Elena Campello1, Alberto Zanetto2, Claudia M Radu1, Cristiana Bulato1, Addolorata Truma1, Luca Spiezia1, Marco Senzolo3, Guadalupe Garcia-Tsao4, Paolo Simioni5. 1. Thrombotic and Hemorrhagic Diseases Unit, General Internal Medicine, Padova University Hospital, Padova, Italy. 2. Digestive Disease Section, Internal Medicine, Yale School of Medicine, New Haven, CT, USA; VA-Connecticut Healthcare System, West Haven, CT, USA; Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, Padova, Italy. 3. Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, Padova, Italy. 4. Digestive Disease Section, Internal Medicine, Yale School of Medicine, New Haven, CT, USA; VA-Connecticut Healthcare System, West Haven, CT, USA. 5. Thrombotic and Hemorrhagic Diseases Unit, General Internal Medicine, Padova University Hospital, Padova, Italy. Electronic address: paolo.simioni@unipd.it.
Abstract
BACKGROUND: Microvesicles (MVs) play a role in inflammation, coagulation, and vascular homeostasis in liver disease. AIM: To characterize circulating plasma MVs profile in patients with decompensated cirrhosis and acute kidney injury (AKI). METHODS: We measured the levels of total, endothelial, platelet, tissue factor (TF)+, leukocyte and hepatocyte MVs by new generation flow-cytometry in a prospective cohort of patients with decompensated cirrhosis with and without AKI. RESULTS: Eighty patients with decompensated cirrhosis were recruited (40 each with and without AKI). Patients with cirrhosis with AKI had significantly higher calcein+ (total), endothelial, and platelet-MVs. Conversely, TF+, leukocyte, and hepatocyte-MVs were comparable between groups. Resolution of AKI was associated with significantly decreased total and endothelial-MVs that became comparable with those in patients without AKI. Platelet MVs significantly decreased but remained higher compared to patients without AKI. TF+MVs significantly decreased and became lower than patients without AKI. Leukocyte and hepatocyte-MVs remained unchanged. Creatinine (OR 4.3 [95%CI 1.8-10.7]), MELD (OR 1.13 [95%CI 1.02-1.27]), any bleeding (OR 9.07 [95%CI 2.02-40.6]), and hepatocyte-MVs (OR 1.04 [95%CI 1.02-1.07]) were independently associated with 30-day mortality. CONCLUSION: AKI worsened vascular and cellular homeostasis in patients with cirrhosis, particularly by inducing endothelial dysfunction and platelet activation. AKI did not worsen systemic inflammation and hepatocytes activation.
BACKGROUND: Microvesicles (MVs) play a role in inflammation, coagulation, and vascular homeostasis in liver disease. AIM: To characterize circulating plasma MVs profile in patients with decompensated cirrhosis and acute kidney injury (AKI). METHODS: We measured the levels of total, endothelial, platelet, tissue factor (TF)+, leukocyte and hepatocyte MVs by new generation flow-cytometry in a prospective cohort of patients with decompensated cirrhosis with and without AKI. RESULTS: Eighty patients with decompensated cirrhosis were recruited (40 each with and without AKI). Patients with cirrhosis with AKI had significantly higher calcein+ (total), endothelial, and platelet-MVs. Conversely, TF+, leukocyte, and hepatocyte-MVs were comparable between groups. Resolution of AKI was associated with significantly decreased total and endothelial-MVs that became comparable with those in patients without AKI. Platelet MVs significantly decreased but remained higher compared to patients without AKI. TF+MVs significantly decreased and became lower than patients without AKI. Leukocyte and hepatocyte-MVs remained unchanged. Creatinine (OR 4.3 [95%CI 1.8-10.7]), MELD (OR 1.13 [95%CI 1.02-1.27]), any bleeding (OR 9.07 [95%CI 2.02-40.6]), and hepatocyte-MVs (OR 1.04 [95%CI 1.02-1.07]) were independently associated with 30-day mortality. CONCLUSION: AKI worsened vascular and cellular homeostasis in patients with cirrhosis, particularly by inducing endothelial dysfunction and platelet activation. AKI did not worsen systemic inflammation and hepatocytes activation.
Authors: Alberto Zanetto; Elena Campello; Cristiana Bulato; Sabrina Gavasso; Graziella Saggiorato; Sarah Shalaby; Patrizia Burra; Paolo Angeli; Marco Senzolo; Paolo Simioni Journal: JHEP Rep Date: 2022-04-20