To study the incidence of relapse and natural history on stopping antiviral therapy in children with chronic hepatitis B

Background: Natural history of chronic hepatitis B after stopping antiviral treatment has not been studied in children and adolescents. Aim: To study the incidence and predictors of relapse after stopping antiviral therapy in children and adolescents with Chronic hepatitis B(CHB). To study the efficacy & safety of retreatmen witht Peg IFN α-2b after relapse. Methods: All CHB children and adolescents were screened (study period 2 years) for inclusion criteria i.e. treatment with antivirals for at least 2 years, HBV DNA undetectable and ALT <1.5 upper limit of normal (ULN) in last 12 months, histology activity index< 5 and fibrosis <3. Patients with family history of cirrhosis or withhepatocellular carcinoma(HCC), decompensation, HCC, HCV/HIV were excluded. Circular covalently closed DNA was also estimated in liver biopsy. Children were monitored for virological (VR:elevation of HBV DNA >2000 IU/mL) and biochemical relapse(BR:ALT levels >2×ULN). BR was treated with Peg IFN alpha 2b for 48 weeks and oral nucleo(t)sides(NA). Results: Thirty nine of the 114 subjects screened got included. Relapse was seen only among 12(35.4%) of the 31 children and adolescents where HBsAg was detectable. BR along with VR and only VR was seen in 16.1%(n=5) and 19.3%(n=7). On Cox regression (Table 1), HBeAg positivity at the time of stopping antiviral(Log rank 10.705, P = 0.001) and time to HBV-DNA becoming undetectable on anti virals(cut off >22.5 months, AUROC 0.743, sensitivity 88.3%) were independent predictors of relapse(Model AUROC 0.855). In those with BR, HBV DNA became undetectable in 2/5 children and adolescents on retreatment without HBeAg or HBsAg seroconversion. Conclusion: Discontinuation of antiviral treatment results in VR in one third of the CHB children and adolescents. Relapse is more often seen in those with HBeAg positivity and >22.5 months time taken for HBV DNA to become undetectable on antivirals.Table 1Univariate and Cox Regression Analysis for predictors of relapse after stopping antiviral treatment in children with chronic hepatitis B.Univariate AnalysesVariableRelapsen=12Median(IQR)/ n(%)No Relpasen= 19Median(IQR)/ n(%)HR (95% CI)P ValueAge (years)at stopping treatment; HBsAg Q = HBsAg Quantitative; HBV DNA Q= HBV DNA Quantitative; ccc DNAq= Circular covalently closed DNA quantitative; IQR : Inter Quartile Range; ALT= Alanine aminotransferase16 (13.5-17)13 (10-17)1.129 (0.96 – 1.326)0.140HBV DNA IU/ml (Log 10)∗at Index presentation;6.07 (4.54 - 6.22)5.53 (3.32 – 7.73)0.947 (0.716 – 1.25)0.705HBsAg Q ∗at Index presentation; (Log 10)5.07 (4.17 – 5.09)4.40 (3.89 – 5.09)2.19 (0.759 – 6.32)-0.135 - 0.854)0.147HBeAg +ve ∗at Index presentation;12(100)18(94.7)1.056 (0.949 -1.174)1.000History of Immunoclearance phase5(41.6)14(73.7)0.255 (0.055 - 1.185)0.130HBsAg Qat stopping treatment; HBsAg Q = HBsAg Quantitative; HBV DNA Q= HBV DNA Quantitative; ccc DNAq= Circular covalently closed DNA quantitative; IQR : Inter Quartile Range; ALT= Alanine aminotransferase (Log 10)3.84 (3.15 – 4.41)3.71 (2.92 – 4.19)1.465 (0.806 – 2.66)0.211HBeAg +veat stopping treatment; HBsAg Q = HBsAg Quantitative; HBV DNA Q= HBV DNA Quantitative; ccc DNAq= Circular covalently closed DNA quantitative; IQR : Inter Quartile Range; ALT= Alanine aminotransferase9(75)4(21)7.058 (1.825 – 27.299)0.005Duration of Anti viral treatment duration(months) at stopping treatment; HBsAg Q = HBsAg Quantitative; HBV DNA Q= HBV DNA Quantitative; ccc DNAq= Circular covalently closed DNA quantitative; IQR : Inter Quartile Range; ALT= Alanine aminotransferase60 (36-78)48 (32-72)0.960 (0.905 – 1.019)0.136History of sequential treatment5( 41.6)8( 42.1)0.982 (0.227 - 4.251)1.000Duration of Normal ALT (months)at stopping treatment; HBsAg Q = HBsAg Quantitative; HBV DNA Q= HBV DNA Quantitative; ccc DNAq= Circular covalently closed DNA quantitative; IQR : Inter Quartile Range; ALT= Alanine aminotransferase16(13.5-33)32(19.5-48)0.979 (0.932 – 1.029)0.07Time taken to HBV DNA not detectable status (months)at stopping treatment; HBsAg Q = HBsAg Quantitative; HBV DNA Q= HBV DNA Quantitative; ccc DNAq= Circular covalently closed DNA quantitative; IQR : Inter Quartile Range; ALT= Alanine aminotransferase46 (23-64)24 (11-39)1.024 (1.003-1.046)0.028Duration of HBeAg negative (months)at stopping treatment; HBsAg Q = HBsAg Quantitative; HBV DNA Q= HBV DNA Quantitative; ccc DNAq= Circular covalently closed DNA quantitative; IQR : Inter Quartile Range; ALT= Alanine aminotransferase24 (12-28)24 (12-36)1.103 (0.417 – 2.919)0.843ccc DNAq (log10) copies/mlat stopping treatment; HBsAg Q = HBsAg Quantitative; HBV DNA Q= HBV DNA Quantitative; ccc DNAq= Circular covalently closed DNA quantitative; IQR : Inter Quartile Range; ALT= Alanine aminotransferase4.19 (3.5-6.99)3.2 (2.5 -5.1)1.176 (0.893-1.550)0.248Cox Regression AnalysisVariables in the EquationBWaldSig.Exp(B)95.0% C.I. for EXP(B)LowerUpperHBeAg Positivity at the time of stopping anti virals1.9757.8290.0057.2061.80728.743Time to DNA becoming undetectable (Months).0294.3560.0371.0301.0021.058∗ at Index presentation;∗∗ at stopping treatment; HBsAg Q = HBsAg Quantitative; HBV DNA Q= HBV DNA Quantitative; ccc DNAq= Circular covalently closed DNA quantitative; IQR : Inter Quartile Range; ALT= Alanine aminotransferase Open table in a new tab