编者按：在第35届亚太肝病研究学会年会（APASL 2026）召开之际，慢性乙型肝炎的功能性治愈成为肝病学界关注的焦点。然而，随着“治愈”目标的逐步明晰，临床医生是否应对所有患者采取统一的治疗策略？在本篇专访中，美国密歇根大学Anna Lok教授以其资深学者的冷静与洞见指出，在当前“扩大治疗”的背景下，我们仍需重视患者群体的高度异质性。她强调，真正的管理优化在于依托疾病特征、医疗资源可及性及患者意愿，实施更为精细化的个体决策。

《国际肝病》

请您和我们分享一下，您如何看慢性乙型肝炎的个体化治疗？

Anna Lok教授：慢性乙型肝炎具有高度的病理复杂性。尽管业界很多专家呼吁简化诊疗流程，但考虑到疾病的固有属性，简化的空间终究有限。若要为每位患者提供最优诊疗，我们就必须摒弃“一刀切”的策略。

诚然，设定“HBsAg阳性即治”的标准固然简便，却忽略了部分患者存在自发血清学转换的可能，也无视了患者对长期治疗的心理准备与耐受性问题。

我所倡导的“个体化治疗”，不仅是对疾病特征的精准分型，更强调纳入患者的主观意愿——即判断患者倾向于即刻干预，还是选择密切随访直至符合治疗指征。此外，社会经济学因素及地域医疗资源差异同样不容忽视。在全球范围内，若监测手段匮乏而治疗成本较低，早期启动治疗往往是阻断疾病进展的务实之选；反之，在具备完善监测体系的地区，患者于专科医生的严密照护下，则更可能在规律监测中暂缓治疗。

个体化医疗已成为现代医学诸多领域的核心理念。它通过统筹权衡疾病分期、风险获益比及患者价值观，实现精准管理。如今，是时候将这一理念全面应用于乙型肝炎的临床实践了。

You gave a talk on Personalized management of chronic hepatitis B, what do you mean by that?

Chronic hepatitis B is a very complex disease, and I know that many experts ask: Can we make it simpler? There's only so much you can simplify a disease that is intrinsically complex. I think it is not possible to have a one-size-fits-all approach if we want to provide the best care for each patient. We could make it very simple by saying that we treat everyone who tests positive for hepatitis B surface antigen, but some of these patients can spontaneously get better and some are not ready to start treatment that goes on for years.

When I talk about personalized therapy, I mean it is not just based on characterizing the disease features of that particular patient but also incorporating the patient's preferences—understanding whether the patient wants to get treated or is more inclined to have regular follow-up until they meet indications for treatmen . We also need to consider social circumstances as well as where the patient lives. In some parts of the world, monitoring and testing are very difficult. If therapy is cheap and monitoring tests are not readily available, people may be more inclined to start treat. On the other hand, there are patients who have access to regular monitoring and treatment. They know that they are under the expert care of specialists. They understand that as long as they keep getting regular monitoring, they don't necessarily need to start treatment immediately.

Personalized care is what we advocate for in many areas of medicine; it takes into consideration disease characteristics, disease stage, evidence of benefit versus risk of treatment and no treatment for that patient, and the patient's preference. It is time for personalized care to be applied to hepatitis B management.

《国际肝病》

关于核苷（酸）类似物（NA）治疗，有人提出停药可能有助于增加HBsAg清除（即功能性治愈）的机会，但这同时也伴随着肝炎发作的风险。请问您会考虑让哪些患者停药？

Anna Lok教授：这确实是一个非常有趣的话题。一方面，学界大力倡导扩大治疗覆盖面；但与此同时，我们也逐渐意识到，让所有患者无限期持续治疗并非总是必要。事实上，在特定患者亚群中，停用口服抗病毒药物反而可能比持续治疗更有助于提高HBsAg清除率。

然而，我们必须持审慎态度。因为仅在极少数患者中，能在HBsAg清除前从NAs停药中获益，这类患者通常表现为定量HBsAg水平较低（< 100 IU/mL）。

即便针对这部分低危人群，重度肝炎发作（severe hepatitis flares）的风险依然存在，尤其是老年患者或已合并进展期肝纤维化/肝硬化者。此外，诸如乙型肝炎核心相关抗原（HBcrAg）阳性或高水平、HBV RNA等指标虽预示着较高的复发风险，但由于缺乏标准化检测且临床可及性较差，目前难以常规推广。

因此，实施停药策略的核心前提在于：确保患者具备接受严密随访的主观意愿。唯有如此，一旦发生病毒学复发，我们才能做到早期发现，并在患者出现临床病情恶化前及时重启治疗。

Regarding NA therapy, it has been proposed that treatment withdrawal may increase chance of HBsAg loss (functional cure) but there is also a risk of hepatitis flare, which patients would you consider NA withdrawal?

Yeah, this is very interesting because on the one hand, there's a lot of push to treat more patients. But at the same time, we are also recognizing that leaving all patients on treatment forever is sometimes unnecessary. In fact, in a select group of patients, taking them off oral antivirals can actually increase the chance of HBsAg loss instead of continuing therapy.

But we have to be very careful because only a small proportion of patients would benefit from stopping nucleos(t)ide analogue treatment before HBsAg loss, and they tend to be those with low quantitative surface antigen levels—less than 100 IU/mL.

Even for these patients, there is a small risk of severe hepatitis flares, particularly if they are older or have advanced fibrosis or cirrhosis. Other markers, such as detectable or high hepatitis B core-related antigen and HBV RNA levels, also indicate a higher risk of relapse, but these tests are not standardized and not readily available.

The most important part is that when we take patients off treatment, we must ensure that the patient is willing to have close follow-up. This way, if they do relapse, we are able to identify it early and put them back on treatment before they experience clinical deterioration.

《国际肝病》

鉴于目前有大量抗病毒药物和免疫调节疗法正处于临床试验阶段，对于这些新药获批后，您会推荐哪些患者尝试这些新疗法？

Anna Lok教授：首先，目前尚无任何一款新药获批上市。尽管众多候选药物正处于临床试验阶段，但仅有极少数进入III期临床，且迄今为止仅完成了一项III期试验。值得注意的是，所有这些新型疗法的临床试验均采用了富集设计，即预先筛选了更可能应答的患者人群——通常是指那些定量HBsAg水平较低的患者。

这意味着，一旦新药获批，若患者的基线特征不符合临床试验的入组标准，其疗效往往难以复刻。举例而言，目前的III期临床试验大多纳入的是无肝硬化、且在NAs治疗下已实现病毒学抑制、同时HBsAg水平较低的患者。而对于合并进展期肝纤维化/肝硬化，或定量HBsAg水平较高的患者，这些新型疗法的安全性和有效性尚未得到评估。

即便对于那些具备有利因素（即符合III期试验入组条件）的患者，这些新药也并非万能的。虽然其成功率预计会高于现有疗法，但大概率仍局限在20%-30%之间。

最后，与现有的NAs相比，许多新疗法的不良反应发生率更高。当前的新兴疗法大多涉及注射给药，存在潜在的副作用风险，且其获益主要局限于特定的经筛选人群，而非普适于所有慢乙肝患者。

With numerous antivirals and immunomodulatory therapies in clinical trials, which patients would you recommend trying these new therapies when they are approved?

First of all, we don't know which ones will be approved. Many are in clinical trials, but only a handful have entered Phase III trial, and only one Phase III trial has been completed thus far. All these new trials have pre-selected patients who are more likely to respond, meaning those with low HBsAg level.

When these new drugs do get approved, if a patient does not meet the same criteria as those enrolled in the clinical trials, the treatment may not work for them. For example, most new clinical trials enroll patients with low quantitative surface antigen levels, no cirrhosis, and who are virally suppressed on nucleos(t)ide analogue. For patients with advanced fibrosis or cirrhosis, or those with high quantitative surface antigen levels, none of these new therapies have been evaluated yet.

Even for patients who have favorable factors like the ones enrolled in the Phase III trials, it's not like these new drugs are going to cure all patients. They will have a higher chance of success than current therapies, but probably not more than 20% or 30%.

Finally, many of these new therapies have more side effects than current NAs (which are very safe oral medications). All the new therapies right now involve injections with the potential for side effects, and they work for a selected group of patients—but not for everyone.

（来源：《国际肝病》编辑部）

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