Natural history of HBV infection in children

Post by Master, Doctor Mai Vien Phuong - Department of Examination & Internal Medicine - Vinmec Central Park International General Hospital

Chronic infection by hepatitis B virus (HBV) and hepatitis C virus (HCV) is a major cause of progressive liver disease and death worldwide. Although considered benign infections in children, their persistence through adulthood is certainly of concern.
Those drugs have completely changed the epidemiology of chronic liver disease in adults in the developed world, but they are still poorly accessible in resource-constrained settings and their use in children just started.

Similar to HCV, HBV infection in children mostly occurs through mother-to-child transmission. In high endemic countries, up to one-third of incidental HBV transmission is through parent-child, household, or intra-family transmission. Unlike adults, the prevalence of HBV infection in children reflects the level of HBV vaccination in neonates and infants, administered with the goal of eradication in the absence of effective antiretroviral therapy. . According to the World Health Organization's final report on hepatitis, the global prevalence of hepatitis B surface antigen (HBsAg) among preschool children has decreased from about 4.7% in the mid-1980s. and in the early 2000s to 1.3% in 2015, following the widespread adoption of universal infant immunization.
Age of transmission determines the development of chronic HBV infection
Age of transmission determines the development of chronic HBV infection, occurring in about 90% of infected infants and neonates compared with only 10% infections acquired later in childhood or in adults. Once a chronic infection is established, subsequent disease progression is the result of an adaptive immune response to HBV, liver damage from immune inflammation, and the pathogen itself.

Child-specific status after infection Until recently, patients were classified according to immune activity and control criteria, assuming that the clinical phenotype of HBV infection represents an immune state. clear. Due to the lack of immunological data, the latest European Society for the Study of the Liver (EASL) classification replaces states with "stages", focusing more on the course of infection in adults, but not suitable for children scenario. In fact, the natural history of chronic HBV infection at any age has been described by several large, long-term prospective studies. After infection, the vast majority of children enter a state characterized by detectable HBsAg and hepatitis B e antigen (HBeAg), high viral load, and normal or near-normal transaminase levels. This 'tolerance' phase can last for decades, and Asian children or those carrying genotypes C or D are more likely to persist. Finally, at a mean age of 30 years, 3%-6% of patients achieve HBeAg/hepatitis B e antibody (HBeAb) seroconversion annually, and most of those patients are successful in achieving this. inhibition of viremia. Spontaneous HBsAg/hepatitis B surface antibody seroconversion, potentially allowing long-term infection control, rarely occurs, at an approximate rate of 0.5%/year Main concern in children Children with chronic HBV infection The main concern in children with chronic HBV infection is the risk of cirrhosis and hepatocellular carcinoma, which occurs in 1%-5% and 0.03%-2% of patients, respectively. . When this risk increases in tandem with chronic hepatitis B (CHB) activity and duration (eg, elevated transaminases in the presence of high viral load), the ultimate long-term goal is to achieve suppression of chronic hepatitis B (CHB) disease. sustained viral suppression, either as a result of immune control or as a result of antiretroviral drug use. Phenotype characteristics of children with chronic HBV infection The current classification of chronic HBV infection recognizes different stages and considers their interchangeability. Stages are defined by the presence or absence of HBeAg (ie, HBeAg positive and HBeAg negative) and by elevations in transaminases, which distinguish chronic hepatitis from chronic infection. These classifications are not appropriate for the pediatric scenario, where HBeAg-positive chronic infection tends to be persistent and HBeAg-negative hepatitis is anecdotal. Classification of patients with HBV infection by clinical phenotype, which reflects immunity against the virus, has several advantages. The phenotypic classification has been progressively improved to harmonize population data, estimate the need for antiviral therapy, and possibly predict the outcome of infection. It describes three childhood phenotypes: (1) immune activity (HBeAg +/-, elevated transaminases, HBV-DNA > log 10 4 IU/mL); (2) immune resistance (HBeAg positive, transaminase normal, HBV-DNA > log 10 4 IU/mL); and (3) inactive carrier (HBeAg +/-, normal transaminase, HBV-DNA ≤ log 10 4 IU/mL); with the remainder being "unknown". As defined, immune phenotypes can help predict fate for infection control. Indeed, children with HBeAg-positive immune activity were more likely to achieve spontaneous HBeAg/HBeAb seroconversion (28% and 7.47%/year) compared with immunocompetent children (11% and 2%). ,29%/year). In a scenario characterized by a lack of clear indications for treatment and disappointing outcomes, the definition of phenotype has been shown to be of prognostic value and helps to identify homogenous groups for treatment. patient selection in future trials.

HBV and HCV infections in childhood often progress to chronic hepatitis through different mechanisms of tolerance and immunodeficiency. For HCV infection, an increasing number of different direct-acting antiviral drug combinations, including the pan genotype combination, are available, with very few adverse effects and an extremely high SVR. For HBV infection, recent cohort studies have clarified that several factors, including immune host phenotype, viral genotype, and ethnicity, contribute to spontaneous control. Viral hepatitis should not be a barrier to the use of immunosuppressants in the treatment of autoimmune diseases, as well as anticancer chemotherapy, as long as timely screening and interventions are implemented. appropriate pharmacology. Finally, new drugs are being developed to treat HBV, which primarily work by promoting tolerance breakdown.