Severe hepatocellular injury with apoptosis induced by a hepatitis C polymerase inhibitor.

Goals: To describe the mechanisms of severe hepatocellular injury with apoptosis in 2 patients receiving hepatitis C virus (HCV)-796.

Background: HCV-796 is a hepatitis C polymerase inhibitor approved by the US Food and Drug Administration for a phase 2 study of the treatment of hepatitis C in combination with PEG-Interferon and ribavirin.

Results: The injury occurred after more than 12 weeks of treatment, with a >20-fold increase in serum alanine aminotransferase and aspartate aminotransferase, and a marked increase in total (and direct) bilirubin in the absence of cholestasis.

Management of chronic hepatitis C in veterans: the potential of integrated care models.

The prevalence of hepatitis C virus (HCV) infection is higher among veterans than nonveterans, but only about 14% of all identified infected veterans have ever received antiviral therapy. High rates of comorbid psychiatric and substance use disorders are major barriers to receiving antiviral treatment for veterans, and characteristics associated with poor virologic response are more common in this population. However, accumulating evidence indicates that patients with psychiatric and substance use disorders can successfully receive interferon-based antiviral therapies in an integrated or multidisciplinary health-care setting.

Prevention of recurrent esophageal variceal hemorrhage: review and current recommendations.

Variceal rebleeding is a very frequent and severe complication in cirrhotic patients; therefore, its prevention should be mandatory. Lately several studies demonstrated that the rate of rebleeding was decreased by 40% and overall survival is improved by 20% with beta-blockers. However, this treatment presents some problems, such as the number of nonresponders and contraindications for its use.

Comparative study between nadolol and 5-isosorbide mononitrate vs. endoscopic band ligation plus sclerotherapy in the prevention of variceal rebleeding in cirrhotic patients: a randomized controlled trial.

Background: After variceal bleeding, cirrhotic patients should receive secondary prophylaxis.

Aim: To compare nadolol plus 5-isosorbide mononitrate (5-ISMN) with endoscopic band ligation. The end points were rebleeding, treatment failure and death.

Ultrasound system to measure esophageal varix pressure: an in vitro validation study.

We report our experience with an ultrasound system to measure esophageal varix pressure in an in vitro model. The ultrasound system consists of a 12.5 MHz frequency intraluminal ultrasound probe, a water infusion catheter, and a manometry catheter, all contained within a nondistensible latex bag.

Nadolol plus spironolactone in the prophylaxis of first variceal bleed in nonascitic cirrhotic patients: A preliminary study.

Treatment with beta-blockers fails to decrease portal pressure in nearly 40% of cirrhotic patients. Recent studies have suggested that treatment with spironolactone reduces pressure and flow in the portal and variceal systems. This trial was designed to assess if nadolol plus spironolactone is more effective than nadolol alone to prevent the first variceal bleeding.

Effects of long-term propranolol and octreotide on postprandial hemodynamics in cirrhosis: a randomized, controlled trial.

Background & Aims: Postprandial increases in portal pressure may influence esophageal variceal rupture. The effects of chronic propranolol and octreotide (100 and 200 microg subcutaneously in a single dose) on postprandial hemodynamics were evaluated.

Methods: FIRST STUDY: 36 cirrhotic patients were studied at baseline and 30 and 60 minutes after a standard meal and then treated with propranolol (139 +/- 9 mg/d during 39 +/- 2 days).

Patients with ascites have higher variceal pressure and wall tension than patients without ascites.

Objective: It has been suggested that ascites is a risk factor for variceal bleeding. Recently, it has been demonstrated that total paracentesis decreases variceal pressure. However, no data are available showing the basal variceal pressure in patients with and without ascites.

Efficacy of octreotide and sclerotherapy in the treatment of acute variceal bleeding in cirrhotic patients. A prospective, multicentric, and randomized clinical trial.

Background: Sclerotherapy is the most widely used method for treatment of acute variceal bleeding. Previous reports have suggested that octreotide infusion is as effective as sclerotherapy. Our aim was to investigate the efficacy and safety of octreotide in comparison with sclerotherapy in controlling variceal bleeding.

Terlipressin is more effective in decreasing variceal pressure than portal pressure in cirrhotic patients.

Background/aims: Terlipressin decreases portal pressure. However, its effects on variceal pressure have been poorly investigated. This study investigated the variceal, splanchnic and systemic hemodynamic effects of terlipressin.

Variceal band ligation and variceal band ligation plus sclerotherapy in the prevention of recurrent variceal bleeding in cirrhotic patients: a randomized, prospective and controlled trial.

Background: The combination treatment of band ligation plus sclerotherapy has been proposed to hasten variceal eradication. The aim of this study was to assess the efficacy of band ligation alone versus band ligation plus sclerotherapy in the prevention of recurrent variceal bleeding.

Methods: Eighty cirrhotic patients were randomized to group I (band ligation) with 41 patients or to group II (band ligation plus sclerotherapy) with 39 patients in whom polidocanol (2%) was injected 1 to 2 cm proximal to each band.

Total volume paracentesis decreases variceal pressure, size, and variceal wall tension in cirrhotic patients.

It has been suggested that ascites is a risk factor for variceal bleeding in cirrhotic patients. However, no data of total volume paracentesis (TVP) effects on variceal hemodynamics has yet been published. The aim of this study was to investigate the effects of TVP on variceal pressure, size, and tension in cirrhotic patients.

Transjugular intrahepatic portosystemic shunt versus sclerotherapy in the elective treatment of variceal hemorrhage.

Background & Aims: Uncontrolled studies suggest that placement of a transjugular intrahepatic portosystemic shunt (TIPS) could be useful in the treatment of variceal bleeding. The aim of this study was to evaluate the efficacy and safety of TIPS in the elective treatment of hemorrhage from esophageal varices in a randomized controlled study that compared the effects of TIPS with those of endoscopic sclerotherapy (ES).

Methods: Sixty-three consecutive cirrhotic patients with hemorrhage from esophageal varices were included.

Ultrasonographic diagnosis of acute alcoholic hepatitis 'pseudoparallel channel sign' of intrahepatic artery dilatation.

Background: In an ultrasound pilot study of acute alcoholic hepatitis (AAH), parallel tubular structures within the liver subsegments were observed. Pulse-Doppler flowmetry revealed that these structures were formed by a dilated hepatic arterial branch and an adjacent portal venous branch. This finding was termed the "pseudoparallel channel sign" (PPCS).

Paracentesis with Dextran 70 vs. paracentesis with albumin in cirrhosis with tense ascites. Results of a randomized study.

Forty-one patients with cirrhosis and tense ascites were randomized to receive daily paracentesis of 5 liters associated with Dextran 70 as volume expander (6 g for each 1000 ml of ascites removed) (group I = 20 patients) or paracentesis with albumin (6 g for each 1000 ml of ascites) (group II = 21 patients). The basal clinical features, laboratory data, and plasma renin activity were similar in both groups. The volume of ascites removed was 12.

Interaction of hemopexin, albumin and liver fatty acid-binding protein with protoporphyrin.

Equilibrium constants for the binding of protoporphyrin to serum albumin and hemopexin and liver cytosolic fatty acid-binding protein of the rat were determined fluorometrically. The experimental equilibrium constant [10(6) M-1 (mean +/- S.D.

Propranolol decreases portal pressure without changing portocollateral resistance in cirrhotic rats.

Propranolol decreases portal pressure by reducing portal blood inflow. Studies in rats with prehepatic portal hypertension due to portal vein stenosis (a model with extensive portosystemic shunting) have shown that propranolol increases the portocollateral resistance, which hinders the fall in portal pressure. The present study examined the effects of propranolol on splanchnic and systemic hemodynamics in rats with portal hypertension due to cirrhosis of the liver, a model which is characterized by mild portosystemic shunting.

Beta-blockade with propranolol and hepatic artery blood flow in patients with cirrhosis.

In patients with cirrhosis and portal hypertension, propranolol administration reduces heart rate and cardiac output and diminishes portal pressure and collateral blood flow. However, there is little information on the possible effects of propranolol on hepatic artery blood flow. The present study addressed this question in 12 cirrhotic patients with end-to-side portacaval shunt, in whom all of the liver blood flow represents the hepatic artery blood flow.

Hemodynamic effects of blood volume restitution following a hemorrhage in rats with portal hypertension due to cirrhosis of the liver: influence of the extent of portal-systemic shunting.

The present study investigated whether, in rats with portal hypertension due to cirrhosis of the liver induced by carbon tetrachloride, blood volume restitution following a hemorrhage produces an increase of portal pressure beyond control values, as observed in rats with prehepatic portal hypertension. Since carbon tetrachloride-induced cirrhosis caused mild portal-systemic shunting, in some of the cirrhotic rats (12 of 29 rats) portal-systemic shunting was enhanced by a transient (4 days) partial constriction of the portal vein, which was removed 1 week prior to the study. After baseline measurements of portal pressure and arterial pressure, 15 ml per kg of blood were withdrawn at a rate of 0.

Endoscopic measurement of variceal pressure in cirrhosis: correlation with portal pressure and variceal hemorrhage.

This study evaluated the clinical application of a pressure-sensitive gauge that allows the noninvasive measurement of the pressure of esophageal varices at endoscopy. The study was performed in 70 patients with cirrhosis and portal hypertension. Among them, 47 had bled from the varices and 23 had varices but had not bled.

Diagnosis and evaluation of portal hypertension.

In the past recent years there have been several major innovations in the diagnosis and evaluation of portal hypertension. These include the application of new endoscopic, ultrasonographic and haemodynamic techniques that allow a better evaluation of the portal hypertensive patient, specially when prophylactic medical therapy is considered. Ultrasonography is very useful to assess the patency of the portal vein.

Effects of vasopressin on the intravariceal pressure in patients with cirrhosis: comparison with the effects on portal pressure.

The present study investigated to what extent measurements of wedged and free hepatic venous pressures adequately reflect the effects of vasopressin at the esophageal varices in patients with cirrhosis. Eleven patients undergoing therapeutic sclerotherapy were studied by measuring wedged hepatic venous pressure, intravariceal pressure, free hepatic venous pressure, superior vena cava pressure and the intravascular pressure gradients wedged hepatic venous pressure-free hepatic venous pressure and intravariceal pressure-superior vena cava pressure, prior to and after vasopressin injection (1 IU, iv). Vasopressin caused a significant reduction in intravariceal pressure (from 22.