最近的临床研究表明，在仅接受直接作用抗病毒药物（DAAs）治疗的丙型肝炎病毒相关的温和淋巴增殖性疾病（LPD）患者中，淋巴瘤反应取得了显著成效。然而，LPD对DAAs的分子机制仍知之甚少。作者在本文中提供了关于这个问题的新的分子见解，报告了在大多数情况下B细胞克隆的内部变异和持续存在，尽管病毒已消除并且有益的临床结果。这些引人注目的数据表明，对这些患者来说，分子反应的获得可能不是“功能性治愈”所必需的。进一步的全面免疫遗传学和突变研究对于解析这一生物谜题，最终在这一领域改进治疗策略都至关重要。对以下论文的评论：Mazzaro等人。在丙型肝炎病毒相关的淋巴增殖性疾病患者中，单克隆B细胞扩展和内部克隆多样化尽管病毒已消除仍持续存在。《英国血液学杂志》，2023年（提前在线访问）。doi：10.1111/bjh.19002。© 2023年英国血液学会和John Wiley & Sons Ltd.

Recent clinical studies demonstrated the achievement of lymphoma responses in patients with Hepatitis C virus-associated indolent lymphoproliferative disorders (LPD) receiving direct-acting antivirals (DAAs) as their sole treatment. However, the molecular mechanisms underlying LPD responses to DAAs are still poorly understood. In their paper the authors provide new molecular insights on this issue, reporting intraclonal diversification and persistence of B-cell clones in most cases, despite viral eradication and beneficial clinical outcome. These provocative data suggest that the achievement of molecular response is probably not required for a 'functional cure' of these patients. Further comprehensive immunogenetic and mutational studies would be fundamental to dissect this biological puzzle and, ultimately, to refine improved treatment strategies in this setting. Commentary on: Mazzaro et al. Persistence of monoclonal B-cell expansion and intraclonal diversification despite virus eradication in patients affected by hepatitis C virus-associated lymphoproliferative disorders. Br J Haematol 2023 (Online ahead of print). doi: 10.1111/bjh.19002.© 2023 British Society for Haematology and John Wiley & Sons Ltd.