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

Abstract

BACKGROUND & AIMS:

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 factor 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, 12 weeks and 24 weeks compared with baseline, whereas protein C significantly increased at 24 weeks and 48 weeks. Cirrhotic patients showed a slight but sustained increase in endogenous thrombin potential (ETP) with a statistically significant difference at EOT, 12 weeks, 24 weeks and 48 weeks compared with baseline. Conversely, thrombomodulin-modified ETP was elevated before treatment and decreased over time to normal levels at 24 weeks and 48 weeks. The ETP ratio decreased slowly at EOT and 12 weeks, and was significantly decreased at 24 weeks and 48 weeks compared with baseline (P < .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 12 weeks. 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.

• Authors: Francesco Paolo Russo, Alberto Zanetto, Elena Campello, Cristiana Bulato, Sarah Shalaby, Luca Spiezia, Sabrina Gavasso, Enrica Franceschet, Claudia Radu, Marco Senzolo, Patrizia Burra, Ton Lisman, Paolo Simioni
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 38 Issue 12 Pg. 2210-2218 (12 2018) ISSN: 1478-3231 [Electronic] United States
• PMID: 29738632 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Anticoagulants
• Antiviral Agents
• Protein C
• Thrombomodulin
• Thrombin

Topics

• Adult
• Aged
• Anticoagulants (therapeutic use)
• Antiviral Agents (therapeutic use)
• Blood Coagulation
• Blood Coagulation Tests
• Female
• Hepatitis C (complications, drug therapy)
• Humans
• Liver Cirrhosis (blood, drug therapy)
• Longitudinal Studies
• Male
• Middle Aged
• Protein C (metabolism)
• Sustained Virologic Response
• Thrombin (analysis)
• Thrombomodulin (blood)
• Thrombophilia (diagnosis, therapy)