Michel Beauchant

Sclerotherapy with or without Octreotide for Acute Variceal Bleeding

BACKGROUND Sclerotherapy is considered the most effective way to stop bleeding from esophageal varices, but acute variceal bleeding is still associated with a high risk of rebleeding and death. We compared sclerotherapy alone with sclerotherapy and octreotide to control acute variceal bleeding and prevent early rebleeding in patients with cirrhosis. METHODS In a double-blind, prospective trial, 199 patients with cirrhosis and acute variceal bleeding who underwent emergency sclerotherapy were randomly assigned to receive a continuous infusion of octreotide (25 micrograms per hour) or placebo for five days. The primary outcome measure was survival without rebleeding five days after sclerotherapy. RESULTS After five days, the proportion of patients who had survived without rebleeding was higher in the octreotide group (85 of 98 patients, or 87 percent) than in the placebo group (72 of 101, or 71 percent; 95 percent confidence interval for the difference, 4 to 27 percent; P = 0.009). The mean number of units of blood transfused within the first 24 hours after sclerotherapy was lower in the octreotide group (1.2 units; range, 0 to 7) than in the placebo group (2.0 units; range, 0 to 10; P = 0.006). A logistic-regression analysis showed that the treatment assignment (P = 0.003) and the number of blood units transfused before any other treatment was undertaken (P = 0.002) were the only two variables independently associated with survival without rebleeding. After adjustment for base-line differences between the two groups, the odds ratio for treatment failure in the placebo group, as compared with the octreotide group, was 3.3 (95 percent confidence interval, 1.5 to 7.3). The mean (+/- SD) 15-day cumulative survival rate (estimated by the Kaplan-Meier method) was 88 +/- 12 percent in both groups. Side effects were minor, and their incidence was similar in the two groups. CONCLUSIONS In patients with cirrhosis, the combination of sclerotherapy and octreotide is more effective than sclerotherapy alone in controlling acute variceal bleeding, but there is no difference between the overall mortality rates associated with the two approaches to treatment.

Early feeding or enteral nutrition in patients with cirrhosis after bleeding from esophageal varices? A randomized controlled study.

The aim of this randomized controlled study wasto assess the nutritional and clinical effects of earlyenteral nutrition (EN) in cirrhotic patients withbleeding from esophageal varices. From August 1994 through August 1995, all patients admitted foracute variceal bleeding underwent emergencysclerotherapy or banding ligation and continuousinfusion of octreotide and were randomized in twogroups. In group A, patients received from day 1 discontinuouspolymeric EN (1665 kcal/day, through nasogastric tube)and in group B, patients were nil by mouth. On day 4,all patients received oral diet. Nutritional status, liver function, and rebleeding were evaluatedon days 4, 7, and 35. Twenty-two patients (17 men, 5women, mean age 56 years) were included. On day 0,patients in group A (N = 12) and group B (N = 10) werecomparable. On day 4, nitrogen balance was 0.7 ± 2.5g/day in group A and –11.2 ± 6.7 g/day ingroup B (P = 0.01, Mann-Whitney test). On days 4, 7, and35, no significant differences between the two groupswere observed for nutritional status and liver function. Four(33%) group A patients rebled compared with one (10%)group B patient (NS). Hospital stay (14.5 ± 4.1days vs 12.9 ± 5.3 days) and mortality (3 vs 2patients), were comparable between the two groups. Inconclusion, our study failed to demonstrate anyfavorable effect of short-term EN on nutritional statusand liver function in cirrhotic patients hospitalizedfor variceal bleeding.

Is ursodeoxycholic acid an effective therapy for total parenteral nutrition-related liver disease?

Cholestasis is the predominant complication in patients with total parenteral nutrition-related liver disease. Ursodeoxycholic acid has been reported to be beneficial for patients with various chronic cholestatic liver diseases. The aim of this prospective study was to determine the effects of short-term administration of ursodeoxycholic acid in nine patients (mean age 54 years) treated with home total parenteral nutrition (31 +/- 2 (mean +/- SEM) kcal/kg per day) for 13.9 +/- 5.2 months for short bowel syndrome; all presented biological evidence of hepatic cholestasis (mean alkaline phosphatase activity 5.2 times the upper limit of the normal) which appeared during nutrition; there was no cause of hepatic dysfunction other than total parenteral nutrition. Patients received 11.2 +/- 0.8 mg/kg per day of ursodeoxycholic acid orally for 1 (n = 9) or 2 (n = 5) 2-month periods, each of which was followed by a 2-month wash-out period. Liver function tests were performed before and at the end of each period. Compared with non-treatment periods, the two periods of ursodeoxycholic acid administration induced a significant reduction in gamma-glutamyl transpeptidase (27.1% and 20.4% respectively; p = 0.001) and alanine aminotransferase serum activities (7.0% and 34.8% respectively; p = 0.01) from baseline values. Alkaline phosphatase activity (p = 0.09), aspartate aminotransferase (p = 0.11) and bilirubin (p = 0.75) serum activities underwent no significant change during the study. These preliminary results strongly suggest that short-term ursodeoxycholic acid administration leads to biochemical improvement in liver function tests in patients with total parenteral nutrition-related liver disease.

Anti-inflammatory drugs and variceal bleeding: a case-control study

Background Non-steroidal anti-inflammatory drugs (NSAIDs) can have severe gastrointestinal effects and cause peptic ulcers to bleed. Acute bleeding from oesophageal varices is a major complication of cirrhosis of the liver. Aims To investigate the role, using a case-control study, of NSAIDs in first bleeding episodes associated with oesophageal or cardial varices in cirrhotic patients. Patients/Methods A structured interview was conducted of 125 cirrhotic patients with bleeding mainly related to oesophageal varices and 75 cirrhotic controls with oesophageal varices who had never bled. Results Cirrhotic patients who were admitted for bleeding related to portal hypertension were more likely to have used NSAIDs during the week before the index day (31 of 125 (25%)) than the cirrhotic controls (eight of 75 (11%); odds ratio = 2.8, p = 0.016). Use of aspirin alone or combined with other NSAIDs was also more prevalent in the cases (21 of 125 (17%)) than in the controls (three of 75 (4%); odds ratio = 4.9, p = 0.007). Logistic regression analysis showed that NSAID use (p = 0.022, odds ratio = 2.9, 95% confidence interval = 1.8 to 4.7) and variceal size (p<0.001, odds ratio = 4.0, 95% confidence interval = 1.4 to 11.5) were the only variables independently associated with the risk of bleeding. Conclusions Aspirin, used alone or combined with other NSAIDs, was associated with a first variceal bleeding episode in patients with cirrhosis. Given the life threatening nature of this complication, the possible benefit of this treatment should be weighed against the risk shown here. No firm conclusions could be drawn on non-aspirin NSAIDs used alone.

Randomised trial of prevention of biliary stent occlusion by ursodeoxycholic acid plus norfloxacin

Biliary stents are liable to clog. We investigated whether a choleretic plus an antibiotic could delay clogging. 20 consecutive patients with a malignant biliary stricture were randomised after endoscopic insertion of a polyethylene stent to receive ursodeoxycholic acid plus norfloxacin (13-15 mg/kg and 400 mg, daily) or conservative treatment. The drug combination was associated with: a longer median patency of first (49 vs 6 weeks) and all stents (38 vs 7 weeks); a prolonged median survival (67 vs 18 weeks); and a shorter mean hospital stay (0.2 vs 1.0 days per week of survival). Thus ursodeoxycholic acid plus norfloxacin may prevent stent clogging.

Cirrhosis and bleeding: the need for very early management.

BACKGROUND/AIMS Retrospective studies suggest that the prognosis of patients with cirrhosis and variceal hemorrhage has improved in more recent decades. In a prospective cohort study in which the choice of prophylactic therapy was left to each practitioner, we followed cirrhotic patients with medium/large varices to determine factors predictive of bleeding and death. METHODS Three hundred fourteen patients with grades 2 or 3 esophageal varices (Child A and B/C: 218 and 96) were enrolled. One hundred seventy-three patients had no previous history of variceal bleeding. Only 245 patients (100% of patients with prior variceal hemorrhage, 61% of patients without prior hemorrhage) were receiving some form of prophylactic therapy. The median follow-up was 18 months. RESULTS There were 76 bleeding events and 14 related deaths (18%); nine of these deaths occurred within 24 h of bleeding onset (two at home, two during hospital transfer, and five in hospital, a mean of 2.5 h after onset; six involved Child C patients). Twenty-five deaths were not due to bleeding but were closely related to cirrhosis. In a Cox model, the presence of tense ascites (relative risk 3.4, 95% confidence interval, CI 2.5-5.9) and a prior history of hemorrhage (relative risk 4.4, 95% CI 2.6-7.5) were independent predictors of variceal hemorrhage. In patients without a prior history of bleeding, bleeding risk was higher with more prolonged prothrombin time and lower when patients were receiving propranolol. CONCLUSIONS Despite the advent of effective drugs and endoscopic therapy for variceal bleeding, about a quarter of deaths occur very early after bleeding onset, confirming the need for rapid specific management.

Treatment and long-term outcome of chronic radiation esophagitis after radiation therapy for head and neck tumors. A report of 13 cases.

The natural history of chronic radiation esophagitis occuring in previously normal esophagus is still unknown. We describe here the long-term outcome of chronic esophagitis arising after neck irradiation for oropharynx and larynx carcinomas in 13 consecutive adult patients. The first clinical signs of radiation esophagitis were dysphagia or impossibility of oral intake, which appeared within 26 months (range 2–120 months) after the end of radiation for pyriform fossae carcinoma (N=5), tonsil carcinomaN=2), larynx carcinoma (N=2), pharynx carcinoma (N=2), base of the tongue (N=1), and thyroid carcinomas (N=1). During upper endoscopy, an esophageal stenosis was found in 11 cases and was associated with ulceration in three cases. An isolated esophageal ulceration was present in only two cases. Chronic radiation esophagitis diagnosis was confirmed by histology and durgery in seven cases. In the last six cases, diagnosis was supported by the absence of first cancer relapses within a median follow-up of two years (16 months to nine years) and by endoscopic findings. Seven patients received parenteral or enteral nutrition. Ten patients were treated by peroral dilatation. These treatments allowed nearly normal oral diet in 11/13 patient. Only one patient was lost of follow-up after 20 months. Four patients died from chronic radiation esophagitis. One of these patients died from massive hemorrhage after peroral dilatation. Four patients died of a second carcinoma with no first cancer recurrence. Four patients were alive after dix months to nine years of follow-up. Moderate dysphagia was still present, allowing nearly normal oral feeding. In conclusion, chronic radiation esophagitis is a severe disease with an underestimated frequency. In our study, peroral dilatations appeared to be necessary and were not associated with an increased morbidity.

Granulomatous hepatitis due to combination of amoxicillin and clavulanic acid

SummaryWe report the case of a patient with amoxicillinclavulanic acid-induced hepatitis with histologic multiple granulomas. This type of lesion broadens the spectrum of liver injury due to this drug combination, mainly represented by a benign cholestatic syndrome. The association of granulomas and eosinophilia favor an immunoallergic mechanism. As penicillin derivatives and amoxicillin alone are known to induce such types of lesions, the amoxicillin component, with or with-out a potentiating effect of clavulanic acid, might have a major role.

Short-term and long-term vital outcomes of cirrhotic patients admitted to an intensive care unit.

Objective To evaluate short-term and long-term vital outcomes of cirrhotic patients admitted to a general ICU, to evaluate the prognostic value of severity scores and to identify risk factors associated with death. Methods Observational retrospective single-center epidemiological study. All cirrhotic patients admitted to the ICU were eligible for the study. Clinical data, general ICU severity scores, and liver-specific severity scores were recorded. The mortality rate was analyzed during the stay in ICU, at day 28 and month 6 after admission. Risk factors for death were identified by univariate and multivariate analyses. Results During the study period, 86 cirrhotic patients were admitted to the ICU. The in-ICU, day-28 and month-6 mortality rates were 37, 48, and 60%, respectively. In the multivariate analysis, mechanical ventilation, the prothrombin time, and the plasma albumin level on admission were associated with the in-ICU mortality, whereas only the plasma albumin level was associated with the 6-month mortality [odds ratio 0.80; 95% confidence interval (0.70–0.92)]. The Sequential Organ Failure Assessment score was more predictive than liver-specific scores for mortality in the ICU, but not at day 28 or month 6. Conclusion ICU admission should not be ruled out for patients with complicated cirrhosis. Although common in cirrhotic patients, low plasma albumin level was the only factor independently associated with short-term and long-term mortalities.

Non-steroidal anti-inflammatory drugs and variceal bleeding: a case-control study

BACKGROUND/AIM The aim of this case-control study was to assess the risk of bleeding from esophageal varices associated with aspirin and non-steroidal anti-inflammatory drug consumption. METHODS Between January 1992 and May 1994, patients admitted for bleeding from esophageal or gastric lesions related to portal hypertension were matched with a control patient of the same age and sex, who was free of gastrointestinal bleeding. A structured interview was conducted with the cases and controls to determine drug consumption during the 2 weeks preceding admission. Fifty-nine cases and 59 controls were recruited. RESULTS/CONCLUSIONS Use of aspirin was more prevalent among the cases than the controls (odds ratio 3.81; 95% confidence interval 1.36-11.64; p = 0.004). This difference remained significant in the subgroups of patients with a first episode of variceal bleeding (odds ratio 3.9; 95% confidence interval 1.2-13.9, p = 0.01), but was not significant in the subgroups of patients with a recurrent episode of variceal bleeding. The use of aspirin was associated with a high risk of a first episode of variceal bleeding, suggesting that patients with portal hypertension should avoid taking these drugs.