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Our laboratory uses a combination of clinical data and patient-derived specimens to study how hepatocellular carcinoma (HCC) in the background of cirrhosis influence key immune populations that impact treatment response and outcomes.

Dr. Ari Cohen

Dr. Paul Thevenot

Dr. Kelley Núñez

Hepatocellular carcinoma (HCC) is the most common form of liver cancer and ranks 4th as the leading cause of cancer-related deaths. Most cases of HCC arise in the background of cirrhosis due to chronic viral infection (Hepatitis B/C) and steatosis liver disease caused by chronic alcohol use and/or metabolic disease. If diagnosed at an early-stage, liver transplantation is the best treatment option for cirrhotic patients with HCC, as transplantation removes not only the cancer but also underlying liver disease which led to HCC. For early- to intermediate-stage disease, liver-directed therapies (LDT) can provide a definitive treatment pathway to address tumor burden or delay palliative care. LDT modalities include microwave ablation, transarterial chemoembolization, and transarterial radioembolization.

Current research in our laboratory is focused on the following projects and are based around an 8-yr ongoing prospective study of early-stage HCC patients being treated with liver-directed therapies:

The role of cirrhosis-associated immune dysfunction in early-stage hepatocellular carcinoma (HCC) and patient outcomes following liver-directed therapy.

Our work has focused on role and health of lymphocytes (T cells) in patients diagnosed with HCC with underlying liver dysfunction. Our work has shown low T cell counts associated with poor response to liver-directed therapies. Using flow cytometry and T cell receptor sequencing, we are studying how T cells phenotypes and T cell repertoires are altered following liver-directed therapy. Our goal is to identify strategies to increase the success of liver-directed therapy in HCC patients.

Implementation of the AFP, AFP-L3, and DCP HCC biomarker panel as a prognostic index of liver-directed therapy and immunotherapy response and patient outcomes.

In the first part of this study, we prospectively track biomarker values HCC diagnosis, through liver transplantation and transplant follow-up. In the second part of this study, we monitor the biomarker panel in patients with advanced HCC who receive immunotherapy alone or in combination with transarterial radioembolization. The goal of these studies is to determine the utility of the biomarker panel as an index of tumor biological aggressiveness and potential resistance to therapy. Further, we are tracking biomarker expression after transplantation to determine if the panel can be utilized in HCC surveillance as an early indicator of tumor recurrence.

Programmed death-1 immunophenotyping as a strategy for optimal patient selection in combined immuno-liver directed therapy.

While immunotherapy targeting programmed death-1 (PD-1) in HCC had low response rates (<20%), combining immunotherapy with liver-directed therapies are gaining momentum. Our work has identified a patient population with elevated PD-1 expression that may benefit from anti-PD-1 immunotherapy. In this study, we monitor PD-1 expression at HCC diagnosis and through treatment cycles with liver-directed therapy to gain insight into how PD-1 expression changes following treatment. Our goal is to identify patients that would benefit from combinational therapy with anti-PD-1 and liver-directed therapy to improve treatment response rates and outcomes.

Imaging delay following liver-directed therapy increases progression risk in patients with HCC.

In this study, we monitor the impact of imaging delay following liver-directed therapy in patients newly diagnosed with HCC. Routine surveillance or following treatment imaging is critical to minimize HCC progress. Our goal for this study is to identify gaps in healthcare scheduling to decrease imaging delays and improve patient outcomes.

90Y Transarterial Radioembolization Versus Microwave Ablation in Small Hepatocellular Carcinoma With Hypoalbuminemia (REALM).

We are conducting a clinical trial that compares 1-year outcomes in patients with hypoalbuminemia and a new diagnosis of small, early-stage hepatocellular carcinoma (HCC) who are candidates for both 90-Yittrium Therasphere transarterial radioembolization (90Y) and microwave ablation (MWA). The study will determine whether treatment with 90Y lowers the risk of disease progression within the first year after diagnosis. [NCT05953961]