Na+-Taurocholate Co-Transporting Polypeptide (NTCP) in Livers, Function, Expression Regulation, and Potential in Hepatitis B Treatment

Chronic hepatitis B virus (HBV) infection has become one of the leading causes of liver cirrhosis and hepatocellular carcinoma globally. The discovery of sodium taurocholate co-transporting polypeptide (NTCP), a solute carrier, as a key receptor for HBV and hepatitis D virus (HDV) has opened new avenues for HBV treatment. Additionally, it has led researchers to generate hepatoma cell lines (including HepG2-NTCP and Huh-7-NTCP) susceptible to HBV infection in vitro, hence, paving the way to develop and efficiently screen new and novel anti-HBV drugs. This review summarizes the history, function and critical findings regarding NTCP as a viral receptor for HBV/HDV, and it also discusses recently developed drugs targeting NTCP.

1204Modelling impact of targeted hepatitis B treatment for culturally and linguistically diverse populations in Australia

Background Antiviral treatment gap in culturally and linguistically diverse (CALD) populations may be a barrier progress in national elimination. Using modelling, we estimated and predicted the impact of antiviral treatment and migration on HBV burden, and HBV-related mortality in CALD populations in Australia. Methods We developed a dynamic, deterministic mathematical model using three antiviral treatment scale-up scenarios - the baseline treatment, intermediate treatment scale-up (80% of eligible by 2030), and optimistic scale-up (20% of all HBV by 2022) to predict the incidence of HBV infection, liver cirrhosis, hepatocellular carcinoma, and HBV-related mortality in four groups of people according to their country of birth. Results The number of chronic HBV cases will remain similar, and HBV-related morbidity and mortality will increase if the baseline approach is followed to 2030. Implementing an optimistic treatment scale-up could reduce the number of new cases of liver cirrhosis (30% in European-born, and 40% in Asia-Pacific-born) by 2030. Following the optimistic scale-up approach, the incidence of HCC decreased by 30% and a 15%-25% reduction in HCC-related mortality could be achieved in the four population subgroups by 2030. Conclusions Following the current antiviral treatment coverage, HBV elimination targets in migrants may not be achieved. A rapid treatment scale-up approach reduces HBV incidence, liver cirrhosis and HCC. Key messages Targeted antiviral treatment for migrants with HBV using rapid scale-up reduces HBV-related disease and mortality and contributes to achievement of national elimination targets.

Chronic Hepatitis B Treatment Strategies Using Polymerase Inhibitor-Based Combination Therapy

Viral polymerase is an essential enzyme for the amplification of the viral genome and is one of the major targets of antiviral therapies. However, a serious concern to be solved in hepatitis B virus (HBV) infection is the difficulty of eliminating covalently closed circular (ccc) DNA. More recently, therapeutic strategies targeting various stages of the HBV lifecycle have been attempted. Although cccDNA-targeted therapies are attractive, there are still many problems to be overcome, and the development of novel polymerase inhibitors remains an important issue. Interferons and nucleos(t)ide reverse transcriptase inhibitors (NRTIs) are the only therapeutic options currently available for HBV infection. Many studies have reported that the combination of interferons and NRTI causes the loss of hepatitis B surface antigen (HBsAg), which is suggestive of seroconversion. Although NRTIs do not directly target cccDNA, they can strongly reduce the serum viral DNA load and could suppress the recycling step of cccDNA formation, improve liver fibrosis/cirrhosis, and reduce the risk of hepatocellular carcinoma. Here, we review recent studies on combination therapies using polymerase inhibitors and discuss the future directions of therapeutic strategies for HBV infection.

Recent Advances in Hepatitis B Treatment

Hepatitis B virus infection affects over 250 million chronic carriers, causing more than 800,000 deaths annually, although a safe and effective vaccine is available. Currently used antiviral agents, pegylated interferon and nucleos(t)ide analogues, have major drawbacks and fail to completely eradicate the virus from infected cells. Thus, achieving a “functional cure” of the infection remains a real challenge. Recent findings concerning the viral replication cycle have led to development of novel therapeutic approaches including viral entry inhibitors, epigenetic control of cccDNA, immune modulators, RNA interference techniques, ribonuclease H inhibitors, and capsid assembly modulators. Promising preclinical results have been obtained, and the leading molecules under development have entered clinical evaluation. This review summarizes the key steps of the HBV life cycle, examines the currently approved anti-HBV drugs, and analyzes novel HBV treatment regimens.

Investigation of Hepatitis B virus DNA among HBsAg positive patients in Kabul, Afghanistan

Background: Hepatitis B virus (HBV) infections are one of the world's health problems that annually kill about 500,000 to 1,200,000 people. Investigation of HBV DNA in the person infected with HBV is a definitive indicator of activation and replication of HBV.Objectives: The aim of this study is to investigate the DNA of HBV in HBsAg positive patients and to study the risk factors for virus activation. Methods: This study was conducted on 106 HBsAg positive patients from January 2020 to July 2020 in Kabul. After informed consent, 3 to 5 milliliters of blood was collected for the HBV-DNA testing using the Real-time PCR method.Result: Out of 106 HbsAg positive patients, 74 (69.8%) were males and 32 (30.2%) females. The patients were aged between 11 and 65 years. Hepatitis B virus DNA was positive in 58 (54.7%) of the samples, 41 (70.7%) were male and 17 (29.3%) were female. The viral DNA load was in the range of 9.85 x 102 to 9.3 x 108 copies/ ml. Most of the patients were aged between 20 and 30 years. Conclusion: From 106 HbsAg positive patients, 23(39.7%) were in the age group of 20 – 30 years, and males were more infected than females. The majority of the patients were married and had an informal job with education below grade 12. No specific differences were found in the availability of HBV DNA between patients who received hepatitis B treatment before and those who did not.