Background & Aims

Hepatitis B flare occurs earlier and is more severe in patients stopping tenofovir (TDF) compared with entecavir (ETV). This study investigated relationship between hepatitis B virus (HBV) kinetics, onset timing, and the severity of flares.

Methods

Hepatitis B e antigen–negative chronic hepatitis B patients who developed off-ETV or off-TDF hepatitis flare were recruited. Their HBV kinetics and the severity of flares were compared between patients with early (<6 months) and late (between 6 and 24 months) flares. Propensity score matching was performed at 1:1 adjusting for age, sex, cirrhosis, and end-of-treatment (EOT) hepatitis B surface antigen between off-ETV and off-TDF flares.

Results

After propensity score matching, 76% and 15% of each 107 off-TDF and off-ETV patients, respectively, developed early flare. A much steeper HBV DNA upsurge (ΔHBV DNA/month) was observed in off-TDF than off-ETV flares (2.12 vs 0.73 log₁₀ IU/mL; P < .01). Greater ΔHBV DNA/month correlated with earlier timing and higher peak alanine aminotransferase levels of flares. ΔHBV DNA/month ≥2.5 log₁₀ IU/mL was an independent factor for severe off-TDF flare, and ≥1 log₁₀ IU/mL was a predictor for severe off-ETV flares.

Conclusions

Greater HBV DNA upsurge rate (ΔHBV DNA/month) ≥1 log₁₀ IU/mL is a key factor for an earlier onset and more severe flare. More frequent ΔHBV DNA/month ≥1 log₁₀ IU/mL in off-TDF than off-ETV flares may explain why off-TDF flare mostly occurred early and was more severe. More stringent monitoring in those with ΔHBV DNA/month ≥1 log₁₀ IU/mL at flare, especially ≥2.5 log₁₀ IU/mL in early off-TDF flares, is important for timely retreatment to prevent decompensation.

中文翻译：

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治疗后病毒动力学在乙型肝炎 e 抗原阴性患者发作时间和严重程度中的作用

背景与目标

与恩替卡韦 (ETV) 相比，停用替诺福韦 (TDF) 的患者乙型肝炎爆发更早且更严重。本研究调查了乙型肝炎病毒 (HBV) 动力学、发病时间和急性发作严重程度之间的关系。

方法

招募了发生非 ETV 或非 TDF 肝炎发作的乙型肝炎 e 抗原阴性慢性乙型肝炎患者。比较早期（<6 个月）和晚期（6 至 24 个月）急性发作患者的 HBV 动力学和急性发作的严重程度。在 off-ETV 和 off-TDF 耀斑之间根据年龄、性别、肝硬化和治疗结束 (EOT) 乙型肝炎表面抗原以 1:1 进行倾向评分匹配。

结果

倾向评分匹配后，107 名非 TDF 患者和非 ETV 患者中分别有 76% 和 15% 出现早期发作。在 off-TDF 中观察到的 HBV DNA 激增（ΔHBV DNA/月）比 off-ETV 耀斑要陡得多（2.12 对 0.73 log ₁₀ IU/mL；P < .01）。更大的 ΔHBV DNA/月与更早的爆发时间和更高的谷丙转氨酶峰值水平相关。ΔHBV DNA/月 ≥2.5 log ₁₀ IU/mL 是严重的 off-TDF 爆发的独立因素，≥1 log ₁₀ IU/mL 是严重的 off-ETV 爆发的预测因子。

结论

更高的 HBV DNA 上升率（ΔHBV DNA/月）≥1 log ₁₀ IU/mL 是更早发作和更严重爆发的关键因素。与非 ETV 相比，非 TDF 中更频繁的 ΔHBV DNA/月≥1 log _{10 IU/mL 可能解释了为什么非 TDF 爆发大多发生在早期并且更严重。}对急性发作时ΔHBV DNA/月≥1 log ₁₀ IU/mL，尤其是早期非 TDF 发作≥2.5 log ₁₀ IU/mL的患者进行更严格的监测，对于及时再治疗以防止失代偿非常重要。