Serum Level of Antibodies Against Hepatitis B Core Protein Is Associated With Clinical Relapse After Discontinuation of Nucleos(t)ide Analogue Therapy

Chi, Heng; Li, Zhandong; Hansen, Bettina E.; Yu, Tao; Zhang, Xiaoyong; Sun, Jian; Hou, Jinlin; Janssen, Harry L.A.; Peng, Jie

doi:10.1016/j.cgh.2018.05.047

Cited by 63 publications

(94 citation statements)

References 31 publications

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“…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).…”

Section: Studies Characteristicsmentioning

confidence: 99%

“…The de nition of VR after NAs cessation was based on HBV DNA levels >20 IU/mL in one [22], >120 IU/mL in one [21], >2000 IU/mL (or 10,000 copies/mL) in 19 [19,20,[22][23][24][25][26][28][29][30][31][33][34][35][38][39][40]43,44], and >20,000 IU/mL (or 100,000 copies/mL) in one study [27]. One study provided two de nitions of VR which were based on HBV DNA levels >2000 IU/mL and >20,000 IU/mL [32].…”

Section: Studies Characteristicsmentioning

confidence: 99%

“…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].…”

Section: Studies Characteristicsmentioning

confidence: 99%

“…In ten studies supplying such data [19,24,26,31,[33][34][35]37,39,42], retreatment was started in 447 (84%) of 534 patients with BR or 447 (52%) of 859 patients with VR.…”

Section: Retreatment After Nas Cessationmentioning

confidence: 99%

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

Xie

Jin

Song

et al. 2020

Preprint

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BackgroudTo address the possibility of safe cessation of nucleos(t)ide analogues (NAs) therapy in chronic hepatitis B (CHB) and to identify factors associated with off-NAs virological relapse (VR).MethodsA published work search was performed to identify all published studies including patients who ceased NAs and were followed for ≥12 months. A meta-analysis was performed.ResultsTwenty-six studies involving 2573 patients who discontinued NAs were included. The pooled rate of off-NAs VR was 0.63, being lower in initially hepatitis B e antigen (HBeAg)-positive than HBeAg-negative patients (0.57 versus 0.62, P = 0.732). The pooled rates of VR were 0.47, 0.55, 0.61, 0.51, 0.73 and 0.64 at 6, 12, 24, 36, 48 and 60 months after NAs cessation, respectively, being relatively lower in initially HBeAg-positive (0.31, 0.45, 0.55, 0.44, 0.48, 0.52) than HBeAg-negative patients (0.50, 0.55, 0.69, 0.57, 0.53, 0.68) ( P = 0.405). The pooled rate of biochemical relapse was 0.44, being lower in initially HBeAg-positive than HBeAg-negative patients (0.43 versus 0.48, P = 0.554). The pooled rates of hepatitis B surface antigen (HBsAg) loss and seroconversion was 0.09 and 0.06, respectively. The pooled rates of VR at 12 months after NAs cessation were significantly different between duration of on-NAs virological response ≤24 months and >24 months in all patients (0.55 versus 0.41, P = 0.011), initially HBeAg-positive patients (0.59 versus 0.41, P = 0.031), and initially HBeAg-negative patients (0.53 versus 0.37, P = 0.025).ConclusionsCessation of NAs therapy seems to be safe in a small subset of CHB patients. On-NAs virological response >24 months reduces the risk of off-NAs VR.

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Section: Studies Characteristicsmentioning

confidence: 99%

Section: Studies Characteristicsmentioning

confidence: 99%

Section: Studies Characteristicsmentioning

confidence: 99%

“…In ten studies supplying such data [19,24,26,31,[33][34][35]37,39,42], retreatment was started in 447 (84%) of 534 patients with BR or 447 (52%) of 859 patients with VR.…”

Section: Retreatment After Nas Cessationmentioning

confidence: 99%

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

Xie

Jin

Song

et al. 2020

Preprint

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“…By combining the studies of both cohorts, Rivino et al concluded that if patients displayed an HBV core or polymerase‐specific T‐cell response that generates over 40 spot‐forming cells per 10 5 cells in an ELISPOT assay, they would have a high probability of controlling HBV without developing severe hepatic flares after termination of NUC therapy. Recently, it was reported that a high level of antibodies against HBV core antigen (HBcAg) at the end of NUC treatments was associated with a reduced risk of clinical relapse . It will be interesting to determine whether this higher level of antibodies against HBcAg is related to higher HBV‐specific T‐cell activities.…”

mentioning

confidence: 99%

Hepatitis B Virus–Specific T Cells as a Biomarker for Discontinuation of Nucleos(t)ide Analogue Therapy for Chronic Hepatitis B

Tian

2019

Hepatology

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Hepatitis B virus (HBV) can cause severe liver diseases and is a major health problem. It chronically infects approximately 250 million people worldwide. Nucleos(t)ide analogs (NUCs), including lamivudine, adefovir, entecavir, tenofovir and telbivudine, are the most frequently used drugs for treating chronic hepatitis B (CHB) patients. NUCs can efficiently suppress HBV DNA replication and reduce viral load, leading to the loss of the HBV e antigen (HBeAg), the appearance of antibodies against HBeAg, and the normalization of the alanine aminotransferase (ALT) level. However, they cannot target the HBV genomic DNA, also known as the covalently closed circular DNA (cccDNA), in infected hepatocytes. For that reason, the discontinuation of the NUC therapy can lead to viral rebound and the development of hepatic flares, and a lifelong treatment of this therapy is often required for CHB patients. Nevertheless, there are also some patients for whom the treatment with NUCs can be safely stopped. Unfortunately, the biomarkers for the identification of this subset of patients are currently lacking. Recently, Rivino et al. found that the population of PD1 HBV-specific T cells was much higher in chronic HBV patients who successfully discontinued the NUC therapy without developing hepatic flares than in those patients who developed hepatic flares (1). Their finding indicated that PD1 HBV-specific T cells might serve as the much-needed biomarker for safe discontinuation of the NUC therapy for CHB patients. This article is protected by copyright. All rights reserved.

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Development and validation of a model for hepatitis B e antigen seroconversion in entecavir‐treated patients with chronic hepatitis B

Shen

Wong

Kuang

et al. 2019

Journal of Medical Virology

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Achieving hepatitis B e antigen (HBeAg) seroconversion is a satisfactory endpoint during antiviral treatment for chronic hepatitis B (CHB). This study aimed to develop and validate a novel scoring system to predict HBeAg seroconversion during entecavir (ETV) treatment. A total of 526 patients with HBeAg‐positive CHB treated with ETV for at least 1 year were randomly assigned to the training and validation cohorts. Baseline parameters including hepatitis B virus DNA, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), and alanine aminotransferase level were quantified. Patients who achieved HBeAg seroconversion were compared with those without HBeAg seroconversion. A prediction model was established to predict HBeAg seroconversion during ETV treatment. After a median follow up of 2.67 years, 93 (36.0%) and 87 (32.5%) patients in the training and validation cohorts developed HBeAg seroconversion. A prediction score composed of age, HBsAg and HBcAb quantification was derived. Areas under receiver operating characteristic curve at 5 years of this prediction score were 0.70 and 0.72 in the training and validation cohorts. By using the dual cutoff values of 0.28 and 0.58, the model was endowed with high sensitivity and specificity to exclude or identify patients developing HBeAg seroconversion (90.3% sensitivity and 90.2% specificity in the training cohort as well as 92.8% sensitivity and 84.4% specificity in the validation cohort, respectively). A novel prediction score that uses baseline clinical variables was developed and validated. The score accurately estimates the probabilities of developing HBeAg seroconversion at 5‐years ETV therapy in patients with CHB.

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Serum Level of Antibodies Against Hepatitis B Core Protein Is Associated With Clinical Relapse After Discontinuation of Nucleos(t)ide Analogue Therapy

Cited by 63 publications

References 31 publications

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

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

Hepatitis B Virus–Specific T Cells as a Biomarker for Discontinuation of Nucleos(t)ide Analogue Therapy for Chronic Hepatitis B

Development and validation of a model for hepatitis B e antigen seroconversion in entecavir‐treated patients with chronic hepatitis B

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