The long-term impact of sustained virological response (SVR) after direct-acting antivirals (DAAs) on the hypercoagulability associated with HCV cirrhosis is unknown. We longitudinally evaluated the effect of DAAs treatment on cirrhotic coagulopathy. METHODS: Pro- and anticoagulant factors levels and thrombin generation were assessed in patients with HCV-related cirrhosis at baseline, end of therapy (EOT), at 12, 24 and 48 weeks (W) after EOT. RESULTS: Fifty-eight patients were enrolled (86% Child's A). SVR was 100%. Median factor VIII activity significantly decreased at EOT, 12W and 24W compared to baseline, whereas protein C significantly increased at 24W and 48W. Cirrhotic patients showed a slight but sustained increase of endogenous thrombin potential (ETP) with a statistically significant difference at EOT, 12W, 24W and 48W compared to baseline. Conversely, thrombomodulin-modified ETP was elevated before treatment and decreased over time to normal levels at 24W and 48W. The ETP ratio decreased slowly at EOT and 12W, and was significantly decreased at 24W and 48W compared to baseline (p<0.001 for both comparisons), being not statistically different from ETP ratio measured in healthy controls. Child's B patients showed a significantly higher ETP ratio compared to Child's A at baseline and did not show any significant improvement in ETP ratio through 12W. Two Child's B patients developed PVT with an incidence rate of 1.1% p-yrs (95%CI, 0.18 to 3.58). CONCLUSIONS: DAAs therapy in HCV-related cirrhotic patients is associated with significant changes in thrombin generation suggesting a reversal of hypercoagulability particularly in Child's A patients. This article is protected by copyright. All rights reserved.

Reversal of hypercoagulability in patients with HCV-related cirrhosis after treatment with direct acting antivirals

Russo, Francesco Paolo
Conceptualization
;
Zanetto, Alberto
Writing – Original Draft Preparation
;
Campello, Elena
Writing – Original Draft Preparation
;
Bulato, Cristiana
Membro del Collaboration Group
;
Shalaby, Sarah
Membro del Collaboration Group
;
Spiezia, Luca;Gavasso, Sabrina;Franceschet, Enrica
Membro del Collaboration Group
;
Radu, Claudia
Membro del Collaboration Group
;
Burra, Patrizia
Supervision
;
Simioni, Paolo
Writing – Review & Editing
2018

Abstract

The long-term impact of sustained virological response (SVR) after direct-acting antivirals (DAAs) on the hypercoagulability associated with HCV cirrhosis is unknown. We longitudinally evaluated the effect of DAAs treatment on cirrhotic coagulopathy. METHODS: Pro- and anticoagulant factors levels and thrombin generation were assessed in patients with HCV-related cirrhosis at baseline, end of therapy (EOT), at 12, 24 and 48 weeks (W) after EOT. RESULTS: Fifty-eight patients were enrolled (86% Child's A). SVR was 100%. Median factor VIII activity significantly decreased at EOT, 12W and 24W compared to baseline, whereas protein C significantly increased at 24W and 48W. Cirrhotic patients showed a slight but sustained increase of endogenous thrombin potential (ETP) with a statistically significant difference at EOT, 12W, 24W and 48W compared to baseline. Conversely, thrombomodulin-modified ETP was elevated before treatment and decreased over time to normal levels at 24W and 48W. The ETP ratio decreased slowly at EOT and 12W, and was significantly decreased at 24W and 48W compared to baseline (p<0.001 for both comparisons), being not statistically different from ETP ratio measured in healthy controls. Child's B patients showed a significantly higher ETP ratio compared to Child's A at baseline and did not show any significant improvement in ETP ratio through 12W. Two Child's B patients developed PVT with an incidence rate of 1.1% p-yrs (95%CI, 0.18 to 3.58). CONCLUSIONS: DAAs therapy in HCV-related cirrhotic patients is associated with significant changes in thrombin generation suggesting a reversal of hypercoagulability particularly in Child's A patients. This article is protected by copyright. All rights reserved.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/3276664
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