Inglot Malgorzata, Pawlowski Tomasz, Szymczak Aleksandra, Malyszczak Krzysztof, Zalewska Malgorzata, Radkowski Marek
Department of Infectious Diseases, Wrocław Medical University, 51-149 Wrocław, Poland.
Postepy Hig Med Dosw (Online). 2013 Mar 11;67:186-91. doi: 10.5604/17322693.1038785.
Hepatitis C virus (HCV) is a primarily hepatotropic virus, but hepatocytes are not the only localization of its replication. It is still unclear if extrahepatic HCV replication, measured as the detection of HCV RNA negative strand in peripheral blood mononuclear cells (PBMCs) before initiation of treatment, has an influence on therapy response. Detection of HCV RNA in extrahepatic sites for assessment of therapy efficacy is not routinely used in clinical practice. The aim of the study was to evaluate whether the replication of HCV in PBMCs affects the rate of sustained virological response (SVR).
The study group comprised 55 patients with chronic hepatitis C, originally treatment naive. They were treated with pegylated interferon (PEG-IFN) alpha 2a and ribavirin, with the standard dosing schedule. Parallel serum samples for HCV RNA and PBMC samples for HCV RNA negative strand were obtained at baseline, at the end of treatment and 24 weeks after finishing therapy.
Undetectable HCV RNA in serum at the end of therapy was found in 48 patients (87.3%), while 33 patients (60.0%) achieved sustained virological response (SVR) (51% for HCV genotype 1 and 78% for genotype 3, respectively). Fifteen individuals (31.3%) were relapsers. Factors associated with significantly higher rate of SVR were young age, mild or no fibrosis and infection with HCV genotype 3. HCV RNA negative strand in PBMCs before treatment was found in 21.8% (12 out of 55 patients). HCV RNA negative strand was detected at baseline more frequently in patients who later achieved SVR. Relapse appeared significantly more often in patients with negative strand at the end of therapy: in 2 out of 15 individuals compared to 0 out of 33 patients (p=0.03).
Presence of negative HCV RNA strand in PBMCs before treatment may be suggested as a potential marker of good treatment response. Detection of negative strand at the end of therapy is a predictor of relapse.
丙型肝炎病毒（HCV）主要是嗜肝病毒，但其复制并非仅局限于肝细胞。治疗开始前在外周血单个核细胞（PBMC）中检测到HCV RNA负链作为肝外HCV复制的指标，其是否会影响治疗反应仍不清楚。在临床实践中，常规不采用检测肝外部位HCV RNA来评估治疗效果。本研究旨在评估PBMC中HCV复制是否会影响持续病毒学应答（SVR）率。
研究组包括55例初治的慢性丙型肝炎患者。他们接受聚乙二醇化干扰素（PEG-IFN）α2a和利巴韦林治疗，采用标准给药方案。在基线、治疗结束时和治疗结束后24周获取平行的血清样本检测HCV RNA以及PBMC样本检测HCV RNA负链。
48例患者（87.3%）治疗结束时血清中HCV RNA检测不到，33例患者（60.0%）实现了持续病毒学应答（SVR）（HCV基因1型为51%，基因3型为78%）。15例个体（31.3%）复发。与SVR率显著更高相关的因素为年龄小、轻度或无纤维化以及感染HCV基因3型。55例患者中有21.8%（12例）在治疗前PBMC中检测到HCV RNA负链。在后来实现SVR的患者中，基线时更频繁地检测到HCV RNA负链。治疗结束时负链患者的复发明显更常见：15例个体中有2例，而33例患者中无复发（p=0.03）。
治疗前PBMC中存在HCV RNA负链可能提示为良好治疗反应的潜在标志物。治疗结束时检测到负链是复发的预测指标。
