The Efficacy And Influencing Factors Of Propranolol And Carvedilol To Reduce Hepatic Venous Pressure Gradient

Background and Objective:Cirrhosis is a serious and irreversible chronic liver lesion, whose main complications are dysfunction and portal hypertension. Portal hypertension often develops with gastroesophageal varices, which may cause bleeding and therefore recognized as a life-threatening complication.Hepatic venous pressure gradient (HVPG) is a gold standard to judge portal hypertension and assess complications of portal hypertension. We define HVPG>10mmHg as Clinical portal hypertension (CSPH). When portal venous pressure gradient increases to 12mmHg, there will be complications of portal hypertension including hydrodynamic vein exposure and varicosity, upper gastrointestinal bleeding caused by stomach esophagus varicosity and burst, portal hypertensive gastropathy, ascites, hepatic encephalopathy, renal dysfunction, and splenomegaly, etc. Studies have shown that when hepatic venous pressure gradient decreases to less than 12mmHg or at least 20% from baseline, the risk of rebleeding and mortality will significantly decrease, which can be called "Response". Clinically, when hepatic venous pressure gradient decreases at least 10% from baseline but doesn’t reach 20%, there is still certain clinical significance in decreasing the frequency of bleeding and mortality rate in patients with gastroesophageal varices, so it is called "Partial Response". If the decline in HVPG doesn’t reach 10%, we call it "No Response".Non-selective beta blockers (NSBBs) are ideal drugs to reduce portal hypertension. Propranolol is one of the most commonly administrated non-selective β-blockers. However, only about 1/3 patients achieve hematologic response after administration. Carvedilol is a novel nonselective beta-blocker, whose acute response has been proved to be better than Propranolol. However, effect of Carvedilol in long-term therapy is uncertain.This study focused on liver cirrhosis patients with esophageal gastric varices, using "Response" and "Partial Response" as evaluation standard to discuss the efficacy and influencing factors for Propranolol and Carvedilol to reduce HVPG.Methods:This study selected 87 cases in which patients were diagnosed with liver cirrhosis in our hospital from October 2010 to January 2015. On one hand, we discussed the efficacy of Propranolol (10mg po tid) and Carvedilol (12.5mg po qd) by analyzing the change of HVPG after administration. On the other hand, the factors for Propranolol and Carvedilol to reduce HVPG were also discussed by comparing relative indexes between "Response" Group and "Paritial Response+ No response" Group, as well as between "Response+Partial Response" Group and "No Response" Group. In addition, side effect and adverse reaction were also evaluated by comparing the indexes before and after administration.Results:Among 87 cases, HVPG of Carvedilol group decreased from 14.45+5.17 mmHg to 11.96+5.51 mmHg (n=56, P<0.001). HVPG of Propranolol group decreased from 15.04±5.94 mmHg to 13.01±6.52 mmHg (n=31, P=0.017). Both Carvedilol and Propranolol could significantly decrease HVPG. "Reach Partial Response" Rate and "Response" Rate for Carvedilol and Propranolol are respectively 64.29%and 61.29%,39.29% and 38.71%. No significant difference was found in "Response" Rate (P=0.958), "Partial Response" Rate (P=0.801) and "No Response" Rate (P=0.781) for these two kinds of medicine.Carvedilol may have a significant effect on HR (P=0.015), WHPG (P=0.003) and PLT (P=0.021), Propranolol may improve PT (P=0.020) and INR (P=0.002).Endoscopic therapy (P=0.015) and ALB (P=0.021) have statistical differences between "Response+Partial Response" Group and "No Response" Group. Child-pugh classification (INR) (P=0.032) and ALB (P=0.002) have statistical differences between "Response" Group and "Partial Response+No Response" Group. Age (P=0.091), Child-pugh (using PT for calculation of coagulation function score) (P=0.082) and history of endoscopic variceal ligation (P=0.052) may have a trend of causing these two kinds of NSBB to reduce the efficacy of HVPG.Conclusions:1、Both Carvedilol and Propranolol can significantly decrease HVPG and there is no statistical difference between them in reducing HVPG.2、Propranolol can improve the indexes of blood coagulation function such as PT and INR; Carvedilol may significantly reduce heart rate, wedged hepatic venous pressure and platelet function.3、Serum albumin concentration, Child-pugh grade (using INR to calculate coagulation function score), endoscopic therapy during hospitalization is an important factor causing Carvedilol and Propranolol to reduce the efficacy of HVPG; age, Child-pugh (using PT to calculate coagulation function score) and history of endoscopic variceal ligation may have a trend of causing these two kinds of NSBB to reduce the efficacy of HVPG, which asks more cases to confirm.