Consolidation period of 18 months no better at promoting off-treatment durability in HBeAg-positive chronic hepatitis B patients with tenofovir disoproxil fumarate treatment than a 12-month period

Abstract

There has been no clear consensus on the optimal consolidation periods following HBeAg seroconversion (SC) in HBeAg-positive chronic hepatitis B (CHB) patients. Our study aimed to prospectively compare relapse rates between 12 months’ and 18 months’ consolidation periods to see whether or not there is beneficial durability of tenofovir disoproxil fumarate (TDF) therapy with longer consolidation periods. We enrolled a total of 137 HBeAg-positive Asian CHB patients treated with TDF monotherapy. Forty-six patients achieved HBeAg SC. Then, they were randomly assigned to consolidation period of either 12 months (group A) or 18 months (group B). After stopping TDF therapy, all patients were followed up for 12 months. Thirteen patients (56.5%) relapsed in group A and 12 patients (52.2%) relapsed in group B after 12 months’ follow-up ( P = .958). Pretreatment HBsAg level is the only significant predictor for off-therapy recurrence by univariate analysis ( P = .024). Baseline HBeAg >1000 S/CO in group B patients were significantly less likely to relapse than those of group A ( P = .046). Baseline alanine aminotransferase (ALT) >133 U/L could significantly predict occurrence of HBeAg SC ( P = .008; 95% CI: 0.545–0.763; AUC: 0.654). Overall, a prolonged consolidation period has no positive effect on TDF therapy on sustained viral suppression in HBeAg-positive Asian CHB patients. However, a prolonged consolidation period was beneficial to patients with high baseline semi-quantitative HBeAg levels in terms of off-treatment durability. Baseline ALT > 133 U/L could significantly predict the occurrence of HBeAg SC.

Serious adverse events after cessation of nucleos(t)ide analogues in individuals with chronic hepatitis B: A systematic review and meta-analysis

“…1 ). [12] , [13] , [14] , [17] , [18] , [19] , 27 , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] One of the studies involved two distinct cohorts, of which one consisted exclusively of individuals with prior severe acute exacerbation and the other consisted of patients who had never experienced such an event. 31 Therefore, 50 studies with 51 cohorts were included in the meta-research analysis.…”

“…A total of 46 of 50 studies reported data on severe flares or hepatic decompensation, but heterogeneously defined them as hyperbilirubinemia (without or without concurrent coagulopathy), ascites, encephalopathy, and/or variceal bleeding, in addition to abrupt elevation of serum ALT. [12] , [14] , [17] , [18] , [19] , 27 , [30] , [31] , [32] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , 69 , 70 , 72 The definition of hyperbilirubinemia was also heterogeneous and could be a level of serum bilirubin ≥2 mg/dl, >3 mg/dl, and >2.5x the upper limit of normal. Similarly, coagulopathy was heterogeneously defined by prolongation of prothrombin time (PT) >3 seconds or an international normalized ratio >1.5 ( Table S7 ).…”

“…Of note, 14 (30.43%) of the 46 articles did not provide specific definitions for the said clinical events. 34 , 42 , 49 , [54] , [55] , [56] , [57] , 59 , 61 , 62 , [64] , [65] , [66] , [67] …”

Novel Biomarkers of Hepatitis B Virus and Their Use in Chronic Hepatitis B Patient Management

“…However, viral activity and ALT fluctuations persist within the HBeAg-negative chronic hepatitis phase of infection due to genomic mutations altering HBeAg expression [ 11 ]. Quantified HBeAg levels have also been shown in the literature to be associated with HBeAg seroconversion and pegylated-interferon α (peg-IFN) and nucleos(t)ide analogue (NA) treatment response [ 12 , 13 , 14 , 15 ]. However, there is no commercially available quantitative method and no standardization between laboratory-developed methods.…”

HBV and HDV: New Treatments on the Horizon

“…Although the approach of finite NA treatment is not completely uniform, there is a consistent agreement among different guidelines: finite NA therapy was suggested in not-cirrhotic patients with undetectable levels of HBV DNA(on three separate occasions, 6 months apart) after 12–18 months from HBeAb seroconversion (consolidation therapy) [ 52 ]. The Asian guidelines, in contrast to EASL and AASLD, consider finite NA treatment also in patients with cirrhosis [ 4 , 53 , 54 , 55 ].…”