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.

Long-term experience with the transpancreatic sphincter pre-cut approach to biliary sphincterotomy.

BACKGROUND: The transpancreatic duct pre-cut to gain access to the bile duct for diagnostic and therapeutic maneuvers has been described as useful, but questions of efficacy and safety remain to be resolved. METHODS: To further evaluate this technique, we performed a review on 200 consecutive endoscopic sphincterotomies. Standard direct biliary sphincterotomy was performed in 143 patients and transpancreatic duct pre-cut in 51 patients. RESULTS: The overall complication rate for the standard sphincterotomy was 2.1%; that for the transpancreatic approach was 1.96%. There were no cases of post-ERCP pancreatitis after transpancreatic duct pre-cut sphincterotomy. The length of hospital stay was 1 day or less for 192 patients, 2 days for 5 patients, 4 days for 1 patient and 7 days for 2 patients. In 2 patients there was failure to enter the bile duct despite the pre-cut. In one, the procedure was successful at a second attempt 48 hours later. CONCLUSIONS: Transpancreatic duct pre-cut is a safe and effective method for gaining quick access to the bile duct in patients in whom cannulation is difficult.

Lansoprazole: a cause of secretory diarrhea.

A case of severe diarrhea and hypergastrinemia after 6 wk of lansoprazole therapy is presented. This represents the only fully evaluated report of severe diarrhea due to lansoprazole and comes to the interesting conclusion that it was a secretory diarrhea likely due to lansoprazole and not a gastrinoma or another cause.

Measuring outcome after liver transplantation: a critical review.

As the number of liver transplantations performed around the world and the survival rates increase, attention is turning to the broad impact this procedure has on patients' quality of life (QOL), including their physical and psychosocial functioning and their perceived sense of well-being. There exists a small body of literature that examines the global effects of liver transplantation on QOL. The purpose of this article is to discuss the general framework used to assess QOL and to critically review the studies that have broadly examined QOL outcomes after liver transplantation. The reviewed studies used measures that led to broad assessment of the various domains of QOL. Although the instruments used to measure QOL in these studies are largely validated, there is significant heterogeneity in this literature in terms of the instruments used, leading to difficulties in making generalizable conclusions among the studies. Although limited by internal validity problems, the available data suggest improvement in QOL by liver transplantation. Additionally, a large recent study that used the Liver Transplant Database Quality of Life Questionnaire also reported a subset of patients in whom QOL seemed to worsen after liver transplantation. Knowledge of the factors related to QOL outcome after liver transplantation is important because it might allow development of new interventions that may have an impact on future allocation decisions.

Percutaneous mesenteric venous thrombectomy and thrombolysis: successful treatment followed by liver transplantation.

Mesenteric vein thrombosis (MVT) is a rare cause of intestinal ischemia. Because of its nonspecific symptoms, diagnosis is often delayed. We describe a patient with liver cirrhosis who developed acute MVT while waiting for liver transplantation. Surgical intervention carried a high risk because of her underlying cirrhosis. Mesenteric venous thrombectomy and thrombolysis were performed with an AngioJet (Possis Medical, Minneapolis, MN) thrombectomy device and streptokinase infusion through transjugular route. The patient subsequently received an orthotopic liver transplant. We also present a review of the literature about the occurrence and treatment options for MVT.

Endoscopic intervention for biliary leaks after laparoscopic cholecystectomy: a multicenter review.

BACKGROUND: Endoscopic therapy of biliary tract leaks was uncommon before laparoscopic cholecystectomy. Studies have demonstrated the efficacy of endoscopic drainage by endoscopic sphincterotomy or stent placement. Various endoscopic therapeutic modalities and long-term follow-up of this problem were studied. METHODS: Members of the Midwest Pancreaticobiliary Group reviewed all patients referred for endoscopic therapy of biliary leaks after laparoscopic cholecystectomy from 1990 to 1994. Long-term follow-up was by direct patient contact. RESULTS: Fifty patients were referred for endoscopic therapy of biliary leaks. Abdominal pain was present in 94%. The mean time from laparoscopic cholecystectomy to referral was 6.9 days. Therapy consisted of sphincterotomy only in 6 patients, stent only in 13, and sphincterotomy with stent in 31. Biliary leaks were healed in 44 patients at a mean of 5.4 weeks. A second or third endoscopic procedure was necessary to achieve healing in five patients. Two stent-related complications were noted. Percutaneous or surgical drainage of biliary fluid collections was required in 16 patients. The mean hospital stay for treatment of the leak was 11.1 days after endoscopic therapy. On follow-up (mean 17.5 months), all patients were well except two with mild abdominal discomfort. CONCLUSIONS: Endoscopic sphincterotomy, stent placement, or sphincterotomy with stent are effective in healing biliary leaks after laparoscopic cholecystectomy. Despite prolonged treatment for the leak, patients did well on long-term follow-up.

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.

Collagenous colitis: histopathology and clinical course.

OBJECTIVES: Collagenous colitis is a chronic diarrheal disease characterized by a normal or near-normal mucosa endoscopically and microscopic inflammation in the lamina propria, surface epithelial injury and a thick subepithelial collagen layer. The symptoms of collagenous colitis vary in duration and intensity, and long periods of remission have been described, but long-term follow-up data are limited. Our goal was to determine the natural clinical history of collagenous colitis and to determine whether there was a relationship between histopathologic changes and course of disease. METHODS: Cases were identified at the University of Michigan Hospitals using surgical pathology records before 1992. All charts, including medical records from other hospitals, were reviewed, and a telephone interview was conducted with each locatable patient (pt). Biopsy specimens were reviewed by two pathologists for degree of collagen layer thickness, epithelial damage, and inflammation. RESULTS: There were 31 patients (26 F, 5 M) with a mean age of 66 yr (range 33-83) and a mean duration of symptoms of 5.4 yr at the time of diagnosis. Of the 31 patients, 18 (56%) had some form of arthritis, and 22 (71%) were using NSAIDS regularly at the time of diagnosis. Follow-up interviews were conducted at least 2 yr after diagnosis (mean 3.5 yr, range 2-5 yr) with 27 of 31 patients (3 could not be located, 1 died). Two definable groups of patients were identified: (1) those with either spontaneous or treatment-related symptom resolution (63%), and (2) those with ongoing or intermittent symptoms requiring at least intermittent therapy (37%). There was no significant difference between the two groups with regard to sex, age, associated diseases, and use of medications. Patients with symptom resolution (mean duration 3.1 yr) had been treated with antidiarrheals (6), sulfasalazine (3), discontinuation of NSAIDS (3), reversal of jejunoilial bypass (1), or nothing (4). Those with ongoing symptoms experienced a wide range of symptom severity. Two required only antidiarrheals, but five required or failed steroids, azathioprine, or sandostatin. There was no significant difference in collagen thickness, epithelial damage, and inflammation between the two groups, but Paneth cell metaplasia was seen more often in those with ongoing symptoms. In 24 of 27 patients, diagnostic changes were present in left-sided biopsies. CONCLUSIONS: In our cohort of patients, 63% had lasting resolution of symptoms after a mean 3.5 yr follow-up. There was a high incidence of arthritis and NSAID use in our population, but there was no relationship between these entities and clinical course or histology. Initial histology, except possibly for Paneth cell metaplasia, did not reliably predict severity or course of disease. Finally, although variable in clinical presentation, treatment-free remissions are common in collagenous colitis.

Response to higher doses of interferon alfa-2b in patients with chronic hepatitis C: a randomized multicenter trial. Hepatitis Interventional Therapy Group.

To evaluate response rates to 3, 5, or 10 million units (MU) of interferon alfa-2b, given thrice weekly, and to determine whether higher doses of interferon increase the likelihood or durability of the response, a multicenter, randomized trial was performed at nine academic medical centers in the United States. Two hundred forty eight patients with chronic hepatitis C were randomized to receive 3, 5, or 10 MU of interferon alfa-2b thrice weekly for 12 weeks. Based on the alanine aminotransferase (ALT) response at treatment-week 12, the patients were rerandomized to additional therapy at the same or at increased doses for an additional 12 to 36 weeks; in the case of no response to the highest dose, the patients were discontinued from the study. Serum ALT concentrations and liver histology were measured. The overall complete response rates to 3, 5, or 10 MU were not different at treatment-week 12 (31% vs. 42% vs. 40%, not significant). The majority of week-12 responders continued to respond during additional treatment. When the treatment was discontinued, 15.4% to 19.0% of patients maintained their response. Of the nonresponders to 3 MU at week 12, who were continued on 3 MU for an additional 12 weeks, none responded. However, response to additional therapy occurred in 12% of week-12 nonresponders, whose dose was escalated from 3 or 5 MU to 10 MU. The only baseline features associated with the treatment response were the absence of fibrosis or cirrhosis on the pretreatment liver biopsy and viral genotype. We conclude that the initial response to interferon in patients with chronic hepatitis C is not increased by treatment with higher doses of the drug. Patients who do not respond to 3 MU by treatment-week 12 will not respond with continued therapy at that dose; however, a proportion of patients who do not respond to 12 weeks of treatment with 3 or 5 MU may respond to higher doses. Although the long-term sustained response rates are marginally increased with interferon doses above 3 MU three times per week, the side effects are difficult to tolerate. The analysis of baseline factors in relation to response identified no single baseline factor associated with a low-enough response rate to warrant withholding interferon therapy from patients with chronic hepatitis C.

Peroral colonoscopy. Technique, depth, and yield of lesions.

Examination of portions of the small bowel beyond the reach of standard upper endoscopes can be done using peroral passage of a colonoscope. Important information can be obtained and directed biopsies and treatment of bleeding lesions can be performed.

Effect of propofol on human sphincter of Oddi.

The effect of propofol was studied in 11 patients who had common bile duct sphincter of Oddi manometry for suspected dysfunction. Patients were initially sedated with midazolam and then further or resedated with propofol for the second set of pressure measurements. Recordings were made about 10 min after giving each drug. No patient had elevated basal pressure initially. Average basal pressure was unchanged (16.7 +/- 16.4 mm Hg), phasic contraction frequency was unchanged (3.4 +/- 3.8/min), and phasic contraction amplitude fell but did not achieve statistical significance (91.8 +/- 77.3 mm Hg, P = 0.1). There was no difference in lowest blood pressure, pulse, or oxygen saturation recorded during midazolam or propofol sedation. Subjectively, the patients were more sedated during propofol administration. It is concluded that propofol is a safe and effective agent for conscious sedation. It does not alter the sphincter of Oddi pressure profile in patients with normal basal sphincter pressures and thus could be used as an alternative and perhaps better form of sedation for ERCP with sphincter of Oddi manometry.

Common bile duct sphincter of Oddi stenting in patients with suspected sphincter dysfunction.

OBJECTIVES: Some patients seem to have symptoms or other findings that imply that they have sphincter of Oddi dysfunction, but when the sphincter pressure is measured, the basal resting pressure is not greater than 40 mm Hg. Because empiric sphincterotomy can alleviate some of these patients'symptoms, it is suspected that they have intermittent spasm or dysfunction. Prolonged stenting of the sphincter would prevent symptoms in patients with this intermittent disorder. Thus, one could determine which patients would benefit from a sphincterotomy without subjecting all the patients to the risk of sphincterotomy. METHODS: Twenty-one patients with suspected sphincter of Oddi dysfunction were studied. All had basal sphincter of Oddi pressures < 40 mm Hg. The gallbladder was in situ in three. The others had persistent abdominal pain after cholecystectomy. Benefit was defined as no symptoms for 2 months after stent placement, followed by continued lack of symptoms once a sphincterotomy was performed. RESULTS: Nine patients benefited and 12 did not. One relapsed, but benefited from a repeat sphincterotomy. Eight patients (38%) met criteria for pancreatitis after stent placement. Two had severe pancreatitis with pseudocyst development. There were no sphincterotomy-related complications. CONCLUSIONS: The results suggest that patients without basal resting sphincter of Oddi pressure criteria may have intermittent spasm or dysfunction which can be deduced by achieving benefit after stenting, but the risk of pancreatitis from this technique as described is too high to recommend stenting as a routine method for detecting patients with intermittent sphincter dysfunction/spasm. Alternate methods need to be developed to identify these patients.

Esophageal varices.

Numerous conditions lead to portal hypertension with the development of esophageal varices. Treatment for acute variceal hemorrhage should progress in a logical, stepwise fashion. Therapy after fluid resuscitation includes vasopressin, somatostatin, or a Sengstaken-Blakemore tube. This is followed by treatment with sclerotherapy, variceal ligation, or a combination of both. Continued bleeding is managed by more invasive measures that include radiologic embolization or shunting, esophageal transection, distal splenorenal shunt, or liver transplantation. Beta-blockade may be useful to prevent recurrent bleeding in compliant patients without medical conditions that would preclude use of beta-blockade. Once control of the bleeding has been achieved, sclerotherapy or ligation should be used to obliterate the varices, but prophylactic use of sclerosant is not particularly beneficial.

Gastroesophageal varices: pathogenesis and therapy of acute bleeding.

Numerous conditions lead to portal hypertension and the development of esophageal or gastric varices, or both. Treatment of patients with acute bleeding should progress in a logical, stepwise fashion. Initial therapy includes vasopressin, somatostatin, or balloon tamponade with a Sengstaken-Blakemore tube. The next step is treatment with sclerotherapy, variceal ligation, or a combination of both. Continued bleeding is managed by more invasive measures, which may include radiologic embolization or shunting, esophageal transection, distal splenorenal shunt, or liver transplantation.

The effect of ethanol on the pancreatic duct sphincter of Oddi.

Alcohol ingestion causes pancreatitis to develop in some people, but the mechanism(s) by which alcohol causes pancreatitis are unclear. The effect of alcohol on the pancreatic duct sphincter of Oddi (PD-SO) may play a significant role. To better understand the effects of alcohol on the PD-SO, we studied 24 alcoholic subject's PD-SO before and after 80 g of alcohol was instilled into their stomachs. Seventeen of the subjects had a prior history of pancreatitis. The mean maximal alcohol level achieved by 30 min after the instillation was 98.1 +/- 47.9 mg/dl. The only prealcohol differences between the pancreatitis group and the nonpancreatitis group were higher mean basal PD-SO pressures and higher mean phasic contraction amplitudes (8.7 and 20.2 mm Hg higher, respectively) in the pancreatitis group. The acute change in the subjects' blood alcohol levels produced similar changes in both groups. A non-statistically significant fall in the mean basal PD-SO pressure of 2.7 mm Hg was observed. The phasic contraction mean amplitude decreased by 24.1 mm Hg (p < 0.001) and the mean duration decreased by 0.6 s (p = 0.0064). The frequency of phasic contractions did not change after ingestion of alcohol. There was a significant fall in the percentage of antegrade phasic contractions (-15.8%, p = 0.016), which was compensated for by nearly equal increases in the percentage of retrograde and simultaneous contractions. We conclude that acute alcohol ingestion in subjects with a history of chronic alcohol consumption changes the PD-SO motor activity in a way that could predipose to duodenopancreatic reflux. Thus, reflux of bile, activated enzymes, or other substances into the pancreatic duct might occur more readily and predispose one to pancreatitis after alcohol ingestion.

Congenital esophageal stenosis presenting as noncardiac, esophageal chest pain.

A case of a 31-year-old female with congenital esophageal stenosis presenting with symptoms of chest pain caused by esophageal dysmotility is described. The involved segment in congenital esophageal stenosis has a characteristic thickening of the muscularis propria layer, as seen by EUS examination. In these patients, symptoms of dysphagia can be managed with esophageal dilation and noncardiac esophageal chest pain responds to pharmacotherapy with diltiazem.

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.

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.