Non-invasive response prediction in prophylactic carvedilol therapy for cirrhotic patients with esophageal varices

Abstract

Background & aims: Non-selective beta-blockers (NSBBs) are the mainstay of primary prophylaxis of esophageal variceal bleeding in patients with liver cirrhosis. We investigated whether non-invasive markers of portal hypertension correlate with hemodynamic responses to NSBBs in cirrhotic patients with esophageal varices.

Methods: In this prospective cohort study, 106 cirrhotic patients with high-risk esophageal varices in the derivation cohort received carvedilol prophylaxis, and completed paired measurements of hepatic venous pressure gradient, liver stiffness (LS), and spleen stiffness (SS) at the beginning and end of dose titration. LS and SS were measured using acoustic radiation force impulse imaging. A prediction model for hemodynamic response was derived, and subject to an external validation in the validation cohort (63 patients).

Results: Hemodynamic response occurred in 59 patients (55.7%) in the derivation cohort, and in 33 patients (52.4%) in the validation cohort, respectively. Multivariate logistic regression analysis identified that ΔSS was the only significant predictor of hemodynamic response (odds ratio 0.039; 95% confidence interval 0.008-0.135; p <0.0001). The response prediction model (Model_ΔSS = 0.0490-2.8345 × ΔSS; score = (exp[Model_ΔSS])/(1 + exp[Model_ΔSS]) showed good predictive performance (area under the receiver-operating characteristic curve [AUC] = 0.803) using 0.530 as the threshold value. The predictive performance of the Model_ΔSS in the validation set improved using the same threshold value (AUC = 0.848).

Conclusion: A new model based on dynamic changes in SS exhibited good performance in predicting hemodynamic response to NSBB prophylaxis in patients with high-risk esophageal varices.

Lay summary: Non-selective beta-blockers are the mainstay of primary prophylaxis to prevent variceal bleeding in patients with cirrhosis and high-risk esophageal varices. This prospective study showed that a prediction model based on changes in spleen stiffness before vs. after dose titration might be a non-invasive marker for response to prophylactic non-selective beta-blocker (carvedilol) therapy in patients with cirrhosis and high-risk esophageal varices. ClinicalTrials.gov Identifier: NCT01943318.

Keywords: Beta-blocker; Elastography; Hemodynamic response; Portal hypertension.