The Clinical Study Of Propranolol To Prevent Bleeding From Esophageal Gastric Varices In Liver Cirrhosis Under The Guidance Of HVPG

PART 1 Influence of CYP2D6 and β2-adrenergic receptor gene polymorphisms on the hemodynamic response to propranolol in Chinese patients with cirrhosisBackground and Aim: Propranolol is widely used to prevent gastroesophageal variceal bleeding;however,some patients could not benefit from propranolol.This study is to evaluate the relationship between CYP2D6 and β2-adrenergic receptor(β2-AR)gene polymorphisms and the hemodynamic response to propranolol in Chinese Han patients.Methods: The clinical data of patients with gastroesophageal varices undergoing Hepatic venous pressure gradient(HVPG)measurement before and 7 days after oral propranolol administration in our department were collected.4 single nucleotide polymorphisms of CYP2D6 and β2-AR genes were detected.The relationship was identified by logistic regression model.Results: 30 patients were involved in the analysis.60 mg propranolol twice each day was well tolerated by all the patients.The initial and secondary average of HVPG was 17.4±5.8 mmHg vs.13.2±4.8 mmHg respectively(t=5.726,P<0.001).21 patients responded to propranolol.The mean reduction value of HVPG was 6.6 ± 3.6 mmHg(range from 3 to 19).Genotype analysis showed: 20 homozygotes for C/C188 and 10 for heterozygous C/T188,8 homozygotes for G/G4268 and 22 heterozygotes for G/C4268,14 homozygotes for Gly16 and 10 heterozygotes and 6 homozygotes for Arg16,27 homozygotes for Gln27 and 3 heterozygotes.The multivariate logistic regression analysis indicated that CYP2D6(188C>T)genotype was an independent predicting factor for HVPG response to propranolol(P=0.033).Conclusions: CYP2D6(188C>T)gene polymorphisms influence the hemodynamic response to propranolol in this population of Chinese Han patients with gastroesophageal varices.However,HVPG response cannot be completely predicted from CYP2D6 and β2-AR gene polymorphisms.PART 2 Dose-dependent effect of propranolol on the hemodynamic response in cirrhotic patients with gastroesophageal varicesBackground and Aim: Propranolol is always titrated to the maximum tolerated dose to prevent gastroesophageal variceal bleeding.However,some patients do not achieve hemodynamic response and experience more intolerance and discontinuation.This study evaluated the dose-dependent effect of propranolol on hemodynamic response and tolerance in cirrhotic patients.Methods: This retrospective study included 95 consecutive patients obtained from our prospective database.After hepatic venous pressure gradient(HVPG)measurement,patients received propranolol 10 mg b.i.d.increased 10 mg daily until to 80 mg/d or 120 mg/d.Secondary HVPG was also measured.For nonresponders at 80 mg/d,propranolol was titrated to 120 mg/d.Results: Fifty-eight patients titrated propranolol to 80mg/d while 37 patients to 120 mg/d.Hemodynamic response was similar between both groups(50% vs.54.1%,P=0.700).Eighteen of the 29 nonresponders at propranolol 80 mg/d received a dose of 120 mg/d.Two patients achieved hemodynamic response but two did not tolerate the dose.Nine patients(15.5%)achieved the target dose of propranolol at 80 mg/d while 16(43.2%)at 120 mg/d achieved this(P=0.003).The difference in patients achieving the target dose between responders and nonresponders was not significant(14 vs.14,P=0.642).Reduction or discontinuation was needed by two patients(6.9%)using 80 mg/d propranolol and six(30%)using 120 mg/d propranolol(P=0.032).Conclusions: There is no dose-dependent effect of 80-120 mg/d of propranolol on the hemodynamic response in cirrhotic patients with gastroesophageal varices.This indicates that low-dose propranolol below the target dose might achieve considerable hemodynamic response and is much safer and well tolerated.