Background & Aims

Direct-acting antivirals (DAAs) cure most cases of chronic hepatitis C virus (HCV) infection. However, a small percentage of patients relapse with reappearance of viremia after a full course of therapy. Although most who relapse require retreatment, some patients spontaneously clear HCV without additional therapy. We studied patients who relapsed with detectable HCV RNA after a full course of DAA therapy and then spontaneously cleared the HCV infection without retreatment.

Methods

We performed a case–control study of patients who spontaneously cleared chronic HCV infection following a documented relapse after DAA therapy at the Toronto Centre for Liver Disease, from January 2014 through December 2017. We collected clinical information at baseline, 12 weeks after treatment, and 6 months after relapse and compared data among spontaneous clearers, patients with persistent relapse, and patients who achieved a sustained virologic response to therapy 12 weeks after treatment (SVR12). The strength and breadth of interferon gamma cytokine secretion by HCV-specific T cells from peripheral blood were quantified using the ELISPOT assay.

Results

Of the 1032 individuals with chronic HCV infection who were treated with DAAs, 93 patients had a documented relapse. Of these patients, 12 patients (13%) spontaneously cleared HCV within 6 months after the documented relapse without additional therapy. The spontaneous clearers had low levels of HCV RNA (<4 log IU/mL in 11 of 12) and normal levels of alanine aminotransferase at the time of relapse, much like patients with an SVR12. There was no significant difference between the spontaneous clearance group and the SVR12 group in magnitude and breadth of HCV-specific T cell responses.

Conclusions

In a case–control study of patients who spontaneously cleared chronic HCV infection following a relapse after DAA therapy, we found that it is important to confirm viremia prior to retreatment after the relapse—particularly for individuals with low levels of HCV RNA and normal or near-normal levels of alanine aminotransferase after treatment.

中文翻译：

---

慢性 HCV 感染直接抗病毒治疗后复发后自发清除

背景与目标

直接作用抗病毒药物 (DAA) 可治愈大多数慢性丙型肝炎病毒 (HCV) 感染病例。然而，一小部分患者在整个疗程后复发并再次出现病毒血症。尽管大多数复发者需要再次治疗，但一些患者无需额外治疗即可自发清除 HCV。我们研究了在完整疗程的 DAA 治疗后出现可检测到的 HCV RNA 复发，然后无需再治疗而自发清除 HCV 感染的患者。

方法

我们对 2014 年 1 月至 2017 年 12 月在多伦多肝病中心 DAA 治疗后记录复发后自发清除慢性 HCV 感染的患者进行了病例对照研究。我们收集了基线、治疗后 12 周的临床信息，以及复发后 6 个月，并比较自发清除者、持续复发患者和治疗 12 周后对治疗取得持续病毒学应答的患者的数据（SVR12）。使用 ELISPOT 测定法量化外周血中 HCV 特异性 T 细胞分泌干扰素 γ 细胞因子的强度和广度。

结果

在接受 DAA 治疗的 1032 名慢性 HCV 感染患者中，有 93 名患者出现复发。在这些患者中，12 名患者 (13%) 在记录的复发后 6 个月内自发清除了 HCV，无需额外治疗。自发清除剂在复发时具有低水平的 HCV RNA（12 个中有 11 个 <4 log IU/mL）和正常水平的丙氨酸转氨酶，很像 SVR12 患者。自发清除组和 SVR12 组在 HCV 特异性 T 细胞反应的幅度和广度上没有显着差异。

结论

在 DAA 治疗后复发后自发清除慢性 HCV 感染的患者的病例对照研究中，我们发现在复发后再次治疗前确认病毒血症很重要——特别是对于 HCV RNA 水平低且正常或接近- 治疗后丙氨酸氨基转移酶水平正常。