Randomised, double blind, placebo controlled trial of interferon, ribavirin, and amantadine versus interferon, ribavirin, and placebo in treatment naïve patients with chronic hepatitis C.

BACKGROUND AND AIM: In this study, we compared the efficacy of triple therapy (interferon alfa, ribavirin, and amantadine) with standard therapy (interferon alfa and ribavirin) in treatment naïve patients with chronic hepatitis C virus (HCV). METHODS: In this prospective, randomised, double blind, placebo controlled, multicentre study, 85 patients (amantadine group) received a three drug regimen of interferon alfa-2b 3 million units three times per week, ribavirin 1000-1200 mg daily in divided doses, and amantadine 100 mg twice daily, and 86 patients (placebo group) received interferon alfa-2b, ribavirin, and identical placebo. Treatment was discontinued at 24 weeks if patients had detectable HCV RNA by polymerase chain reaction (PCR). All patients were followed for 24 weeks after completion of treatment. The primary end point was undetectable HCV-RNA by PCR at 24 weeks (sustained viral clearance) after completion of treatment. RESULTS: At the end of treatment, HCV RNA clearance was seen in 32.9% of the amantadine group and 38.4% of the placebo group (p=0.3). Sustained virological response was seen in 24.7% of the amantadine group and in 27.9% of the placebo group by intention to treat analysis; response rate was 30.4% and 34.8%, respectively, in those who completed 24 weeks of treatment. Poor response was seen in both groups among cirrhotics, African-Americans, genotype 1, and those with a higher viral load. By multivariate analysis, genotype 1, high viral load, and low serum albumin were the only predictors of poor response. Addition of amantadine to the standard regimen did not result in any unexpected side effects. CONCLUSION: Response to triple therapy of interferon alfa, ribavirin, and amantadine was similar to standard therapy of interferon alfa and ribavirin. Our results suggest that amantadine has no role in the management of HCV.

Antireflux surgery for symptomatic gastroesophageal reflux: mechanism of action.

To determine the effects of Nissen fundoplication upon the symptoms of reflux and the diagnostic tests employed to evaluate reflux and to examine the relationship between gastroesophageal reflux and lower esophageal sphincter pressure before and after fundoplication, 10 patients with symptomatic reflux were studied before and after operation. Clinical evaluation, barium esophagography, endoscopy with mucosal biopsy, esophageal manometry, acid-perfusion and acid-reflux testing, and gastroesophageal scintiscaning were performed on each patient before and after surgery. Following fundoplication, marked symptomatic, radiographic, endoscopic, and histologic improvement was observed. Serial acid-reflux tests at increasing gastroesophageal pressure gradients returned to normal after surgery. Lower-esophageal-sphincter (LES) pressure increased from 8.2 +/- 1.3 to 12.0 +/- 1.5 mm Hg (P less than 0.01). In addition, surgery resulted in a significant decrease in the gastroesophageal reflux index from 17.4 +/- 2.4 to 2.7 +/- 1.1% (P less than 0.001). Surprisingly, the pre- and postoperative resting LES pressures did not correlate significantly with corresponding gastroesophageal reflux indices for individual patients. We conclude that increased LES pressure alone does not explain adequately the functional and clinical improvement which follows fundoplication.

The lower esophageal sphincter as a barrier to gastroesophageal reflux.

UNLABELLED: To correlate lower esophageal (LES) pressure and gastroesophageal (GE) reflux, esophageal manometry and GE scintiscanning have been used to study 40 consecutive patients. Serial scintiscanning was performed as the GE pressure gradient was increased in increments. Reflux was calculated from the ratio of esophageal to gastric radioactivity. The relationship between GE reflux and LES pressure was inverse (r = 0.60, P less than 0.005). Two subgroups of 10 patients were studied further. After atropine, LES pressure decreased from 11.2 +/- 1.1 to 5.3 +/- 0.9 mm Hg (P less than 0.01) at 20 min. The GE reflux index increased from 8.3 +/- 2.1 to 13.4 +/- 2.2% (P less than .05). After bethanechol, LES pressure increased from 8.9 +/- 0.8 to 18.5 +/- 1.0 mm Hg (P less than 0.001) at 30 min. GE reflux decreased from 11.9 +/- 2.4 to 5.8 +/- 1.7% (P less than 0.01). CONCLUSIONS: first, GE reflux correlated with basal LES pressure by an inverse relationship; second, atropine decreased LES pressure and increased reflux; third, bethanechol increased LES pressure and decreased reflux. These data suggest that LES pressure is an important determinant of GE competence.

Gastroesophageal (GE) scintiscanning to detect and quantitate GE reflux.

To evaluate the gastroesophageal (GE) scintiscan, a technique which detects and quantitates GE reflux, 30 patients with heartburn and a positive acid-reflux test and 20 normal control subjects were studied. Conventional diagnostic tests including barium esophagography, fluoroscopy, esophagogastroscopy, esophageal biopsy, acid perfusion testing, and esophageal manometry were performed on each patient with GE reflux. None of these techniques was sufficiently sensitive in detecting GE reflux. In contrast, GE reflux was visualized by scintiscanning in 27 out of 30 (90%) of patients. The GE reflux index was significantly greater in reflux patients, 11.7 +/- 1.8%, compared to controls 2.7 +/- 0.3%. These studies suggest that GE scintiscanning can detect GE reflux accurately, rapidly, noninvasively, and with greater sensitivity than other diagnostic techniques. In addition, it can be employed to quantitate GE reflux.