Combining hepatitis B core‐related and surface antigens at end of nucleos(t)ide analogue treatment to predict off‐therapy relapse risk

Abstract

Summary Background There remains an unmet need for convenient biomarkers to assess the risks of discontinuing nucleos(t)ide analogues (NAs) in chronic hepatitis B (CHB). Aim To investigate if hepatitis B core‐related antigen (HBcrAg) is an independent of surface antigen (HBsAg) for risk prediction of NA cessation. Methods This prospective multicentre study enrolled 135 CHB patients who stopped entecavir or tenofovir after achieving viral remission for a median of 25.2 months. All patients stopped NA with negative HBeAg and undetectable viral DNA, and were then observed for clinical relapse and HBsAg loss. Predictors including HBsAg and HBcrAg levels were explored using Cox proportional hazard model and weighted to develop a risk score. Results During a median follow‐up of 25.9 months, clinical relapse and HBsAg loss occurred in 66 and eight patients, respectively, with a 5‐year cumulative incidence of 56.1% (95% CI 46.7‐66.0%) and 8.8% (95% CI 4.3‐17.4%), respectively. HBcrAg was an independent relapse predictor, as well as HBsAg, age, ALT and tenofovir use. A score (SCALE‐B) was calculated by the equation of 35*HBsAg (log IU/mL) + 20*HBcrAg (log U/mL) + 2*age (year) + ALT (U/L) + 40 for tenofovir use. The concordance rates for clinical relapse were 0.87, 0.88, 0.87, 0.85 and 0.90 at 1, 2, 3, 4 and 5 years, respectively. Moreover, HBsAg loss occurred exclusively in low‐risk patients predicted by the score. Conclusions Serum HBcrAg and HBsAg levels were independent predictors of off‐NA relapse and can be factored into a risk score to guide treatment cessation in patients with CHB.

Letter: distinct hepatitis B virus relapse rates after discontinuing tenofovir and entecavir therapy in chronic hepatitis B patients

“…https://orcid.org/0000-0002-1657-010X Recent studies have shown that HBcrAg and serum GGT levels are significant predictors of HBV relapse after discontinuing NA therapy. 3,4 However, the HBcrAg assay is not available in Taiwan, and serum GGT was not checked routinely in our study. Thus, we could not provide these data after cessation of either ETV or TDF therapy.…”

“…2 Furthermore, serum gamma-glutamyl transferase (GGT) levels at treatment start and at HBeAg seroconversion were also reported to impact the clinical relapse for CHB patients after nucleos(t)ide analogue cessation. 3 However, the levels of HBcrAg and GGT in CHB patients in the ETV and TDF groups were not provided by the authors. 1 Multicenter prospective cohort studies with large sample size are still needed to confirm whether HBV relapse occurs sooner and is more severe after TDF cessation than after the cessation of ETV in CHB patients.…”

The role of hepatitis B core‐related antigen in predicting hepatitis B virus recurrence after liver transplantation

“…Therefore, baseline HBcrAg measurements may help clinicians prescribe preventive treatment if the presence of HBcrAg can be confirmed. Many studies have shown that HBcrAg can predict the development of HCC and the outcome of NA therapy . However, few studies have focused on the relationship between HBcrAg levels and HBV recurrence after LT. Yasunaka et al first reported on this relationship, and found that HBcrAg levels were linearly correlated with post‐LT cccDNA levels .…”

Cessation of nucleos(t)ide analogues therapy in chronic hepatitis B: a systematic review and meta-analysis

“…At baseline, 337 (13.9%) of the 2433 patients with cirrhosis (information of cirrhosis was not reported in two studies [24,27], including 140 off-NAs patients), which was diagnosed by histology ndings and/or imaging studies. [32], entecavir in three [23,24,28], tenofovir in two [20,34], several NAs in fteen [19,21,22,26,30,31,33,[35][36][37][38][39][40][41]44], and NAs was not reported in the remaining ve studies [25,27,29,42,43] ( Table 1).…”

“…As to the three studies [32,36,37] provided more than one de nition of VR, when calculating the overall pooled rates of VR, we adopted the de nition of VR based on HBV DNA level >2000 IU/mL. BR after NAs cessation was de ned as ALT above the upper limit of normal (ULN) in three [24,31,41], >1.2 ULN in one [20], and >2 ULN in fteen studies [19,22,[25][26][27][28][29][32][33][34][35]38,39,43,44]. One study speci ed two de nitions of BR which were based on ALT >ULN and > 2 ULN [36].…”