Liver Unit, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
Aliment Pharmacol Ther. 2021 Aug;54(4):462-469. doi: 10.1111/apt.16485. Epub 2021 Jun 28.
Spontaneous HDV-RNA fluctuations, assessed by nonstandardised in-house assays, have been reported during the course of chronic hepatitis delta (CHD).
To evaluate changes in serum HDV-RNA concentrations in untreated CHD patients and correlate these changes with other HBV markers.
A total of 323 consecutive serum samples from 56 CHD patients (detectable HDV-RNA) followed for >3 years were retested for HDV-RNA levels by a sensitive technique using the first WHO international HDV-RNA standard. Quantitative HBsAg, HBV-DNA, and HBV-RNA were also determined.
Most participants were male, middle-aged, white European, and HBeAg-negative (82%). Almost half had liver cirrhosis and 64% were receiving nucleos(t)ide analogues. At inclusion, median-HDV-RNA was 5.3 (4.2-6.5) log IU/mL, HBsAg 4.0 (3.5-4.3) log IU/mL, and HBV-DNA 1.6 (1.0-2.6) log IU/mL; ALT values were normal in 13 (23%). During a mean follow-up of 5.6 (3-16) years, 14 (25%) showed ≥2log HDV-RNA decline, including 11 (20%) who spontaneously achieved undetectable HDV-RNA. Four patients (7%) lost HBsAg, with undetectable HDV-RNA. The remaining 42 (75%) had persistently detectable HDV-RNA. During follow-up, patients with a ≥2log HDV-RNA decline showed a greater HBsAg drop (-0.7 ± 1.1 vs -0.09 ± 0.9 log IU/mL; P = 0.039) than those with a <2 log HDV-RNA decline. Overall, ALT and HBV-DNA levels decreased over time. There were no differences in clinical outcomes between groups.
One-quarter of untreated CHD patients showed a ≥2log decline in HDV-RNA and 20% reached HDV-RNA undetectability during a mean follow-up of 5.6 years. The decline was associated with ALT decrease. These findings have implications for designing new therapies for CHD.
在慢性丁型肝炎（CHD）的病程中，使用非标准化的内部检测方法已报告了自发的 HDV-RNA 波动。
评估未经治疗的 CHD 患者血清 HDV-RNA 浓度的变化，并将这些变化与其他 HBV 标志物相关联。
对 56 例 CHD 患者（可检测到 HDV-RNA）的 323 份连续血清样本进行了检测，这些患者的随访时间均超过 3 年，使用首次世界卫生组织（WHO）国际 HDV-RNA 标准的敏感技术对 HDV-RNA 水平进行了重新检测。还定量检测了 HBsAg、HBV-DNA 和 HBV-RNA。
大多数参与者为男性，年龄在中年，为白种欧洲人，HBeAg 阴性（82%）。近一半的人患有肝硬化，64%的人正在接受核苷（酸）类似物治疗。纳入时，HDV-RNA 的中位数为 5.3（4.2-6.5）log IU/mL，HBsAg 为 4.0（3.5-4.3）log IU/mL，HBV-DNA 为 1.6（1.0-2.6）log IU/mL；13 名（23%）患者的 ALT 值正常。在平均 5.6（3-16）年的随访期间，14 名（25%）患者的 HDV-RNA 下降了≥2log，其中 11 名（20%）患者自发地达到了不可检测的 HDV-RNA。4 名患者（7%）失去了 HBsAg，同时 HDV-RNA 也不可检测。其余 42 名患者（75%）的 HDV-RNA 仍持续可检测。在随访期间，HDV-RNA 下降≥2log 的患者 HBsAg 下降更明显（-0.7±1.1 与-0.09±0.9 log IU/mL；P=0.039），而 HDV-RNA 下降<2log 的患者 HBsAg 下降不明显。总体而言，ALT 和 HBV-DNA 水平随时间下降。各组间临床结局无差异。
在平均 5.6 年的随访中，25%的未经治疗的 CHD 患者的 HDV-RNA 下降了≥2log，20%的患者的 HDV-RNA 达到了不可检测的水平。这种下降与 ALT 降低有关。这些发现对设计新的 CHD 治疗方法具有重要意义。
