Functional Cure of Chronic Hepatitis B with Antiviral Treatment in Children having High-level Viremia and Normal or Mildly Elevated Serum Aminotransferase

Jing Li; Peiyao Fan; Zhiqiang Xu; Yi Dong; Fuchuan Wang; Weiguo Hong; Jinfang Zhao; Yinjie Gao; Jianguo Yan; Lili Cao; Chao Zhang; Shishu Zhu; Fu-Sheng Wang; Min Zhang

doi:10.14218/JCTH.2023.00014

Functional Cure of Chronic Hepatitis B with Antiviral Treatment in Children having High-level Viremia and Normal or Mildly Elevated Serum Aminotransferase

J Clin Transl Hepatol. 2023 Oct 28;11(5):1011-1022. doi: 10.14218/JCTH.2023.00014. Epub 2023 Apr 10.

Authors

Jing Li^{1

2}, Peiyao Fan^{1

3}, Zhiqiang Xu³, Yi Dong³, Fuchuan Wang³, Weiguo Hong², Jinfang Zhao², Yinjie Gao³, Jianguo Yan³, Lili Cao³, Chao Zhang², Shishu Zhu³, Fu-Sheng Wang^{1

2}, Min Zhang³

Affiliations

¹ Peking University 302 Clinical Medical School, Beijing, China.
² Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China.
³ Senior Department of Liver Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.

Abstract

Background and aims: There is a lack of data supporting the notion that antiviral treatments can benefit children with chronic hepatitis B (CHB) having high viremia and normal or mildly elevated serum alanine aminotransferase (ALT) levels. We aimed to analyze the efficacy of antiviral treatments in children with CHB and explore the factors associated with functional cure.

Methods: Forty-eight children with CHB having high viremia and normal or mildly elevated serum ALT levels were screened in this real-world study. Thirty-two children received either interferon-alpha (IFN-α) monotherapy, IFN-α therapy with a nucleoside analog (NA) add-on, or IFN-α and NA combination therapy. The 16 children in the control group did not receive antiviral treatment. All 48 children were available for follow-up assessments for the entire 36-month study period. We identified a functional cure with respect to hepatitis B virus (HBV) DNA loss, loss /seroconversion of circulating hepatitis B e antigen (HBeAg), and loss of hepatitis B surface antigen (HBsAg) with or without seroconversion. Cox regression analysis was employed to evaluate the factors that may have influenced the functional cure.

Results: After 36 months, the cumulative functional cure rate was 56.25% (18/32) in the treated group and 0% (0/16) in the control group (p<0.001). In the treated group, the serum HBV DNA levels declined rapidly at the end of a 6-month visit and the cured children achieved a loss rate of 100% (18/18) within 16 months of beginning treatment, compared with 64.29% (9/14) of the uncured children (p<0.001). The rates of HBeAg seroconversion were significantly higher among the cured children than among the uncured children (p<0.001). All 16 children in the control group maintained high levels of serum HBV DNA and were positive for both serum HBeAg and HBsAg during the entire 36 months of the study period. Functional cure was associated with younger ages (1-6 vs. 7-14 years, p=0.013), CD8⁺ T lymphocyte counts (p=0.013), and B lymphocyte counts (p=0.003). No serious adverse events were observed.

Conclusions: Antiviral treatment achieved a functional cure of CHB in a high proportion of children having high-level viremia and normal or mildly elevated ALT levels. Younger age and high peripheral lymphocyte counts were associated with this functional cure.

Keywords: Antiviral therapy; Child; Chronic hepatitis B; Functional cure; HBV.