Chronic hepatitis B virus infection acquired in childhood: special emphasis on prognostic and therapeutic implication of delayed HBeAg seroconversion

Abstract

In high endemic areas of hepatitis B virus (HBV) infection, the vast majority of infection is acquired perinatally or during early childhood. The age of the patient is, therefore, almost equivalent to the duration of HBV infection. The natural history of chronic HBV infection consists of three chronological phases: immune tolerance, immune clearance and low replicative phases. The prevalence of hepatitis B e antigen (HBeAg) in asymptomatic HBV carriers is around 90% before 15 years of age, and decreases remarkably to less than 10% after 40 years of age. The immune clearance phase is characterized by a series of hepatitis flares and remissions. These will be followed eventually by HBeAg seroconversion, which is usually accompanied by remission of liver disease and confers favourable outcome. However, patients with persistent HBeAg seropositivity over 40 years of age are associated with a significantly higher risk for progression to cirrhosis than those with HBeAg seroconversion before 40 years of age, and thus should be considered as patients with 'delayed' HBeAg seroconversion. Antiviral or immunomodulatory therapy should be considered seriously for these patients.

HBeAg seroconversion as an important end point in the treatment of chronic hepatitis B

“…2) [14]. This is supported by evidence from studies of asymptomatic, HBeAg-positive HBV carriers that persistent HBeAg positivity or a prolonged immune clearance phase is associated with a higher risk of developing cirrhosis [10,11]. On the basis of these results, it can be concluded that the persistence of HBeAg positivity in patients beyond the age of 40 years was associated with a poorer prognosis.…”

“…In contrast, the off-treatment durability of HBeAg seroconversion for patients treated with entecavir at week 96 was only 77% [23]. As discussed previously, it is clear that the timing of HBeAg seroconversion has an important impact on disease progression, with delayed seroconversion associated with poorer outcomes [10]. It is now evident that HBeAg seroconversion in association with PCR-undetectable serum HBV-DNA levels is an achievable goal with oral NA treatment and can provide the possibility of improved outcomes with a finite course of therapy for individuals with HBeAg-positive CHB.…”

“…Spontaneous loss of HBeAg and development of antibodies to HBeAg (anti-HBe), referred to as HBeAg seroconversion, are associated with low HBV-DNA levels and clinical remission of liver disease in the majority of patients [8][9][10][11]. Earlier HBeAg seroconversion, or a shorter HBeAg-positive phase, is associated with a higher chance of sustained remission, lower rate of HBeAg reversion, and slower progression of liver disease and even increased hepatitis B surface antigen (HBsAg) seroclearance [10][11][12][13][14].…”

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

“…To this end, the cut-off value for age of HBeAg seroconversion has been suggested; patients with HBeAg seroconversion above 40 years of age were shown to have a substantially high rate of progression to cirrhosis than those below 40 years of age [44].…”

A mathematical model of the intracellular replication and within host evolution of hepatitis type B virus: Understanding the long time course of chronic hepatitis

“…Over 350 million people are chronically infected with HBV. More than 150 000 people die annually of hepatitis B-related liver disease (Villeneuve, 2005;Yim & Lok, 2005;Chu & Liaw, 2007). The mechanism of the persistence of HBV infection has not been fully elucidated.…”