Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Hepatology. 2021 Jun;73(6):2155-2166. doi: 10.1002/hep.31610.
HBsAg seroclearance is considered a realistic goal in patients with chronic hepatitis B (CHB), known as "functional cure." However, it remains elusive whether nucleos(t)ide analogue (NUC)-induced HBsAg seroclearance, compared with spontaneous HBsAg seroclearance, differs in its association with favorable long-term clinical outcomes.
A total of 1,972 CHB patients with confirmed HBsAg seroclearance at least two consecutive times, 6 months apart, were retrospectively analyzed. Risks of HCC development and composite clinical events, including HCC, liver-related death, and liver transplantation, were compared between spontaneous and NUC-induced HBsAg seroclearance. Of 1,972 patients, mean patient age was 53.7 years, and 64.4% were men. Cirrhosis was present in 297 (15.1%) patients. HBsAg seroclearance was achieved spontaneously in 1,624 (82.4%) patients and by NUC treatment in 348 (17.6%). HCC developed in 49 patients, with an annual incidence of 0.38 of 100 person-years (PY) during a median follow-up of 5.6 years. With 336 propensity-score-matched pairs, risks of HCC (P = 0.52) and clinical events (P = 0.14) were not significantly different between NUC-induced and spontaneous HBsAg seroclearance. By multivariable analysis, NUC-induced HBsAg seroclearance, compared with spontaneous HBsAg seroclearance, was not associated with the significantly higher risk of HCC (adjusted HR [AHR], 1.49; P = 0.26) and clinical events (AHR, 1.78; P = 0.06).
Risks of HCC and clinical events were not significantly different between spontaneous and NUC-induced HBsAg seroclearance. Nonetheless, annual risk of HCC exceeds the recommended cutoff for HCC surveillance even after HBsAg seroclearance, suggesting that continued HCC surveillance is required.
HBsAg 血清学清除被认为是慢性乙型肝炎（CHB）患者的一个现实目标，也被称为“功能性治愈”。然而，核苷（酸）类似物（NUC）诱导的 HBsAg 血清学清除与自发 HBsAg 血清学清除在与良好的长期临床结局的关联方面是否存在差异，目前仍不清楚。
共回顾性分析了 1972 例 HBsAg 血清学清除至少连续 2 次且两次检测时间间隔至少 6 个月的 CHB 患者。比较了自发和 NUC 诱导的 HBsAg 血清学清除患者 HCC 发生风险和包括 HCC、肝相关死亡和肝移植在内的复合临床事件的风险。在 1972 例患者中，平均患者年龄为 53.7 岁，64.4%为男性。297 例（15.1%）患者存在肝硬化。1624 例（82.4%）患者自发获得 HBsAg 血清学清除，348 例（17.6%）患者经 NUC 治疗获得 HBsAg 血清学清除。49 例患者发生 HCC，中位随访 5.6 年后每年 HCC 发生率为 0.38/100 人年。通过 336 对倾向评分匹配对，NUC 诱导和自发 HBsAg 血清学清除的 HCC 风险（P=0.52）和临床事件风险（P=0.14）无显著差异。多变量分析显示，与自发 HBsAg 血清学清除相比，NUC 诱导的 HBsAg 血清学清除与 HCC（调整后的 HR [AHR]，1.49；P=0.26）和临床事件（AHR，1.78；P=0.06）的发生风险显著升高无关。
自发和 NUC 诱导的 HBsAg 血清学清除的 HCC 和临床事件风险无显著差异。然而，即使在 HBsAg 血清学清除后，每年 HCC 的发生风险仍超过 HCC 监测的推荐临界值，提示仍需要继续进行 HCC 监测。
