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Getting to HBV cure: The promising paths forward

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Article Immunology

Hepatitis B Virus RNA as Early Predictor for Response to Pegylated Interferon Alpha in HBeAg-Negative Chronic Hepatitis B

Mina S. Farag et al.

Summary: During PEG-IFN treatment for HBeAg-negative CHB, HBV-RNA showed a rapid and significant decrease that correlated with treatment response and HBsAg loss at long-term follow-up.

CLINICAL INFECTIOUS DISEASES (2021)

Article Gastroenterology & Hepatology

Toll-Like Receptor 8 Agonist GS-9688 Induces Sustained Efficacy in the Woodchuck Model of Chronic Hepatitis B

Stephane Daffis et al.

Summary: GS-9688 treatment in woodchucks with WHV infection showed significant antiviral efficacy, with a >5 log(10) reduction in viral load and sustained response even after treatment cessation. The treatment also resulted in reduced intrahepatic WHV RNA and DNA levels, and enhanced immune responses in woodchucks.

HEPATOLOGY (2021)

Article Immunology

Circulating Pregenomic Hepatitis B Virus RNA Is Primarily Full-length in Chronic Hepatitis B Patients Undergoing Nucleos(t)ide Analogue Therapy

Mark Anderson et al.

Summary: The study found that full-length pregenomic RNA is the primary source of circulating HBV RNA in infected patients, clarifying the major identity of HBV RNA species in circulation.

CLINICAL INFECTIOUS DISEASES (2021)

Article Gastroenterology & Hepatology

Role of serum HBV RNA and hepatitis B surface antigen levels in identifying Asian patients with chronic hepatitis B suitable for entecavir cessation

Wai-Kay Seto et al.

Summary: In patients with chronic HBV infection, measurement of serum HBV RNA is crucial in determining the suitability of cessation of entecavir treatment, especially for those with low HBsAg levels. Patients can be stratified based on viral determinants to assess their risk of off-treatment relapse.
Article Gastroenterology & Hepatology

Ultra-Long-term Follow-up of Interferon Alfa Treatment for HBeAg-Positive Chronic Hepatitis B Virus Infection

Hannah S. J. Choi et al.

Summary: The study found that using interferon-alpha to treat chronic hepatitis B patients can lead to high rates of HBsAg loss in ultra-long-term follow-up, with a single treatment having persistent effects. Baseline factors associated with higher HBsAg loss rates include male sex, Caucasian race, older age, genotype A, and cirrhosis. Early treatment response (loss of HBeAg) is associated with higher HBsAg loss rates and better patient outcomes.

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY (2021)

Article Gastroenterology & Hepatology

Therapeutic Potential of TLR8 Agonist GS-9688 (Selgantolimod) in Chronic Hepatitis B: Remodeling of Antiviral and Regulatory Mediators

Oliver E. Amin et al.

Summary: GS-9688 activates immune cell subsets and induces the production of immunomodulatory mediators in healthy controls and CHB patients. It boosts antiviral effector functions by activating HBV-specific CD8(+) T cells, CD4(+) follicular helper T cells, NK cells, and mucosal-associated invariant T cells. Additionally, GS-9688 modulates immunoregulatory subsets, potentially optimizing its antiviral efficacy.

HEPATOLOGY (2021)

Article Gastroenterology & Hepatology

Viral and immune factors associated with successful treatment withdrawal in HBeAg-negative chronic hepatitis B patients

Mireia Garcia-Lopez et al.

Summary: Factors contributing to successful outcome upon nucleos(t)ide analogue treatment withdrawal in HBeAg-negative chronic hepatitis B patients include low HBsAg levels, decreased cccDNA transcription, and the presence of functional HBV-specific T cells. Moreover, a high frequency of functional HBV-specific CD8+ T cells at baseline is associated with sustained viral control off treatment. This study highlights the importance of virological and immunological factors in guiding individualized therapy for chronic hepatitis B patients.

JOURNAL OF HEPATOLOGY (2021)

Article Immunology

Memory-like HCV-specific CD8+ T cells retain a molecular scar after cure of chronic HCV infection

Nina Hensel et al.

Summary: The study reveals a progenitor-progeny relationship between memory-like and terminally exhausted HCV-specific CD8(+) T cells via an intermediate subset. Following DAA therapy to eliminate chronic antigen stimulation, memory-like cells are maintained while terminally exhausted cells are lost, resulting in a memory polarization of the overall HCV-specific CD8(+) T cell response. However, an exhausted core signature of memory-like CD8(+) T cells is still detectable even after viral clearance.

NATURE IMMUNOLOGY (2021)

Article Biochemistry & Molecular Biology

Safety, tolerability and antiviral activity of the antisense oligonucleotide bepirovirsen in patients with chronic hepatitis B: a phase 2 randomized controlled trial

Man-Fung Yuen et al.

Summary: Chronic infection with hepatitis B virus (HBV) poses a high risk of death from cirrhosis and hepatocellular carcinoma. Current treatment options have low functional cure rates. Bepirovirsen, an antisense oligonucleotide, shows promise in reducing HBV-derived RNAs, HBV DNA, and viral proteins. Preliminary observations from a phase 2 trial suggest that bepirovirsen has a favorable safety profile and can significantly reduce HBsAg concentrations in some patients. Further investigation in a larger population is warranted.

NATURE MEDICINE (2021)

Article Medicine, General & Internal

Randomized Trial of a Vaccine Regimen to Prevent Chronic HCV Infection

Kimberly Page et al.

Summary: This trial assessed the safety and efficacy of an HCV vaccine in adults at risk for the infection due to injection drug use. The vaccine did not cause serious adverse events, elicited HCV-specific T-cell responses, and lowered peak HCV RNA levels, but it did not prevent chronic HCV infection.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

Article Multidisciplinary Sciences

Checkpoint inhibition through small molecule-induced internalization of programmed death-ligand 1

Jang-June Park et al.

Summary: A mechanism of inhibiting programmed death-ligand 1 through small molecule-induced dimerization and internalization was reported, showing potential therapeutic implications in oncology and chronic viral infections.

NATURE COMMUNICATIONS (2021)

Article Gastroenterology & Hepatology

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

Thomas Berg et al.

Summary: The appropriateness of considering HBsAg loss before discontinuation of nucleos(t)ide analogues (NA) treatment in the HBeAg-negative phase remains highly controversial. Although some HBeAg-negative patients can be cured by stopping NA treatment, concerns about discontinuation-associated relapse and uncertainty in predicting off-therapy response have led to low implementation of this concept in the clinic.

JOURNAL OF HEPATOLOGY (2021)

Review Virology

Mechanism of Hepatitis B Virus cccDNA Formation

Lei Wei et al.

Summary: Hepatitis B virus (HBV) is a small DNA virus that undergoes a complex replication cycle in human hepatocytes to produce covalently closed circular DNA, relying on host factors for conversion. Research utilizing genetic and biochemical approaches has provided insights into the complex mechanism of HBV cccDNA formation, critical for the development of new therapies towards viral suppression and potential cure.

VIRUSES-BASEL (2021)

Article Gastroenterology & Hepatology

Therapeutic vaccine BRII-179 restores HBV-specific immune responses in patients with chronic HBV in a phase Ib/IIa study

Haiyan Ma et al.

Summary: BRII-179, alone or with a low dose of interferon-alpha, was safe, well tolerated, and induced enhanced HBV-specific antibody and T-cell responses in patients with chronic hepatitis B. However, BRII-179 treatment alone had minimal effect on patient's virological status.

JHEP REPORTS (2021)

Article Medicine, Research & Experimental

Permanent Inactivation of HBV Genomes by CRISPR/Cas9-Mediated Non-cleavage Base Editing

Yu-Chan Yang et al.

MOLECULAR THERAPY-NUCLEIC ACIDS (2020)

Article Multidisciplinary Sciences

Fc-optimized antibodies elicit CD8 immunity to viral respiratory infection

Stylianos Bournazos et al.

NATURE (2020)

Article Multidisciplinary Sciences

Epigenetic signature of PD-1+TCF1+CD8 T cells that act as resource cells during chronic viral infection and respond to PD-1 blockade

Rohit R. Jadhav et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2019)

Article Gastroenterology & Hepatology

Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance

Norah A. Terrault et al.

HEPATOLOGY (2018)

Article Medicine, Research & Experimental

Hepatitis B virus-specific T cells associate with viral control upon nucleos(t)ide-analogue therapy discontinuation

Laura Rivino et al.

JOURNAL OF CLINICAL INVESTIGATION (2018)

Article Gastroenterology & Hepatology

Safety, efficacy and pharmacodynamics of vesatolimod (GS-9620) in virally suppressed patients with chronic hepatitis B

Harry L. A. Janssen et al.

JOURNAL OF HEPATOLOGY (2018)

Article Gastroenterology & Hepatology

Natural history of serum HBV-RNA in chronic HBV infection

J. Wang et al.

JOURNAL OF VIRAL HEPATITIS (2018)

Article Medicine, Research & Experimental

PD-1 blockade partially recovers dysfunctional virus-specific B cells in chronic hepatitis B infection

Loghman Salimzadeh et al.

JOURNAL OF CLINICAL INVESTIGATION (2018)

Article Medicine, Research & Experimental

Circulating and intrahepatic antiviral B cells are defective in hepatitis B

Alice R. Burton et al.

JOURNAL OF CLINICAL INVESTIGATION (2018)

Article Gastroenterology & Hepatology

New treatments to reach functional cure: Rationale and challenges for emerging immune-based therapies

Adam J. Gehring

BEST PRACTICE & RESEARCH CLINICAL GASTROENTEROLOGY (2017)

Article Gastroenterology & Hepatology

Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update

S. K. Sarin et al.

HEPATOLOGY INTERNATIONAL (2016)

Article Gastroenterology & Hepatology

HBV DNA Integration and Clonal Hepatocyte Expansion in Chronic Hepatitis B Patients Considered Immune Tolerant

William S. Mason et al.

GASTROENTEROLOGY (2016)

Article Gastroenterology & Hepatology

Higher lifetime chance of spontaneous surface antigen loss in hepatitis B carriers with genotype C infection

T. -C. Tseng et al.

ALIMENTARY PHARMACOLOGY & THERAPEUTICS (2015)

Article Gastroenterology & Hepatology

The oral toll-like receptor-7 agonist GS-9620 in patients with chronic hepatitis B virus infection

Edward J. Gane et al.

JOURNAL OF HEPATOLOGY (2015)

Review Gastroenterology & Hepatology

Strategies to Inhibit Entry of HBV and HDV Into Hepatocytes

Stephan Urban et al.

GASTROENTEROLOGY (2014)

Article Gastroenterology & Hepatology

Changes of HBsAg and HBV DNA levels in Chinese chronic hepatitis B patients after 5 years of entecavir treatment

Wai-Kay Seto et al.

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY (2014)

Review Cell Biology

Regulation of microRNA biogenesis

Minju Ha et al.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2014)

Editorial Material Gastroenterology & Hepatology

BASIC AND TRANSLATIONAL-LIVER

Robert E. Lanford et al.

GASTROENTEROLOGY (2013)

Article Immunology

T cells maintain an exhausted phenotype after antigen withdrawal and population reexpansion

Daniel T. Utzschneider et al.

NATURE IMMUNOLOGY (2013)

Article Gastroenterology & Hepatology

Restored Function of HBV-Specific T Cells After Long-term Effective Therapy With Nucleos(t)ide Analogues

Carolina Boni et al.

GASTROENTEROLOGY (2012)

Article Biotechnology & Applied Microbiology

Zinc-finger Nucleases as a Novel Therapeutic Strategy for Targeting Hepatitis B Virus DNAs

Thomas J. Cradick et al.

MOLECULAR THERAPY (2010)

Article Medicine, General & Internal

Tenofovir Disoproxil Fumarate versus Adefovir Dipivoxil for Chronic Hepatitis B

Patrick Marcellin et al.

NEW ENGLAND JOURNAL OF MEDICINE (2008)

Article Medicine, General & Internal

Telbivudine versus lamivudine in patients with chronic hepatitis B

Ching-Lung Lai et al.

NEW ENGLAND JOURNAL OF MEDICINE (2007)

Article Gastroenterology & Hepatology

A one-year trial of entecavir treatment in patients with HBeAg-positive chronic hepatitis B

Fen-Yu Ren et al.

WORLD JOURNAL OF GASTROENTEROLOGY (2007)

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A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B

TT Chang et al.

NEW ENGLAND JOURNAL OF MEDICINE (2006)

Article Biochemistry & Molecular Biology

Platelets mediate cytotoxic T lymphocyte-induced liver damage

M Iannacone et al.

NATURE MEDICINE (2005)

Article Gastroenterology & Hepatology

Four years of lamivudine treatment in Chinese patients with chronic hepatitis B

TT Chang et al.

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY (2004)

Article Medicine, General & Internal

Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B

P Marcellin et al.

NEW ENGLAND JOURNAL OF MEDICINE (2003)

Article Multidisciplinary Sciences

Depletion of neutrophils blocks the recruitment of antigen-nonspecific cells into the liver without affecting the antiviral activity of hepatitis B virus-specific cytotoxic T lymphocytes

G Sitia et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2002)