APASL guidance on stopping nucleos(t)ide analogues in chronic hepatitis B patients

Chronic hepatitis B virus (HBV) infection is currently incurable. Long-term treatment with potent and safe nucleos(t)ide analogs (NAs) can reduce hepatocellular carcinoma (HCC) and cirrhosis-related complications through profound viral suppression. However, indefinite therapy raises several crucial...

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Published inHepatology international Vol. 15; no. 4; pp. 833 - 851
Main Authors Kao, Jia-Horng, Jeng, Wen-Juei, Ning, Qin, Su, Tung-Hung, Tseng, Tai-Chung, Ueno, Yoshiyuki, Yuen, Man-Fung
Format Journal Article
LanguageEnglish
Published New Delhi Springer India 01.08.2021
Springer Nature B.V
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ISSN1936-0533
1936-0541
1936-0541
DOI10.1007/s12072-021-10223-5

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Abstract Chronic hepatitis B virus (HBV) infection is currently incurable. Long-term treatment with potent and safe nucleos(t)ide analogs (NAs) can reduce hepatocellular carcinoma (HCC) and cirrhosis-related complications through profound viral suppression. However, indefinite therapy raises several crucial issues with pros and cons. Because seroclearance of hepatitis B surface (HBsAg) as functional cure is not easily achievable, a finite therapy including sequential 48-week pegylated interferon therapy may provide an opportunity to facilitate HBsAg seroclearance by the rejuvenation of exhausted immune cells. However, the cost of stopping NA is the high incidence of virological relapse and surge of alanine aminotransferase (ALT) levels, which may increase the risk of adverse outcomes (e.g., decompensation, fibrosis progression, HCC, or liver-related mortality). So far, the APASL criteria to stop NA treatment is undetectable HBV DNA levels with normalization of ALT; however, this criterion for cessation of treatment is associated with various incidence rates of virological/clinical relapse and more than 40% of NA-stoppers eventually receive retreatment. A very intensive follow-up strategy and identification of low-risk patients for virological/clinical relapse by different biomarkers are the keys to stop the NA treatment safely. Recent studies suggested that decreasing HBsAg level at the end-of-treatment to < 100–200 IU/mL seems to be a useful marker for deciding when to discontinue NAs therapy. In addition, several viral and host factors have been reviewed for their potential roles in predicting clinical relapse. Finally, the APASL guidance has proposed rules to stop NA and the subsequent follow-up strategy to achieve a better prognosis after stopping NA. In general, for both HBeAg-positive and HBeAg-negative patients who have stopped treatment, these measurements should be done every 1–3 months at the minimum until 12 months.
AbstractList Chronic hepatitis B virus (HBV) infection is currently incurable. Long-term treatment with potent and safe nucleos(t)ide analogs (NAs) can reduce hepatocellular carcinoma (HCC) and cirrhosis-related complications through profound viral suppression. However, indefinite therapy raises several crucial issues with pros and cons. Because seroclearance of hepatitis B surface (HBsAg) as functional cure is not easily achievable, a finite therapy including sequential 48-week pegylated interferon therapy may provide an opportunity to facilitate HBsAg seroclearance by the rejuvenation of exhausted immune cells. However, the cost of stopping NA is the high incidence of virological relapse and surge of alanine aminotransferase (ALT) levels, which may increase the risk of adverse outcomes (e.g., decompensation, fibrosis progression, HCC, or liver-related mortality). So far, the APASL criteria to stop NA treatment is undetectable HBV DNA levels with normalization of ALT; however, this criterion for cessation of treatment is associated with various incidence rates of virological/clinical relapse and more than 40% of NA-stoppers eventually receive retreatment. A very intensive follow-up strategy and identification of low-risk patients for virological/clinical relapse by different biomarkers are the keys to stop the NA treatment safely. Recent studies suggested that decreasing HBsAg level at the end-of-treatment to < 100-200 IU/mL seems to be a useful marker for deciding when to discontinue NAs therapy. In addition, several viral and host factors have been reviewed for their potential roles in predicting clinical relapse. Finally, the APASL guidance has proposed rules to stop NA and the subsequent follow-up strategy to achieve a better prognosis after stopping NA. In general, for both HBeAg-positive and HBeAg-negative patients who have stopped treatment, these measurements should be done every 1-3 months at the minimum until 12 months.Chronic hepatitis B virus (HBV) infection is currently incurable. Long-term treatment with potent and safe nucleos(t)ide analogs (NAs) can reduce hepatocellular carcinoma (HCC) and cirrhosis-related complications through profound viral suppression. However, indefinite therapy raises several crucial issues with pros and cons. Because seroclearance of hepatitis B surface (HBsAg) as functional cure is not easily achievable, a finite therapy including sequential 48-week pegylated interferon therapy may provide an opportunity to facilitate HBsAg seroclearance by the rejuvenation of exhausted immune cells. However, the cost of stopping NA is the high incidence of virological relapse and surge of alanine aminotransferase (ALT) levels, which may increase the risk of adverse outcomes (e.g., decompensation, fibrosis progression, HCC, or liver-related mortality). So far, the APASL criteria to stop NA treatment is undetectable HBV DNA levels with normalization of ALT; however, this criterion for cessation of treatment is associated with various incidence rates of virological/clinical relapse and more than 40% of NA-stoppers eventually receive retreatment. A very intensive follow-up strategy and identification of low-risk patients for virological/clinical relapse by different biomarkers are the keys to stop the NA treatment safely. Recent studies suggested that decreasing HBsAg level at the end-of-treatment to < 100-200 IU/mL seems to be a useful marker for deciding when to discontinue NAs therapy. In addition, several viral and host factors have been reviewed for their potential roles in predicting clinical relapse. Finally, the APASL guidance has proposed rules to stop NA and the subsequent follow-up strategy to achieve a better prognosis after stopping NA. In general, for both HBeAg-positive and HBeAg-negative patients who have stopped treatment, these measurements should be done every 1-3 months at the minimum until 12 months.
Chronic hepatitis B virus (HBV) infection is currently incurable. Long-term treatment with potent and safe nucleos(t)ide analogs (NAs) can reduce hepatocellular carcinoma (HCC) and cirrhosis-related complications through profound viral suppression. However, indefinite therapy raises several crucial issues with pros and cons. Because seroclearance of hepatitis B surface (HBsAg) as functional cure is not easily achievable, a finite therapy including sequential 48-week pegylated interferon therapy may provide an opportunity to facilitate HBsAg seroclearance by the rejuvenation of exhausted immune cells. However, the cost of stopping NA is the high incidence of virological relapse and surge of alanine aminotransferase (ALT) levels, which may increase the risk of adverse outcomes (e.g., decompensation, fibrosis progression, HCC, or liver-related mortality). So far, the APASL criteria to stop NA treatment is undetectable HBV DNA levels with normalization of ALT; however, this criterion for cessation of treatment is associated with various incidence rates of virological/clinical relapse and more than 40% of NA-stoppers eventually receive retreatment. A very intensive follow-up strategy and identification of low-risk patients for virological/clinical relapse by different biomarkers are the keys to stop the NA treatment safely. Recent studies suggested that decreasing HBsAg level at the end-of-treatment to < 100–200 IU/mL seems to be a useful marker for deciding when to discontinue NAs therapy. In addition, several viral and host factors have been reviewed for their potential roles in predicting clinical relapse. Finally, the APASL guidance has proposed rules to stop NA and the subsequent follow-up strategy to achieve a better prognosis after stopping NA. In general, for both HBeAg-positive and HBeAg-negative patients who have stopped treatment, these measurements should be done every 1–3 months at the minimum until 12 months.
Chronic hepatitis B virus (HBV) infection is currently incurable. Long-term treatment with potent and safe nucleos(t)ide analogs (NAs) can reduce hepatocellular carcinoma (HCC) and cirrhosis-related complications through profound viral suppression. However, indefinite therapy raises several crucial issues with pros and cons. Because seroclearance of hepatitis B surface (HBsAg) as functional cure is not easily achievable, a finite therapy including sequential 48-week pegylated interferon therapy may provide an opportunity to facilitate HBsAg seroclearance by the rejuvenation of exhausted immune cells. However, the cost of stopping NA is the high incidence of virological relapse and surge of alanine aminotransferase (ALT) levels, which may increase the risk of adverse outcomes (e.g., decompensation, fibrosis progression, HCC, or liver-related mortality). So far, the APASL criteria to stop NA treatment is undetectable HBV DNA levels with normalization of ALT; however, this criterion for cessation of treatment is associated with various incidence rates of virological/clinical relapse and more than 40% of NA-stoppers eventually receive retreatment. A very intensive follow-up strategy and identification of low-risk patients for virological/clinical relapse by different biomarkers are the keys to stop the NA treatment safely. Recent studies suggested that decreasing HBsAg level at the end-of-treatment to < 100–200 IU/mL seems to be a useful marker for deciding when to discontinue NAs therapy. In addition, several viral and host factors have been reviewed for their potential roles in predicting clinical relapse. Finally, the APASL guidance has proposed rules to stop NA and the subsequent follow-up strategy to achieve a better prognosis after stopping NA. In general, for both HBeAg-positive and HBeAg-negative patients who have stopped treatment, these measurements should be done every 1–3 months at the minimum until 12 months.
Author Su, Tung-Hung
Tseng, Tai-Chung
Jeng, Wen-Juei
Yuen, Man-Fung
Kao, Jia-Horng
Ueno, Yoshiyuki
Ning, Qin
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  surname: Kao
  fullname: Kao, Jia-Horng
  email: kaojh@ntu.edu.tw
  organization: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Department of Medical Research, National Taiwan University Hospital
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  givenname: Wen-Juei
  surname: Jeng
  fullname: Jeng, Wen-Juei
  organization: Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, College of Medicine, Chang Gung University
– sequence: 3
  givenname: Qin
  surname: Ning
  fullname: Ning, Qin
  organization: Department of Infectious Disease, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology
– sequence: 4
  givenname: Tung-Hung
  surname: Su
  fullname: Su, Tung-Hung
  organization: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital
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  givenname: Tai-Chung
  surname: Tseng
  fullname: Tseng, Tai-Chung
  organization: Department of Medical Research, National Taiwan University Hospital
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  givenname: Yoshiyuki
  surname: Ueno
  fullname: Ueno, Yoshiyuki
  organization: Department of Gastroenterology, Faculty of Medicine, Yamagata University
– sequence: 7
  givenname: Man-Fung
  surname: Yuen
  fullname: Yuen, Man-Fung
  organization: Department of Medicine, Queen Mary Hospital, The University of Hong Kong
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IsPeerReviewed true
IsScholarly true
Issue 4
Keywords Functional cure
Antiviral therapy
Treatment discontinuation
Relapse
Hepatitis B surface antigen
Monitor
Predictor
Outcome
Finite therapy
Hepatitis B virus
Language English
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crossref_citationtrail_10_1007_s12072_021_10223_5
crossref_primary_10_1007_s12072_021_10223_5
springer_journals_10_1007_s12072_021_10223_5
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PublicationCentury 2000
PublicationDate 2021-08-01
PublicationDateYYYYMMDD 2021-08-01
PublicationDate_xml – month: 08
  year: 2021
  text: 2021-08-01
  day: 01
PublicationDecade 2020
PublicationPlace New Delhi
PublicationPlace_xml – name: New Delhi
– name: Tokyo
PublicationTitle Hepatology international
PublicationTitleAbbrev Hepatol Int
PublicationYear 2021
Publisher Springer India
Springer Nature B.V
Publisher_xml – name: Springer India
– name: Springer Nature B.V
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  doi: 10.1016/j.cgh.2020.12.005
– volume: 23
  start-page: 677
  year: 2018
  ident: 10223_CR129
  publication-title: Antivir Ther
  doi: 10.3851/IMP3256
SSID ssj0055616
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Snippet Chronic hepatitis B virus (HBV) infection is currently incurable. Long-term treatment with potent and safe nucleos(t)ide analogs (NAs) can reduce...
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SubjectTerms Alanine
Alanine transaminase
Antiviral drugs
Biomarkers
Chronic infection
Cirrhosis
Colorectal Surgery
Complications
Deoxyribonucleic acid
DNA
Fibrosis
Guidelines
Hepatitis
Hepatitis B
Hepatitis B e antigen
Hepatitis B surface antigen
Hepatocellular carcinoma
Hepatology
Immune system
Interferon
Liver cancer
Liver cirrhosis
Medicine
Medicine & Public Health
Patients
Risk groups
Strategy
Surgery
Therapy
Viruses
Title APASL guidance on stopping nucleos(t)ide analogues in chronic hepatitis B patients
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