The remarkable success of direct-acting antivirals in curing hepatitis C led to concerted efforts in developing a cure for hepatitis B. Unlike hepatitis C, it is accepted that a sterilising cure is not feasible in the foreseeable future. Instead, functional cure defined as hepatitis B surface antigen (HBsAg) loss (below detection) and HBV DNA suppression (below quantification) sustained for at least 24 weeks after completion of treatment has been embraced.1 Nucleos(t)ide analogues (NA) currently in use, entecavir and tenofovir, are highly effective in maintaining suppression of HBV DNA replication and yields substantial clinical benefits including reduced rates of cirrhosis and hepatocellular carcinoma, but HBsAg loss remains elusive. Yet, if a functional cure is achieved, the benefits are multiple, with further reductions in the risk for liver-related outcomes,2 elimination of the need for long-term monitoring and NA treatment and addressing the stigma associated with HBsAg-positivity. Strategies to increase rates of HBsAg loss among persons on long-term NA therapy included NA withdrawal and peginterferon add-on or switch. It should be noted that such studies focus on the population who are HBeAg-negative and on NA therapy with suppressed HBV DNA for years. Studies show that NA withdrawal can increase the rate of HBsAg loss compared with continued treatment with NA but the rates of HBsAg loss are modest at best (10–20% at 3–5 years after NA discontinuation) and lower in persons of Asian origin (<5%) and can be associated with hepatitis flares and hepatic decompensation.3 Furthermore, half the patients require resumption of treatment within 4 years of NA withdrawal. Peginterferon add-on therapy to NA similarly increases rates of HBsAg loss to~10% but has more limited applicability due to the side effect profile of peginterferon.4 Clearly, these results are underwhelming, but they provide a useful benchmark …

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探索 HBV 功能治愈：我们从沉默 RNA 中学到了什么？


直接作用的抗病毒药物在治愈丙型肝炎方面取得了显著的成功，这促使人们齐心协力开发乙型肝炎的治疗方法。与丙型肝炎不同，人们普遍认为，在可预见的未来，绝育治疗是不可行的。相反，功能性治愈定义为乙型肝炎表面抗原 （HBsAg） 丢失（低于检测）和 HBV DNA 抑制（低于定量）在完成治疗后持续至少 24 周。目前使用的核苷（酸）类似物 （NA），恩替卡韦和替诺福韦，在维持抑制 HBV DNA 复制方面非常有效，并产生巨大的临床益处，包括降低肝硬化和肝细胞癌的发病率， 但 HBsAg 的损失仍然难以捉摸。然而，如果实现功能性治愈，好处是多方面的，进一步降低肝脏相关结果的风险，2 消除了长期监测和 NA 治疗的需求，并解决了与 HBsAg 阳性相关的耻辱感。增加长期 NA 治疗患者 HBsAg 丢失率的策略包括 NA 戒断和聚乙二醇干扰素附加或转换。应该注意的是，此类研究侧重于 HBeAg 阴性人群和多年来 HBV DNA 抑制的 NA 治疗。研究表明，与继续使用 NA 治疗相比，停用 NA 会增加 HBsAg 丢失的比率，但 HBsAg 的丢失率充其量是适度的（停用 NA 后 3-5 年为 10-20%），而亚洲血统的人较低 （<5%），并且可能与肝炎发作和肝脏失代偿有关。 半数患者需要在 NA 停用后 4 年内恢复治疗。 NA 的聚乙二醇干扰素附加治疗同样将 HBsAg 的丢失率提高到 ~10%，但由于聚乙二醇干扰素的副作用，其适用性更加有限。4 显然，这些结果并不令人满意，但它们提供了一个有用的基准......