The Influence And Significance Of Propranolol On Portal Venous Hemodynamics In Liver Cirrhosis Patients With Esophageal Gastric Varices

The influence and significance of propranolol on portal venous hemodynamics in liver cirrhosis patients with esophageal gastric varicesBackground and Aims:Esophageal gastric varices(EGV)is a common complication of liver cirrhosis patients with portal hypertension.Non-selective beta blockers(NSBBs)such as propranolol,blocking adrenaline receptor betal to slow the heart rate,decrease cardiac output and blocking beta2 adrenergic receptors to induce splanchnic vasoconstriction,reduce portal vein flow,thus decrease portal vein pressure.There are many researchs on propranolol prevention esophageal gastric variceal bleeding(EGVB)in Europe and in the United States,but there is rare research data in China,leading to the low utilization rate of propranolol in our country.Many patients use propranolol without normative dosage and method,which affect the effects of propranolol treatment,make the doctor and the patient lack confidence in propranolol.Therefore,it is urgently needed to carry out research among our national population on propranolol preventing EGVB in cirrhosis.This study investigate the hemodynamic response to the short-term administration of oral propranolol and further explore the Clinical significance.of this response for EGVB in cirrhosis patients with esophageal gastric varices.Methods:Collect and analyze the clinical data of a prospective cohort of 45 consecutive liver cirrhosis patients with EGV from February 2013 and October 2015 in department of Gastroenterology,Drum Tower Hospital,Medical School of Nanjing University.Screening patients according to inclusion and exclusion criteria,patients should undergo hepatic venous pressure gradient(HVPG)measurement before and after 7-day oral propranolol administration.HVPG is equal to the wedged hepatic venous pressure(WHVP)minus the free hepatic vein pressure(FHVP).The hemodynamic response was defined as HVPG decrease by at least 20%or absolute value<12 mmHg.The responders continued taking the same dose of propranolol after discharge to prevent bleeding episodes.Non-responders with previous variceal bleeding,standardization endoscopic treatment is recommended,and non-responders without previous variceal bleeding,taking regular follow-up is necessary.We followed up all the eligible patients who successfully completed twice HVPG measurement.The primary endpoint of this study was clinically significant variceal bleeding,the secondary endpoint was death.Statistical analysis of clinical datawere performed with SPSS.Results:Among the total 34 patients included in the final analysis,15 patients were responders,the total respond rate was 44.1%(15/34).There was no obvious difference,such as age,sex,etiology and liver function between responders and non-responders.The average follow-up time was 22.0±11.3months,range of 1.8-41.6months.After short-term oral propranolol therapy,overall HVPG and WHVP were significantly lower than the baseline values,but overall FHVP increased significantly after taking the medicine.The HVPG decreased significantly from 18.2±4.9 mmHg to 14.9±4.9 mmHg(t=4.84,P<0.001).Meanwhile,mean arterial pressure(MAP)and resting heart rate(HR)were signifieantly lower than the baseline values.Secondary HVPG values of the responders were significantly lower than those of thenon-responders(t=-4.829,P<0.001),and the decreases in HVPG amplitude and percentage of the responders were significantly higher than non-responders.Among the 34 liver cirrhosis patients with EGV,12 patients had a history of variceal bleeding,other 22 patients without previous variceal bleeding prevent EGVB for the primary prophylaxis.The response rates to short-term oral propranolol were 45.5%and 41.7%,respectively in patientswith primary and secondary prevention of EGVB(x2=0.045,P=0.045).During the follow-up,a total of 9 patients experienced EGVB for the first-time or again.The total cumulative probability of remaining free of variceal bleeding was significantly higher in the responders than in the non-responders(x2=6.069,P=0.014).In univariate analysis,previous variceal bleeding,hemodynamic response,the secondary HVPG and the percentage reduction in HVPG were significantly associated with EGVB.Multivariate Cox regression analysis showed that only previous variceal bleeding was an independent risk factor that predicted EGVB(OR 6.807,95%Cl 1.551-29.868,P=0.011).Conclusion:Liver cirrhosis patients with EGV have a good hemodynamic response to short-term application of propranolol with hemodynamic response rate of 44.1%.Responders with long-term use of propranolol have significantly lower risk of EGVB than non-responders.Patients have a higher risk of variceal rebleeding with a history of EGVB.