Hepatitis B virus (HBV) infection is a serious threat to public health globally with a prevalence rate of up to 7% in Asia and Africa[1]. Chronic hepatitis B infection affects approximately 800 million individuals in China. Among them, approximately one million people die from cirrhosis or hepatitis B-associated liver cancer annually[1]. In the area with a high prevalence of hepatitis B, mother-to-child transmission (MTCT) contributes largely to the new cases of HBV chronic infection[2]. The World Health Organization (WHO) has set a goal to eliminate HBV infection by 2030. Thus, the prevention of MTCT and the management of mothers with hepatitis B are critical steps to achieve the goal set by the WHO. It is estimated that the prevalence rate of hepatitis B infection in childbearing-age women in China is 6.61%[3]. Current practice guidelines[4–6] recommend that mothers with HBV DNA levels over 200,000 IU/mL should receive antiviral treatment during pregnancy to reduce the risk of MTCT. However, detailed guidance is lacking on the postpartum management of mothers with chronic hepatitis B. The practice patterns are inconsistent across different clinical settings in terms of when to stop the antiviral therapy and how to monitor mothers after delivery due to lacking high-quality evidence.
In young mothers with hepatitis B infection and high viral load without significant hepatitis, postpartum disease activation or hepatitis flare has been reported in the range of 15%-35%[7, 8]. In a multicenter and prospective randomized controlled trial (RCT), Pan et al. observed that postpartum ALT elevation occurs in both mothers who were treated with tenofovir disoproxil fumarate (TDF) or received no therapy during pregnancy (45% vs 30%)[9]. Another prospective study also showed that 36.3% of pregnant women who received antiviral therapy during pregnancy had postpartum hepatitis flares. Some of the ALT flares might further progress to acute exacerbation of hepatitis or even hepatic decompensation without timely antiviral treatment[7, 8]. In mothers without antiviral treatment during pregnancy, a large retrospective cohort study with 4236 hepatitis B mothers in China found that the postpartum ALT elevation rate was 28.27%[9]. Several independent predictors for postpartum ALT elevations were found in this subpopulation, which included high viral load or elevated transaminase during pregnancy. The peak period of ALT flares occurred between postpartum weeks 4–6 and weeks 9–12, with a bimodal distribution[9]. However, several limitations were noted in the study including the lack of data on maternal virological features such as genotype, basal core promoter, precore mutation, and pre-S mutant. In addition, the postpartum follow-ups were within 12 weeks in most mothers. In chronic hepatitis B patients at the immune tolerance phase, basal Core Promoters (BCP) and precore (PC) mutations are common in HBeAg-positive patients (up to 60%) and have been linked to immune activation[10, 11]. Recently, a study by Luo et al[12] suggested that the mutations of PC and BCP in HBeAg-positive pregnant women during antepartum could predict spontaneous HBeAg seroconversion after delivery. However, the postpartum elevation of ALT or hepatitis B flares has not been clearly described and analyzed.
Because of the inconsistent data and lack of details, the current International Association Guidelines have not provided clear recommendations and a risk-stratified monitoring schedule. Furthermore, data are lacking on the definition of normal ALT in the postpartum period in mothers with chronic hepatitis B. Lastly, the clinical features and ALT flare patterns have not been well defined in HBeAg-positive mothers versus HBeAg-negative mothers. We hypothesize that the frequency and severity of postpartum ALT flares differ between chronic hepatitis B mothers and healthy mothers. Furthermore, the patterns of postpartum ALT flares may also be influenced by the HBeAg status or antiviral therapy during pregnancy. Therefore, we will conduct a prospective cohort study and assess the incidence of postpartum ALT flares in mothers with chronic hepatitis B with subgroup analysis based on HBeAg status. In addition, we evaluate the normal range of postpartum ALT in healthy mothers without hepatitis B. In mothers with hepatitis B, the independent risk factors for predicting postpartum ALT flares are also investigated. Our data will serve as a piece of evidence to assist healthcare providers in the better management of mothers with hepatitis B.