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.
Highlights
Chronic infection with Hepatitis B virus (HBV) is a major global health problem, an important cause of morbidity and mortality sequelae such as hepatic decompensation, liver cirrhosis (LC) and/or hepatocellular carcinoma (HCC) development [1]
This review aims to assess and discuss current and evolving trends in the antiviral therapy of chronic HBV infection
Our large study involving 691 patients (308 with cirrhosis), so far the largest on this issue, showed clinical relapse in 419 (61%), hepatitis flare (ALT > 5 × ULN) in 280 (41%), total bilirubin >2 mg/dL in 72 (10%), prolongation of prothrombin time with international normalized ratio (INR) > 1.5 in 16 (2%) during a median follow-up of three years after end-of-treatment (EOT), and the calculated annular incidence of hepatic decompensation was 0.28%, with a five-year cumulative incidence of 0% in 383 patients with chronic Hepatitis B (CHB) and 2.95% in 308 patients with cirrhosis, during a median follow-up of 155 (2–614) weeks [48]. These studies have shown that finite nucleos(t)ide analogues (NUC) therapy in hepatitis B e antigen (HBeAg)-negative patients is feasible and reasonably safe, even in patients with cirrhosis [39]
Summary
Chronic infection with Hepatitis B virus (HBV) is a major global health problem, an important cause of morbidity and mortality sequelae such as hepatic decompensation, liver cirrhosis (LC) and/or hepatocellular carcinoma (HCC) development [1]. It affects ~290 million people worldwide; 64% of them reside in the Asia Pacific region, and approximately 2 billion people have been infected worldwide and about 1 million die from it annually [2]. Basic and clinical studies have provided a better understanding of the virus, its natural history and the immunopathogenesis of chronic HBV infection [1,2,3]. This review aims to assess and discuss current and evolving trends in the antiviral therapy of chronic HBV infection
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