Chronic Hepatitis B Infection in Children

Abstract

Source: Ling SC, Lin HHS, Murray KF, et al. Chronic hepatitis is common and often untreated among children with hepatitis B infection in the United States and Canada. J Pediatr. 2021;237:24-33.e12; doi:10.1016/j.jpeds.2021.05.035Investigators from multiple institutions conducted a prospective cohort study of children in North America with chronic hepatitis B to assess outcomes over time. The study was conducted by the Hepatitis B Research Network at 6 clinical sites in the US and 1 in Canada. Study participants were children >6 months and <18 years old at baseline with hepatitis B surface antigen (HBsAg) positivity and were enrolled between 2010 and 2017. After a baseline visit, study participants had follow-up visits at 24 and 48 weeks, and annually thereafter. Data collected included demographics and clinical information, and blood specimens were obtained for measurement of alanine aminotransferase (ALT), platelet count, HBsAg, Hepatitis B e antigen (HBeAg), and hepatitis B virus (HBV) DNA on a regular basis. Treatment with anti-HBV therapy was documented, as was meeting criteria for this treatment based on guidelines from the American Association for the Study of Liver Diseases (AASLD). ALT was classified as normal or elevated when levels were greater than the upper limits of normal (ULN). Study outcomes included clinical events such as death, development of cirrhosis, liver transplantation, development of hepatocellular cancer, ALT flares (ALT levels ≥400 U/L in male patients and ≥350 U/L in female patients), hepatitis B serologic and virologic outcomes, anti-HBV treatment, and decreases in platelet counts (as an indicator of liver fibrosis progression).Data were analyzed on 362 children. Overall, 79% of study participants were Asian, 74% were born outside of the US or Canada, and 98% acquired HBV through vertical transmission. At baseline, 81% of study patients had elevated ALT values, with 66% having values >1–3 times >ULN; 75% were HBeAg positive. Median duration of follow-up in participants was 4.2 years (range 0.8–7.9 years). One study child died from a cause not related to liver disease, and 1 participant developed cirrhosis at age 14 years. Over the course of the study, 13 children had ALT flares, and there was an association between acute fall in platelet counts and occurrence of an ALT flare. At the last follow-up, ALT levels were elevated in 72% of patients. There were 40 patients treated with anti-HBV drugs. However, of 129 children who met AASLD criteria for anti-HBV treatment, only 25 (19%) received it. During the follow-up period, 2.4% of study patients became HBsAg negative, 15% of those who had detectable HBV DNA at baseline had unquantifiable levels measured at least once, and 20.8% of those who were HBeAg positive at baseline became HBeAg negative.The authors conclude that, among children in the US and Canada with chronic hepatitis B, many remained at risk for chronic liver disease.Dr Brady has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.HBV is efficiently transmitted from infected pregnant women to their newborn infants via blood exposures during labor and delivery.1 These infants are at increased risk of chronic HBV infection and its late complications of end-stage liver disease and liver cancer.2 The best strategies to prevent chronic HBV infection are to test pregnant women for HBsAg, refer women with positive HBsAg for potential treatment, immunize all infants with HBV vaccine at birth, and for those infants born to mothers with positive HBsAg, provide both HBV vaccine and hepatitis B immune globulin (HBIG), preferably within 12 hours of delivery.1 These strategies may not be available to infants born outside the US and Canada, and therefore screening for HBV infection should be included in the initial testing of immigrant and internationally adopted children, especially those from Asia.3Children who are positive for HBsAg need follow-up testing to see if the antigen clears. Those who have persistent positive HBsAg for at least 6 months are defined as chronically infected.1 Diet and exercise should be optimized to minimize their development of nonalcoholic fatty liver disease, which can contribute to additional liver injury.4 Referral to a hepatologist facilitates additional investigations and early appropriate initiation of anti-HBV therapies.5Another group of children and adolescents who need screening for chronic HBV infection is those with inflammatory bowel disease and rheumatologic conditions who are candidates for tumor necrosis factor alpha (TNF-α) inhibitor therapies.6 Because TNF-α is a mediator of the immune response against HBV infection, TNF-α inhibitors may promote viral reactivation and potentially fatal liver failure.Chronic HBV infection can lead to liver cancer and liver failure. The major prevention strategy is receipt of the birth dose of HBV vaccine.