Francisco Vilardell

Nadolol plus Isosorbide Mononitrate Compared with Sclerotherapy for the Prevention of Variceal Rebleeding

BACKGROUND Patients who have bleeding from esophageal varices are at high risk for rebleeding and death. We compared the efficacy and safety of endoscopic sclerotherapy with the efficacy and safety of nadolol plus isosorbide mononitrate for the prevention of variceal rebleeding. METHODS Eighty-six hospitalized patients with cirrhosis and bleeding from esophageal varices diagnosed by endoscopy were randomly assigned to treatment with repeated sclerotherapy (43 patients) or nadolol plus isosorbide-5-mononitrate (43 patients). The primary outcomes were rebleeding, death, and complications. The hepatic venous pressure gradient was measured at base line and after three months. RESULTS Base-line data were similar in the two groups, and the median follow-up was 18 months in both. Eleven patients in the medication group and 23 in the sclerotherapy group had rebleeding. The actuarial probability of remaining free of rebleeding was higher in the medication group for all episodes related to portal hypertension (P = 0.001) and variceal rebleeding (P = 0.002). Four patients in the medication group and nine in the sclerotherapy group died (P = 0.07 for the difference in the actuarial probability of survival). Seven patients in the medication group and 16 in the sclerotherapy group had treatment-related complications (P = 0.03). Thirty-one patients in the medication group underwent two hemodynamic studies; 1 of the 13 patients with more than a 20 percent decrease in the hepatic venous pressure gradient had rebleeding, as compared with 8 of the 18 with smaller decreases in the pressure gradient (P = 0.04) for the actuarial probability of rebleeding at two years). CONCLUSIONS As compared with sclerotherapy, nadolol plus isosorbide mononitrate significantly decreased the risk of rebleeding from esophageal varices.

Norfloxacin Prevents Bacterial Infection in Cirrhotics With Gastrointestinal Hemorrhage

To assess the efficacy of selective intestinal decontamination with norfloxacin in the prevention of bacterial infections in cirrhotic patients with gastrointestinal hemorrhage, 119 patients were included in a prospective randomized study. Group 1 (n = 60) received norfloxacin orally or through a nasogastric tube, 400 mg twice daily for 7 days beginning immediately after emergency gastroscopy; group 2 (n = 59) was the control group. We found a significantly lower incidence of infections (10% vs. 37.2%; P = 0.001), bacteremia and/or spontaneous bacterial peritonitis (3.3% vs. 16.9%; P less than 0.05), and urinary infections (0% vs. 18.6%; P = 0.001) in patients receiving norfloxacin, as a consequence of decrease in the incidence of infections caused by aerobic gram-negative bacilli. The decrease in mortality observed in the treated group (6.6% vs. 11.8%) did not reach statistical significance. The cost for antibiotic treatment showed a 62% reduction in the treated group compared with the control group. The results show that selective intestinal decontamination with norfloxacin is useful in preventing bacterial infections in cirrhotics with gastrointestinal hemorrhage.

Selective intestinal decontamination prevents spontaneous bacterial peritonitis

In a prospective randomized study, selective intestinal decontamination with norfloxacin was performed during hospitalization in 32 cirrhotic patients with low ascitic fluid total protein levels. The incidence of infections was compared with that in a control group of 31 nontreated cirrhotic patients of similar characteristics. We found a significantly lower incidence of infections [1/32 (3.1%) vs. 13/31 (41.9%); P less than 0.005] and spontaneous bacterial peritonitis [0/32 (0%) vs. 7/31 (22.5%); P less than 0.05] in patients receiving norfloxacin. The lower incidence of extraperitoneal infections [1/32 (3.1%) vs. 7/31 (22.5%); P = 0.052] in the treated group did not reach statistical significance. The incidence of infections [1/28 (3.6%) vs. 9/22 (40.9%); P less than 0.01] and spontaneous bacterial peritonitis [0/28 (0%) vs. 5/22 (22.7%); P less than 0.05] in cirrhotic patients admitted because of ascites was also significantly lower in the treated group. The decrease in the rate of mortality observed in the group undergoing selective intestinal decontamination did not reach statistical significance. These data show that selective intestinal decontamination is useful to prevent spontaneous bacterial peritonitis and extraperitoneal infections in hospitalized cirrhotic patients with low ascitic fluid total protein levels.

Controlled trial of tamoxifen in patients with advanced hepatocellular carcinoma

Thirty-six consecutive patients with advanced hepatocellular carcinoma and chronic liver disease were randomly allocated to two groups: group I included 20 patients who were treated with 10 mg bid. tamoxifen and group II with 16 non-treated patients. The two groups were homogeneous according to clinical and analytical data. Survival curves in the tamoxifen-treated patients improved significantly when compared with the non-treated group (p = 0.01). Cumulative survival at the end of the first year was 48.5% in the treated patients and 9.1% in controls. Median survival was 261 days in the treated group vs. 172 in the non-treated group (p < 0.05). Complications of cirrhosis and worsening of the performance status test occurred less in the treated patients than in the controls, but not significantly so. Tamoxifen was well tolerated and no marked side effects were observed. In this series, tamoxifen improved survival in patients with advanced hepatocellular carcinoma.

Low C3 in cirrhotic ascites predisposes to spontaneous bacterial peritonitis

The risk of developing spontaneous bacterial peritonitis (SBP) in relation to the concentration of C3 in ascitic fluid (AF) has been studied prospectively in 33 patients with cirrhosis of the liver, seven of whom had one or more episodes of SBP during hospitalization. C3 concentrations in the AF of patients who developed infection (9.0 +/- 2.67 mg/dl) were significantly lower than in those who did not (18.26 +/- 8.11 mg/dl) (P less than 0.01). C4 concentrations were similar in both groups. A direct correlation was found between AF C3 and total protein concentrations (P less than 0.001). We conclude that a low C3 concentration in AF may predispose to SBP.

Value of second-look endoscopy after injection therapy for bleeding peptic ulcer: A prospective and randomized trial

A prospective and randomized trial involving 104 patients was performed to assess whether second-look endoscopy could improve the efficacy of injection therapy for bleeding ulcers. The inclusion criteria were the presence of active arterial bleeding or a non-bleeding visible vessel at emergency endoscopy. All the patients received emergency injection of 1:10,000 adrenaline and were subsequently randomized (52 patients in each group) according to whether or not they would receive a second elective endoscopy within the first 24 hours with repeated injection if a visible vessel was still identified. Both groups were well matched for clinical and endoscopic data. A tendency towards better results was noted in the group that received a second-look endoscopy; the two groups were compared in regard to further bleeding (21% versus 29%, 95% confidence interval of the difference = -24.3 to 8.5), need for emergency surgery (8% versus 15%, 95% confidence interval of the difference = -19.9 to 4.5), transfusion requirements (1.7 +/- 1.9 versus 2.5 +/- 2.5 units, 95% confidence interval of the difference = -1.6 to 0.07), length of hospital stay (9.3 +/- 8.6 versus 11.8 +/- 10.8 days, 95% confidence interval of the difference = -6.2 to 1.4), and mortality rate (2% versus 4%). Although these trends did not achieve statistical significance, a type II error cannot be ruled out. However, according to our results, several hundred patients would be required to demonstrate statistically these relatively small differences.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence of thyroid autoantibodies is not increased in blood donors with hepatitis C virus infection

Serum autoimmune reactions are found in many patients with hepatitis C. A high prevalence of thyroid dysfunction and antithyroid antibodies in patients with chronic hepatitis C was recently reported. We have compared the prevalence of thyroid dysfunction and antithyroid peroxidase antibodies in blood donors with hepatitis C virus (HCV) infection (study group) and in seronegative anti-HCV donors (control group). One hundred and ninety-two blood donors were studied: 96 were anti-HCV positive by ELISA 2 (48 males and 48 females; age 48 +/- 12.9 years, mean +/- SD), and 96 were HCV seronegative (55 males and 41 females; age 37 +/- 14.8 years). In all patients, serum TSH (0.25-4.2 mU/l) and fT4 (9-23 pmol/l) were measured by immunochemiluminiscent assays and antithyroid peroxidase antibodies (normal < 100 U/ml) by RIA. In all anti-HCV positive donors, hepatitis C viremia was tested using the nested polymerase chain reaction. Thyroid dysfunction was found in three females (3.1%) in the anti-HCV positive group (three cases of hypothyroidism), and in four (4.1%) anti-HCV negative blood donors (three cases of hypothyroidism, two females and one male; one case of hyperthyroidism, a female), (p = NS). Antithyroid peroxidase antibody titers were above normal values in 5 (5.2%) anti-HCV positive individuals and in eight (8.3%) anti-HCV negative blood donors (p = NS). These results do not show an increase prevalence of thyroid dysfunction and antithyroid peroxidase antibodies in blood donors with HCV infection when compared with a control group.

Endoscopic injection therapy of bleeding ulcer: a prospective and randomized comparison of adrenaline alone or with polidocanol.

In a prospective randomized trial involving 63 patients with bleeding peptic ulcer, we assessed whether the addition of 1% polidocanol improved the results achieved by 1/10(4) adrenaline alone for injection therapy. The inclusion criterion was the presence of active arterial bleeding or a nonbleeding visible vessel at emergency endoscopy. Thirty patients were treated with 1/10(4) adrenaline (group A) and 33 with adrenaline plus 1% polidocanol (group B). Initial hemostasis was achieved in 97% of cases in both groups and permanent hemostasis in 87% patients in group A and in 76% in group B (p = NS). Mortality was 6% in group A and 3% in group B. There were no differences between the two groups regarding requirements for emergency surgery, the number of transfusions, or the length of hospital stay. One patient in group B had a perforation. No other relevant complications were noted. In conclusion, combined therapy does not improve the results achieved with adrenaline alone.

Systemic prostacyclin in cirrhotic patients: Relationship with portal hypertension and changes after intestinal decontamination

The total body production of prostacyclin was shown to be increased in cirrhotic patients, suggesting that its synthesis by blood vessels of the systemic circulation is enhanced. However, the mechanism by which the synthesis of systemic prostacyclin is stimulated is not known. The present study investigated the urinary excretion of 2,3-dinor-6-keto-PGF1 alpha, an index of total body prostacyclin synthesis, first, in cirrhotics with portal hypertension (n = 19) as compared with cirrhotics with reduced portal pressure after portacaval shunt surgery (n = 18) and with control noncirrhotic subjects (n = 11), and; second, in cirrhotics before and after intestinal decontamination by oral nonabsorbable antibiotics (n = 9 antibiotic treated patients, n = 10 control nontreated cirrhotics). Control noncirrhotic subjects showed lower urinary excretion of 2,3-dinor-6-keto-PGF1 alpha than both groups of cirrhotics (P less than 0.001). Interestingly, urinary excretion of 2,3-dinor-6-keto-PGF1 alpha was significantly higher in cirrhotics with portacaval shunt than in those with portal hypertension (P less than 0.01). The urinary excretion of 2,3-dinor-6-keto-PGF1 alpha decreased significantly after intestinal decontamination in the antibiotic-treated group (580.1 +/- 232.4 vs. 431.2 +/- 219.2 pg/mg creatinine; P less than 0.05) but not in nontreated patients (543.9 +/- 214.4 vs. 581.2 +/- 281.4 pg/mg creatinine; P = NS). These data suggest that the increased urinary excretion of 2,3-dinor-6-keto-PGF1 alpha observed in cirrhotics is not directly related to portal hypertension itself but to portal blood factors that bypass the liver. Some such factors may be of intestinal bacterial origin.

Early microbiologic diagnosis of spontaneous bacterial peritonitis with BacT/ALERT

BACKGROUND/AIMS Inoculation of ascitic fluid into conventional blood culture bottles is more sensitive than conventional culture in the diagnosis of spontaneous bacterial peritonitis. BacT/ALERT is an automated colorimetric microbial detection system that has been shown to be faster than conventional blood culture bottles in the diagnosis of bacteremia. The aim of the study was to compare the BacT/ALERT system with the conventional culture and the conventional blood culture bottles method in the diagnosis of spontaneous bacterial peritonitis. METHODS All the ascitic fluid samples from patients with cirrhosis hospitalized in our Department between September 1992 and May 1994 (n=1032) were prospectively evaluated. In all cases, an aliquot of ascitic fluid was sent for Grams stain and conventional culture, and 20 ml were inoculated at the bedside into blood culture bottles: 10 ml into conventional blood culture bottles and 10 ml into BacT/ALERT. RESULTS Thirty ascitic fluid infections (23 spontaneous bacterial peritonitis and 7 neutrocytic ascites) and 20 bacterascites were diagnosed. Conventional culture was positive in 10/30 ascitic fluid infections (33.3%), conventional blood culture bottles in 22/30 (73.3%) (p<0.01 compared to conventional culture) and BacT/ALERT in 20/30 (66.6%) (p<0.05 compared to conventional culture, pNS compared to conventional blood culture bottles). The time elapsed for culture positivity was 43.4+/-34.2 h for conventional blood culture bottles and 13.3+/-9.2 h for BacT/ALERT (p<0.001). Thirteen of the 23 cases of spontaneous bacterial peritonitis (56.5%) were detected within the first 12 h with BacT/ALERT, as compared to only three (13%) with conventional blood culture bottles (p<0.03). CONCLUSION The automated system BacT/ALERT provides an earlier microbiologic diagnosis of spontaneous bacterial peritonitis than conventional blood culture bottles with similar sensitivity.