Relapse rates in chronic hepatitis <scp>B</scp> naïve patients after discontinuation of antiviral therapy with entecavir

Ridruejo, Ezequiel; Marciano, Sebastián; Galdame, Omar; Reggiardo, María Virginia; Muñoz, Alberto; Adrover, Raúl; Cocozzella, Daniel; Fernández, Nora; Estepo, Claudio; Mendizábal, Manuel; Romero, Gustavo; Levi, Diana; Schroder, Teresa; Paz, Suzanne; Fainboim, Hugo; Mandó, Oscar G.; Gadano, Adrián; Silva, M. O.

doi:10.1111/jvh.12200

Cited by 27 publications

(45 citation statements)

References 18 publications

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“…Nine developed virological relapse including 3 with HBeAg seroreversion and 4 who became anti-HBe negative. In contrast, none of the 18 patients who underwent HBeAg and HBsAg seroconversion prior to stopping ETV experienced virological relapse [28]. In a study comprising HBeAg-positive CHB patients who were treated with either ETV or clevudine, 15 of 31 ETV-treated patients relapsed compared to 5 of 17 patients treated with clevudine.…”

Section: Discussionmentioning

confidence: 99%

Durability of Hepatitis B e Antigen Seroconversion in Chronic Hepatitis B Patients Treated with Entecavir or Tenofovir

Fong

Tien

et al. 2015

Dig Dis Sci

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Introduction Loss of HBeAg and development of anti-HBe (seroconversion) is seen as a milestone and endpoint in the treatment of HBeAg-positive patients with chronic hepatitis B (CHB). Among patients treated with nucleos (t)ide analogs (NA), recurrent viremia is common after discontinuation of therapy. Entecavir (ETV) and tenofovir (TDF) are highly potent NA. The durability of virological response and HBeAg seroconversion in patients treated with these agents is not well studied. Methods We retrospectively studied the outcomes of 54 HBeAg-positive CHB patients who were treated with either ETV (n = 30) or TDF (23) or both (n = 1) that achieved virological response and underwent seroconversion and consolidation therapy before cessation of treatment. Results Only 4 (7 %) patients had sustained virological, serological, and biochemical remission. Thirteen patients (24 %) continued to have HBV DNA levels below 2000 IU/mL and normal alanine aminotransferase activity (ALT). Thirty-seven patients (69 %) developed HBV DNA >2000 IU/mL, with 20 having elevated ALT. Among these 37 patients, 23 (62 %) remained HBeAg negative/anti-HBe positive, 12 (32 %) became HBeAg positive, and 2 (5 %) were HBeAg and anti-HBe negative. Duration of consolidation therapy did not correlate with low versus high level of virological relapse. Conclusions Durability of HBeAg seroconversion associated with ETV or TDF was not superior to that reported in patients treated with less potent NA. Our results, aggregated with others, suggest HBeAg seroconversion should not be considered as a treatment endpoint for most HBeAg-positive patients treated with NA. Future updates of treatment guidelines should reconsider HBeAg seroconversion as an endpoint to therapy.

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Section: Discussionmentioning

confidence: 99%

Durability of Hepatitis B e Antigen Seroconversion in Chronic Hepatitis B Patients Treated with Entecavir or Tenofovir

Fong

Tien

et al. 2015

Dig Dis Sci

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“…The literature search initially identified 972 papers; of those, 25 fulfilled the inclusion and exclusion criteria for this review (http://onlinelibrary.wiley.com/doi/10.1002/hep.28438/suppinfo). The main characteristics of the included studies and patients are presented in Tables and .…”

Section: Methodsmentioning

confidence: 99%

“…In total, 2332 (each study contribution from 11 to 401) patients were included in the 25 studies. All but one were cohort studies (three prospective, one retrospective‐prospective, and 20 retrospective, while one was a randomized study comparing the effects of 12 versus 24 months of additional therapy after response to lamivudine in HBeAg‐negative CHB . One study was found to have high quality, 14 to have acceptable quality, and 10 to have low quality based on their risk of bias assessments (http://onlinelibrary.wiley.com/doi/10.1002/hep.28438/suppinfo).…”

Section: Methodsmentioning

confidence: 99%

Discontinuation of oral antivirals in chronic hepatitis B: A systematic review

et al. 2016

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The possibility of safe discontinuation of therapy with nucleos(t)ide analogues (NAs) remains one of the most controversial topics in the management of chronic hepatitis B. Therefore, we systematically reviewed the existing data on NA discontinuation in this setting and tried to identify factors affecting the probability of posttherapy remission. A literature search was performed in order to identify all published studies including patients who discontinued NAs in virological remission (VR) and were followed for 12 months thereafter. Twenty-five studies with 1716 patients were included. The pooled rates of durable VR remission were 51.4%, 39.3%, and 38.2% at 12, 24, and 36 months, respectively, after NA discontinuation, being relatively higher in initially hepatitis B e antigen (HBeAg)-positive patients (62.5%, 53.4%, 51.5%) than HBeAg-negative patients (43.7%, 31.3%, 30.1%) (P 5 0.064). The weighted probability of durable biochemical remission was 65.4%, being numerically higher in HBeAg-positive than HBeAg-negative patients (76.2% versus 56.7%, P 5 0.130). The weighted probability of hepatitis B surface antigen loss was 2.0%. The rates of durable VR did not significantly differ according to the VR definition (hepatitis B virus DNA <200, < 2000, < 20,000 IU/mL) or duration of on-therapy VR in HBeAg-positive patients, but they were significantly higher in studies with HBeAg-negative patients and on-therapy VR > 24 than £ 24 months (VR at 12 months off-NAs: 75.0% versus 35.6%, P 5 0.005). The weighted probability of durable HBeAg seroconversion was 91.9% and 88.0% at 12 and 24 months, respectively, after NA discontinuation without being affected by the duration of on-therapy VR or consolidation therapy (>6 months in all studies). Conclusion: Durable VR seems to be feasible in a substantial proportion of patients who discontinue long-term NA therapy; on-therapy VR > 24 months offers higher chances of off-NA VR in patients with HBeAg-negative chronic hepatitis B. (HEPATOLOGY 2016;63:1481-1492 T reatment against hepatitis B virus (HBV) has dramatically improved over the last 15 years, but HBV eradication remains a rarely attainable target. (1-3) Pegylated interferon-alfa therapy given for a finite duration of usually 48 weeks can achieve sustained off-therapy responses, with almost half of the responders clearing hepatitis B surface antigen (HBsAg) in the long term. However, only 20%-30% of patients with hepatitis B e antigen (HBeAg)-positive or HBeAg-negative chronic hepatitis B (CHB) may achieve sustained off-therapy responses after a course of pegylated interferon-alfa. (1)(2)(3) Many patients are reluctant to start treatment with this agent because interferon-alfa may have severe side effects as well as an unfavorable safety profile. Thus, oral antiviral agents, nucleos(t)ide analogues (NAs), represent the main therapeutic option for the majority of CHB patients. (4) Abbreviations: ALT, alanine aminotransferase; BR, biochemical remission; CHB, chronic hepatitis B; CI, confidence interval; HBeAg, hepatitis B e a...

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“…In similar studies on patients with HBsAg loss, relapse did not occur during the follow-up period, irrespective of whether the patient was HBeAg positive or HBeAg negative [8][9][10][11][12]. In similar studies on patients with HBsAg loss, relapse did not occur during the follow-up period, irrespective of whether the patient was HBeAg positive or HBeAg negative [8][9][10][11][12].…”

Section: Discussionmentioning

confidence: 88%

Long-term outcomes after nucleos(t)ide analogue discontinuation in HBeAg-positive chronic hepatitis B patients

Guo

Zhu

et al. 2014

Clinical Microbiology and Infection

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Nucleos(t)ide analogue (NUC) resistance is an important clinical risk resulting from long-term therapy in chronic hepatitis B (CHB) management. Discontinuation of NUCs is a feasible strategy to reduce resistance. We aimed to observe the outcomes after NUC withdrawal in HBeAg-positive CHB patients. A total of 97 patients (11 patients with HBsAg loss and 86 patients with sustained HBeAg seroconversion) were enrolled. HBV DNA levels and alanine aminotransferase (ALT) levels were monitored regularly after discontinuation. Relapse was defined as HBV DNA levels >2000 IU/mL in at least two determinations more than 4 weeks apart. HBeAg seroconversion was achieved within 48 weeks (interquartile range (IQR), 24-72 weeks). The time on consolidation therapy was 96 weeks (IQR, 84-144 weeks). No relapses occurred for HBsAg loss patients. Evidence of relapse was observed in 9.3% of HBeAg seroconversion patients. All relapse cases occurred within 48 weeks after discontinuation. The time to relapse was 33 ± 15 weeks. Elevation of HBV DNA and ALT levels over baseline were only observed in 12.5% of relapse patients. There were no significant differences in baseline characteristics (sex, HBV genotype, age or ALT levels) or time on consolidation therapy between patients with relapse or sustained response. NUC discontinuation in HBeAg-positive CHB patients is feasible after achieving HBeAg seroconversion at a minimum of 24 weeks. There is further benefit to prolonging the time on consolidation therapy to reduce relapse. More than 48 weeks of sustained response is a predictive marker for long-term sustained response.

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Relapse rates in chronic hepatitis B naïve patients after discontinuation of antiviral therapy with entecavir

Cited by 27 publications

References 18 publications

Durability of Hepatitis B e Antigen Seroconversion in Chronic Hepatitis B Patients Treated with Entecavir or Tenofovir

Durability of Hepatitis B e Antigen Seroconversion in Chronic Hepatitis B Patients Treated with Entecavir or Tenofovir

Discontinuation of oral antivirals in chronic hepatitis B: A systematic review

Long-term outcomes after nucleos(t)ide analogue discontinuation in HBeAg-positive chronic hepatitis B patients

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