PB0774 - The role of platelets in chemotherapy-associated steatohepatitis

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Co-Author(s)

PS

Patrizia Spitzenstätter

Master student
University of Graz
Graz, Steiermark, Austria
JS

Julia Sturm

Master student
University of Graz
Graz, Steiermark, Austria
MD

Martina Derler, MSc

PhD Student
University of Graz
Graz, Steiermark, Austria
DP

David Pereyra

Medical doctor
Division of Visceral Surgery, Medical University of Vienna
Vienna, Wien, Austria
PS

Patrick Starlinger

Professor
Medical University Vienna
Vienna, Wien, Austria
Alice Assinger, PhD

Associate professor
Medical University of Vienna
Vienna, Wien, Austria

Presenting Author(s)

Marion Mussbacher, PhD

Ass.-Prof
University of Graz
Graz, Steiermark, Austria

Background: The use of anti-tumoral drugs such as irinotecan or 5-fluorouracil is linked to causing chemotherapy-associated steatohepatitis (CASH) during neoadjuvant chemotherapy for colorectal carcinoma. CASH is characterized by inflammatory and metabolic adaptations of the liver restricting effective recovery. Preliminary data indicate that antiplatelet medication such as acetylsalicylic acid or ticagrelor might reduce CASH severity and point to a role for platelets in the development of CASH.

Aims: The aim of this project is to investigate the role of platelet in the development of CASH and associated inflammatory processes.

Methods: Mice were treated with the anti-tumoral drug irinotecan in the absence and presence of antiplatelet medication. Plasma and liver samples were analyzed for platelet activation and lipid accumulation, respectively. Moreover, an in vitro CASH cell culture model was established using the hepatocyte cell line AML-12 and the anti-tumoral drugs irinotecan and 5-fluorouracil, which were both coincubated with platelet lysates.

Results: In vivo experiments showed significantly elevated plasma levels of the platelet degranulation marker platelet factor 4 as well as increased hepatic apoptosis and inflammation in platelet-inhibited, irinotecan-treated mice. In vitro co-incubation of AML12 cells with platelets reduced the degree of lipid accumulation in irinotecan-treated cells.

Conclusion(s): Platelets become activated during the development of CASH and potentially contribute to disease development in a dual manner.