Incidence And Predictors of Relapse After Stopping Antiviral Therapy In Pediatric Chronic Hepatitis B

Objective: The objective was to evaluate the incidence of relapse after stopping antiviral therapy and to identify the predictors of relapse. Methods: All HBsAg positive children with who had been on antivirals for at least 2 years with undetectable HBV-DNA and normal alanine-aminotransferase (ALT) on three consecutive occasions over last 12 months were included. Antivirals were stopped if liver biopsy showed histological activity index <5 and fibrosis (metavir) <3. Children were monitored for virological relapse (elevation of HBV-DNA >2000 IU/mL) and biochemical relapse (ALT levels >2 × upper limit of normal (ULN)). Those having biochemical relapse were started on pegylated interferon alpha-2b based sequential therapy. Results: Antivirals were stopped in 31 HBsAg positive children. Virological and biochemical relapse was seen in 12 (38.7%) and 5 (16.1%) children within 12 months of stopping antiviral treatment. Majority of virological relapse occurred within a month and biochemical relapses within 6 months of stopping therapy. HBeAg positive status at the time of stopping antiviral therapy (HR: 7.206, p =0.005) and longer time taken for HBV-DNA to become undetectable while on antivirals (HR: 1.030, p=0.037) were found to be the 2 independent predictors of relapse after stopping antiviral treatment. Conclusion: Discontinuation of antiviral treatment in children with CHB resulted in relapse in one third of the patients. Relapse was more common in those with HBeAg positivity at the time of stopping therapy and in those with longer time taken for HBV-DNA to become undetectable on antivirals.

Antiviral Therapy for Chronic HBV Infection With Persistently Normal Alanine Aminotransferase: Controversy and Consensus

ALT is one of the most sensitive biochemical indexes to reflect liver injury. It is generally believed that hepatitis B virus (HBV) infected patients with normal ALT levels are in either immune tolerance or low replication stage of the natural history of hepatitis B, and there is no or only mild inflammation in liver tissue, so antiviral therapy is not recommended. However, chronic HBV-infected patients with normal ALT levels are not always in a stable state. A considerable number of patients will develop active hepatitis or occult progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Therefore, whether antiviral therapy should be recommended for chronic HBV infection with normal ALT level has been a hot topic in clinical practice. In this paper, the definition of immune tolerance, the relationship between ALT and liver inflammation, and the benefits of antiviral therapy were reviewed, and we hope it will be helpful for clinicians to have a deeper understanding of whether antiviral therapy should be considered for chronic HBV infection with normal ALT.

Clinical relevance of T lymphocyte subsets in pediatric Graves’ disease

ObjectivesGraves’ disease (GD) is an autoimmune disease involving intimate response of both T cells and B cells. Immunophenotyping of peripheral blood lymphocyte subsets in GD children with different clinical characteristics can provide further information of the pathogenesis of GD.MethodsWe studied the lymphocyte subsets in peripheral blood of 141 children with GD. We repeatedly divided the patients into two groups in accordance with different clinical characteristics (abnormal or normal alanine aminotransferase (ALT) levels, the presence or absence of Graves’ orbitopathy (GO), and the presence or absence of hematuria. Then we compared the lymphocyte subsets measurements between two paired groups.ResultsWe found that serum ALT levels correlated positively with CD3+CD8+ T cell percentages in children with GD. Moreover, we detected higher percentages of CD3−CD19+ cells and higher ratio of CD4/CD8 in patients with GO. However, no correlation was found between GO status and lymphocyte subsets after excluding confounding effect of TRAb. No difference of lymphocyte subset percentages was found between groups with or without hematuria.ConclusionsSerum ALT levels correlate positively with cytotoxic T cell percentages in the peripheral blood of children with GD. The cytotoxic T cell may play a role in the pathogenesis of hepatic dysfunction in children with GD.