Lamivudine Maintenance Beyond One Year After Hbeag Seroconversion Is A Major Factor for Sustained Virologic Response in Hbeag-Positive Chronic Hepatitis B

Lee, Hyun Woong; Lee, Heon Ju; Hwang, Jae Seok; Sohn, Joo Hyun; Jang, Jae Young; Han, Ki Jun; Park, Jun Yong; Kim, Do Young; Ahn, Sang Hoon; Paik, Yong Han; Lee, Chun Kyon; Lee, Kwan Sik; Chon, Chae Yoon; Han, Kwang Hyub

doi:10.1002/hep.23323

Cited by 109 publications

(119 citation statements)

References 26 publications

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“…However, when consolidation treatment [2,4,5,8] was performed before termination of lamivudine treatment or when patients were young [4][5][6][7][8], the rate of virologic relapse was dramatically reduced. In 178 patients with HBeAg-positive chronic HBV infection that showed HBV DNA loss as well as HBeAg loss with lamivudine treatment, virologic relapse rates of 15.9% and 30.2% 1 and 5 years after stopping treatment, respectively were seen.…”

Section: Discussionmentioning

confidence: 99%

“…In 178 patients with HBeAg-positive chronic HBV infection that showed HBV DNA loss as well as HBeAg loss with lamivudine treatment, virologic relapse rates of 15.9% and 30.2% 1 and 5 years after stopping treatment, respectively were seen. It has also been reported that when patients were younger than 40 or underwent 1 or more year(s) of consolidation treatment the durability of sustained viral suppression was increased [8]. Patients who used clevudine or entecavir (n=48) to maintain HBV DNA levels at less than 300 copies/mL and HBeAg seroconversion for 6 months or more, experienced an accumulated virologic relapse of 41% and 60% after 12 and 24 months off therapy respectively [10].…”

Section: Discussionmentioning

confidence: 99%

“…Patients that reach sustained viral suppression (HBV DNA negativity and HBeAg loss or seroconversion) with lamivudine usage show a virologic relapse rate of 15.9-48%, 29-50%, 54-55.7%, and 44-64.8% 1, 2, 3, and 4 years after discontinuation of lamivudine respectively [2][3][4][5][6][7][8]. A considerable number of patients that undergo HBeAg seroconversion upon oral antiviral…”

Section: Hbeag-positive Chronic Hbv Infectionmentioning

confidence: 99%

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Oral Antiviral Therapy for Chronic Hepatitis B Virus Infection: Is Continuous Treatment Needed?

Lee¹

2014

GHOA

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AbbreviationsNA: Nucleos(T)Ide Analogue; HBV: Hepatitis B Virus; cccDNA: covalently closed circular DNA IntroductionLong-term usage of oral antiviral is highly effective in treating chronic hepatitis B virus (HBV) infection and can effectively suppress HBV proliferation which may prevent the progression of liver fibrosis and the development of HCC after long term use of NAs but cannot completely eradicate the virus. Furthermore, the safety of long-term usage of antivirals is still a concern that needs to be assessed and the increasing cost of antiviral treatments can be a serious financial burden. It is still unclear how long antiviral treatment needs to be continued and how to determine when discontinuation of the treatment is appropriate. The presence of covalently closed circular DNA (cccDNA) in hepatocytes correlates to immune activity and is used as a predictive factor to evaluate sustained viral suppression after termination of antiviral treatment [1]. Unlike pegylated interferon, oral antivirals do not have direct immunomodulatory effects and only temporarily induce a modest increase in immune function. Therefore, oral antiviral treatments are unlikely to provide continued viral suppression after termination. Discussion HBeAg-positive chronic HBV infectionPatients that reach sustained viral suppression (HBV DNA negativity and HBeAg loss or seroconversion) with lamivudine usage show a virologic relapse rate of 15.9-48%, 29-50%, 54-55.7%, and 44-64.8% 1, 2, 3, and 4 years after discontinuation of lamivudine respectively [2][3][4][5][6][7][8]. A considerable number of patients that undergo HBeAg seroconversion upon oral antiviral AbstractPotent nucleos(t)ide analogues (NAs) have improved patient prognosis via suppression of viral load, HBeAg seroconversion and in some cases, HBsAg seroconversion. However, the duration and end point of NA treatment are still debatable. Current international guidelines recommend that discontinuation of NA treatment can be considered when HBeAg seroconversion and undetectable HBV DNA status is maintained for at least 6-12 months for HBeAg-positive patients and undetectable HBV DNA status on 3 separate occasions 6 months apart for HBeAgnegative patients if they have been treated for at least 2 years. Durability of NA, particularly after off-treatment, remains uncertain. A proportion of patients who discontinue NA therapy after HBeAg seroconversion may require retreatment if sustained serological and/or virological response fails and high off-treatment virological relapse can develop in HBeAg-negative patients. Therefore, NA treatment may be continued until HBsAg clearance with or without antibodies to HBsAg, particularly in patients with severe fibrosis or cirrhosis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Hbeag-positive Chronic Hbv Infectionmentioning

confidence: 99%

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Oral Antiviral Therapy for Chronic Hepatitis B Virus Infection: Is Continuous Treatment Needed?

Lee¹

2014

GHOA

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“…The rates of anti-HBe seroconversion with entecavir at 4 years and with tenofovir at 5 years are 38% and 40%, respectively [Marcellin et al 2013;Ono et al 2012]. A sustained off-treatment response (persistence of anti-HBe seroconversion) can be expected in 40-80% of these patients [Reijnders et al 2010;Lee et al 2010]. Anti-HBe seroconversion is less durable after therapy is stopped compared with spontaneous anti-HBe seroconversion [Chaung et al 2012] and compared with pegylated interferon therapy [Wong et al 2010].…”

Section: Stopping Nucsmentioning

confidence: 99%

Hepatitis B virus treatment beyond the guidelines: special populations and consideration of treatment withdrawal

Vallet-Pichard

Pol

2014

Therap Adv Gastroenterol

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Abstract:The goal of chronic hepatitis B (CHB) treatment is to improve survival by preventing disease progression to decompensated cirrhosis and hepatocellular carcinoma which is the cause of over 1 million deaths annually. The risk of disease progression is reduced when a sustained reduction of hepatitis B virus (HBV) DNA to undetectable levels and suppression of HBV replication are obtained which can result in regression of liver fibrosis and may even reverse cirrhosis. However, even if HBsAg loss occurs, HBV is not completely eradicated by treatment, and long-term therapy is required in patients who are HBeAg -and HBeAg + who do not maintain off-treatment virological suppression and in those with advanced liver disease. The recently updated European Association of the Study of the Liver (EASL) clinical practical guidelines for HBV have clarified, first, how to treat HBV (interferon or the most potent oral drugs with optimal resistance profiles, i.e. entecavir and tenofovir disoproxil fumarate, should be used as first-line monotherapies); second, who should be treated (CHB in patients with significant liver disease but also patients who are HBsAg + and are receiving immunosuppressive treatment, patients coinfected with HBV and human immunodeficiency virus, mothers who are HBsAg + with high viral load in late pregnancy associated with sero vaccination to reduce the risk of vertical transmission of HBV; and third, when to stop antiviral therapies. The aim of this review was to clarify how to treat HBV and who should be treated, as well as when to stop treatment. Although the answer to these questions is clear for pegylated interferon, it is more debatable for nucleos(t)ide analogues (anti-HBe seroconversion, HBsAg loss or anti-HBs seroconversion with undetectable HBV DNA are clear indications to discontinue treatment but sustained undetectable HBV DNA in patients who are anti-HBe + without significant fibrosis might be another indication).

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“…After the occurrence of HBeAg seroconversion, additional antiviral therapy is needed for at least one more year to prevent relapse in HBeAg positive chronic hepatitis B [39]. In HBeAg negative chronic hepatitis B patients, it is recommended to treat with an oral antiviral agent until HBsAg loss occurs, because the moment of HBeAg seroconversion does not appear [2].…”

Section: When To Stop?mentioning

confidence: 99%

Strategy to Overcome Drug Resistance That Develops during Treatment of Chronic Hepatitis B in Children

Hong

Choe

2012

Pediatr Gastroenterol Hepatol Nutr

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Development of antiviral resistance to lamivudine is the most important factor for the treatment failure. It is necessary to establish proper guidelines to overcome drug resistance for children with chronic hepatitis B. Primary treatment with lamivudine should be considered if patients are in immune-clearance phase and have persistently elevated ALT levels more than twice the upper limit of normal value. Before initiating the therapy, careful consideration of the patient's status is required to exclude abnormal liver function tests due to other causes. The treatment option should be carefully decided to suppress the viral replication effectively. To obtain good compliance, clinicians should educate patients and their parents. Appropriate monitoring for virologic breakthrough and genotypic resistance is important in deciding to change the treatment plan. Sequential monotherapy should be avoided and a combination of drugs in other categories is recommended. New antiviral agents, such as entecavir and tenofovir, which have high potency and high genetic barrier, are soon expected to be available for use with children. (Pediatr Gastroenterol Hepatol Nutr 2012; 15: 63∼73)

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Lamivudine Maintenance Beyond One Year After Hbeag Seroconversion Is A Major Factor for Sustained Virologic Response in Hbeag-Positive Chronic Hepatitis B

Cited by 109 publications

References 26 publications

Oral Antiviral Therapy for Chronic Hepatitis B Virus Infection: Is Continuous Treatment Needed?

Oral Antiviral Therapy for Chronic Hepatitis B Virus Infection: Is Continuous Treatment Needed?

Hepatitis B virus treatment beyond the guidelines: special populations and consideration of treatment withdrawal

Strategy to Overcome Drug Resistance That Develops during Treatment of Chronic Hepatitis B in Children

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