All three patients (two viral and one alcoholic cirrhosis, who had nadolol stopped for impotence) remained abstinent during all follow-ups (range, 50-80 months), and none of them rebled. On the other hand, the two patients with dose reduction and loss of hemodynamic response rebled (at 13 and 17 months, respectively). Both patients in this

subgroup had mixed viral and alcohol cirrhosis and had resumed alcohol drinking prior to the rebleeding episode. Drug therapy in the remaining 43 patients was Tamoxifen datasheet well tolerated, and all of them were kept during all follow-up on the same maximal tolerated doses they had at the moment of the second HVPG. To evaluate whether the differences between alcohol abstinents and nonabstinents in long-term response and outcomes may have been related to baseline differences or beta-blocker doses received compliance, a comparison of the most relevant among these parameters was performed (Table 4). Both subgroups were comparable. Cox multivariate analysis identified Cilomilast order loss of hemodynamic response (HR, 7.5; 95% CI, 2.1-27.0; P = 0.002) and history of previous variceal bleeding

(HR, 8.6; 95% CI, 2.1-34.5; P = 0.002) as risk factors for rebleeding, and viral etiology (HR, 4.1; 95% CI, 1.0-18.6; P = 0.05) and Child-Pugh score at 1 year (HR, 1.5; 95% CI, 1.1-2.1; P = 0.015) as main determinants of death/LT. It is currently accepted in clinical guidelines1, 2 that, in an HVPG-guided prophylactic strategy after a variceal hemorrhage, those patients meeting the accepted criteria

of hemodynamic response are reasonably MCE protected from rebleeding under drug therapy alone. This view is supported by longitudinal and randomized trials in which the responder status is based on HVPG measurements taken shortly (from 2 weeks to 3 months) after the index hemorrhage, with no subsequent reassessments during the usual 2-year follow up of these studies (range, 8-28 months).5, 6 Nevertheless, although it is assumed that these patients should be kept indefinitely on drug therapy only, there is no evidence that the initial hemodynamic response is maintained after this 2-year period. In this longitudinal observational study, we followed up for a median of 4 years a large cohort of hemodynamic responders treated with beta-blockers and nitrates after a variceal bleeding, and found that this response was lost in the long term in one out of three patients, an observation that was associated with a clear negative impact on their outcomes. This is the only available report in which sequential protocol HVPG measurements were performed in responders after a variceal bleeding to check their hemodynamic status. The previous study by Merkel et al.10 shared a similar approach and reported analogous results, but it was performed in patients with no previous history of bleeding, a setting with clearly lower baseline risk of progression of portal hypertension and incidence of related complications.