Immune Reset or Immune Dysfunction? Single-Cell Profiling of Liver Microenvironments After DAA-Driven HCV Clearance

Building on observations from Sasaki et al. (2018) and Muzica et al. (2020) about unexpected HCC recurrence rates after direct-acting antiviral (DAA) therapy, this project proposes using cutting-edge single-cell and spatial transcriptomics to map liver immune cell states before and after SVR (sustained virologic response). Unlike prior studies that focus on bulk immune markers or cytokines, this approach can unravel cell-type-specific changes, immune cell crosstalk, and spatial niches that might drive tumorigenesis. By comparing patients with and without HCC recurrence, this work could reveal whether DAAs cause a “reset” of immune surveillance or leave pockets of immune dysfunction that support tumor growth. This mechanistic insight could drive biomarker discovery and inform new follow-up protocols or adjunctive therapies to prevent malignancy after HCV cure—a major clinical gap highlighted in current literature.

References:

1. Hepatitis C virus-associated hepatocellular carcinoma after sustained virologic response. Reina Sasaki, T. Kanda, N. Kato, O. Yokosuka, M. Moriyama (2018). World Journal of Hepatology.
2. Hepatocellular carcinoma after direct-acting antiviral hepatitis C virus therapy: A debate near the end. C. Muzica, C. Stanciu, L. Huiban, A. Sîngeap, C. Sfarti, S. Zenovia, C. Cojocariu, A. Trifan (2020). World Journal of Gastroenterology.