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Reuters Health Information (2014-04-02): Nonalcoholic fatty liver disease linked to procoagulant imbalance


Nonalcoholic fatty liver disease linked to procoagulant imbalance

Last Updated: 2014-04-02 15:48:41 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Patients with nonalcoholic fatty liver disease (NAFLD) have a procoagulant imbalance that worsens as the disease progresses, researchers from Italy report.

"Knowing that NAFLD is associated with an increased risk of cardiovascular disease and liver fibrosis, I thought that plasma hypercoagulability has something to do with NAFLD," Dr. Armando Tripodi from Universita degli Studi di Milano told Reuters Health by email.

He added that the new study, online March 19 in the Journal of Hepatology, is the first to demonstrate such hypercoagulability by means of a global coagulation assay.

Although a link between a hypercoagulable state and the increased cardiovascular risk in NAFLD had been proposed before, a direct link had not been established, perhaps because of the lack of appropriate laboratory tests for exploring coagulation under conditions mimicking those in vivo, the researchers write.

They used two thrombin-generation assays (endogenous thrombin potential (ETP) and Protac-induced coagulation inhibition (PICI)) to investigate the overall coagulant balance in 113 patients with NAFLD.

Dr. Tripodi noted that the assays are still research tools, but could become useful in the future for risk assessment in individual patients.

The researchers also used the ratio of factor VIII to protein C as their traditional index of the procoagulant imbalance (with higher values reflecting an increasing procoagulant imbalance).

They found that the factor VIII-to-protein C ratio was nonsignificantly higher in patients with simple steatosis and significantly higher in patients with nonalcoholic steatohepatitis (NASH) and in patients with metabolic or alcoholic/viral cirrhosis than in controls.

Thrombin generation in the presence/absence of thrombomodulin was significantly higher in all three groups of patients with NAFLD and in patients with alcoholic/viral cirrhosis compared with controls, and there was a progressive increase in the ETP ratio from simple steatosis or NASH to metabolic cirrhosis.

The ETP ratio correlated directly with factor VIII and the factor VIII-to-protein C ratio and inversely with antithrombin and protein C.

PICI median percentage values were nonsignificantly lower in patients with simple steatosis and significantly lower in patients with NASH and in those with metabolic or alcoholic/viral cirrhosis compared with controls. PICI% values correlated directly with antithrombin and protein C and inversely with factor VIII and the factor VIII-protein C ratio; they also correlated significantly and inversely with the ETP ratio.

The procoagulant imbalance was more marked among patients with metabolic syndrome, fibrosis, steatosis, lobar inflammation, and higher NAFLD activity scores (NAS).

"Since activated factor VIII is inhibited in vivo by activated protein C, the above results suggest that in general the procoagulant imbalance observed in NAFLD appears to result from increased factor VIII combined with decreased protein C activity," the researchers say.

"Presently, it is difficult to say what to do after finding hypercoagulability," Dr. Tripodi said. "I guess that patients would benefit from anticoagulation that should decrease the risk of cardiovascular disease and liver fibrosis. Clinical trials are needed, and our work could pave the way for such studies."

"We can start treating appropriately any disease when we understand the mechanisms behind it," he added. "We have just started to learn a bit more about NAFLD, a condition that is highly prevalent in Western countries and will become more and more prevalent if one considers the changing life style."


J Hepatol 2014.

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