在我们的系列中，我们无法确定任何实现 HDV-RNA 抑制的预测因子。尽管在所有患者中引入替诺福韦后 HBV-DNA 很快变为阴性，但清除 HDV 的 10 名个体达到 HDV-RNA 阴性的中位时间为 54 个月。这一观察结果表明，替诺福韦对 delta 肝炎的任何益处只有在延长时间后才会显现。
长期替诺福韦治疗对 HIV 感染患者的丁型肝炎的疗效
AIDS 2014 Vincent Sorianoa,b, Eugenia Vispoa, Rocı ́o Sierra-Enguitaa,Carmen de Mendozac, Jose ́ V. Ferna ́ndez-Monteroa,Pablo Labargaa 和 Pablo Barreiroa,b作者: StephenW 时间: 2022-6-8 17:57
NATAP: TDF Efficacy on HDV
In summary, thanks to the unique opportunity represented by a population of HIV patients with delta hepatitis, we investigated the long-term effect of tenofovir, which exhibits dual antiviral effect against both HIV and HBV, and was marketed as an antiretroviral agent 10 years ago. Serum HDV-RNA steadily declined in all patients receiving tenofovir and became undetectable in more than a half of them by 5 years. This virological outcome resulted in significant improvements in hepatic fibrosis as measured by transient elastography, with regression of cirrhosis in five out of nine patients. In our knowledge, this study is the first to provide robust evidence in favour of a clinical benefit of oral antivirals on chronic hepatitis delta. In the absence of current, more well tolerated medications, we propose that tenofovir should be considered as a therapeutic option for HDV infection, acknowledging its benefit would mainly be recognized after prolonged exposure and perhaps not in all patients.
In our study, we report outcomes for viral markers and histological estimates in a relatively large series of chronic hepatitis delta patients treated with tenofovir and followed for a median of nearly 5 years. Complete HBV suppression was achieved in all patients along with significant reductions in HDV replication (with clearance of HDV-RNA in more than a half) along with improvements in liver fibrosis (with regression of cirrhosis in five out of 10). In our knowledge, this is the first study that demonstrates unquestionably a clinical benefit of oral antivirals on chronic hepatitis delta. On the basis of these data, we propose that tenofovir should be considered as a therapeutic option for HDV infection, being aware that its benefit would mainly be recognized in the long term and perhaps not in all patients.
Our results suggest that the benefit of tenofovir on delta hepatitis is most likely the result of an indirect effect that follows the potent antiviral activity of the drug on HBV. Reduction and/or suppression of HDV-RNA occurred over months and followed complete HBV-DNA suppression in all patients. However, concentrations of serum HBsAg did not follow the same trend and remained relatively stable during the whole length of the study. Similar unaffected kinetics for HBsAg in patients treated with tenofovir have been reported by others [34–39], which argues against a benefit of tenofovir on delta hepatitis throughout reducing the production of the HBV envelope protein. However, we did not check whether a dysbalance in the release of distinct HBsAg fractions under prolonged tenofovir therapy had occurred in our patients. Hypothetically, a reduction in the production of the large HBsAg isoform on long-term tenofovir treatment could impair HDV infectivity of new hepatocytes and in this way ultimately result in HDV-RNA suppression [40].
It is noteworthy that the improvement in liver fibrosis was significantly linked to the achievement of complete suppression of serum HDV-RNA. Although almost all our patients with delta hepatitis experienced declines in serum HDV-RNA on long-term tenofovir, liver fibrosis did not improve in those who did not completely suppress HDV-RNA, suggesting that hepatic damage in delta patients is mainly driven by HDV replication rather than by HBV infection.
We could not identify any predictor of the achievement of HDV-RNA suppression in our series. Whereas HBV-DNA became negative soon after introducing tenofovir in all patients, the median time to reach negative HDV-RNA in the 10 individuals who cleared HDV was 54 months. This observation suggests that any benefit of tenofovir on delta hepatitis would be manifest only after extended periods.
Efficacy of prolonged tenofovir therapy on hepatitis delta in HIV-infected patients
AIDS 2014 Vincent Sorianoa,b, Eugenia Vispoa, Rocı ́o Sierra-Enguitaa,Carmen de Mendozac, Jose ́ V. Ferna ́ndez-Monteroa,Pablo Labargaa and Pablo Barreiroa,b