Quantification of serum hepatitis B core antibody to predict off-entecavir relapse in patients with chronic hepatitis B

Abstract

This pilot study suggests a trend for an inverse association between anti-HBc levels and clinical relapse in CHB patients off entecavir.

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.…”

“…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]. On the contrary, more than 10 of the studies do not support that age is a predictive factor of off-treatment relapses [15,[22][23][24][25][26]28,[30][31][32][33]35,44]. In addition, age was not associated with HBsAg loss in any study assessing such an association [14,22,33,36,39].…”

“…Nevertheless, most of the studies did not show any association between pretreatment ALT and the probability of post-NA virological [14][15][16]18,[22][23][24][25]44], clinical relapse [16,23,34,35] or HBsAg loss [14,15,22,33,39]. There were, though, two studies suggesting that higher pretreatment ALT levels were associated with higher probability of HBsAg loss [14,36] and four studies showing that they were associated with lower risk of virological [15] and clinical relapse [28,31,33]. This association, although not widely confirmed, seems rational and might be explained by the fact that if a patient had high ALT levels before treatment, which would suggest strong immune response and absence of the "T-cell exhaustion" phenomenon, they may still host functional HBV-specific T-cells.…”

“…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].…”

“…Interestingly, very recent data from two cohorts highlighted the importance of serum titers of antibody against hepatitis B core antigen (anti-HBc) as a predictive marker for clinical relapses. Tseng et al [28] showed that there is a trend for inverse association between anti-HBc titers and the risk of clinical relapses. More recently, Chi et al reported 4-year clinical relapse rate of 21% in patients with EOT anti-HBc levels ≥ 1000 IU/mL in comparison to 85% of patients with levels < 100 IU/mL (p < 0.001) [35].…”