相反，许多专家同意其他患者不太可能需要治疗，例如 HBV DNA 水平持续 <2000 IU/mL 的患者，尤其是定量检测 HBsAg 水平低、无肝纤维化/炎症和 ALT 持续正常的患者。
扩大治疗对象
最近的专家讨论围绕扩大 HBV 治疗标准展开，特别是考虑治疗 HBV DNA 水平高的年轻个体，即使他们肝酶正常且无纤维化，历史上称为免疫耐受（高复制性/非炎症性 HBeAg 阳性慢性乙肝病毒）。
对于那些不属于严格指南推荐的治疗适应症的人，例如 ALT 轻度升高的人，尤其是患有代谢相关性脂肪肝等合并症的人，也存在争议。如果有 HCC 家族史，专家指南建议考虑治疗，但具体的家族史细节通常未知。此外，HBV DNA 可以从低水平波动到中等水平，即使通过连续监测也可能无法捕获。在一些患者中，定量 HBsAg 水平可以帮助指导治疗决策，但需要更多不同患者队列（例如，具有不同基因型）的数据，并且需要改进的病毒血清生物标志物。在我的实践中，我还讨论了获得肝活检以确认没有炎症和纤维化。
扩大治疗的基本原理包括： (1) NAs 安全且耐受性良好，并且可以以大大降低的成本获得通用选择； (2) 有证据表明，由于 HBV 整合到宿主基因组中，年轻患者的中高水平 HBV DNA 与长期肝硬化和 HCC 风险增加有关； (3) 治疗可减少污名，以及对易感人群的传染性。
Individualizing Strategies for Chronic Hepatitis B—What Should We Do About Patients in the Gray Zone?
Carla Coffin, MD
Current guidelines recommend antiviral therapy for persons living with chronic HBV infection with active liver inflammation and/or liver fibrosis. The long-term goal is to reduce liver injury, progression to cirrhosis, and development of hepatocellular carcinoma (HCC). Although the approved oral antivirals—ie, nucleos(t)ide analogues (NAs)—are highly effective at suppressing viral replication, reversing liver fibrosis, and reducing risk of end-stage liver disease, NA treatment rarely leads to hepatitis B surface antigen (HBsAg) loss, which is considered a functional cure. Discontinuation of NA treatment can lead to clinical relapse, even after many decades. Furthermore, the risk of HCC is reduced with NA therapy—but not eliminated.
Whom to Treat and Whom to Monitor
There is little debate regarding the need for treatment of certain groups (Table), specifically:
Patients with cirrhosis
Patients with HCC
Patients with persistently elevated ALT and HBV DNA ≥2000 IU/
Patients coinfected with hepatitis delta virus
Patients coinfected with HIV
Patients who are immunocompromised
Pregnant patients with high-level viremia (>200,000 IU/mL) during late pregnancy (second/third trimester) to reduce risk of vertical transmission
Patients with extrahepatic manifestations of HBV
Conversely, many experts agree that other patients are unlikely to need treatment, such as those with HBV DNA levels persistently <2000 IU/mL—especially with low HBsAg levels by quantitative assay, no liver fibrosis/inflammation, and persistently normal ALT.
Expanding Whom to Treat
Recent expert discussions have revolved around expanding HBV treatment criteria—in particular, considering treatment of younger individuals with high HBV DNA levels even if they have normal liver enzymes and no fibrosis, historically referred to as immune tolerant (high replicative/noninflammatory HBeAg-positive chronic HBV).
There is also controversy regarding treating those who fall outside the strict guideline-recommended indications for treatment, such as persons with minimally elevated ALT, especially if they have comorbid conditions such as metabolic-associated fatty liver disease. Expert guidelines recommend consideration of treatment if there is a family history of HCC, but specific family history details are often unknown. Further, HBV DNA can fluctuate from low to moderate levels that may not be captured even with serial monitoring. In some patients, a quantitative HBsAg level can help guide treatment decisions, but more data are needed in diverse patient cohorts (eg, with different genotypes), and there is a need for improved viral serum biomarkers. In my practice, I also discuss obtaining a liver biopsy to confirm absence of inflammation and fibrosis.
The rationales for expanding treatment include: (1) NAs are safe and well tolerated, and generic options are available at greatly reduced cost; (2) there is evidence suggesting that moderate to high levels of HBV DNA in young patients are linked to increased risk for cirrhosis and HCC in the long term due to HBV integration into the host genome; and (3) treatment reduces stigma, as well as infectivity to susceptible persons.
In summary, current HBV treatment paradigms are being challenged. The risks vs benefits of treatment need to be weighed and must account for patient preference, cost, and long-term adherence.
A cure for chronic hepatitis B may still be many years away, and to me, it is important that we use all of our available tools in the fight against HBV—including HBV vaccination for prevention, along with safe and effective treatments to reduce the risk of liver disease progression and liver cancer development. 作者: StephenW 时间: 2022-8-20 22:27