A prospective clinical study in hepatitis B e antigen-negative chronic hepatitis B patients with stringent cessation criteria for adefovir

Ha, Minghao; Zhang, Guotong; Diao, Shu; Lin, Ming-Fang; Sun, Liping; She, Huiyuan; Kuan, Chenbao; Shen, Lihui; Huang, ChunHong; Shen, Wenjuan; Huang, Zhongming

doi:10.1007/s00705-011-1163-0

Cited by 40 publications

(79 citation statements)

References 19 publications

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“…Recent studies on HBsAg loss in HBeAg-negative patients demonstrated that relapse did not occur during the follow-up period [9,10]. This indicates that HBsAg loss is the preferred endpoint for therapy discontinuation.…”

Section: Discussionmentioning

confidence: 99%

Long-term outcomes after nucleos(t)ide analogues discontinuation in chronic hepatitis B patients with HBeAg-negative

Guo

Chen

et al. 2013

BMC Infect Dis

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BackgroundHepatitis B e Antigen (HBeAg)-negative chronic hepatitis B (CHB) patients have an active liver disease with a high risk of progression to decompensated cirrhosis and hepatocellular carcinoma. The management strategy for HBeAg-negative CHB patients treated with nucleos(t)ide analogues (NUCs) is a topic of concern. To observe the outcomes for this population after NUCs withdrawal, HBeAg-negative CHB patients with loss of hepatitis B surface antigen (HBsAg) or sustained undetectable HBV DNA levels who had discontinued NUCs therapy were included in the study.MethodsA total of 66 patients (2 patients with HBsAg loss and 64 patients with sustained undetectable HBV DNA levels) were examined. HBV DNA levels and alanine aminotransferase (ALT) levels were monitored regularly after discontinuation of NUCs therapy. Relapse was defined as HBV DNA levels >2,000 IU/mL while off therapy in at least two determinations more than 4 weeks apart.ResultsThe time to achieve undetectable HBV DNA levels was 14 weeks (interquartile range (IQR): 12–24 weeks). The time until consolidation therapy was 144 weeks (IQR: 96–168 weeks). No relapses occurred in either of the HBsAg loss patients. Among the 64 patients with undetectable HBV DNA levels, 19 (29.7%) patients demonstrated evidence of relapse. All the relapses occurred within 96 weeks after discontinuation. The median duration of relapse was 36 weeks (IQR: 12–48 weeks). Elevation of HBV DNA and ALT levels over baseline was only observed in 10% of the relapse patients. There were no significant differences among the baseline characteristics (sex, HBV genotype, age, or ALT level) or the time until consolidation therapy between relapse and sustained-response patients.ConclusionsNUC discontinuation is feasible after achieving undetectable HBV DNA levels in HBeAg-negative CHB patients. Prolonging the time until consolidation therapy may be a good strategy to decrease the rate of relapse. More than 96 weeks of sustained response is a predictive marker of long-term sustained response.

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Section: Discussionmentioning

confidence: 99%

Long-term outcomes after nucleos(t)ide analogues discontinuation in chronic hepatitis B patients with HBeAg-negative

Guo

Chen

et al. 2013

BMC Infect Dis

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“…In HBeAg-positive CHB patients, the duration of consolidation therapy after HBeAg seroconversion [25][26][27][28], age [29,30], serum HBV DNA and ALT levels at baseline [25,28], HBV genotype [31], and interleukin 28 B (IL-28B) genotype (IFNλ3/4) [32] have all been suggested as possible factors affecting the probability of sustained response after NA discontinuation. In HBeAg-negative CHB patients, younger age [33,34], earlier disease stage [35,36], higher levels of ALT at baseline and at the end of treatment [31,37], lower serum HBV DNA levels at baseline [37, 38•], low serum HBsAg levels at the end of treatment [37,39], or decreasing HBsAg levels during therapy [39][40][41] have all been associated with a better chance of sustained offtreatment response. However, not all the above factors have been confirmed in all relevant studies, which often report discrepant results for the same parameters making strong conclusions difficult to reach.…”

Section: Discontinuation Of Nucleos(t)ide Analoguesmentioning

confidence: 99%

Controversial Issues in Current Treatment of Chronic HBV Infection

Siakavellas

Papatheodoridis

2015

Curr Hepatology Rep

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The management of patients with progressive chronic hepatitis B infection (CHB) has undergone dramatic changes in the last decade, with the introduction of newer and more potent agents. Detailed international guidelines exist that provide advice for the optimal care of CHB patients. Despite that, several topics such as optimal treatment indication, choice of treatment type, and the discontinuation of nucleos(t)ide analogue therapy remain controversial, as relevant recommendations and expert opinions often vary widely. This review addresses these topics in more detail aiming to provide some clarifications taking into account the most recent data from the available literature.

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“…Out of 145 patients taking adefovir who were HBV DNA-negative for more than 18 months by PCR, 95 patients (61.4%) underwent virologic relapse as observed by serum HBV DNA >2000 IU/mL. Ninetythree percent of all virologic relapse cases occur within 1 year of stopping treatment [19]. However, young patients (20-25 years old) showed a dramatically reduced rate of post-treatment virologic relapse [18,19].…”

Section: Hbeag-negative Chronic Hbv Infectionmentioning

confidence: 99%

“…Ninetythree percent of all virologic relapse cases occur within 1 year of stopping treatment [19]. However, young patients (20-25 years old) showed a dramatically reduced rate of post-treatment virologic relapse [18,19]. When entecavir was administered to patients for 52 weeks and then stopped, sustained viral suppression was only observed in 48% of patients after 24 weeks [20].…”

Section: Hbeag-negative Chronic Hbv Infectionmentioning

confidence: 99%

“…As the above studies show, the post-treatment relapse rate appears to be approximately 50%, regardless of the suppressive ability of antiviral treatment or the likelihood of drug resistance [16,[18][19][20]22,[24][25][26]. Therefore, it may be important to apply APASL guidelines for stopping antiviral treatments to patients who find long-term treatment financially burdensome or who are experiencing side effects associated with long-term usage of drugs or treatments.…”

Section: Hbeag-negative 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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A prospective clinical study in hepatitis B e antigen-negative chronic hepatitis B patients with stringent cessation criteria for adefovir

Cited by 40 publications

References 19 publications

Long-term outcomes after nucleos(t)ide analogues discontinuation in chronic hepatitis B patients with HBeAg-negative

Long-term outcomes after nucleos(t)ide analogues discontinuation in chronic hepatitis B patients with HBeAg-negative

Controversial Issues in Current Treatment of Chronic HBV Infection

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

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