Rafael Bañares

Clinical events after transjugular intrahepatic portosystemic shunt: Correlation with hemodynamic findings

BACKGROUND & AIMS Transjugular intrahepatic portosystemic shunt (TIPS) procedures are increasingly being used, but the relationship between the hemodynamic effects of TIPS and the clinical events on follow-up remains undefined. Hence, we have investigated the hemodynamic correlations of portal hypertension-related events after a TIPS procedure. METHODS Prospective follow-up of 122 cirrhotic patients who had a TIPS procedure performed because of variceal hemorrhage was conducted. RESULTS The portacaval pressure gradient (PPG) significantly decreased after the TIPS procedure (from 19.7 +/- 4.6 to 8.6 +/- 2.7 mm Hg; P > 0.001), but increased thereafter and at rebleeding (n = 25) was > 12 mm Hg in all patients (18.4 +/- 4.6 mm Hg). Twenty-six patients developed ascites; the PPG (measured in 19) was always > 12 mm Hg. Increasing the PPG to > 12 mm Hg occurred very frequently (83% at 1 year). Within 1 year, 77% of patients underwent balloon angioplasty or restenting. However, 80% had again a PPG of > 12 mm Hg 1 year after reintervention. Hepatic encephalopathy developed in 31% of patients at 1 year; 21 of 23 patients had a PPG of < 12 mm Hg. CONCLUSIONS Total protection from the risk of recurrent complications of portal hypertension after a TIPS procedure requires that the PPG be decreased and maintained < 12 mm Hg. However, reintervention will be required in most patients within 1 year and again the second year. On the other hand, such portal decompression is associated with an increased risk of hepatic encephalopathy.

Simvastatin Lowers Portal Pressure in Patients With Cirrhosis and Portal Hypertension: A Randomized Controlled Trial

BACKGROUND & AIMS Simvastatin improves liver generation of nitric oxide and hepatic endothelial dysfunction in patients with cirrhosis, so it could be an effective therapy for portal hypertension. This randomized controlled trial evaluated the effects of continuous simvastatin administration on the hepatic venous pressure gradient (HVPG) and its safety in patients with cirrhosis and portal hypertension. METHODS Fifty-nine patients with cirrhosis and portal hypertension (HVPG > or =12 mm Hg) were randomized to groups that were given simvastatin 20 mg/day for 1 month (increased to 40 mg/day at day 15) or placebo in a double-blind clinical trial. Randomization was stratified according to whether the patient was being treated with beta-adrenergic blockers. We studied splanchnic and systemic hemodynamics and variables of liver function and safety before and after 1 month of treatment. RESULTS Simvastatin significantly decreased HVPG (-8.3%) without deleterious effects in systemic hemodynamics. HVPG decreases were observed in patients who were receiving beta-adrenergic blockers (-11.0%; P = .033) and in those who were not (-5.9%; P = .013). Simvastatin improved hepatic, fractional, and intrinsic clearance of indocyanine green, showing an improvement in effective liver perfusion and function. No significant changes in HVPG and liver function were observed in patients receiving placebo. The number of patients with adverse events did not differ significantly between groups. No patient was withdrawn from the study based on adverse events. CONCLUSIONS Simvastatin decreased HVPG and improved liver perfusion in patients with cirrhosis. These effects were additive with those of beta-adrenergic blockers. The beneficial effects of simvastatin should be confirmed in long-term clinical trials for portal hypertension.

Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute‐on‐chronic liver failure: The RELIEF trial

Acute‐on‐chronic liver failure (ACLF) is a frequent cause of death in cirrhosis. Albumin dialysis with the molecular adsorbent recirculating system (MARS) decreases retained substances and improves hemodynamics and hepatic encephalopathy (HE). However, its survival impact is unknown. In all, 189 patients with ACLF were randomized either to MARS (n = 95) or to standard therapy (SMT) (n = 94). Ten patients (five per group) were excluded due to protocol violations. In addition, 23 patients (MARS: 19; SMT: 4) were excluded from per‐protocol (PP) analysis (PP population n = 156). Up to 10 6‐8‐hour MARS sessions were scheduled. The main endpoint was 28‐day ITT and PP survival. There were no significant differences at inclusion, although the proportion of patients with Model for Endstage Liver Disease (MELD) score over 20 points and with spontaneous bacterial peritonitis (SBP) as a precipitating event was almost significantly greater in the MARS group. The 28‐day survival was similar in the two groups in the ITT and PP populations (60.7% versus 58.9%; 60% versus 59.2% respectively). After adjusting for confounders, a significant beneficial effect of MARS on survival was not observed (odds ratio [OR]: 0.87, 95% confidence interval [CI] 0.44‐1.72). MELD score and HE at admission and the increase in serum bilirubin at day 4 were independent predictors of death. At day 4, a greater decrease in serum creatinine (P = 0.02) and bilirubin (P = 0.001) and a more frequent improvement in HE (from grade II‐IV to grade 0‐I; 62.5% versus 38.2%; P = 0.07) was observed in the MARS group. Severe adverse events were similar. Conclusion: At scheduled doses, a beneficial effect on survival of MARS therapy in patients with ACLF could not be demonstrated. However, MARS has an acceptable safety profile, has significant dialysis effect, and nonsignificantly improves severe HE. (HEPATOLOGY 2013)

Efficacy and Safety of Anticoagulation on Patients With Cirrhosis and Portal Vein Thrombosis

BACKGROUND & AIMS Portal vein thrombosis (PVT) is a frequent event in patients with cirrhosis; it can be treated with anticoagulants, but there are limited data regarding safety and efficacy of this approach. We evaluated this therapy in a large series of patients with cirrhosis and non-neoplastic PVT. METHODS We analyzed data from 55 patients with cirrhosis and PVT, diagnosed from June 2003 to September 2010, who received anticoagulant therapy for acute or subacute thrombosis (n = 31) or progression of previously known PVT (n = 24). Patients with cavernomatous transformation were excluded. Thrombosis was diagnosed, and recanalization was evaluated by using Doppler ultrasound, angio-computed tomography, and/or angio-magnetic resonance imaging analyses. RESULTS Partial or complete recanalization was achieved in 33 patients (60%; complete in 25). Early initiation of anticoagulation was the only factor significantly associated with recanalization. Rethrombosis after complete recanalization occurred in 38.5% of patients after anticoagulation therapy was stopped. Despite similar baseline characteristics, patients who achieved recanalization developed less frequent liver-related events (portal hypertension-related bleeding, ascites, or hepatic encephalopathy) during the follow-up period, but this difference was not statistically significant (P = .1). Five patients developed bleeding complications that were probably related to anticoagulation. A platelet count <50 × 109/L was the only factor significantly associated with higher risk for experiencing a bleeding complication. There were no deaths related to anticoagulation therapy. CONCLUSIONS Anticoagulation is a relatively safe treatment that leads to partial or complete recanalization of the portal venous axis in 60% of patients with cirrhosis and PVT; it should be maintained indefinitely to prevent rethrombosis.

Influence of hepatic venous pressure gradient on the prediction of survival of patients with cirrhosis in the MELD era

Measurements of portal pressure, usually obtained via the hepatic venous pressure gradient (HVPG) may be a prognostic marker in cirrhosis. The aim of this study was to evaluate the impact of HVPG on survival in patients with cirrhosis in addition to the Model for End‐Stage Liver Disease (MELD) score. We also examined whether inclusion of HVPG in a model with MELD variables improves its prognostic ability. Retrospective analyses of all patients who had HVPG measurements between January 1998 and December 2002 were considered. Proportional hazards Cox models were developed. Prognostic calibrative and discriminative ability of the model was evaluated. In this period, 693 patients had a hepatic hemodynamic study, and 393 patients were included. Survival was significantly worse in those patients with greater HVPG value (univariate HR, 1.05; 95% CI, 1.02‐1.08; P = .001). HVPG remained as an independent variable in a model adjusted by MELD, ascites, encephalopathy, and age (multivariate HR, 1.03; 95% CI, 1.00‐1.06; P = .05) so that each 1‐mmHg increase in HVPG had a 3% increase in death risk. In addition, HVPG as well as MELD score variables and age, significantly contributes to the calibrative predictive capacity of the prognostic model; however, discriminative ability improved only slightly (overall C statistic [95% CI]; MELD score variables: 0.71 [0.62‐0.80], MELD score variables, age, and HVPG 0.76: [0.69‐0.83]). In conclusion, HVPG has an independent effect on survival in addition to the MELD score. Although inclusion of HVPG and age in a survival predicting model would improve the calibrative ability of MELD, its discriminative ability is not significantly improved. (HEPATOLOGY 2005;42:793–801.)

Comparison of transcatheter arterial embolization and surgery for treatment of bleeding peptic ulcer after endoscopic treatment failure.

PURPOSE To compare the outcomes of embolotherapy and surgery as salvage therapy after therapeutic endoscopy failure in the treatment of upper gastrointestinal peptic ulcer bleeding. MATERIALS AND METHODS Retrospective analysis of 70 cases of refractory peptic upper gastrointestinal hemorrhage was performed. Thirty-one cases were managed with embolotherapy and 39 were managed surgically. Demographic variables, underlying conditions, clinical findings, endoscopic treatment, transfusion requirements before and after alternative therapeutic approach, length of hospital stay, and outcomes including recurrent bleeding, need for surgery after initial alternative treatment, and in-hospital death were recorded. RESULTS Patients who received embolotherapy were older (75.2 years +/- 10.9 vs 63.3 years +/- 14.5; P <.001) and had greater incidences of heart disease (67.7% vs 20.5%; P <.001) and previous anticoagulation treatment (25.8% vs 5.1%; P =.018). There were no differences in the rest of the pretreatment variables. No differences were found between the embolotherapy and surgery groups in the incidence of recurrent bleeding (29% vs 23.1%), need for additional surgery (16.1% vs 30.8%), or death (25.8% vs 20.5). CONCLUSIONS The lack of differences between these two treatment alternatives, despite the more advanced age and greater prevalence of heart disease in the embolotherapy group, provides support for future prospective randomized studies aimed to evaluate the role of embolotherapy in the management of refractory peptic ulcer bleeding.

Antiviral therapy decreases hepatic venous pressure gradient in patients with chronic hepatitis C and advanced fibrosis.

BACKGROUNDS:Antiviral therapy (AVT) may improve liver histology in patients with advanced viral hepatitis but its effect on portal pressure remains unknown.AIM:This study was aimed to evaluate the influence of antiviral therapy (AVT) on hepatic venous pressure gradient (HVPG) in hepatitis C virus infected patients with portal hypertension.METHODS:Twenty compensated patients with chronic hepatitis C, fibrosis stage 3 or 4 and HVPG > 5 mmHg received PEG-IFN α2b plus ribavirin. Every patient underwent liver biopsy and portal pressure measurements before and immediately after AT. Biopsies were evaluated according to METAVIR score.RESULTS:HVPG significantly dropped in all but one treated patient, with a mean (SD) reduction of 28.2 (12)% [13.8 (5.6) Vs. 10.2 (3.8) mmHg, p = 0.005]. The percentage of HVPG decrease was significantly greater in patients who achieved a virological end of treatment response [26.2 (12.5)% Vs. 12.7 (8.5)%, p = 0.05] and in those with a decrease of at least 2 points in the grade of inflammation [35.7 (4.5)% Vs. 22.1 (9.5)%, p = 0.015]. Nine out of 11 patients with baseline HVPG ≥ 12 mmHg showed a decrease greater than 20% (3/11) or under the 12 mmHg threshold (6/11).CONCLUSIONS:AVT reduces HVPG in compensated patients with advanced hepatitis C (fibrosis stage 3 or 4) and portal hypertension.

Multicenter randomized controlled trial comparing different schedules of somatostatin in the treatment of acute variceal bleeding

BACKGROUND/AIMS The dose of somatostatin used for variceal bleeding (250 microg/h) is lower than that proven to effectively decrease portal pressure and azygos blood flow (500 microg/h). Moreover, i.v. somatostatin boluses have greater effects than continuous infusions. The aim of this study was to investigate whether higher doses of somatostatin and repeated boluses may increase its efficacy in controlling variceal bleeding. METHODS A total of 174 patients with acute variceal bleeding were randomized to receive for 48 h: (A) one 250 microg bolus +250 microg/h infusion; (B) three 250 microg boluses +250 microg/h infusion; (C) three 250 microg boluses +500 microg/h infusion. RESULTS The three schedules of somatostatin were equally effective in controlling variceal bleeding (73, 75 and 81%, respectively, NS). Multivariate analysis showed active bleeding at endoscopy (n=75) as the only predictor of failure to control bleeding. In these patients, the 500 microg/h infusion dose achieved a higher rate of control of bleeding (82 vs. 60%, P<0.05), less transfusions (3.7 +/- 2.7 vs. 2.5 +/- 2.3 UU, P=0.07) and better survival (93 vs. 70%, P<0.05) than schedules A/B. CONCLUSIONS Somatostatin is highly effective in controlling variceal bleeding. Patients with active bleeding at emergency endoscopy may benefit from higher doses of somatostatin infusion.

Continuous prazosin administration in cirrhotic patients: Effects on portal hemodynamics and on liver and renal function☆☆☆

BACKGROUND & AIMS Hepatic vascular resistance is influenced by alpha-adrenergic tone. The aim of this study was to investigate the effects of continuous blockade of alpha-adrenoceptors with prazosin on hemodynamics, liver function, and renal function and whether the association of propranolol or furosemide enhances the portal pressure lowering effect of prazosin. METHODS Cirrhotic patients with portal hypertension were studied at baseline and after a 3-month course of prazosin (n = 18) or placebo (n = 10). RESULTS No changes were observed in the placebo group. Prazosin decreased the hepatic venous pressure gradient (HVPG) while increasing hepatic blood flow. Liver function improved as shown by an increase in hepatic and intrinsic hepatic clearances of indocyanine green and galactose elimination capacity. A significant reduction in mean arterial pressure and systemic vascular resistance was associated with increases in plasma renin activity and aldosterone concentration and a decrease in glomerular filtration rate. The plasma volume increased significantly, and 6 patients developed edema. The association of propranolol (n = 8) but not furosemide (n = 7) to prazosin increased the reduction in HVPG and attenuated the increase in plasma renin activity. CONCLUSIONS In cirrhotic patients, continuous prazosin administration reduces portal pressure and improves liver perfusion and function but favors sodium and water retention. The association of propranolol enhances the decrease in portal pressure, suggesting a potential benefit from this combined therapy.

Urgent Transjugular Intrahepatic Portosystemic Shunt for Control of Acute Variceal Bleeding

Objective:Endoscopic sclerotherapy and pharmacological therapy are widely used in the treatment of acute variceal hemorrhage. However, they fail at arresting acute bleeding in 20–30% of bleeding episodes. The efficacy of transjugular intrahepatic portosystemic shunt (TIPS) in the prevention of recurrent variceal bleeding has been proved recently, but the effectiveness and safety of urgent TIPS in the treatment of acute variceal bleeding refractory to conventional therapy are still under evaluation.Methods:Over 4.5 yr, 358 variceal hemorrhage episodes were treated in our hospital. Pharmacological and endoscopic therapy failed to control hemorrhage in 93 episodes. Thirty-two patients died because of uncontrolled massive bleeding. In 56 patients, TIPS (Strecker stent) was performed after temporary control of the episode with balloon tamponade.Results:Eleven of 56 patients with urgent TIPS belonged to Child-Pugh class A, 22 to class B, and 23 to class C. The mean time between indication and insertion was 17 ± 10 h (range 4–24 h). Control of bleeding was achieved in 53 patients (95%). Eight patients had recurrent bleeding at 1 month after TIPS, seven of them during the first week after the procedure. The 1-month actuarial probability of rebleeding was 22%. The main complications of the procedure were massive hemoperitoneum (n = 1), cardiorespiratory arrest (n = 2), cardiac failure (n = 1), acute renal failure-(n = 2), and bacteremia (n = 7). Operative mortality (30 days) was 28%. The actuarial probability of survival at 30 days was significantly lower in Child-Pugh class C than in class A or B (48%vs 90%; p < 0.001). The presence of ascites, hepatic encephalopathy, and serum albumin level before TIPS were independent prognostic factors associated with the risk of operative mortality.Conclusions:Urgent TIPS is an effective alternative for the treatment of acute variceal bleeding refractory to endoscopic and pharmacological therapy, but sometimes is associated with major complications. Because of the high operative mortality rate in patients with severe liver failure, careful selection of patients is required before TIPS.