Changes in Coagulation and Fibrinolytic Factors in Patients With Cirrhotic Refractory Ascites Undergoing Cell-free and Concentrated Ascites Reinfusion Therapy: A Retrospective Observational Study in Japan

Abstract

Background/Aim: The management of refractory ascites is critical for the treatment of patients with decompensated cirrhosis. This study aimed to evaluate the feasibility and safety of cell-free and concentrated ascites reinfusion therapy (CART) in patients with cirrhosis and refractory ascites, with a focus on changes in coagulation and fibrinolytic factors in ascitic fluid following CART. Patients and Methods: This was a retrospective cohort study including 23 patients with refractory ascites undergoing CART. Serum endotoxin activity (EA) before and after CART and the levels of coagulation and fibrinolytic factors and proinflammatory cytokines in original and processed ascitic fluid were measured. The Ascites Symptom Inventory-7 (ASI-7) scale was used for subjective symptom assessment before and after CART. Results: Body weight and waist circumference significantly decreased after CART, whereas serum EA did not significantly change after CART. Similar to the previous reports, ascitic fluid concentrations of total protein, albumin, high-density lipoprotein cholesterol, γ-globulin, and immunoglobulin G levels were significantly increased after CART; mild elevations in body temperature and interleukin 6 and tumor necrosis factor-alpha levels in ascitic fluid were also observed. Importantly, the levels of antithrombin-III, factor VII, and X, which are useful for patients with decompensated cirrhosis, were markedly increased in the reinfused fluid during CART. Finally, the total ASI-7 score was significantly lower following CART, compared with the pre-CART score. Conclusion: CART is an effective and safe approach for the treatment of refractory ascites that allows the intravenous reinfusion of coagulation and fibrinolytic factors in the filtered and concentrated ascites.Cirrhosis, which is a terminal-stage liver disease, is associated with serious complications including refractory ascites resulting in decline in quality of life (1). Every year, approximately 10% of patients with cirrhosis develop refractory ascites despite treatment with fluid restriction, conventional diuretics, and the vasopressin-2 antagonist tolvaptan (2). The overall survival probability is very poor in patients with decompensated cirrhosis and refractory ascites, with an approximate rate of 30% at 2 years, and more than 50% of these patients develop hepatorenal syndrome (3, 4). Refectory ascites carry a high symptom burden with associated pain, nausea, need for hospital admission and limitation of function and mobility.According to the Evidence-Based Clinical Practice Guidelines for Liver Cirrhosis 2020, resistance or poor response to diuretics is a clear indication for large-volume paracentesis (LVP) with albumin replacement or cell-free and concentrated ascites reinfusion therapy (CART) in 1226

Management of cirrhotic ascites: Seven‐step treatment protocol based on the Japanese evidence‐based clinical practice guidelines for liver cirrhosis 2020

“…50 Combining CART and LVP may allow for an extension of the interval between paracentesis procedures and improve patient QoL, 50 although further research is required. An in vivo study found an additional benefit of CART: antithrombin 3 and coagulation factor levels are concentrated and returned to the body (Yorioka et al 51 ). Concomitant use of LVP and CART may lead to an improvement of subjective symptoms as well as patient prognosis.…”