Hepatitis B e antigen-negative chronic hepatitis B

Abstract

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 ...

Characterization of HBeAg-negative chronic hepatitis B in western Brazilian Amazonia

“…This confirms the data found by other authors that the HCB HBeAg negative is a late manifestation of a chronic evolution disease [18].…”

“…During the follow-up period, the most prevalent symptoms in the patients with hepatitis were: dyspepsia, asthenia and loss of libido, while the most common in carriers was the asymptomatic form, where this condition is generally discovered during blood donation or in the evaluation of elevated ALT levels in routine examinations, similar to those reported in the literature [18].…”

Role of viral factors in the natural course and therapy of chronic hepatitis B

“…They thus enter the immune clearance phase shortly after the establishment of persistent infection [21]. This difference in age of HBV infection may explain, at least in part, the different clinical course and treatment response to immunomodulatory agents between Asian and Western HBV carriers [22].…”

Should chronic HBV infected patients with normal ALT treated: debate

“…The fourth phase (re-activation of HBV replication/ HBeAg-negative chronic hepatitis B) is characterized by negative HBeAg, positive anti-HBe, detectable HBV DNA, elevated aminotransferases, and continued necroinflammation [4]. Whereas most patients reach this phase after a variable duration of inactive carrier state, some progress directly from HBeAg-positive chronic hepatitis to HBeAgnegative chronic hepatitis.…”