Response to discontinuation of long-term nucleos(t)ide analogue treatment in HBeAg negative patients: Results of the Stop-NUC trial

Bömmel, Florian van; Stein, K; Heyne, R.; Möller, Hjördis; Petersen, Jörg; Buggisch, Peter; Berg, Christoph; Werner, Christoph; Zeuzem, Stefan; Herrmann, Andreas; Reuken, Philipp; Sprinzl, Martin; Grambihler, Annette; Schott, Eckart; Benckert, Julia; Pathil, Anita; Arnim, Ulrike von; Keitel, Verena; Trauth, Janina; Georg, Simon Karl; Trein, Andreas; Hüppe, D; Cornberg, Markus; Lammert, Frank; Ingiliz, Patrick; Zachoval, Reinhart; Hinrichsen, Holger; Zipprich, Alexander; Klinker, Hartwig; Wiesch, Julian Schulze zur; Brosteanu, Oana; Schmiedeknecht, Anett; Berg, Thomas

doi:10.1016/s0168-8278(20)30755-8

Cited by 24 publications

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“…These studies provided strong evidence that discontinuation of NA, compared to continued NA therapy, is overall safe and associated with a more pronounced decline in HBsAg levels and a significantly higher rate of HBsAg loss, which can reach 10-20% during a relatively short follow-up period of 2-3 years (11,12). In addition, up to 40% enter a true offtreatment carrier stage with suppressed viral activity (10)(11)(12)(13)(14). From these studies, it also became evident that HBV infection goes through different phases after discontinuation of NA treatment, the lag phase, the reactivation phase, and the consolidation phase (15).…”

Section: Outcome Studies -Geographical Differences Mattermentioning

confidence: 98%

“…However, recent long-term follow-up studies after cessation of NA treatment in HBeAg-negative patients after prolonged on-treatment suppression of HBV replication showed a relatively high proportion of patients remaining in treatment-free remission or even achieving functional cure, i.e. loss of HBsAg, a finding which has challenged the dogma of lifelong treatment necessity in these circumstances (10)(11)(12)(13)(14).…”

Section: Treatment Concepts Of Chronic Hepatitis B -Times They Are a Changingmentioning

confidence: 99%

“…This is one of the strongest arguments for physicians, as well as patients, not to discontinue NA before HBsAg loss. Indeed, a rebound of HBV replication with detectable HBV DNA levels after NA discontinuation is almost universal (10)(11)(12)(13)(14). Whether this rebound warrants an increased risk of HCC development in the long-term is still unknown.…”

Section: Na-discontinuation In Hbeag-negative Chronic Hepatitis B -Where Do We Stand?mentioning

confidence: 99%

“…The HBsAg cut-off at the end-of-treatment that best predicts functional cure is still under debate and appears to differ between Caucasian and Asian patient populations. However, it has now been convincingly demonstrated that HBsAg levels of < 1000 IU/mL in the Caucasian population and < 100 IU/mL in the Asian population are associated with HBsAg loss rates of more than 20%-30% (13,21,29,31,42). These functional cure rates appear to justify the effort related to discontinuing NAs, and they are in the range of what we are also targeting as efficacy endpoints for novel antiviral and immunomodulatory agents currently being studied to cure HBV infection (43).…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

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The times they are a-changing – A refined proposal for finite HBV nucleos(t)ide analogue therapy

Berg

Lampertico

2021

Journal of Hepatology

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Section: Outcome Studies -Geographical Differences Mattermentioning

confidence: 98%

Section: Treatment Concepts Of Chronic Hepatitis B -Times They Are a Changingmentioning

confidence: 99%

Section: Na-discontinuation In Hbeag-negative Chronic Hepatitis B -Where Do We Stand?mentioning

confidence: 99%

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

See 2 more Smart Citations

The times they are a-changing – A refined proposal for finite HBV nucleos(t)ide analogue therapy

Berg

Lampertico

2021

Journal of Hepatology

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“…3). (32,63,70) In many cases, this is followed by an ALT flare. The reactivation phase ends when HBV DNA and ALT levels return to a stable plateau (Fig.…”

Section: Reactivation Phasementioning

confidence: 99%

Risks and Benefits of Discontinuation of Nucleos(t)ide Analogue Treatment: A Treatment Concept for Patients With HBeAg‐Negative Chronic Hepatitis B

Boemmel

2021

Hepatol Commun

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Systematic discontinuation of long-term treatment with nucleos(t)ide analogues (NAs) is one strategy to increase functional cure rates in patients with chronic hepatitis B e antigen (HBeAg)-negative hepatitis B. Currently, available study results are heterogeneous; however, long-term hepatitis B surface antigen (HBsAg) loss rates of up to 20% have been reported in prospective trials. This review proposes criteria that can be used when considering NA discontinuation in patients with chronic hepatitis B virus (HBV). Discontinuing NA treatment frequently results in a virologic and biochemical relapse that runs through different phases: the lag phase, reactivation phase, and consolidation phase. The HBV-DNA flares observed during the reactivation phase are often transient and most likely represent a trigger for inducing a long-term immune control by specific CD8+ T cells, and therefore do not need immediate interventions but close follow-up evaluation. Low HBsAg levels at the time of treatment cessation predict a positive long-term response to NA discontinuation associated with a higher likelihood of HBsAg clearance. Other host and viral biomarkers are currently under evaluation that may prove to be helpful to further characterize the population that may benefit most from the finite NA treatment concept. Potential harmful biochemical flares during the reactivation phase need to be identified early and can be effectively terminated by reintroducing NA treatment. Hepatic decompensation represents a risk to patients with cirrhosis undergoing NA discontinuation. Therefore, the finite NA approach should only be considered after excluding advanced fibrosis and cirrhosis and if a close follow-up of the patient and supervision by an experienced physician can be guaranteed. Conclusion: For selected patients, NA discontinuation has become a powerful tool to achieve control over HBeAg-negative HBV infections. Its significant effect represents a challenge to novel treatment approaches, but it may also serve as their enhancer. (Hepatology Communications 2021;0:1-17).C hronic hepatitis B virus (HBV) infection is a major global health concern. Approximately 250 million people are chronically infected with the virus, putting them at risk of serious liver disease, including cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). ( 1) Nucleos(t) ide analogue (NA) treatments for chronic hepatitis B are available, which provide sustained suppression of HBV replication, thus slowing or preventing disease progression. (1)(2)(3) Endpoints for treatment with NA are stages of stable immune control over the infection, which are characterized by either undetectable hepatitis B e antigen (HBeAg) and the appearance of antibody to hepatitis B e antigen (anti-HBe) in formerly

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Getting to HBV cure: The promising paths forward

et al. 2022

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Chronic HBV infection is a global public health burden estimated to impact nearly 300 million persons worldwide. Despite the advent of potent antiviral agents that effectively suppress viral replication, HBV cure remains difficult to achieve because of the persistence of covalently closed circular DNA (cccDNA), HBV‐DNA integration into the host genome, and impaired immune response. Indefinite treatment is necessary for most patients to maintain level of viral suppression. The success of direct‐acting antivirals (DAAs) for hepatitis C treatment has rejuvenated the search for a cure for chronic hepatitis B (CHB), though an HBV cure likely requires an additional layer: immunomodulators for restoration of robust immune responses. DAAs such as entry inhibitors, capsid assembly modulators, inhibitors of subviral particle release, cccDNA silencers, and RNA interference molecules have reached clinical development. Immunomodulators, namely innate immunomodulators (Toll‐like receptor agonists), therapeutic vaccines, checkpoint inhibitors, and monoclonal antibodies, are also progressing toward clinical development. The future of the HBV cure possibly lies in triple combination therapies with concerted action on replication inhibition, antigen reduction, and immune stimulation. Many obstacles remain, such as overcoming translational failures, choosing the right endpoint using the right biomarkers, and leveraging current treatments in combination regimens to enhance response rates. This review gives an overview of the current therapies for CHB, HBV biomarkers used to evaluate treatment response, and development of DAAs and immune‐targeting drugs and discusses the limitations and unanswered questions on the journey to an HBV cure.

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Response to discontinuation of long-term nucleos(t)ide analogue treatment in HBeAg negative patients: Results of the Stop-NUC trial

Cited by 24 publications

References 0 publications

The times they are a-changing – A refined proposal for finite HBV nucleos(t)ide analogue therapy

The times they are a-changing – A refined proposal for finite HBV nucleos(t)ide analogue therapy

Risks and Benefits of Discontinuation of Nucleos(t)ide Analogue Treatment: A Treatment Concept for Patients With HBeAg‐Negative Chronic Hepatitis B

Getting to HBV cure: The promising paths forward

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