World‐wide epidemiology of HBeAg‐negative chronic hepatitis B and associated precore and core promoter variants

Abstract

Hepatitis B is a serious disease that is endemic in many parts of the world. A significant proportion of patients with chronic hepatitis B (CHB) are infected with a variant form of the hepatitis B virus (HBV) which decreases or abolishes the production of hepatitis B e-antigen (HBeAg). The purpose of this literature review is to describe the epidemiology of HBeAg-negative CHB (e-CHB) worldwide. A literature search was conducted to identify studies pertaining to e-CHB and underlying variants (precore and core promoter). Fifty studies were included in our analysis. The median prevalence of e-CHB among patients with chronic HBV infection was 33% in the Mediterranean, 15% in Asia Pacific, and 14% in the USA and Northern Europe. The pre core stop codon variant was detected in a median of 60% (range 0-100%) of HBeAg-negative patients overall, 92% in the Mediterranean, 50% in Asia Pacific and 24% in the USA and Northern Europe. There were very few data on the prevalence of core promoter variants outside Asia where the median prevalence among HBeAg-negative patients was 77%. This literature review revealed that e-CHB is more common than previously suspected and that it is present worldwide with marked variations in the prevalence of associated HBV variants across different geographical regions. Additional research using population based samples of adequate size based on a consensus definition of e-CHB and using standardized HBV DNA assays is needed to better estimate the true prevalence of e-CHB and its associated HBV variants.

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

“…Meanwhile, other authors studying the prevalence of these cases observed that in the last decades there has been a gradual increase in the prevalence of HBeAg-negative CHB [6]. However, a more recent multi-center study of the world prevalence of HBeAg-negative CHB showed an increased prevalence of HBeAg-negative disease in chronic HBsAg carriers (33%) [11]. The elevated prevalence of HBeAgnegative CHB obtained in this study confirms the progressive tendency of the prevalence of HBeAg-negative CHB, possibly influenced by the type of prevalent transmission and by the high endemicity of the area studied [11].…”

“…The precore mutation was detected in up to 95% of HBeAg-negative patients, but it is more prevalent in Mediterranean countries. There are few data with respect to core promoter mutations outside Asia where mean values of prevalence among HBeAg-negatives was found to be 77% [11]. Based on studies conducted in Campinas (Brazil), about 70% of HBsAg-positive patients are HBeAg negative, with elevated potential of mutations in the precore or core promoter region [45].…”

A case–control study on sequence variations in the enhancer II/core promoter/precore and X genes of hepatitis B virus in patients with hepatocellular carcinoma

“…The other common HBV variants include double mutations in the basal core promotor (BCP) region (A1762T/ G1764A), which overlap with the ORF of the X gene and result in substantial decreases in HBeAg production [5]. These dual mutants have been reported in up to 50-80% of patients with HBeAg-negative chronic hepatitis B in Europe and Asia [6], and have been implicated in HCC development [7][8][9]. Apart from these variants, other mutations, such as T1753C/A/G in the BCP region and C1653T in the enhancer II region (EnhII) have become increasingly recognized as being associated with the outcome of chronic HBV infection, including HCC development [10][11][12].…”

Management of Chronic Hepatitis B: An Overview of Practice Guidelines for Primary Care Providers

“…31 Importantly, HBV reactivation may occur, either as a result of HBeAg seroreversion (ie, restored HBeAg positivity caused by reactivation of wildtype HBV), or, more frequently, as a result of the emergence of HBV mutants that no longer express HBeAg (ie, precore or basal core promoter [PC/BCP] mutants); the latter event, which results in HBeAg-negative CHB, is particularly common among patients from Asia or the Mediterranean, where the prevalence of PC/BCP mutants is high. 32 HBV reactivation can occur after years or decades of the inactive carrier state and represents, especially in the case of HBeAg-negative CHB, a late stage of the infection generally associated with advanced liver disease. [21][22][23] 37 ), (2) people who were not vaccinated as infants and whose parents were born in regions with high HBV endemicity (Southeast Asia, China, sub-Saharan Africa), (3) people needing chemotherapy or immunosuppressive therapy, (4) people with multiple sexual partners or a history of sexually transmitted disease, (5) people who have ever used injecting drugs, (6) individuals infected with human immunodeficiency virus or hepatitis C virus, and (7) household contacts or sexual partners of HBV-infected people.…”