Liver Research Unit, Chang Gung Memorial Hospital and University College of Medicine, 199 Tung Hwa North Road, Taipei 105, Taiwan.
Viruses. 2022 Feb 21;14(2):434. doi: 10.3390/v14020434.
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.
由于乙型肝炎病毒（HBV）的活跃复制是肝坏死炎症和疾病进展的关键驱动因素，慢性乙型肝炎（CHB）的治疗目标是永久抑制 HBV 复制，以防止肝失代偿、肝硬化和/或肝细胞癌，并延长生存时间。目前，聚乙二醇干扰素（Peg-IFN）、恩替卡韦（ETV）、富马酸替诺福韦二吡呋酯（TDF）和替诺福韦艾拉酚胺（TAF）是首选的一线药物。由于 Peg-IFN 需要皮下注射，且具有显著的副作用，因此很少使用。每天口服一次的 ETV、TDF 和 TAF 可以深度抑制 HBV DNA，但对 HBV 感染肝细胞中的 cccDNA 没有直接作用，因此通常需要长期治疗来维持 HBV 抑制，但很少能达到 HBsAg 消失的最终目标（10 年 2%）。此外，长期 NUC 治疗存在成本增加、药物依从性和失访等问题。来自台湾的研究表明，在 HBeAg 阴性患者中进行两到三年的有限 NUC 治疗是可行、安全的，并且极大地提高了 HBsAg 丢失率，达到 30%/5 年。这导致了全球范围内对 HBeAg 阴性患者进行有限 NUC 治疗的范式转变。然而，HBV 复发可能会导致乙型肝炎发作，并有肝失代偿甚至危及生命的风险。因此，适当的监测、评估和再治疗决策对于确保安全性至关重要。理想情况下，再治疗不应太晚以确保安全，也不应太早，以允许进一步的免疫反应，使 HBsAg 进一步下降，达到 HBsAg 丢失。在乙型肝炎发作期间，结合 HBsAg/ALT 动力学进行评估比单独使用生化标志物更能做出正确的再治疗决策。有限 NUC 治疗策略为新的抗 HBV 药物设定了一个高 HBsAg 丢失率的基准，这些药物正在进行临床前或早期研究。
