L. Barbara

A pilot study of combination therapy with ribavirin plus interferon alfa for interferon alfa-resistant chronic hepatitis C

BACKGROUND/AIMS In chronic hepatitis C, interferon alfa (IFN-alpha) therapy fails to achieve a sustained response in approximately 75% of patients. Similarly, ribavirin induces only a transient response. The aim of this study was to evaluate whether ribavirin and IFN-alpha in combination could be effective in IFN-alpha-resistant chronic hepatitis C. METHODS Twenty patients with chronic hepatitis C resistant to a previous course of IFN-alpha were randomly assigned to receive either ribavirin combined with IFN-alpha or IFN-alpha alone for 6 months. RESULTS Serum alanine aminotransferase levels decreased significantly during therapy in both treatment groups, but after therapy, the levels remained significantly decreased only in the combination therapy group. Nine months after treatment, sustained normalization of aminotransferase levels, associated with sustained loss of serum hepatitis C virus RNA, was observed in 40% of the patients in the combination therapy group but in none of the patients treated with IFN-alpha alone (P < 0.05). The sustained response was accompanied by reduced hepatic necroinflammatory activity on biopsy. CONCLUSIONS These findings suggest that ribavirin plus IFN-alpha combination therapy is able to induce a sustained biochemical and virological response in a significant proportion of patients with IFN-alpha-resistant chronic hepatitis C.

Fat-induced heal brake in humans: A dose-dependent phenomenon correlated to the plasma levels of peptide YY

BACKGROUND Upper gastrointestinal motility is regulated by the presence of nutrients in the distal gut. The present study evaluated whether lipid-induced ileal brake on gastric emptying (1) can be elicited by low fat concentrations; (2) is a dose-dependent phenomenon; and (3) is related to gastrointestinal peptide release. METHODS Seven patients were studied in the defunctionalized stage of total colectomy, on three separate occasions. On each study day, patients ate a meal labeled in the solid component; 30 minutes later, one of the following solutions was randomly infused into the ileal pouch: 0.9% saline, 2% oleic acid, and 20% oleic acid. Plasma concentrations of peptide YY (PYY), enteroglucagon, neurotensin, and motilin were measured. RESULTS Both oleic acid solutions slowed gastric emptying compared with saline (P < 0.001), the effect being dose dependent (P < 0.001). Ileal infusions did not modify neurotensin and enteroglucagon levels but induced a dose-dependent increase of PYY (P < 0.01) and a borderline decrease of motilin (P = 0.05) levels. Slower rates of gastric emptying were related to increased plasma concentrations of PYY (r = 0.615; P < 0.05). CONCLUSIONS This study shows that (1) the ileal brake on gastric emptying can be evoked by low doses of lipids in the distal ileum; (2) the delay of gastric emptying is related to the release of PYY; and (3) both phenomena are dose dependent.

Helicobacter pylori infection and gastric function in patients with chronic idiopathic dyspepsia

Helicobacter pylori infection, histological features of the gastric mucosa, and gastric motor and secretory functions were evaluated in 45 consecutive patients with chronic idiopathic dyspepsia. H. pylori infection was found in 60% of dyspeptic patients, compared with 33% of 15 healthy controls (P = 0.1). No difference was detected in basal or stimulated gastric acid secretion between dyspeptic patients and healthy controls. Gastric emptying was significantly (P less than 0.01) delayed in dyspeptic patients compared with healthy controls when standardized for age and sex. Delayed gastric emptying was associated with a low frequency of H. pylori infection, female gender, and young age. Epigastric pain or burning and postprandial fullness were, respectively, more severe in patients with H. pylori infection (P less than 0.02) and in those with delayed gastric emptying (P less than 0.01). These findings support the existence of separate subsets of patients with chronic idiopathic dyspepsia. Despite the presence of overlaps, there appear to be partially different functional derangements and clinical features in different subgroups of dyspeptic patients.

Persistent hepatitis C viraemia without liver disease

In viral infections persistence of the virus is not always associated with virus-induced disease. To find out if active hepatitis C virus (HCV) infection can persist without liver disease we selected four symptom-free individuals with antibodies to HCV but normal aminotransferase levels. They were followed up for 3 years by monthly serology and a liver biopsy was done. At presentation, all four had both antibodies to HCV and circulating HCV RNA. During follow-up their sera remained persistently positive for all HCV antibodies and RNA yet aminotransferase levels did not increase and liver biopsy was normal. These findings indicate that persistent hepatitis C viraemia is not invariably associated with liver damage.

Effect of chronic administration of cisapride on gastric emptying of a solid meal and on dyspeptic symptoms in patients with idiopathic gastroparesis.

In a double blind crossover comparison with placebo, the effects of cisapride (10 mg tid for two weeks), a non-antidopaminergic gastrointestinal prokinetic drug, on gastric emptying times and on symptoms were evaluated in 12 patients with chronic idiopathic dyspepsia and gastroparesis. Gastric emptying was studied by a radioisotopic gamma camera technique. The test meal was labelled in the solid component (99mTc-sulphur colloid infiltrated chicken liver). Nine symptoms (nausea, belching, regurgitations, vomiting, postprandial drowsiness, early satiety, epigastric pain or burning, heartburn) were graded weekly on a questionnaire. Cisapride was significantly more effective than placebo in shortening the t1/2 of gastric emptying (p2 = 0.04), but no significant difference was observed between the two treatments with regard to the improvement of total symptom score (p2 = 0.09). No side effects were reported during the study.

Fasting and postprandial gastrointestinal motility in ulcer and non-ulcer dyspepsia.

This study aimed to compare fasting and postprandial gastrointestinal motor patterns in patients with ulcer and non-ulcer dyspepsia. Forty five subjects were studied: 10 with uncomplicated gastric ulcer, eight with uncomplicated duodenal ulcer, 18 with chronic idiopathic dyspepsia, and nine healthy asymptomatic controls. Gastrointestinal fasting and postprandial motor patterns were recorded using a low compliance perfusion technique. The interdigestive antral cumulative motility index, computed for 30 minutes before the appearance of duodenal activity fronts, and the number of activity fronts with an antral component were significantly less in patients with ulcers and those with non-ulcer dyspepsia compared with asymptomatic controls. The patient groups also had a reduced antral motor response to a solid-liquid test meal compared with healthy controls. Intestinal motor abnormalities (bursts of non-propagated phasic pressure activity and discrete clustered contractions) were recorded in a minority of patients, all with associated irritable bowel symptoms. In conclusion, antral hypomotility is a frequent but nonspecific motor abnormality in dyspepsia; abnormal motor patterns of the small bowel are less frequent and seem to be confined to patients with concomitant irritable bowel syndrome.

Enzymatic determination of cholesterol in bile

Abstract A simple, sensitive and rapid method for measuring the cholesterol concentration in bile is described. The method is based on the combination of an enzymatic technique and spectrophotometry. In the present study the results obtained with this method are compared with those obtained by the standard Liebermann-Burchard reaction on the same samples and are found to be in close agreement.

Endoscopic Demonstration of Loss of Duodenal Folds in the Diagnosis of Celiac Disease

Among 873 patients undergoing upper gastrointestinal endoscopy for various reasons over a two-year period, four had a loss of Kerckrings folds in the descending duodenum. Endoscopic duodenal biopsy in all four patients revealed subtotal villous atrophy due to celiac disease. We undertook a prospective study to evaluate the extent to which this finding predicted celiac disease in 65 consecutive patients referred for intestinal biopsy. Duodenal folds were absent or markedly decreased in 15 of 17 patients with subtotal villous atrophy and in 8 of 48 patients with partial villous atrophy or normal duodenal mucosa, giving a sensitivity of 88 percent and a specificity of 83 percent for this endoscopic finding with respect to celiac disease. We recommend that all patients undergoing upper gastrointestinal endoscopy be examined for the loss or reduction of duodenal folds and, should this be found, that the examination include duodenal biopsy. The value of this procedure as an aid in the diagnosis of celiac disease should be particularly great in patients with minimal, transient, or unrelated symptoms.

Value of measurement of mean portal flow velocity by Doppler flowmetry in the diagnosis of portal hypertension

To establish the sensitivity and specificity of the mean portal flow velocity in the diagnosis of portal hypertension, a population of 304 consecutive cirrhotic patients, in whom 246 abdominal Doppler examinations were performed, was prospectively analysed between June 1988 and December 1990. To avoid equipment-related variability only examinations performed using the same equipment were considered. Further inclusion criteria were the absence of portal vein thrombosis or reversed flow in the portal vessels and the absence of spontaneous, ultrasonographically detectable, portosystemic shunts. The parameter evaluated was mean portal flow velocity calculated directly from the Doppler trace by specific, operator-independent, software. 123 patients satisfied the inclusion criteria. As a control group 60 healthy age- and sex-matched subjects were examined. Mean portal flow velocity was significantly lower in cirrhotic patients than healthy subjects (13.0 +/- 3.2 cm/s vs. 19.6 +/- 2.6 cm/s; p < 0.001). There was also a decrease in mean portal flow velocity in cirrhotics in each Child-Pugh category (13.8 +/- 2.8 cm/s in Child-Pugh A class; 12.1 +/- 3.5 cm/s in Child-Pugh B class and 11.0 +/- 2.4 cm/s in Child-Pugh C class) with a statistically significant difference between each Child-Pugh category and healthy subjects (p < 0.001), between Child-Pugh A and B (p < 0.01) and between Child-Pugh A and C (p < 0.005). The sensitivity and specificity of mean portal flow velocity in the detection of portal hypertension was then analyzed with the receiver operating characteristic curve.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of cessation of alcohol use on the course of pancreatic dysfunction in alcoholic pancreatitis

Exocrine pancreatic function was studied sequentially by means of the secretin-cerulein test in 32 patients with alcoholic chronic pancreatitis to elucidate the long-term course of pancreatic dysfunction, and to determine whether the cessation of alcohol use had any influence on the natural history of pancreatic functional changes caused by this disease. At initial studies, 5 patients had normal pancreatic function, and the remaining 27 had pancreatic insufficiency, which was mild to moderate in most subjects. The final studies, carried out at an average of 7.3 yr (range, 4-11 yr) after the first, showed a significant deterioration in pancreatic function, both in patients who stopped alcohol after the initial study (n = 18) and in those who did not (n = 14). The deterioration, however, was significantly less marked in patients who stopped drinking alcohol than in those who continued. These data indicate that pancreatic functional changes caused by alcoholic pancreatitis progress even after cessation of alcohol use; however, the progression is slower and less severe when alcohol intake is stopped.