48-Week Outcome after Cessation of Nucleos(t)ide Analogue Treatment in Chronic Hepatitis B Patient and the Associated Factors with Relapse

Abstract

Background and Aims We aimed to ascertain the feasibility and safety of NA cessation, the status of patients after cessation, and the predictive factors for relapse and subsequent retreatment. Methods A total of 92 patients were enrolled in this prospective study. Patients were monitored every month for the first 3 months after cessation and every 3 months thereafter. Results Sixty-two patients finished 48 weeks of follow-up. None died or developed liver failure, cirrhosis, or HCC. The 62 patients could be divided into 4 categories according to the 48-week clinical development of relapse. Virologic relapses occurred in 39 (62.9%) patients, with 72.7% occurring in the first 24 weeks in origin HBeAg positive patients and 82.4% in the first 12 weeks in origin HBeAg negative patients. Age (OR = 1.06, 95% CI = 1.02–1.10; p = 0.003), the HBsAg level (OR = 2.21, 95% CI = 1.47–3.32; p < 0.001), and positive origin HBeAg status (OR = 0.32, 95% CI = 0.14–0.74; p = 0.008) were predictive factors to virologic relapse. HBV DNA level (OR = 1.34, 95% CI = 1.13–1.58; p < 0.001) was predictive factor to retreatment. Conclusions NA cessation is safe under supervision. Age, HBsAg level, and origin HBeAg status can be predictive factors for virologic relapse. The study was submitted to ClinicalTrials.gov Protocol Registration and Results System with the assigned NCT ID NCT02883647.

Emerging Diagnostic Tools to Decide When to Discontinue Nucleos(t)ide Analogues in Chronic Hepatitis B

“…This idea was first suggested in the pivotal study of Hadziyannis et al, where HBsAg levels at EOT were associated with subsequent HBsAg loss in 33 non-cirrhotic HBeAg-negative CHB patients [36]. Since then, this finding has been confirmed in a number of studies, where it has been reported that lower EOT qHBsAg levels are associated with higher probability of off-NAs HBsAg loss [14,15,21,22,[37][38][39], while higher EOT qHBsAg levels may be associated with higher probability of virological [14,16,18,19,21,22,24,[27][28][29] or clinical relapses in other cohorts [16,27,28,32,34,35,44]. Of note, there has been no negative study assessing the association between EOT HBsAg and off-NAs HBsAg loss.…”

“…Regarding HBsAg-positive patients' outcomes after NAs discontinuation, serum HBsAg levels are a tool of great importance [42]. A number of studies have evaluated HBsAg levels during NAs treatment [14,16,18,22,37,38,43,44] or most commonly at the end of treatment (EOT) as possible predictors [14][15][16][17][18][21][22][23][24][26][27][28][29][30]32,[34][35][36][37][38][39]44]. This idea was first suggested in the pivotal study of Hadziyannis et al, where HBsAg levels at EOT were associated with subsequent HBsAg loss in 33 non-cirrhotic HBeAg-negative CHB patients [36].…”

“…Serum viral load, which is measured via serum HBV DNA quantification, has been assessed in various settings as a tool for treatment decisions in CHB patients, but in respect to patient management after NAs discontinuation, only few studies showed that there is association between higher pretreatment HBV DNA levels and post-NAs relapses [17,18,21,22,29,30,32] or HBsAg loss [14,33]. On the other hand, negative results were provided by a number of other cohorts that have examined the association between pretreatment serum HBV DNA levels and virological relapses [14,16,17,[23][24][25]44], clinical relapses [23,31,[33][34][35]44,45] or HBsAg loss [14,22,36,37,39].…”

“…There are five studies suggesting that older age is associated with post-NAs virological relapses [14,[16][17][18]29] and one with clinical relapses [34]. In some of these studies, patients older than 40 or 50 years old were reported to be at higher risk of virological relapses [16][17][18].…”

Clinical Implications of Hepatitis B Virus RNA and Covalently Closed Circular DNA in Monitoring Patients with Chronic Hepatitis B Today with a Gaze into the Future: The Field Is Unprepared for a Sterilizing Cure

“…Monitoring cccDNA, including cccDNA epigenetics and mutations, and novel surrogate markers of cccDNA activity, such as secreted HBV RNA, are important for (i) helping to define groups of patients susceptible to IFN therapy [ 29 , 30 , 31 ]; (ii) determining end-points of NA treatment [ 16 , 32 ]; (iii) predicting the risk of HCC and cirrhosis [ 33 ]; and, (iv) identifying potential drug resistance [ 34 ]. It should be underscored that in patients receiving these therapeutics, a decline of HBV biomarkers below certain threshold levels testifies to a sustained antiviral response, in which HBV replication is suppressed dramatically and immune cells can effectively control the disease [ 35 , 36 , 37 ]. While challenges in detecting cccDNA prevent it from being used for monitoring patients with CHB, HBV RNA has been recently proposed as a valuable alternative.…”