Current Trend in Antiviral Therapy for Chronic Hepatitis B

Abstract

Since active hepatitis B virus (HBV) replication is the key driver of hepatic necroinflammation and disease progression, the treatment aim of chronic hepatitis B (CHB) is to suppress HBV replication permanently to prevent hepatic decompensation, liver cirrhosis and/or hepatocellular carcinoma and prolong survival. Currently, pegylated interferon (Peg-IFN), entecavir (ETV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) are the first-line drugs of choice. Peg-IFN therapy has been used rarely due to its subcutaneous injection and significant side effect profile. Once daily oral ETV, TDF and TAF can suppress HBV DNA profoundly but have no direct action on cccDNA of the HBV-infected hepatocytes, hence continuing long-term therapy is usually needed to maintain HBV suppression, but the ultimate goal of HBsAg loss was rarely achieved (10 year 2%). In addition, long-term NUC therapy comes with several concerns such as increasing cost, medication adherence and loss-to-follow-up. Studies, mainly from Taiwan, have shown that finite NUCs therapy of two to three years in HBeAg-negative patients is feasible, safe and has a great benefit of much increasing HBsAg loss rate up to 30%/5 year. These have led an emerging paradigm shift to finite NUC therapy in HBeAg-negative patients globally. However, off-NUC relapse with hepatitis B flares may occur and have a risk of decompensation or even life-threatening outcomes. Therefore, proper monitoring, assessment, and retreatment decisions are crucial to ensure safety. Ideally, retreatment should be not too late to ensure safety and also not too early to allow further immune response for further HBsAg decline toward HBsAg loss. Assessment using combined HBsAg/ALT kinetics during hepatitis flare is better than biochemical markers alone to make a right retreatment decision. The strategy of finite NUC therapy has set a benchmark of high HBsAg loss rate to be achieved by the new anti-HBV drugs which are under preclinical or early phase study.

Impact of National Centralized Drug Procurement Policy on Antiviral Utilization and Expenditure for Hepatitis B in China

“…Effective antiviral therapy with high-efficiency and low-resistance drugs, including ETV and TDF, is recommended as the preferred treatment for CHB patients. [19][20][21] Without treatment scale-up, it is estimated that there will be 10 million HBV-related deaths in the next decade. 22 However, the treatment rates and patient compliance are hindered by the high cost of antiviral agents and insufficient reimbursement by health insurance.…”

Arthrospira Enhances Seroclearance in Patients with Chronic Hepatitis B Receiving Nucleos(t)ide Analogue through Modulation of TNF-α/IFN-γ Profile

“…Therefore, it is estimated that NA therapy for several decades is required to reduce HBsAg levels, and lifelong NA treatment is necessary in almost all cases [ 41 ]. Off-NA therapy in HBeAg-negative patients with undetectable HBV DNA may increase HBsAg loss rates up to 30%/5 years [ 42 ]. Serum HBsAg may decline successively before ascending ALT reaches its peak during some hepatitis flares, followed by spontaneous resolution [ 42 ].…”

“…Off-NA therapy in HBeAg-negative patients with undetectable HBV DNA may increase HBsAg loss rates up to 30%/5 years [ 42 ]. Serum HBsAg may decline successively before ascending ALT reaches its peak during some hepatitis flares, followed by spontaneous resolution [ 42 ]. However, off-NA relapse with HBV flares may occur, which may result in decompensation or even death.…”

“…In this study, HBsAg declined parallel to moderately increased ALT and IFN-γ expression in both HBeAg-positive and qHBsAg low patients in Arthrospira add-on groups ( Supplementary Figures S1C,D,G and Figure 3 C,D,G). Interestingly, the ALT level ( Supplementary Figure S1G ) is not as high as “beneficial flare” in patients with effective qHBsAg loss rate during off-NA therapy (ALT > 5× upper limit of normal, 40 U/L) [ 42 ]. In addition, the IL-6 levels and liver stiffness degrees were decreased in Arthrospira add-on groups, suggesting that Arthrospira attenuates hepatic inflammation and fibrosis ( Figure 3 E,F and Supplementary Figure S1E,F ).…”

Promising Role of Emodin as Therapeutics to Against Viral Infections

“…Chronic HBV infection is a major global health problem and an important cause of complications, including liver failure, development of liver cirrhosis (LC) and hepatocellular carcinoma (HCC) ( Liaw and Chu, 2009 ). There are approximately two billion people worldwide infected by HBV, resulting in approximately one million deaths each year ( Polaris Observatory Collaborators, 2018 ; Chien and Liaw, 2022 ). The population of infection with HBV is still increasing even though vaccination can prevent HBV, and the currently recognized effective antiviral treatment drugs have disadvantages such as high adverse effects and high prices.…”