Indeed, patients treated with enoxaparin had a significantly lower incidence of PVT.

Beyond this effect, patients receiving enoxaparin also had a significantly lower incidence of liver decompensation (mainly ascites) and of mortality than controls. A drop in circulating biomarkers of intestinal integrity and immune activation in response to bacterial products was also observed in the enoxaparin group in association with Dabrafenib in vitro a reduction in the incidence of bacterial infections. The authors suggested that these changes may be responsible for the observed additional benefits of enoxaparin besides preventing PVT. In any case, as stated by the authors, the study was not designed to clarify the ultimate mechanism of enoxaparin action. It is important to note that the prophylactic doses of enoxaparin used in the study showed a good safety profile, as no differences in bleeding complications were observed between groups, and only one patient needed to stop enoxaparin because of a reversible heparin-induced

thrombocytopenia. Thus, the study by Villa et al. shows that the use of prophylactic doses of enoxaparin in patients with cirrhosis is safe and improves prognosis. So, are we ready to introduce enoxaparin in the treatment of our patients with cirrhosis? Or, are we just facing the first steps of a long road? Before answering this pivotal question we should discuss some points. Absence of a blinded control group and the small sample size of the study are important issues to consider. In addition, a careful review of Torin 1 fig. 1 of the article shows that only 22/34 (65%) of patients in the enoxaparin arm and 17/36 (47%) in the control arm were

at risk of developing PVT at 1 year of treatment, suggesting that there were a significant number of patients who were lost to follow-up without reaching 1 year of treatment. In addition, the investigators do not state whether patients MCE who developed PVT were anticoagulated; therefore, it is not possible to assess whether the significant benefit of treating all patients with enoxaparin remains if the strategy to use anticoagulation only in patients suffering from PVT is applied. All patients included in the study had a Child-Pugh score between 7 and 10 points and we do not know if the potential benefit of enoxaparin may be extrapolated to all patients with cirrhosis. Last, but not least, the study shows that most benefits of treatment are lost early after enoxaparin discontinuation. Thus, efficacy, safety, and tolerability of more long-term regimens deserve further investigation. It is our view that many unanswered questions currently preclude the use of prophylactic enoxaparin in the treatment of patients with cirrhosis without PVT. However, this relevant study opens new therapeutic paths for the management of patients with cirrhosis, even though further evidence is still needed prior to recommending enoxaparin in routine clinical practice. Susana Seijo, M.D.