ArticleScience translational medicine2021
Clearance of pegylated interferon by Kupffer cells limits NK cell activation and therapy response of patients with HBV infection.
Article in Science translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Immunomodulation by bepirovirsen may induce killing of infected hepatocytes (B-Together study).Hepatology international · 2026Trial
- Viral persistence and immune dysfunction in chronic hepatitis B: Mechanisms of post-treatment antigen asynchrony.iScience · 2026Review
- Macrophages in oncoviral infections: from immune regulators to therapeutic targets.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Natural Killer Cell Assays: Clinical Applications and Future Directions.Annals of laboratory medicine · 2026Review
- Systemic immune profiling uncovers divergent mechanisms and predictive biomarkers of response to combination immunotherapies in hepatocellular carcinoma.Journal for immunotherapy of cancer · 2026Article
- The APOBEC3 family: a narrative review of an alternative therapeutic agent for hepatitis B virus-induced hepatocellular carcinoma.Journal of gastrointestinal oncology · 2026Review
- Beyond viral suppression: combining PEG-interferon with novel immunotherapies for functional cure of chronic hepatitis B.Frontiers in cellular and infection microbiology · 2026Review
- Hepatitis B functional cure: Current and future perspective.World journal of hepatology · 2025Review
- Review
- HBV capsid assembly modulators differentially modulate the assembly of wild-type and drug-resistant core protein chimeric nucleocapsids and empty capsids.PLoS pathogens · 2025Article
- Interferon therapy for chronic hepatitis B virus infection affects nucleoside metabolism: a metabolomics study.BMC gastroenterology · 2025Article
- Targeting HBV with RNA interference: Paths to cure.Science translational medicine · 2025Review
- Auto-antibodies against interferons are common in people living with chronic hepatitis B virus infection and associate with PegIFNα non-response.JHEP reports : innovation in hepatology · 2025Article
- Drug development for chronic hepatitis B functional cure: Recent progress.World journal of hepatology · 2025Review
- Peripheral Blood CD4Journal of clinical and translational hepatology · 2025Article
- MicroRNA-122 protects against interferon-α-induced hepatic inflammatory response via the Janus kinase-signal transducer and activator of transcription pathway.Endocrine journal · 2025Article
- Toward a better understanding of chronic hepatitis B virus infection.The Journal of clinical investigation · 2024Article
- Safety and efficacy of 48-week pegylated interferon-Frontiers in medicine · 2024Article
- Guidance on treatment endpoints and study design for clinical trials aiming to achieve cure in chronic hepatitis B and D: Report from the 2022 AASLD-EASL HBV-HDV Treatment Endpoints Conference.Journal of hepatology · 2023Review
- Guidance on treatment endpoints and study design for clinical trials aiming to achieve cure in chronic hepatitis B and D: Report from the 2022 AASLD-EASL HBV-HDV Treatment Endpoints Conference.Hepatology (Baltimore, Md.) · 2023Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Pegylated interferon-α (PEG-IFN-α), where IFN-α is attached to polyethylene glycol (PEG), is an approved treatment for chronic hepatitis B virus (HBV) infection, a disease that causes liver-related morbidity and mortality in 257 million people worldwide. It is unknown why only a minority of patients respond to PEG-IFN-α. Using sequential blood samples and liver biopsies of patients with chronic HBV infection before, during, and after PEG-IFN-α treatment, we find that patients with early natural killer (NK) cell activation after PEG-IFN-α injection experienced greater liver inflammation, lysis of HBV-infected hepatocytes, and hepatitis B surface antigen (HBsAg) decline than those without. NK cell activation was associated with induction of interferon-stimulated genes and determined by PEG-IFN-α pharmacokinetics. Patients with delayed increases in PEG-IFN-α concentrations had greater amounts of PEG-specific immunoglobulin M (IgM) immune complexes in the blood and more PEG and IgM detected in the liver than patients with rapid increase in PEG-IFN-α concentration. This was associated with reduced NK cell activation. These results indicate that the immunomodulatory functions of PEG-IFN-α, particularly activation of NK cells, play a pivotal role in the response to treatment and further demonstrate that these functions are affected by PEG-IFN-α pharmacokinetics. Accelerated clearance of antibody-complexed pegylated drugs by Kupffer cells may be important beyond the field of HBV therapeutics. Thus, these findings may contribute to improving the efficacy of pegylated drugs that are now being developed for other chronic diseases and cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.