Predictors of hepatitis B surface antigen loss, relapse and retreatment after discontinuation of effective oral antiviral therapy in noncirrhotic HBeAg‐negative chronic hepatitis B

Abstract

Reliable predictors of outcomes after treatment discontinuation in HBeAg-negative chronic hepatitis B (CHB) patients have not been established. We investigated the role of hepatitis B surface antigen (HBsAg), interferon-inducible protein-10 (IP10) and hepatitis B core-related antigen (HBcrAg) serum levels as predictors of HBsAg loss, relapse and retreatment in noncirrhotic HBeAg-negative CHB patients who discontinued long-term antiviral therapy. All HBsAg-positive (n = 57) patients of the prospective DARING-B study were included and followed monthly for 3 months, every 2/3 months until month-12 and every 3/6 months thereafter. HBsAg, IP10 and HBcrAg levels were measured by enzyme immunoassays, and SCALE-B score was calculated. Twelve patients achieved HBsAg loss before retreatment with 18-month cumulative incidence of 25%. Independent predictors of HBsAg loss were baseline HBsAg and month-1 IP10 levels. Of 10 patients with baseline HBsAg ≤100 IU/mL, 70% cleared HBsAg and 10% required retreatment. Of 23 patients with baseline HBsAg >1000 IU/mL, 4% cleared HBsAg and 43% required retreatment. Of 24 patients with intermediate baseline HBsAg (100-1000 IU/mL), 17% cleared HBsAg and 21% required retreatment; in this subgroup, month-1 IP10 was significantly associated with HBsAg loss, which occurred in 30% and 7% of cases with IP10 >150 and ≤150 pg/mL, respectively. Baseline HBcrAg was undetectable in all patients who cleared HBsAg and was associated with retreatment. SCALE-B was associated with HBsAg loss but not with relapse or retreatment. In conclusion, HBsAg, IP10 and HBcrAg serum levels can be useful for the decisions and management of treatment discontinuation in noncirrhotic Caucasian patients with HBeAg-negative CHB. | 119PAPATHEODORIDI ET Al.

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

“…Hsu et al also showed that HBcrAg was independently associated with relapses after NAs discontinuation and they additionally combined it with other predictive markers to create a predictive score model, SCALE-B score [34]. Finally, results from the DARING-B study confirmed the predictive value of HBcrAg for prediction of serious relapses that require retreatment in Caucasian HBeAg-negative CHB patients who discontinued entecavir (ETV) or tenofovir disoproxil fumarate (TDF) therapy, showing that detectable EOT HBcrAg levels could rule out the probability of HBsAg loss and were independently associated with more than 3-fold increased risk of retreatment [39].…”

“…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.…”

“…In that study, Chen et al showed that high pretreatment qHBsAg levels (>1000 IU/mL) were independently associated with increased risk of virological relapse defined as HBV DNA >2000 IU/mL in initially HBeAg-positive patients who discontinued NAs [16]. Furthermore, declining qHBsAg levels during or after treatment have also been found to predict subsequent HBsAg loss [16,38,39] or off-therapy virological remission [37]. Therefore, studying qHBsAg kinetics has gathered researchers' interest, since it seems that serial measurements of qHBsAg can be useful in guiding clinical decisions and managing these patients.…”

“…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].…”