肝硬化患者β_2肾上腺素能受体基因多态性在血流动力学对普萘洛尔反应的影响

The beta-2-adrenergic receptor (β2-AR) has several single- nucleotide polymorphisms. These influence the functional response to adrenergic stimulation; genotypes homozygous for Gly16-Glu27 or Gly16-Gln27 alleles (Gly16-Glu/Gln27 haplotypes) are associated with enhanced response, whereas genotypes homozygous for Arg16-Gln27 alleles (Arg16-Gln27) show a decreased response. We hypothesized that gene polymorphisms at the β2-AR may influence the hemodynamic response to propranolol in patients with cirrhosis. The β2-AR gene polymorphisms were determined by direct sequencing of the polymerase chain reaction (PCR) products in 48 patients with cirrhosis. All patients also had hepatic and systemic hemodynamic studies before and after propranolol administration. Prevalence of Gly16-Glu/Gln27 haplotypes was 29.1%, Arg16-Gln27 haplotype was 16.7%,and 54.2%were compound heterozygotes. Patients with cirrhosis with Gly16-Glu/Ghl27 haplotypes had a greater decrease in heart rate, cardiac index, and hepatic blood flow after propranolol administration than those with Arg16-Gln27 haplotype. However, the HVPG response to propranolol was similar in both groups, whereas estimated hepatic sinusoidal resistance increased significantly in Gly16-Glu/Gln27 haplotypes but not in Arg16-Gln27 (+27.1 ±17.8%vs -17.9 ±13.9%, P = .042), suggesting that unopposed vasoconstrictive activity at the intrahepatic circulation hinders the fall in HVPG despite enhanced hemodynamic response to propranolol in Gly16-Glu/Ghi27 haplotypes. In conclusion, β2-AR gene polymorphisms influence the response to beta-blockade. However, HVPG reduction cannot be predicted from polymorphism analysis. Patients with the Gly16-Glu/Gln27 haplotypesmay benefit from the association of hepatic vasodilators to propranolol therapy.

维生素C可改善肝硬化和门脉高压患者肝内皮细胞的功能障碍

Patients with cirrhosis show intrahepatic endothelial dysfunction,characterized by an impaired flow-dependent vasorelaxation.This alteration is responsible for the marked postprandial increase in portal pressure and is attributed to an insufficient release of nitric oxide(NO).Ascorbic acid reverts endothelial dysfunction in other vascular disorders,via the increase of NO bioavailability through the neutralization of superoxide anions,thus preventing the scavenging of NO by superoxide.This study examined whether acute ascorbic acid administration might improve endothelial dysfunction in cirrhosis.Thirty-seven portal hypertensive patients with cirrhosis had measurements of hepatic and systemic hemodynamics,ascorbic acid,and malondialdehyde(MDA).Patients were randomly allocated to receive ascorbic acid(3 g,intravenously,n = 15)or placebo(n = 12)followed by a liquid meal.A third group received ascorbic acid followed by a sham meal(n = 10).Measurements were repeated after 30 minutes(hepatic venous pressure gradient at 15 and 30 minutes).Patients with cirrhosis had significantly lower ascorbic acid levels and higher MDA than healthy controls.Ascorbic acid significantly reduced MDA levels and markedly attenuated the postprandial increase in the hepatic venous pressure gradient(4%±7%vs.18%±10%in placebo at 30 minutes,P <.001).Ascorbic acid followed by sham meal did not modify hepatic or systemic hemodynamics.In conclusion,patients with cirrhosis exhibited intrahepatic endothelial dysfunction,associated with decreased levels of ascorbic acid and increased levels of MDA.Ascorbic acid improved intrahepatic endothelial dysfunction,blunting the postprandial increase in portal pressure.These results encourage the performance of further studies testing antioxidants as adjunctive therapy in the treatment of portal hypertension.

覆有PTEF膜的支架可改善布-加综合症患者TIPS的开放

Transjugular intrahepatic portosystemic shunt (TIPS) have been shown to be an efficient portal systemic derivative treatment for Budd Chiari syndrome (BCS) patients uncontrolled by medical therapy. However, the main drawback of TIPS for this condition is a very high rate of shunt dysfunction. Recently, polytetrafluoroethylene (PTFE) covered stents have been shown to reduce the incidence of TIPS dysfunction in patients with cirrhosis. The aim of the study was to assess the incidence of TIPS dysfunction in 2 cohorts of BCS patients treated with bare or PTFE covered stents. The study included 25 TIPS procedures (16 bare stents and 9 covered stents) with a median follow up period of 20.4 months (range, 3.9-124.8). Fourteen of 16 patients (87%) receiving bare stents had TIPS dysfunction compared to 3 of the 9 patients (33%) receiving PTFE covered stents (P = .005). The actuarial rates of primary patency in the bare stent group were 19%at 1 year compared with 67%in the PTFE covered stent group (P= .02; log rank test). The number of additional interventional procedures to maintain TIPS patency was significantly greater in the bare stent than in the PTFE covered stent group (1.9 ±1.2 vs. 0.6 ±0.9; P=.007). The number of patients with clinical relapses was greater in the bare stent group compared to the PTFE covered stent group (13 vs. 5 episodes in 9 and 3 patients, respectively). In conclusion, PTFE covered stents have a considerable advantage over bare stents for the TIPS treatment of BCS patients, with a lower dysfunction rate, a lower number of reinterventions, and fewer prosthesis requirements. PTFE covered stents are preferable in patients with Budd Chiari Syndrome.