慢性乙型肝炎（chronic hepatitis B，CHB）是全球重大健康挑战，而功能性治愈是CHB的理想治疗终点。CHB发病机制复杂，涉及乙型肝炎病毒（hepatitis B virus，HBV）DNA整合、共价闭合环状DNA的持续存在，以及针对HBV的免疫功能受损，给CHB功能性治愈带来了巨大挑战。现有药物在实现功能性治愈方面成效有限，核苷（酸）类似物[nucleos（t）ide analogs，NAs]单药治疗10年，功能性治愈率不足5%；聚乙二醇干扰素（pegylated interferon，Peg-IFN）单药治疗48周，功能性治愈率不足15%。NAs治疗实现HBV e抗原（HBV e antigen， HbeAg）阴性且基线HBV表面抗原（HBV surface antigen，HBsAg）<1 500 IU/mL的优势人群，序贯Peg-IFN治疗后，功能性治愈率可达20％以上，其中基线HBsAg为500~1 500 IU/mL的患者功能性治愈率可达30%以上；基线HBsAg<100 IU/mL的患者功能性治愈率可达60%以上。满足指南推荐的停药标准的非肝硬化患者，停用NAs可能会加速HBsAg清除，助力实现功能性治愈。然而，需要严密监测这些患者发生肝炎暴发和肝细胞癌的风险。为解决现有药物对CHB功能性治愈率低的问题，研究人员正在研发新药，包括靶向HBV生命周期不同阶段的直接抗病毒药物和恢复针对HBV的免疫功能的免疫调节药物。基于目前研究结果，尚无新药能够通过单药治疗实现30%以上的CHB功能性治愈率，基于新药的联合治疗策略是当前的研究热点。

Chronic hepatitis B (CHB) remains a major global health challenge. Functional cure represents the ideal therapeutic endpoint for CHB. The pathogenesis of CHB is complex, including hepatitis B virus (HBV) DNA integration, persistent covalently closed circular DNA, and impaired specific immune response against HBV, which poses significant challenges to achieving functional cure in CHB. Current therapeutic drugs have limited efficacy in achieving functional cure. After 10 years of nucleos(t)ide analogs (NAs) monotherapy, less than 5% of patients achieve functional cure, while less than 15% of patients achieve functional cure after 48 weeks of pegylated interferon (Peg-IFN) monotherapy. For the favorable population that achieves HBV e antigen (HBeAg) negativity with NAs treatment and has baseline HBV surface antigen (HBsAg) <1 500 IU/mL, the functional cure rate with sequential Peg-IFN therapy is over 20%, with a functional cure rate of over 30% for patients with baseline HBsAg between 500 and 1 500 IU/mL and over 60% for those with baseline HBsAg <100 IU/mL. For non-cirrhotic patients who meet the recommended drug discontinuation criteria in the guidelines, NAs cessation may accelerate HBsAg clearance and facilitate functional cure. However, close monitoring of hepatitis flares and hepatocellular carcinoma is required. To overcome the low functional cure rate of current drugs for CHB, researchers are exploring novel drugs, including direct-acting antivirals targeting different stages of HBV life cycle, and immunomodulatory drugs aimed at restoring immune function against HBV. Based on current research results, no new drug has achieved a functional cure rate of CHB above 30% through monotherapy. Therefore, combination therapy strategies based on new drugs are currently a research focus.