Josep Terés

Relation between portal pressure response to pharmacotherapy and risk of recurrent variceal haemorrhage in patients with cirrhosis

In patients with variceal bleeding as a complication of hepatic cirrhosis, propranolol therapy reduces the risk of recurrent variceal haemorrhage. However, the relation between portal pressure response to pharmacological treatment and clinical events has not been well defined. This relation was prospectively investigated in 69 cirrhotic patients receiving continued propranolol therapy after an episode of variceal bleeding. Hepatic venous pressure gradient (HVPG) was measured before and at 3 months of continued drug therapy. At 3 months HVPG had fallen by 20% or more in 25 patients. During follow-up of 28 (SD 17) months rebleeding occurred in 2 of these 25 patients compared with 23 of 44 who had lesser reductions in HVPG. Cumulative probability of rebleeding at 1, 2, and 3 years was 4%, 9%, and 9% in patients with a decrease in HVPG > or = 20%, and 28%, 39%, and 66% in patients with a decrease in HVPG < 20% (p < 0.001, log-rank test). On multivariate analysis, a decrease in HVPG > or = 20% was the only independent predictor of rebleeding (relative risk 0.09, 95% CI 0.02-0.41. Of the 8 patients in whom the HVPG fell to 12 mm Hg or less, none rebled. This study suggests that measurement of the HVPG response to pharmacotherapy will provide useful prognostic information on the long-term risk of variceal rebleeding.

Is Hepatitis C Virus Infection a Trigger of Porphyria Cutanea Tarda

The causes of liver disease, ranging from fatty changes to cirrhosis and hepatocellular carcinoma, in porphyria cutanea tarda (PCT) remain unclear. We tested 100 consecutive PCT patients for antibodies to hepatitis C virus (HCV) by enzyme-linked immunosorbent assay and a recombinant immunoblot assay. 75 (79%) patients with sporadic PCT but none of 5 with familial PCT were positive. HCV RNA was found in serum of all 18 anti-HCV-positive patients tested. There were no significant differences in the prevalence of anti-HCV between treated and untreated patients or between those with and without various HCV risk factors. The frequency of anti-HCV increased with the severity of liver histology. These findings implicate HCV in the aetiology of PCT-associated liver disease.

Randomised trial of endoscopic sphincterotomy with gallbladder left in situ versus open surgery for common bileduct calculi in high-risk patients

BACKGROUND Morbidity and mortality after surgical treatment of bileduct stones increase with age and associated diseases. A proposed alternative therapy is endoscopic sphincterotomy (ES) with the gallbladder left in situ, and we elected to compare this option with standard open surgery in high-risk patients. METHODS 98 patients (mean age 80 years) with symptoms likely to be due to bileduct stones or a recent episode of biliary pancreatitis were randomised to be treated either by open cholecystectomy with operative cholangiography and (if necessary) bileduct exploration (n=48) or by endoscopic sphincterotomy alone (n=50). FINDINGS The procedure was accomplished successfully in 94% of the surgery group and 88% of the ES group, and there were no significant differences in immediate morbidity (23% vs 16%) or mortality (4% vs 6%). During mean follow-up of 17 months biliary symptoms recurred in three surgical patients, none of whom underwent repeat surgery, and in 10 ES patients, seven of whom had biliary surgery. By multivariate regression analysis endoscopic sphincterotomy was an independent predictor of recurrent biliary symptoms (odds ratio 6.9; 95% Cl 1.46 to 32.54). INTERPRETATION In elderly or high-risk patients, surgery is preferable to endoscopic sphincterotomy with the gallbladder left in situ as a definitive treatment for bileduct stones or non-severe biliary pancreatitis.

Increased gastric mucosal perfusion in cirrhotic patients with portal hypertensive gastropathy

To characterize gastric mucosal perfusion in cirrhotic patients with portal hypertensive gastropathy, 34 cirrhotics with this lesion and 24 noncirrhotics were studied by reflectance spectrophotometry and laser-Doppler flowmetry during endoscopy. A significant correlation was observed between the hemoglobin content of the gastric mucosa, measured by reflectance spectrophotometry, and the serum hemoglobin concentration both in cirrhotics (r = 0.72) and in noncirrhotics (r = 0.87). IHb ratio (hemoglobin content of gastric mucosa divided by blood hemoglobin concentration) was higher in cirrhotics with portal hypertensive gastropathy than in noncirrhotics (P < 0.001), whereas the oxygen content of the gastric mucosa was similar in both groups. This pattern indicates that cirrhotics with portal hypertensive gastropathy have increased gastric perfusion without congestion. Gastric blood flow estimated by laser-Doppler was significantly higher in cirrhotics with portal hypertensive gastropathy than in noncirrhotics (P < 0.001). In cirrhotic patients, gastric areas with cherry red spots showed a significantly higher IHb ratio than areas with a mosaic or scarlatina pattern (P < 0.05). The magnitude of changes in gastric perfusion and the endoscopic severity of portal hypertensive gastropathy had no relationship with the degree of portal hypertension or the azygos blood flow.

Randomized trial of portacaval shunt, stapling transection and endoscopic sclerotherapy in uncontrolled variceal bleeding

Seventy consecutive cirrhotic patients with persistent or recurrent variceal bleeding were included in a clinical trial to compare the efficacy and safety of portacaval shunt (PCS) and stapler transection (ST) in patients with low surgical risk, and of stapler transection and endoscopic sclerotherapy (ES) in patients with high surgical risk. To classify the patients into low- and high-risk groups a new scoring system was used, based on an analysis of factors influencing operative mortality in an earlier series of emergency portacaval shunt. Thirty-eight low-risk patients were randomly allocated for treatment with portacaval shunt (19 patients) or stapler transection (19 patients), and 32 high-risk patients for stapler transection (17 patients) or ES (15 patients). The operative mortality of patients treated by PCS was close to that expected according to retrospective data, this indicating that the proposed scoring system is highly discriminant. In low-risk patients, portacaval shunt evidenced greater haemostatic efficacy and fewer complications than stapler transection. However, hepatic encephalopathy during follow-up was more frequent in the portacaval shunt group and there were no significant differences in operative mortality and long-term survival between the two groups. In high-risk patients, stapler transection and sclerotherapy had a similar haemostatic efficacy, operative mortality and long-term survival. However, sclerotherapy occasioned fewer complications than stapler transection. Our results motivate us to recommend stapler transection for low-risk patients and to consider sclerotherapy as an alternative for high-risk patients in the emergency treatment of uncontrolled variceal bleeding.

Distal spleno-renal shunt versus endoscopic sclerotherapy in the prevention of variceal rebleeding A meta-analysis of 4 randomized clinical trials

Meta-analysis was used to evaluate 4 clinical trials comparing distal spleno-renal shunt (DSRS) with endoscopic sclerotherapy (EVS) in the prevention of variceal rebleeding: the interval between bleeding and therapy ranges from < 14 days to > 100 days. A questionnaire was sent to each author of the published trials concerning methods, definitions and results of the trials in order to obtain more detailed and up-to-date information. The selected end-points for the meta-analysis were: rebleeding, mortality and chronic encephalopathy. Analysis of the results in the questionnaires was made using the method proposed by Collins. The pooled relative risk (i.e. the combined Odds ratio of each trial as an estimate of overall efficacy) of rebleeding was statistically reduced by DSRS (0.16; 95% confidence interval 0.10-0.27). Despite this, the overall risk of death following DSRS was only marginally decreased (0.78; 95% confidence interval 0.47-1.29); the lack of homogeneity in the results does not permit any significant conclusions on this end-point. However, in non-alcoholic patients, the decrease in risk of death was greater, and this without heterogeneity, following DSRS than EVS (0.59; 95% confidence interval 0.23-1.50). The overall risk of chronic encephalopathy was slightly increased after DSRS (1.86; 95% confidence interval 0.90-3.86). In conclusion, DSRS significantly reduced the risk of rebleeding compared to EVS without increasing the risk of chronic hepatic encephalopathy. However, DSRS did not significantly affect the overall death risk. Only in non-alcoholic disease did it seem to show an advantage over EVS.

A prospective randomized trial of heater probe thermocoagulation versus injection therapy in peptic ulcer hemorrhage

BACKGROUND A prospective, randomized study was performed to compare the hemostatic effect of injection therapy and heater probe thermocoagulation in the treatment of peptic ulcer bleeding. METHODS This study includes 104 patients with upper gastrointestinal bleeding in whom endoscopy revealed a gastric or duodenal ulcer with nonbleeding or bleeding vessel (n = 66), oozing hemorrhage (n = 21), or adherent red clot (n = 17). Patients with other stigmata or clean ulcers were excluded. Patients were randomly assigned during endoscopy to receive injection therapy (adrenaline and polidocanol) (n = 51) or heater probe thermocoagulation (10F probe, at setting of 30 J (n = 53). Therapy was considered successful if there was no further hemorrhage or only minor rebleeding that was controlled with a second endoscopic procedure. Patients with major rebleeding or failure of retreatment underwent emergency surgery. RESULTS There were no significant differences in effectiveness between injection therapy and thermocoagulation in any of the assessed parameters: the percentage of patients with major recurrent hemorrhage (4% vs 6%) or minor rebleeding (16% vs 17%), need for emergency surgery (two patients from each group), transfusion requirement (0.45 +/- 0.9 units vs 0.51 +/- 1.1 units), the mean number of hospitalization days (7.1 +/- 4.2 vs 6.9 +/- 4.9), and mortality (one patient from each group died). CONCLUSION Injection therapy and heater probe have similar efficacies in the treatment of bleeding peptic ulcers.

Propranolol versus sclerotherapy in preventing variceal rebleeding: a randomized controlled trial.

BACKGROUND Sclerotherapy has been widely recommended as initial treatment for prevention of variceal rebleeding. The present study was aimed at comparing the efficacy of endoscopic sclerotherapy and long-term administration of propranolol in the prevention of rebleeding and long-term survival in patients who had bled from varices. METHODS One hundred sixteen consecutive cirrhotic patients admitted because of variceal bleeding were randomly allocated to either continuous administration of propranolol to reduce the resting heart rate by 25% (58 patients) or weekly intravariceal sclerotherapy sessions using 5% ethanolamide oleate until varices disappeared (58 patients). Results were analyzed on an intention-to-treat basis. RESULTS Rebleeding occurred in 37 patients of the propranolol group and in 26 patients of the sclerotherapy group (RR = 1.45; 95% CI, 1.03-2.03). The actuarial probability of rebleeding was lower in the sclerotherapy group (P = 0.02). No differences were found in rebleeding index, hospitalization requirements, survival, and causes of death. Complications were significantly more frequent and severe in the sclerotherapy group. CONCLUSIONS Despite the higher efficacy of sclerotherapy decreasing the probability of rebleeding when compared with propranolol, no beneficial effects were observed on other parameters also reflecting the efficacy of therapy. Moreover, complications of sclerotherapy were more frequent and severe than those of propranolol, which probably shall restrict the use of long-term elective sclerotherapy.

Effects of acute normovolemic anemia on gastric mucosal blood flow in rats: Role of nitric oxide

The present study investigates the effects of acute normovolemic anemia induced by isovolemic hemodilution on gastric mucosal blood flow (GMBF), measured by hydrogen gas clearance, and on the oxygen and hemoglobin content in the gastric mucosa, estimated by reflectance spectrophotometry. GMBF significantly increased after 3 and 6 mL of isovolemic hemodilution (from 50 +/- 5 to 70 +/- 7 and 77 +/- 6 mL.min-1.100 g-1, respectively; P less than 0.05) compared with basal values (50 +/- 5.mL-1.min-1.100 g-1; P less than 0.05). Oxygen content remained unchanged, whereas hemoglobin concentration decreased in parallel with the decrease in hematocrit. In a second set of experiments, the role of endogenous nitric oxide (NO) as a possible mediator of the gastric vascular changes induced by hemodilution was investigated by using the specific inhibitor of NO biosynthesis, NG-monomethyl-L-arginine (L-NMMA). The increase in GMBF induced by 3 mL of isovolemic hemodilution (delta 23 +/- 7 mL.min-1.100 g-1) was attenuated in a dose-related manner with L-NMMA, 6.25 mg/kg IV (delta 15 +/- 4 mL.min-1.100 g-1) or 50 mg/kg IV (delta 5 +/- 2 mL.min-1.100 g-1 g; P less than 0.05). The concurrent administration of L-arginine (the precursor of NO biosynthesis) abolished the effects of L-NMMA on GMBF changes. The current findings show that acute normovolemic anemia causes an increase in GMBF that is dependent on the endogenous formation of NO.

Helicobacter pylori, hyperammonemia and subclinical portosystemic encephalopathy: effects of eradication

BACKGROUND/AIMS An involvement of Helicobacter pylori in the development of hepatic encephalopathy in cirrhotic patients has been proposed, but data confirming such an association are lacking. This prospective study aimed to assess whether ammonia levels and indicators of subclinical portosystemic encephalopathy were influenced by H. pylori status in a series of 62 cirrhotic patients. The effects of H. pylori eradication on such parameters were also investigated. METHODS Fasting blood ammonia levels, mental state, number connection test, flapping tremor, and EEG tracings were recorded at baseline, and in H. pylori-positive patients (as diagnosed by rapid urease test and 14C-urea breath test) these parameters were reassessed 2 months following eradication therapy. RESULTS In this series of non-advanced cirrhotic patients, the prevalence of H. pylori infection was 52%. No significant differences were observed between H. pylori+ and H. pylori- cases with respect to fasting venous blood ammonia concentration (47+/-24 vs. 43+/-22 micromol/l) or to the remaining parameters assessing portosystemic encephalopathy. In addition, H. pylori eradication failed to induce any significant variation in either fasting blood ammonia levels (from 45+/-23 to 48+/-26 micromol/l) or neurologic disturbances. CONCLUSION These results indicate that H. pylori infection is not a major contributing factor to either fasting blood ammonia levels or parameters assessing subclinical portosystemic encephalopathy in patients with non-advanced liver cirrhosis.