The role of hepatitis B virus core‐related antigen in predicting hepatitis B virus relapse after cessation of entecavir in hepatitis B e antigen‐negative patients

Abstract

This study investigated the ability of hepatitis B core-related antigen (HBcrAg) to predict hepatitis B virus (HBV) relapse in HBeAg-negative patients after cessation of entecavir therapy. A total of 301 HBeAg-negative patients without cirrhosis who had stopped entecavir therapy for at least 12 months were recruited. All patients fulfilled the stopping criteria proposed by the APASL 2012 guidelines. The five-year cumulative rates of virological relapse, clinical relapse and HBsAg loss were 71.6%, 57.3% and 18.7%, respectively. Serum HBsAg at end of treatment (EOT) was an independent predictor of virological relapse, clinical relapse and HBsAg loss; an EOT HBsAg of 150 IU/ml was the optimal cut-off value. The 5-year virological relapse rates for patients with <150 and ≥150 IU/ml HBsAg at EOT were 43.3% and 82.2% (p < 0.001), clinical relapse rates were 32.3% and 66.3% (p < 0.001), and HBsAg loss rates were 46.1% and 5.2% (p < 0.001), respectively. A baseline HBcrAg of 4 IU/ml was the optimal cut-off value for predicting HBV relapse. Among patients with an EOT HBsAg <150 IU/ml, the five-year virological relapse rates for patients with baseline HBcrAg levels ≤4 and >4 log U/ml were 27.9% and 59.1% (p = 0.006) and the clinical relapse rates were 18% and 48.1% (p = 0.014), respectively. EOT HBcrAg was not a significant predictor of virological or clinical relapse after cessation of entecavir. In conclusion, the combination of an EOT HBsAg of 150 IU/ml and baseline HBcrAg of 4 log U/ml can effectively predict the risk of HBV relapse after stopping entecavir therapy.

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 ).…”

KASL clinical practice guidelines for management of chronic hepatitis B

“…HBcrAg level is useful for predicting off-treatment sustained response after cessation of NA therapy. Recently, HBcrAg level alone or a combination of HBsAg levels has been proposed [ 247 , 275 ]. SCALE-B score (HBsAg level [S], HBcrAg [C], age [A], ALT [L], and tenofovir [E] used for HBV [B]) including HBsAg and HBcrAg levels at NA discontinuation was suggested for prediction of post-NA relapse and HBsAg loss in Asian CHB patients [ 276 - 278 ].…”

Serum Pregenomic RNA Combined With Hepatitis B Core-Related Antigen Helps Predict the Risk of Virological Relapse After Discontinuation of Nucleos(t)ide Analogs in Patients With Chronic Hepatitis B

“…Studies have also reported that HBcrAg can be detected even when serum HBV DNA becomes undetectable or HBsAg is lost ( Seto et al, 2014 ). In a Taiwanese study, the independent risk factor of VR was EOT HBcrAg >4 log U/mL ( Huang et al, 2021 ). Jung et al (2016) showed that EOT HBcrAg >3.7 log U/mL was independently associated with more than three-times higher risk of VR in HBeAg-negative CHB patients.…”