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Persistence of Hepatitis C Virus during and after Otherwise Clinically Successful Treatment of Chronic Hepatitis C with Standard Pegylated Interferon α-2b and Ribavirin Therapy

机译:标准聚乙二醇化干扰素α-2b和利巴韦林治疗在慢性丙型肝炎的临床成功治疗期间及之后持续存在丙型肝炎病毒

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摘要

Resolution of chronic hepatitis C is considered when serum HCV RNA becomes repeatedly undetectable and liver enzymes normalize. However, long-term persistence of HCV following therapy with pegylated interferon-α/ribavirin (PegIFN/R) was reported when more sensitive assays and testing of serial plasma, lymphoid cells (PBMC) and/or liver biopsies was applied. Our aim was to reassess plasma and PBMCs collected during and after standard PegIFN/R therapy from individuals who became HCV RNA nonreactive by clinical testing. Of particular interest was to determine if HCV genome and its replication remain detectable during ongoing treatment with PegIFN/R when evaluated by more sensitive detection approaches. Plasma acquired before (n = 11), during (n = 25) and up to 12–88 weeks post-treatment (n = 20) from 9 patients and PBMC (n = 23) from 3 of them were reanalyzed for HCV RNA with sensitivity <2 IU/mL. Clone sequencing of the HCV 5′-untranslated region from plasma and PBMCs was done in 2 patients. HCV RNA was detected in 17/25 (68%) plasma and 8/10 (80%) PBMC samples collected from 8 of 9 patients during therapy, although only 5.4% plasma samples were positive by clinical assays. Among post-treatment HCV RNA-negative plasma samples, 9 of 20 (45.3%) were HCV reactive for up to 59 weeks post-treatment. Molecularly evident replication was found in 6/12 (50%) among PBMC reactive for virus RNA positive strand collected during or after treatment. Pre-treatment point mutations persisted in plasma and/or PBMC throughout therapy and follow-up. Therefore, HCV is not completely cleared during ongoing administration of PegIFN/R otherwise capable of ceasing progression of CHC and virus commonly persists at levels not detectable by the current clinical testing. The findings suggest the need for continued evaluation even after patients achieve undetectable HCV RNA post-treatment.
机译:当血清HCV RNA反复检测不到且肝酶正常化时,可考虑解决慢性丙型肝炎。然而,据报道,当采用更敏感的测定和系列血浆,淋巴样细胞(PBMC)和/或肝活检的方法进行更灵敏的检测和试验后,使用聚乙二醇化干扰素-α/利巴韦林(PegIFN / R)治疗后,HCV会长期持续存在。我们的目标是重新评估在标准PegIFN / R治疗期间和之后从临床测试中变为HCV RNA无反应的个体的血浆和PBMC。当通过更敏感的检测方法进行评估时,确定正在进行的PegIFN / R治疗过程中HCV基因组及其复制是否仍可检测到,是引起人们特别关注的问题。对9例患者在治疗前(n = 11),治疗期间(n = 25)和治疗后12-88周(n = 20)血浆和其中3例的PBMC(n = 23)进行了HCV RNA重新分析灵敏度<2 IU / mL。从两名患者中进行了血浆和PBMC HCV 5'非翻译区的克隆测序。在治疗过程中,从9名患者中的8名患者中采集的17/25(68%)血浆和8/10(80%)PBMC样品中检测到HCV RNA,尽管根据临床分析,只有5.4%血浆样品为阳性。在治疗后HCV RNA阴性血浆样本中,有20个中的9个(45.3%)在治疗后长达59周的时间内对HCV有反应。在治疗过程中或治疗后收集到的对病毒RNA阳性链有反应性的PBMC中,有6/12(50%)的分子明显复制。在整个治疗和随访过程中,血浆和/或PBMC中仍存在治疗前点突变。因此,在持续施用PegIFN / R期间,HCV不能完全清除,否则能够终止CHC和病毒进程的病毒通常会以当前临床测试无法检测到的水平持续存在。研究结果表明,即使患者在治疗后达到无法检测到的HCV RNA,也需要继续进行评估。

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