Article
Gastroenterology & Hepatology
Jordan J. Feld, Anna S. Lok, Fabien Zoulim
Summary: Current therapy for chronic hepatitis B rarely achieves a functional cure, but novel treatments are being developed. Understanding the mechanisms of hepatitis B virus persistence has helped identify new treatment targets and evaluate novel agents in clinical trials. Combining different agents appears to be a promising strategy to reduce viral replication, invigorate immune responses, and induce specific adaptive immune responses.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Mojisola Ogunnaike, Srijanee Das, Samiksha S. Raut, Ashrafi Sultana, Mohammad Ullah Nayan, Murali Ganesan, Benson J. Edagwa, Natalia A. Osna, Larisa Y. Poluektova
Summary: Chronic hepatitis B virus (HBV) infection can lead to the development of cirrhosis and hepatocellular carcinoma. Lifelong treatment with nucleotides/nucleoside antiviral agents is effective but adherence can be challenging. This review discusses recent advances in the development of long-acting formulations and curative strategies for HBV treatment, highlighting promising antivirals and genome editing approaches.
Article
Immunology
Marion G. Peters, Man-Fung Yuen, Norah Terrault, John Fry, Pietro Lampertico, Ed Gane, Carey Hwang, Luisa M. Stamm, Mitchell Leus, Mala K. Maini, Patricia Mendez, Isabelle Lonjon-Domanec, Thomas Berg, Su Wang, Poonam Mishra, Eric Donaldson, Stephanie Buchholz, Veronica Miller, Oliver Lenz
Summary: This article discusses the timing and methods to stop finite therapy for curing chronic hepatitis B, in order to demonstrate sustained efficacy and safety. The consensus among the stakeholders is outlined in detail regarding various aspects of stopping finite therapy.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Gastroenterology & Hepatology
Samuel Anthony Lachlan Hall, Sara Vogrin, Olivia Wawryk, Gareth S. Burns, Kumar Visvanathan, Vijaya Sundararajan, Alexander Thompson
Summary: A meta-analysis was conducted on clinical outcomes after nucleot(s)ide analogue (NA) discontinuation for HBeAg-negative CHB patients, revealing that virological relapse is common but clinical relapse occurs in only one-third of patients at 12 months post-NA discontinuation. Discontinuation of NA therapy can lead to HBsAg clearance, with higher rates observed with longer follow-up periods.
Review
Gastroenterology & Hepatology
Yun-Fan Liaw
Summary: Consensus has been reached in the understanding and management of chronic hepatitis B virus infection and HBV-cirrhosis, but challenges to existing consensus in concept and definitions have emerged. These controversial issues include alanine aminotransferase upper limit of normal, nomenclature for phases of chronic HBV infection, indication of antiviral therapy, and finite vs indefinite long-term therapy. The pros and cons of these issues have been reviewed and discussed in order to clarify and resolve the controversy.
JOURNAL OF GASTROENTEROLOGY
(2022)
Review
Immunology
Jianyu Ye, Jieliang Chen
Summary: IFN therapy has unique advantages in treating chronic hepatitis B, but its efficacy is limited and side effects are common. To seek a cure for HBV, improving IFN therapy and combining it with other antiviral agents may be considered.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Gastroenterology & Hepatology
Hye-Lin Kim, Gi-Ae Kim, Jae-A Park, Hye-Rim Kang, Eui-Kyung Lee, Young-Suk Lim
Summary: This study found that starting antiviral therapy in the immune-tolerant phase is more cost-effective compared with delaying treatment until the active hepatitis phase in CHB patients, especially with increasing hepatocellular carcinoma risk, decreasing drug costs, and consideration of productivity loss.
Review
Medicine, General & Internal
Yanhua Tang, Hongyan Liang, Ge Zeng, Sheng Shen, Jian Sun
Summary: Chronic hepatitis B virus infection is a global health burden, and existing antiviral drugs can improve prognosis but have low success rates for functional cure and complete cure. Therefore, new antiviral drugs, including direct-acting antiviral drugs and immunotherapeutic approaches, are needed.
CHINESE MEDICAL JOURNAL
(2022)
Article
Medicine, General & Internal
Jun Li, Zhao Wu, Gui-Qiang Wang, Hong Zhao
Summary: The study revealed correlations between HBcrAg and antiviral efficacy, virological, and histological variables in chronic hepatitis B patients, with a decreased HBcrAg predicting HBeAg loss after antiviral therapy.
CHINESE MEDICAL JOURNAL
(2021)
Review
Gastroenterology & Hepatology
Sheikh Mohammad Fazle Akbar, Osamu Yoshida, Yoichi Hiasa
Summary: Patients with chronic hepatitis B (CHB) are a long-term reservoir of hepatitis B virus (HBV). If not properly treated, these CHB patients may develop serious complications. Current antiviral drugs for CHB treatment cannot eradicate all forms of HBV and cannot stop the progression of complications for most patients. Therefore, there is an urgent need for the development of new therapies for CHB. Immune dysregulation may be responsible for HBV persistence and liver damage in CHB. Despite 30 years of immune therapies for CHB, an effective regimen of immune therapy is yet to be realized. This review discusses the pros and cons of different immune therapies for CHB patients in the past 30 years to provide insights for the development of an evidence-based, effective, and patient-friendly immune therapy regimen for CHB treatment.
JOURNAL OF GASTROENTEROLOGY
(2022)
Letter
Gastroenterology & Hepatology
Ivan Rankovic, Vladimir Milivojevic, Aleksandra Pavlovic Markovic, Mihailo Bezmarevic
Summary: This study highlights the significance of extrahepatic manifestations of hepatitis B infection and the bidirectional relationship between hepatitis B infection and carotid atherosclerosis.
WORLD JOURNAL OF GASTROENTEROLOGY
(2022)
Article
Immunology
Do Seon Song, Jeong Won Jang, Sun Hong Yoo, Jung Hyun Kwon, Soon Woo Nam, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon
Summary: This study identified end-of-therapy HBsAg levels, consolidation duration, and cirrhosis as key determinants of off-therapy relapse. Extended consolidation therapy for >= 2 years, in combination with low HBsAg levels, is recommended for HBeAg-positive patients, while the risk of relapse in HBeAg-negative patients is mainly associated with HBsAg levels.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Chemistry, Multidisciplinary
Ramisha Khan, Amjad Ali, Sadia Bibi, Shazia Rafique, Muhammad Idrees, Sobia Ahsan Halim, Muhammad Waqas, Haji Bahadar, Jalal Uddin, Ajmal Khan, Ahmed Al-Harrasi
Summary: This study evaluated the expression of three TRIM family genes in patients with chronic hepatitis C and found that TRIM25 and TRIM14 had the highest expression levels in the group with good treatment response. The expression levels of TRIM genes were also linearly correlated with the viral load of hepatitis C virus.
Review
Virology
Manasa Suresh, Stephan Menne
Summary: Infection with hepatitis B virus (HBV) is a global burden, and finding a cure for this viral disease is challenging. Animal models play a crucial role in studying gene expression and viral inhibition, and are significant for clinical trials.
Article
Gastroenterology & Hepatology
Adam J. Gehring, Patricia Mendez, Kirsten Richter, Hildegund Ertl, Eric F. Donaldson, Poonam Mishra, Mala Maini, Andre Boonstra, Georg Lauer, An de Creus, Kathleen Whitaker, Sara Ferrando Martinez, Jessica Weber, Emily Gainor, Veronica Miller
Summary: This paper discusses the importance of developing clinically applicable immunological biomarkers to evaluate the mechanism of action in the treatment of chronic hepatitis B, and to guide rational treatment strategies and drug use. Immune assays must be incorporated into clinical trials, with deeper immunological analysis provided by ancillary studies. Standardizing immunological assays and data will provide deployable biomarkers for clinical use independent of specialized immunology laboratories.
JOURNAL OF HEPATOLOGY
(2022)
Review
Gastroenterology & Hepatology
Young-Suk Lim, Wai-Kay Seto, Masayuki Kurosaki, Scott Fung, Jia-Horng Kao, Jinlin Hou, Stuart C. Gordon, John F. Flaherty, Leland J. Yee, Yang Zhao, Kosh Agarwal, Pietro Lampertico
Summary: Switching to TAF treatment maintains or improves virological and biochemical responses, and has better bone and renal safety for patients with CHB. These data support the concept of switching to TAF based on individual circumstances.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Gastroenterology & Hepatology
Roberta D'Ambrosio, Elisabetta Degasperi, Maria Paola Anolli, Ilaria Fanetti, Marta Borghi, Roberta Soffredini, Massimo Iavarone, Giulia Tosetti, Riccardo Perbellini, Angelo Sangiovanni, Vana Sypsa, Pietro Lampertico
Summary: This study evaluated the incidence of liver-related and non-liver-related events, as well as mortality, in cirrhotic patients treated with DAAs, finding that patient history significantly influences long-term outcomes. Hepatocellular carcinoma was the most common liver-related complication after viral cure in HCV-related cirrhotic patients, who also faced a significant proportion of non-liver-related events due to improved long-term outcomes.
JOURNAL OF HEPATOLOGY
(2022)
Review
Gastroenterology & Hepatology
Elisabetta Degasperi, Maria P. Anolli, Pietro Lampertico
Summary: Chronic hepatitis delta (CHD) is a severe form of chronic viral hepatitis, affecting millions of people worldwide. The only treatment option for CHD, interferon, has limited efficacy and significant side effects. Bulevirtide (BLV) has shown promising results as a new HBV-HDV entry inhibitor, with high virological response rates and good tolerability. BLV has received conditional approval for the treatment of compensated CHD, providing a new treatment option for patients.
LIVER INTERNATIONAL
(2023)
Article
Gastroenterology & Hepatology
Massimo Iavarone, Giulia Tosetti, Floriana Facchetti, Matilde Topa, Joey Ming Er, Shou Kit Hang, Debora Licari, Andrea Lombardi, Roberta D'Ambrosio, Elisabetta Degasperi, Alessandro Loglio, Chiara Oggioni, Riccardo Perbellini, Riccardo Caccia, Alessandra Bandera, Andrea Gori, Ferruccio Ceriotti, Luigia Scudeller, Antonio Bertoletti, Pietro Lampertico
Summary: This study found that patients with cirrhosis have a suboptimal immune response to COVID-19 vaccines, particularly in those who have not been infected with SARS-CoV-2 before. However, the cellular immune response in patients with cirrhosis remains preserved, and a low rate of breakthrough infections was observed.
DIGESTIVE AND LIVER DISEASE
(2023)
Article
Gastroenterology & Hepatology
Harry L. A. Janssen, Jinlin Hou, Tarik Asselah, Henry L. Y. Chan, Fabien Zoulim, Yasuhito Tanaka, Ewa Janczewska, Ronald G. Nahass, Stefan Bourgeois, Maria Buti, Pietro Lampertico, Oliver Lenz, Thierry Verbinnen, Joris Vandenbossche, Willem Talloen, Ronald Kalmeijer, Maria Beumont, Michael Biermer, Umesh Shukla
Summary: The study evaluated the efficacy and safety of JNJ-56136379 in patients with chronic hepatitis B. The results showed that JNJ-56136379+NA significantly reduced HBV DNA and HBV RNA levels, but had limited effects on HBsAg or HBeAg declines in HBeAg-positive patients. Overall, JNJ-56136379 did not demonstrate clear superiority over NA in terms of efficacy.
Article
Gastroenterology & Hepatology
Marzia Rossi, Andrea Vecchi, Camilla Tiezzi, Valeria Barili, Paola Fisicaro, Amalia Penna, Ilaria Montali, Stephane Daffis, Simon P. Fletcher, Anuj Gaggar, Jonathan Medley, Michael Graupe, Latesh Lad, Alessandro Loglio, Roberta Soffredini, Marta Borghi, Teresa Pollicino, Cristina Musolino, Arianna Alfieri, Federica Brillo, Diletta Laccabue, Marco Massari, Chiara Boarini, Gianluca Abbati, Giuseppe Pedrazzi, Gabriele Missale, Pietro Lampertico, Carlo Ferrari, Carolina Boni
Summary: This study characterized the functional impairment of exhausted HBV-specific CD8 T cells in patients with chronic HBV infection. It identified subsets of patients with different capacities to control infection and respond to immune modulation. It also found that functionally more efficient HBV-specific CD8 T cell subsets with lower expression of coinhibitory molecules were present in some chronic viraemic patients. The ability to distinguish patient cohorts with different responses to immune modulation through phenotypic CD8 T cell exhaustion profiling is clinically significant.
Review
Gastroenterology & Hepatology
Elisabetta Degasperi, Maria Paola Anolli, Pietro Lampertico
Summary: Chronic hepatitis Delta (CHD) is a rare and severe form of chronic viral hepatitis. The current treatment approach is the off-label use of PegInterferon alpha (PegIFN alpha), but it has suboptimal efficacy and significant side effects. The entry inhibitor Bulevirtde (BLV) has been conditionally approved for the treatment of compensated CHD and has shown promising results in clinical trials and real-life studies.
JOURNAL OF VIRAL HEPATITIS
(2023)
Article
Gastroenterology & Hepatology
Elisa Farina, Alessandro Loglio, Giulia Tosetti, Elisabetta Degasperi, Mauro Vigano, Carmine Gentile, Sara Monico, Riccardo Perbellini, Marta Borghi, Floriana Facchetti, Sara Colonia Uceda Renteria, Ferruccio Ceriotti, Federica Cerini, Massimo Primignani, Pietro Lampertico
Summary: In patients with HBV-related compensated cirrhosis receiving long-term TDF/ETV treatment, the risk of developing/progessing EV is negligible, challenging the current endoscopic surveillance recommendations in patients without EV at baseline.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Gastroenterology & Hepatology
Marc G. Ghany, Maria Buti, Pietro Lampertico, Hannah M. Lee
Summary: Representatives from academia, industry, regulatory agencies, and patient advocacy groups convened under the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) in June 2022 to achieve consensus on chronic HBV and HDV treatment endpoints. The conference focused on the primary goal of guiding clinical trials aiming to cure HBV and HDV, and reached agreements on key points such as preferred endpoints for trials, suitable patient candidates, and the role of novel biomarkers and existing therapies.
Article
Infectious Diseases
Giuseppina Brancaccio, Barbara Coco, Alessandra Nardi, Maria Giovanna Quaranta, Maria Elena Tosti, Luigina Ferrigno, Irene Cacciola, Vincenzo Messina, Luchino Chessa, Filomena Morisco, Michele Milella, Francesco Barbaro, Alessia Ciancio, Francesco Paolo Russo, Nicola Coppola, Pierluigi Blanc, Ernesto Claar, Gabriella Verucchi, Massimo Puoti, Anna Linda Zignego, Liliana Chemello, Salvatore Madonia, Stefano Fagiuoli, Alfredo Marzano, Carlo Ferrari, Pietro Lampertico, Vito Di Marco, Antonio Craxi, Teresa Antonia Santantonio, Giovanni Raimondo, Maurizia R. Brunetto, Giovanni Battista Gaeta, Loreta A. Kondili
Summary: The study examined the characteristics of patients with chronic hepatitis B virus in Italy and found that a significant proportion of patients were non-Italian natives, and there was a decline in HBeAg prevalence and stable anti-HDV prevalence. Cirrhosis was common in both cohorts, with a higher proportion in the PITER cohort, and variables such as age, sex, BMI, and anti-HDV positivity were associated with cirrhosis. The study also observed an increase in adherence to antiviral treatment recommendations over time. In conclusion, chronic hepatitis B virus infection in Italy appears to be under control, but HDV infection remains a health concern.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Gastroenterology & Hepatology
Maria Paola Anolli, Elisabetta Degasperi, Lena Allweiss, Angelo Sangiovanni, Marco Maggioni, Caroline Scholtes, Valerie Oberhardt, Christoph Neumann-Haefelin, Maura Dandri, Fabien Zoulim, Pietro Lampertico
Summary: Bulevirtide has received conditional approval from the EMA for treating chronic hepatitis delta, but the optimal duration of therapy remains unknown. In this study, a patient with compensated cirrhosis and esophageal varices achieved hepatitis delta cure after 3 years of bulevirtide monotherapy. Virological and biochemical responses were maintained during the 72-week off-therapy follow-up, and significant improvements were observed in liver biopsy results.
JOURNAL OF HEPATOLOGY
(2023)
Article
Gastroenterology & Hepatology
Serena Pelusi, Cristiana Bianco, Massimo Colombo, Giuliana Cologni, Paolo del Poggio, Nicola Pugliese, Daniele Prati, Marie Graciella Pigozzi, Roberta D'Ambrosio, Pietro Lampertico, Stefano Fagiuoli, Luca Valenti
Summary: This study aimed to examine the impact of metabolic dysfunction (MD) on patients cured of chronic hepatis C (CHC). The results showed that MD had a significant effect on liver stiffness in patients with advanced fibrosis and was associated with increased risk of hepatocellular carcinoma (HCC). Further classification based on diagnostic criteria improved risk stratification. Therefore, MD is an effective way to identify individuals at risk of developing HCC in CHC patients.
LIVER INTERNATIONAL
(2023)
Review
Microbiology
Fabrizio Fabrizi, Maria Francesca Donato, Federica Tripodi, Anna Regalia, Pietro Lampertico, Giuseppe Castellano
Summary: The aim of this review is to assess the role of antiviral therapy for HBV in improving survival after a kidney transplant. The results suggest a negative correlation between HBV-positive status and survival after a kidney transplant. Antiviral therapy has been shown to improve patient and graft survival in HBV-positive individuals.
Editorial Material
Gastroenterology & Hepatology
Benjamin Maasoumy, Pietro Lampertico
LIVER INTERNATIONAL
(2023)
Review
Gastroenterology & Hepatology
Pietro Lampertico, Elisabetta Degasperi, Lisa Sandmann, Heiner Wedemeyer
Summary: Chronic infection with hepatitis delta virus (HDV) affects millions of people worldwide, leading to severe liver disease and complications. While progress has been made in understanding the virus, there is still much to learn about its natural history and the immune system's role. Diagnosis and treatment of HDV remain challenging, but recent advancements in antiviral therapy, such as bulevirtide, offer hope for improved outcomes. The first international Delta Cure meeting provided a platform for sharing the latest research and discussing potential strategies for HDV treatment.
