Reduction of hepatitis B surface antigen in sequential versus add-on pegylated interferon to nucleoside/nucleotide analogue therapy in HBe-antigen-negative chronic hepatitis B patients: A pilot study

Tatsukawa, Yumiko; Tsuge, Masataka; Kawakami, Yoshiiku; Hiyama, Yuichi; Murakami, Eisuke; Kurihara, Mio; Nomura, Motonobu; Tsushima, Ken; Uchida, Takuro; Nakahara, Takashi; Miki, Daiki; Kawaoka, Tomokazu; Abe‐Chayama, Hiromi; Ochi, Hidenori; Hayes, C. Nelson; Kawakami, Hiroiku; Chayama, Kazuaki

doi:10.3851/imp3240

Cited by 11 publications

(6 citation statements)

References 26 publications

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“…Last, as recent studies concluded, sequential therapy with interferon after long-term NAs enhanced the reduction of HBsAg and may represent a treatment option to promote HBsAg loss. (25,26) Thus, sequential treatment with interferon after NAs discontinuation should also be included as an important issue to be investigated.…”

Section: Discussionmentioning

confidence: 99%

The Role of Hepatitis B Surface Antigen in Nucleos(t)ide Analogues Cessation Among Asian Patients With Chronic Hepatitis B: A Systematic Review

et al. 2019

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In actual clinical practice, infinite nucleos(t)ide analogues (NAs) treatment for chronic hepatitis B virus (HBV) infection is unrealistic. The most commonly used endpoint is suppression of HBV DNA to undetectable levels with normalization of alanine aminotransferase. However, this criterion for cessation of treatment is associated with various incidences of virological and clinical relapse. Recent studies suggest that decreasing the hepatitis B surface antigen (HBsAg) level at the end of treatment (EOT) to an appropriate cut‐off value appears to be a practicable and attainable cessation criterion. We performed a systematic review to explore the optimal cut‐off value of HBsAg at EOT for the cessation of NAs treatment. Eleven studies with 1,716 patients were included in this review. When the HBsAg levels at EOT were <100 IU/mL and >100 IU/mL, the respective off‐therapy virological relapse rates were 9.1%‐19.6% (range) and 31.4%‐86.8% (range) at ≥12 months off therapy, regardless of hepatitis B e antigen (HBeAg) status; the respective off‐therapy clinical relapse rates were 15.4%‐29.4% (range) and 48.1%‐63.6% (range) at ≥12 months off therapy, regardless of HBeAg status; and the respective off‐therapy HBsAg loss rates were 21.1%‐58.8% (range) and 3.3%‐7.4% (range) for HBeAg‐negative patients at ≥39 months off therapy. Conclusion: Cessation of long‐term NAs therapy before HBsAg seroclearance in patients with chronic hepatitis B is a feasible alternative to indefinite treatment. An HBsAg level <100 IU/mL at EOT seems to be a useful marker for deciding when to discontinue NAs therapy. However, regular monitoring is required after the cessation of NAs treatment, and long‐term outcomes must be further evaluated.

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Section: Discussionmentioning

confidence: 99%

The Role of Hepatitis B Surface Antigen in Nucleos(t)ide Analogues Cessation Among Asian Patients With Chronic Hepatitis B: A Systematic Review

et al. 2019

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“…Indeed, anti-PD-1 antibody treatment in clinical trial (a phase Ib study) can significantly decrease HBsAg [16]. In addition, the low level of HBsAg in NUCtreated patients with negative HBV DNA is an indicator to discontinue the therapy [24], or to add on or switch to rIFNα treatment [28]. Thus, the serum sPD-L1 may serve as an additional indicator to make such treatment decisions.…”

Section: Discussionmentioning

confidence: 99%

Serum soluble programmed death ligand-1 is correlated with HBsAg level and nucleos(t)ide analogue therapy in chronic hepatitis B

Rm¹,

Wx²,

Lj³

et al. 2020

Preprint

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Background The restoration of immune responses is thought as a complementary approach to the nucleos(t)ide analogue (NUC) therapy of chronic HBV infection. The antiviral immunity is negatively regulated by the programmed cell death-1/programmed death ligand-1 (PD-1/PD-L1) axis. Here, the soluble form of PD-L1 (sPD-L1) that represents the amount of PD-L1 expression cells was used as an indicator to investigate the involvement of this axis in chronic HBV infection, especially in the setting of NUC therapy. Methods A total of 273 adult patients with chronic HBV infection, regardless of the treatment, and 86 healthy controls were consecutively enrolled. Serum sPD-L1 was measured using an ELISA assay. Its correlations with clinical/virological characteristics were analyzed. Results Serum sPD-L1 levels in patients with chronic HBV infection (median 425.2 IQR 245.8-558.6 pg/mL) were significantly higher than those in healthy controls (median 81.69 IQR 54.62-121.1 pg/mL). Among patients at various disease phases, those with immune-tolerant CHB had the lowest sPD-L1 levels (median 205.3 IQR 92.27-340.7 pg/mL). These results indicated that serum sPD-L1 was significantly increased in a manner of two steps from health to infection and from immunotolerance to immunoactivation in chronic HBV infection. Furthermore, the serum sPD-L1 in immune-active CHB was correlated with HBsAg positively, HBV DNA negatively and liver damage marginally. Interestingly, the increased serum sPD-L1 levels were strongly associated with the treatment of NUCs, especially in HBeAg-positive immune-active CHB. Conclusions Serum sPD-L1 might be a meaningful indicator to monitor the immune status and disease progression in chronic HBV infection. The correlations of the increased sPD-L1 with HBsAg and NUC treatment suggest that the activated PD-1/PD-L1 axis may explain the rarity of HBsAg seroconversion of NUC therapy and the clinically available checkpoint inhibitors may serve as partners for NUCs to improve their anti-HBV efficacy in the future

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“…There are several reports regarding combination therapy of NUCs and pegylated interferon-alpha for HBV-infected patients [5]. Previous Japanese pilot study demonstrated that add-on therapy, in which 48 weeks of pegylated interferonalpha-2a are administered simultaneously with ongoing long-term NUC therapy, is superior to sequential therapy, in which 48 weeks of pegylated interferon-alpha-2a (180 μg/ week) are administered from 1 month prior to discontinuation of long-term NUC therapy to 11 months post-discontinuation, for HBV surface antigen (HBsAg) reduction [6].…”

Section: Abbreviationsmentioning

confidence: 99%

No additive effects of peginterferon on the short-term improvement of liver histology by entecavir monotherapy in chronic hepatitis B patients

Kanda

2021

Hepatol Int

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Reduction of hepatitis B surface antigen in sequential versus add-on pegylated interferon to nucleoside/nucleotide analogue therapy in HBe-antigen-negative chronic hepatitis B patients: A pilot study

Abstract: Sequential therapy may be superior to add-on therapy in reducing HBsAg levels during long term NA therapy in chronic hepatitis B patients.

Cited by 11 publications

References 26 publications

The Role of Hepatitis B Surface Antigen in Nucleos(t)ide Analogues Cessation Among Asian Patients With Chronic Hepatitis B: A Systematic Review

The Role of Hepatitis B Surface Antigen in Nucleos(t)ide Analogues Cessation Among Asian Patients With Chronic Hepatitis B: A Systematic Review

Serum soluble programmed death ligand-1 is correlated with HBsAg level and nucleos(t)ide analogue therapy in chronic hepatitis B

No additive effects of peginterferon on the short-term improvement of liver histology by entecavir monotherapy in chronic hepatitis B patients

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