Hepatitis B surface antigen, core‐related antigen and HBV RNA: Predicting clinical relapse after NA therapy discontinuation

Kaewdech, Apichat; Tangkijvanich, Pisit; Sripongpun, Pimsiri; Witeerungrot, Teepawit; Jandee, Sawangpong; Tanaka, Yasuhito; Piratvisuth, Teerha

doi:10.1111/liv.14606

Cited by 34 publications

(73 citation statements)

References 30 publications

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“…Close monitoring every 3 months and prompt initiation of NUCs may be more cost-effective. In the future with more solid evidence, new biomarkers, such as HBV RNA, HBcrAg, may be helpful to decide when to terminate NUCs after completion of IST [ 103 ].…”

Section: Methodsmentioning

confidence: 99%

APASL clinical practice guideline on hepatitis B reactivation related to the use of immunosuppressive therapy

Lau

Wong

et al. 2021

Hepatol Int

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Background & Aim Hepatitis B reactivation related to the use of immunosuppressive therapy remains a major cause of liver-related morbidity and mortality in hepatitis B endemic Asia-Pacific region. This clinical practice guidelines aim to assist clinicians in all disciplines involved in the use of immunosuppressive therapy to effectively prevent and manage hepatitis B reactivation. Methods All publications related to hepatitis B reactivation with the use of immunosuppressive therapy since 1975 were reviewed. Advice from key opinion leaders in member countries/administrative regions of Asian-Pacific Association for the study of the liver was collected and synchronized. Immunosuppressive therapy was risk-stratified according to its reported rate of hepatitis B reactivation. Recommendations We recommend the necessity to screen all patients for hepatitis B prior to the initiation of immunosuppressive therapy and to administer pre-emptive nucleos(t)ide analogues to those patients with a substantial risk of hepatitis and acute-on-chronic liver failure due to hepatitis B reactivation.

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Section: Methodsmentioning

confidence: 99%

APASL clinical practice guideline on hepatitis B reactivation related to the use of immunosuppressive therapy

Lau

Wong

et al. 2021

Hepatol Int

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“…Virological and CR rates in patients with detectable EOT HBcrAg were 53.0–74.1%, and 39.5–48.3%, respectively, compared with 14.0–44.1% and 7.3–13.9%, respectively, in patients with undetectable HBcrAg 20,22,25,26,36 . Cut‐off values for EOT HBcrAg in these studies ranged from undetectable (<2 or 3 log 10 IU/mL) to 4.5 log 10 IU/mL with area under the receiver operating characteristic curve (AUROC) of 0.69–0.70 for predicting VR and 0.61–0.77 for predicting CR 18,20,22,26,30,38 . Because HBeAg status might affect the predictive value of HBcrAg, we divided the studies according to HBeAg status.…”

Section: Resultsmentioning

confidence: 86%

“…As shown in Table 2, stopping rules varied among studies. These rules include (i) stopping at physician's discretion in three studies, 31,34,37 (ii) adopting Asian‐Pacific Association for Study of the Liver guidelines in three studies, 22,26,32 (iii) after achieving virological remission on NA therapy in seven studies, 20,21,24,25,28–30 (iv) after achieving biochemical remission in one study, 18 and (v) after achieving both virological and biochemical remission in two studies 23,36 . All studies that enrolled HBeAg‐positive CHB patients required HBeAg seroconversion prior to the cessation of NA therapy.…”

Section: Resultsmentioning

confidence: 99%

Novel viral markers and the prediction of off‐treatment relapse in chronic hepatitis B patients: A systematic review

Jaroenlapnopparat

Chayanupatkul

Tangkijvanich

2021

J of Gastro and Hepatol

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Background and Aim Hepatitis B core‐related antigen (HBcrAg) and hepatitis B virus RNA (HBV RNA) are novel markers that reflect intrahepatic cccDNA and could be useful in the prediction of relapse after nucleos(t)ide analogues (NA) discontinuation. The aim of the study is to perform a systematic review on this issue. Methods Medline/Pubmed database was searched using text terms related to HBcrAg, RNA, NAs, discontinuation, and relapse. Included studies were those that enrolled adult patients who had been on NAs for more than 6 months with available information on end‐of‐treatment (EOT) HBcrAg and/or HBV RNA and relapse rates. Results Sixteen studies were included. Virological and clinical relapse rates ranged from 11% to 100% and 11% to 73%, respectively. Low or undetectable EOT HBcrAg levels were associated with low off‐treatment relapse rates in most studies with area under the receiver operating characteristic curve (AUROC) of 0.69–0.70 for predicting virological relapse (VR) and 0.61–0.77 for predicting clinical relapse (CR). Undetectable EOT HBV RNA was associated with a lower risk of off‐treatment relapse with AUROC of 0.65–0.76 for predicting VR and 0.66–0.73 for predicting CR. Combined EOT HBcrAg and HBV RNA performed better in predicting off‐treatment relapse than either test alone with AUROC of 0.816–0.846 for predicting CR. None of the patients with double‐negative HBV RNA and HBcrAg developed CR. Conclusion Combining HBcrAg with HBV RNA or HBsAg improved the discriminating abilities in the prediction of off‐treatment relapse of each test. Patients with double‐negative HBcrAg and HBV RNA at EOT had low risks of relapse and could be considered for NA discontinuation.

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“…A recent report indicated that no clinical relapse occurred after cessation of NAs therapy among HBeAg-positive and HBeAg-negative patients with undetectable HBV RNA and HBcrAg at EOT. 29 It would be interesting to investigated whether the combination of HBcrAg with HBV RNA could further reduce the risk of HBV relapse in HBeAg-negative patients who discontinued entecavir treatment.…”

Section: Discussionmentioning

confidence: 99%

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

Huang

Wang

Hung

et al. 2021

Journal of Viral Hepatitis

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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.

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Hepatitis B surface antigen, core‐related antigen and HBV RNA: Predicting clinical relapse after NA therapy discontinuation

Cited by 34 publications

References 30 publications

APASL clinical practice guideline on hepatitis B reactivation related to the use of immunosuppressive therapy

APASL clinical practice guideline on hepatitis B reactivation related to the use of immunosuppressive therapy

Novel viral markers and the prediction of off‐treatment relapse in chronic hepatitis B patients: A systematic review

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

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