Treatment of chronic hepatitis C with amantadine.

Hepatitis C is usually treated with interferon or a combination of interferon and ribavirin, but these agents have numerous side effects, and interferon must be given by injection three time a week. An alternative oral medication would be a welcome advance for treating hepatitis C. Amantadine has been reported to have the potential to produce viral suppression in patients with hepatitis C. To gain further knowledge about the effects of amantadine on hepatitis C, we treated 24 patients for 3-12 months (average = 5.5 months; median = 4.5 months) with 100 mg amantadine twice daily. Twelve patients had stage 3 or 4 fibrosis on biopsy. Eleven patients had a fall in viral titer, but complete viral suppression was not seen in any patient. Three patients had no viral titer obtained after treatment, but their elevated transaminase levels did not change with treatment. Of the 15 patients with a decrease in enzyme levels, only two patients had normalization. Six patients had side effects during the treatment, but in only one was amantadine stopped solely because of side effects. Based on these results and a literature review, we do not believe amantadine is an effective single agent for the treatment of chronic hepatitis C.

Endoscopic variceal ligation is superior to combined ligation and sclerotherapy for esophageal varices: a multicenter prospective randomized trial.

Patients who have bled from varices remain at risk for rebleeding. There is interest in methods that would enable rapid eradication of varices. The present trial was designed to study whether combining ligation with sclerotherapy will allow quicker eradication of varices than either modality alone. Patients with bleeding esophageal varices were randomized into ligation or combination therapy groups. Patients in the ligation group were treated with endoscopic rubber band ligation alone. In combination group patients, each variceal column was ligated distally and 1 mL of ethanolamine was injected proximal to each ligated site. Subsequent treatment sessions were at 7- to 14-day intervals until varices were eradicated. The clinical and endoscopic characteristics of 25 patients in the ligation group were similar to those of 22 patients in the combination group. Follow-up was up to 30 months. Active bleeding was controlled in 100% of patients in the ligation group and 75% of those in combination group (P = NS). It took 3.3 +/- .4 (range, 1-7) sessions to eradicate varices with ligation and 4.1 +/- .6 (1-7) with combination therapy (P = NS). Survival (four deaths in ligation group, 8 in combination group), rebleeding rate (25% vs. 36%), and varix recurrence (16% vs. 23%) also were similar. There were more complications with combination therapy, including deep ulcers (65% vs. 20%; P < .05); dysphagia (30% vs. 0%; P < .05), with three strictures requiring dilation; and pain (30% vs. 10%; P = NS). Our results show that sclerotherapy combined with ligation offers no benefit over ligation alone. The higher complication rate with combination therapy does not warrant this approach.

Three years experience with endoscopic variceal ligation for treatment of bleeding varices.

Endoscopic variceal ligation (EVL) was developed as an alternative to endoscopic variceal sclerosis (ES) because of the high complication rate seen with ES. The new technique involves placement of small elastic bands around the variceal channels in the distal esophagus. The first 146 consecutive patients treated with EVL during the period from August, 1986 to July, 1989 are reported. Portal hypertension was caused by alcoholic liver disease in 93 of these patients. The average age of the patients was 53 years and 66% were males. All of the patients had recently bled from esophageal varices. At the time of treatment, 23% of the patients were actively bleeding. They were all treated acutely with EVL and had repeated treatments with the long-term goal of variceal eradication. The overall survival was 73%. Varices were eradicated or reduced to grade one in 78% of the 125 patients who were followed for more than 30 days. Variceal eradication required a mean of 5.5 sessions. Recurrent bleeding occurred in 44% of the total patient population. There were no major complications from EVL. It is concluded from this non-randomized experience that EVL is an effective treatment for bleeding esophageal varices and that it appears to be as effective as sclerotherapy with fewer complications.

Endoscopic sclerotherapy as compared with endoscopic ligation for bleeding esophageal varices.

BACKGROUND: Endoscopic sclerotherapy is an accepted treatment for bleeding esophageal varices, but it is associated with substantial local and systemic complications. Endoscopic ligation, a new form of endoscopic treatment for bleeding varices, may be safer. We compared the effectiveness and safety of the two techniques. METHODS: In this randomized trial we compared endoscopic sclerotherapy and endoscopic ligation in 129 patients with cirrhosis who had proved bleeding from esophageal varices. Sixty-five patients were treated with sclerotherapy, and 64 with ligation. Initial treatment for acute bleeding was followed by elective retreatment to eradicate varices. The patients were followed for a mean of 10 months, during which we determined the incidence of complications and recurrences of bleeding, the number of treatments needed to eradicate varices, and survival. RESULTS: Active bleeding at the first treatment was controlled by sclerotherapy in 10 of 13 patients (77 percent) and by ligation in 12 of 14 patients (86 percent). Slightly more sclerotherapy-treated patients had recurrent hemorrhage during the study (48 percent vs. 36 percent for the ligation-treated patients, P = 0.072). The eradication of varices required a lower mean (+/- SD) number of treatments with ligation (4 +/- 2 vs. 5 +/- 2, P = 0.056) than with sclerotherapy. The mortality rate was significantly higher in the sclerotherapy group (45 percent vs. 28 percent, P = 0.041), as was the rate of complications (22 percent vs. 2 percent, P less than 0.001). The complications of sclerotherapy were predominantly esophageal strictures, pneumonias, and other infections. CONCLUSIONS: Patients with cirrhosis who have bleeding esophageal varices have fewer treatment-related complications and better survival rates when they are treated by esophageal ligation than when they are treated by sclerotherapy.

Precholecystectomy endoscopic cholangiography and stone removal is not superior to cholecystectomy, cholangiography, and common duct exploration.

Thirty-four patients with suspected common bile duct stones were randomized to undergo endoscopic cholangiography and stone removal prior to open cholecystectomy or to have open cholecystectomy, operative cholangiography, and common bile duct exploration. Sixteen underwent the first protocol, and 18 the second. Analysis of the ability to clear stones from the common bile duct, morbidity, mortality, hospital stay, length of operation, and hospital cost showed no difference in outcome between patients treated by either method. These data suggest there is neither an advantage nor a disadvantage to treating patients with suspected duct stones by precholecystectomy endoscopic cholangiography and stone removal.

The effect of intravenous diazepam on esophageal motility in normal subjects.

Controversy exists over whether diazepam can be used for sedation during esophageal manometry studies without affecting the results. To evaluate the effect of diazepam, 20 healthy asymptomatic volunteers were studied using a standard manometry protocol employing an Arndorfer capillary infusion system. Following a baseline manometry, each subject received 0.1 mg/kg diazepam intravenously over 1 min and underwent repeat manometry 5 min after completion of the injection. All manometry recordings were coded and read blindly. The amplitude of the lower esophageal sphincter was significantly reduced by diazepam from 26.2 +/- 10.9 and 30.0 +/- 10.9 mm Hg to 18.8 +/- 7.6 and 24.5 +/- 9.7 mm Hg by rapid and station pull-through methods, respectively (P less than 0.01 both methods). Esophageal contraction wave duration was significantly increased following diazepam at 3, 8, and 13 cm above the lower esophageal sphincter (P less than 0.01 all levels). There was a trend toward increased contraction wave amplitude following diazepam administration in the lower three fourths of the esophagus. On the basis of these results, we conclude that diazepam sedation may produce misleading results when used during esophageal manometric testing. It is recommended that diazepam not be used in manometric studies of normal subjects or patients with reflux esophagitis and that manometric findings in patients with hypertensive or spastic disorders be interpreted with caution if diazepam is given as a premedication.

Increased secondary bile acids in a choledochal cyst. Possible role in biliary metaplasia and carcinoma.

Choledochal cysts are uncommon congenital or acquired lesions of the biliary tree. The incidence of biliary tract carcinoma in patients with choledochal cysts is 5-35 times greater than that of the general population. Factors responsible for the increased risk of carcinoma are unknown. The case of a young woman who underwent excision of a choledochal cyst 16 years after initial diagnosis and treatment by choledochocystduodenostomy is reported. Metaplasia of the epithelial lining of the cyst was found in the resected specimen. The relative composition of bile acids in cyst contents was as follows: lithocholate, 2%; deoxycholate, 88%; chenodeoxycholate, 5%; and cholate, 5%. Virtually all bile acids were recovered in unconjugated form. In contrast, the bile acid composition of hepatic bile was as follows: lithocholate, 0%; deoxycholate, 34%; chenodeoxycholate, 43%; and cholate, 23%. Bile acids were fully conjugated. These data suggest that stasis of bile within choledochal cysts contributes to bacterial overgrowth and generation of unconjugated secondary bile acids.

Endoscopic ligation of esophageal varices.

One hundred consecutive patients with bleeding esophageal varices were treated with a new endoscopic ligating device that effects strangulation of varices using small elastic "O" rings. Treatments were continued after initial hospitalization to achieve variceal eradication. Follow-up ranged from 6 to 26 (mean: 15) months. Bleeding was controlled until discharge from hospital or death in 18 of 21 patients who were actively bleeding at index endoscopy. Overall, 26 patients died during the study, 12 during the index hospitalization. Cause of death was organ failure in 21, exsanguination in 3, and cancer in 2. Forty-one of 88 initial survivors experienced 72 episodes of recurrent bleeding (1 to 4 per patient). All but five rebleeds occurred before eradication. Sixty of 88 patients (68%) who survived index hospitalization had their varices eradicated. A median of 5 (1 to 12) treatments was required. Nine patients eventually had other forms of treatment for recurrent bleeding. Only 3 non-bleeding complications resulted from 462 endoscopic treatment sessions. We conclude that endoscopic ligation controls active variceal bleeding and eradicates varices with efficacy similar to that of sclerotherapy and with minimal risk of complications.

Endoscopic sclerotherapy versus endoscopic variceal ligation: esophageal symptoms, complications, and motility.

Endoscopic sclerotherapy is an effective method for treating bleeding esophageal varices. However, a number of complications may limit its usefulness. A newly developed method for treating bleeding varices, endoscopic variceal ligation, that uses small rubber bands to occlude and eradicate the varices, may cause less damage to the esophagus. Twenty-eight patients (seven with no prior treatment, eight undergoing sclerotherapy, and 12 undergoing variceal ligation) were evaluated with a symptom questionnaire and esophageal manometry. The lower esophageal sphincter (LES) pressures in the three groups did not differ. The percent LES relaxation was significantly (p = 0.04) less in the sclerotherapy group than in the untreated group. Contraction waves in the esophageal body were not different in amplitude, duration, and propagation speed in the three groups. There was no increase in the amount of heartburn after either form of treatment. Eight of the nine sclerotherapy patients had a stricture after treatment that required dilatation, whereas none of the ligation patients had strictures. We conclude from this that early in the course of sclerotherapy, stricture formation is common, but any long-lasting adverse effect on esophageal function is minimal. We also conclude variceal ligation therapy causes less esophageal dysfunction and has fewer local complications. Thus, endoscopic variceal ligation may be a safer and more easily tolerated alternative to endoscopic sclerotherapy.