 31 publications

The precore mutation is associated with severity of liver damage in Brazilian patients with chronic hepatitis B

The precore mutation is associated with severity of liver damage in Brazilian patients with chronic hepatitis B

A large population study of spontaneous HBeAg seroconversion and acute exacerbation of chronic hepatitis B infection: implications for antiviral therapy

Hepatitis B e antigen-negative chronic hepatitis B

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