Michael Turgeon presents 20-institution study at ASA Annual Meeting

April 2021

Michael Turgeon and Shishir Maithel

Michael Turgeon, Shishir K. Maithel

Michael Turgeon, MD, general surgery resident and Abraham J. & Phyllis Katz Foundation surgical oncology research fellow, under the mentorship of Shishir K. Maithel, MD, presented his and Dr. Maithel's study "Optimal timing of administration of direct acting antivirals for patients with hepatitis C-associated hepatocellular carcinoma undergoing liver transplantation" at the 141st Annual Meeting of the prestigious American Surgical Association, April 15-16, 2021. The complete manuscript will be published in Annals of Surgery.

Dr. Turgeon was first author and Dr. Maithel senior author of this multi-institutional study, which involved 20 of the highest volume liver transplant centers in the United States. Shimul Shah, MD, MHCM, from the University of Cincinnati College of Medicine, and William Chapman, MD, from Washington University School of Medicine in St. Louis, served as co-mentors.

Given significant practice pattern variability and controversial literature linking direct-acting antiviral medications (DAAs) with an increased risk for hepatocellular carcinoma (HCC), the investigators sought to determine the most effective time to administer DAAs to achieve sustained virologic response (SVR) or hepatitis C (HCV) cure, as well as improved oncologic outcomes for patients with HCV-associated HCC undergoing LT.

Drs. Turgeon and Maithel determined that the scheduling of DAA therapy delivery was indeed important for these patients. Specifically, they observed that the ideal window to offer DAA therapy appeared to be in the early post-operative period rather than before liver transplantation (LT), due to improved rates of SVR and HCC recurrence-free survival.

The investigators also suggest that administration of DAAs more than three months after LT should be avoided because the exaggerated regulatory T cell impairment created by the DAAs could combine with the post-LT induction of immunosuppression and prolonged exposure to HCV to create an increased risk of HCC recurrence. Additionally, recent data has described decreased cytotoxic function of natural killer cells and increased frequencies of myeloid-derived suppressor cells after DAA therapy, which could contribute to an immunologic milieu where the hazard of HCC recurrence would be heightened.

These findings have generated significant interest among liver transplant surgeons, surgical oncologists, infectious disease researchers, and immunologists. To validate their observations further, Drs. Turgeon and Maithel have developed a clinical trial concept and are planning correlative experiments to better understand the immunologic mechanisms responsible for these processes.