Efficacy of oral pancreatic enzyme therapy for the treatment of fat malabsorption in HIV-infected patients.

BACKGROUND: Nutrient malabsorption is a negative prognostic factor in acquired immunodeficiency syndrome and recent studies have shown that pancreatic insufficiency is a codetermining factor of malabsorption. AIMS: To evaluate the effectiveness of open-label oral pancreatic enzyme supplementation therapy in acquired immunodeficiency syndrome patients with fat malabsorption. PATIENTS AND METHODS: Twenty-four consecutive patients with human immunodeficiency virus infection and fat malabsorption were recruited (11 males, 13 females; median age, 9.1 years). Faecal fat loss was evaluated by steatocrit assay at entry to the study (T-0), after 2 weeks (T-1) without pancreatic enzyme treatment and after a further 2 weeks (T-2) of treatment with pancreatic extracts (Creon 10 000 at a dose of 1000 units of lipase per gram of ingested dietary fat). Faecal elastase-1 and chymotrypsin were assayed at entry. RESULTS: Six patients (25%) had abnormally low elastase-1 and/or chymotrypsin faecal concentration. In all patients, steatocrit values were elevated at both T-0 and T-1. Five patients proved intolerant to pancreatic enzyme treatment because of the onset of abdominal pain, and therapy was discontinued. In the 19 patients who concluded the study, steatocrit values during pancreatic enzyme treatment (T-2) were significantly lower than at entry (P < 0.0001). At T-2, in eight of 19 patients, steatocrit values were within the normal limit and the frequency of cases cured or improved on pancreatic enzyme therapy (at T-2) was significantly higher than that observed during the previous study period without enzyme treatment (T-1) (P < 0.01). A positive significant correlation was found between steatocrit values at entry and the Centers for Disease Control class (P < 0.0005); also, the decrease in steatocrit values during pancreatic enzyme therapy (difference between steatocrit value at T-2 and steatocrit value at T-0) positively correlated with the Centers for Disease Control class (P < 0.05). CONCLUSIONS: This pilot, open-label study showed that pancreatic enzyme supplementation therapy is highly effective in reducing faecal fat loss in human immunodeficiency virus-infected patients with nutrient malabsorption. Further double-blind studies must be undertaken to verify these results and, if they are confirmed, pancreatic enzymes can be added to our weapons in the fight against human immunodeficiency virus-associated nutrient malabsorption.

Diagnostic accuracy of fecal elastase 1 assay in patients with pancreatic maldigestion or intestinal malabsorption: a collaborative study of the Italian Society of Pediatric Gastroenterology and Hepatology.

Several reports have indicated that fecal elastase-1 (EL-1) determination is a new, sensitive, and specific noninvasive pancreatic function test; however, very few patients with malabsorption due to small intestine diseases have been included in the previous studies. The aim of the study was to compare the diagnostic accuracy of fecal EL-1 and fecal chymotrypsin (FCT) in distinguishing between pancreatic maldigestion and intestinal malabsorption. Three groups of subjects were studied: group A included 49 patients with known cystic fibrosis (25 males, median age 5 years); group B included 43 subjects with various small intestine diseases (17 males, median age 6 years); and group C included 45 children without any history of gastrointestinal disease (22 males, median age 5 years). In all patients, stools were collected for 72 h on a standard diet and fecal EL-1, FCT, and steatocrit tests were performed. Both EL-1 and FCT were below normal limits in all CF patients with pancreatic maldigestion not treated with pancreatic enzyme (100% sensitivity for both assays); El-1, but not FCT, was also below normal in all the CF patients with pancreatic maldigestion treated with pancreatic extracts. Both EL-1 and FCT values in the CF group were significantly lower than in subjects with various small intestinal diseases and in children without any history of gastrointestinal disease (P < 0.0001). FCT, but not EL-1, values showed an inverse statistically significant correlation with steatocrit values in the whole CF group (P < 0.001); FCT was below normal in three of four CF patients with steatorrhea on pancreatic enzyme therapy. Both EL-1 and FCT had 100% specificity when calculated in children without any history of gastrointestinal disease; in contrast, specificity was 86% for EL-1 and 76% for FCT if we considered the control group with small intestinal diseases: low EL-1 was observed in two cases of intestinal giardiasis, two cases of short bowel syndrome, one case of celiac disease, and one case of intestinal pseudobstruction; FCT was abnormal in four cases of intestinal giardiasis, three cases of celiac disease, one case of short bowel syndrome, one case of Crohn's disease, and one case of intestinal pseudobstruction. Diagnostic accuracy was 92% for fecal EL-1 and 82% for FCT. Steatocrit values were over the normal limit in 11 patients with small intestine diseases; in 7/11 of these patients at least one of the pancreatic test results was below the normal limit. In conclusions, in patients with CF, fecal EL-1 determination is not more sensitive than FCT in identifying pancreatic maldigestion; however, fecal EL-1 assay is more specific than FCT determination in distinguishing pancreatic maldigestion from intestinal malabsorption.

Usefulness of faecal elastase-1 assay in monitoring pancreatic function in childhood coeliac disease.

BACKGROUND: In coeliac disease it has been demonstrated that the indirect pancreatic function tests detect a greater percentage of subjects with exocrine pancreatic insufficiency than the secretin-caerulein test. AIMS: To evaluate faecal pancreatic elastase-1 assay in monitoring patients with coeliac disease. PATIENTS: Thirty patients with coeliac disease (11 m; age range 1-7 years) completed a 2-month follow-up. As controls, we studied two sex-, age-matched patient groups: a) 15 patients with cystic fibrosis, b) 40 surgical patients without gastroenterological disease. METHODS: In all coeliac subjects, stools were collected over 24 hours at diagnosis and then 30 and 60 days after commencement of the gluten-free diet; on a sample of the faeces we assayed elastase-1 activity. In the control patients, faeces were collected over 24 hours for elastase-1 assay only once. The coeliac patients only underwent the secretin-caerulein test, at diagnosis. RESULTS: Ten out of 30 coeliac patients (33%) had subnormal faecal elastase-1 values at diagnosis, while all the surgical controls had values within the normal range; median values in coeliac patients were significantly lower than those of the surgical controls (median 287 mcg/g, 95% CI 271-430, versus 487 mcg/g, 95% CI 426-538, p < 0.007). Cystic fibrosis patient values (median 10 mcg/g, 95% CI 7-155) were significantly lower than both those of coeliac patients and those of the surgical controls (p < 0.0001). The secretin-caerulein test showed that 7/30 coeliac patients (23%) had a deficiency in one or more pancreatic enzymes; all these subjects had below normal faecal elastase-1 values. During the follow-up, we observed a progressive reduction in the number of coeliacs with pancreatic impairment; however, after 2 months of gluten-free diet, faecal elastase-1 deficiency persisted in 2/30 coeliacs. CONCLUSIONS: Faecal elastase-1 determination in coeliac patients reveals a similar frequency and duration of pancreatic impairment to those observed in studies performed using the faecal chymotrypsin assay; a reduction in faecal elastase-1 values can be linked to "non-typical pancreatic diseases".

Pancreatic dysfunction and its association with fat malabsorption in HIV infected children.

BACKGROUND: Nutrient malabsorption frequently occurs in HIV infected children, but very few studies have investigated exocrine pancreatic digestive capacity in these cases. AIMS: To investigate pancreatic function in HIV infected children and to determine whether faecal fat loss, a prominent feature of intestinal dysfunction, is associated with pancreatic dysfunction. PATIENTS: Forty seven children with HIV infection without apparent pancreatic disease and 45 sex and age matched healthy controls. METHODS: Pancreatic function was evaluated by measuring elastase 1 concentration and chymotrypsin activity in stools by ELISA and colorimetric methods, respectively. Intestinal function was evaluated by measuring fat and protein loss by the steatocrit method and by faecal alpha1 antitrypsin concentration. RESULTS: 14 (30%) had abnormal pancreatic function tests: seven had isolated elastase activity deficiency, three isolated chymotrypsin deficiency, and four pancreatic deficiencies in both enzymes. Patient enzyme values were significantly lower than those of controls. Low faecal pancreatic enzymes were not associated with symptoms. Twelve children had steatorrhoea and four had increased alpha1 antitrypsin. Steatorrhoea was significantly associated with reduced faecal pancreatic enzymes. There was a significant negative correlation between elastase 1 concentration and steatocrit. Children with pathological faecal elastase 1 or chymotrypsin values did not differ from the other HIV infected children with respect to nutritional and immunological status, stage of HIV disease, presence of opportunistic infections, or drug administration. CONCLUSIONS: Abnormal pancreatic function tests are a frequent feature of paediatric HIV infection; this condition is associated with steatorrhoea, which probably contributes to the disease.

Serum pancreatic enzymes in human immunodeficiency virus-infected children. A collaborative study of the Italian Society of Pediatric Gastroenterology and Hepatology.

BACKGROUND: Numerous studies have shown pancreatic disease in adult human immunodeficiency virus (HIV)-infected patients, but there are very few reports on pediatric patients. Our aim was to determine the prevalence of increased serum pancreatic enzyme levels and their relationship to clinical manifestations of acute pancreatitis in HIV-infected children. METHODS: Forty-seven consecutive, symptomatic HIV-infected children (24 male; median age, 7.3 years; range, 1-17 years) and 45 sex- and age-matched controls without gastroenterologic disease were enrolled. In all subjects serum total amylase, pancreatic amylase, and lipase were assayed with commercial kits. The following were recorded: disease progression (CDC class), nutritional status (weight Z-score), CD4 lymphocyte count, drug treatment during the previous 12 months, presence of opportunistic infections, clinical evidence of acute pancreatitis (increased serum pancreatic enzymes associated with vomiting, abdominal distention, and intolerance when eating). RESULTS: Ten of 47 HIV patients had increased serum total amylase values; however fewer patients had increased specific pancreatic enzymes: 6 of 47 for pancreatic amylase (range, 1.8- to 19.8-fold normal limit) and 7 of 47 for lipase (range, 1.4- to 4-fold normal limit). Values were normal in all controls. Two HIV patients with increased total amylase had clinically evident parotid inflammation. None of the patients with increased serum pancreatic amylase and/or lipase had clinical symptoms of acute pancreatitis. Regression analysis showed no correlation between increased serum pancreatic enzyme levels and disease progression (CDC class), immunologic status (CD4 count), nutritional status, drug administration, or opportunistic infections. CONCLUSIONS: Fifteen per cent of HIV-infected children had biochemical evidence of pancreatic involvement; however, this condition was unrelated to clinical signs of pancreatitis. Neither drug administration nor opportunistic infections seem to determine the increased serum pancreatic enzyme levels.

HDL subfractions distribution in renal transplant recipients: lack of evidence of a reduction of HDL2 particles.

Since the high rate of cardiovascular disease in renal transplant recipients, alterations of lipoprotein profile in such patients were extensively evaluated, but the HDL subclass profile was not completely clarified. Renal transplant recipients usually show normal to high plasma levels of HDL cholesterol, even if some investigations suggested a persistence of low HDL2 levels: this was not useful in terms of cardiovascular protection. We designed this study in order to evaluate HDL subfractions distribution in renal transplant recipients. We studied 55 renal transplant recipients, treated with prednisone, azathioprine and/or cyclosporine, and 34 healthy normolipidemics as controls. In all subjects cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, apolipoproteins A-I and B levels and HDL subfractions, as determined by nondenaturing polyacrylamide gradient gel electrophoresis, were assayed. Renal transplant recipients had cholesterol, triglycerides, LDL cholesterol and apolipoproteins A-I and B levels significantly higher than controls; HDL cholesterol levels were slightly, but not significantly, increased in comparison with controls (respectively 51.1 +/- 15.5 and 46.1 +/- 10.8 mg/dl). Multivariate analysis showed that only the time since transplantation was significantly associated with HDL cholesterol levels. When HDL subfractions were analyzed, renal transplant recipients presented significantly lower levels of HDL3a and HDL3b and, in males, higher levels of HDL2b than controls. HDL cholesterol levels were positively correlated with HDL2b levels in both renal transplant recipients and controls, and negatively correlated with HDL3b in controls. In conclusion, in renal transplant recipients, we failed to demonstrate any decrease of HDL2 particles. On the basis of a nonatherogenic HDL profile, we suggest that the increased cardiovascular risk in renal transplant recipients might be accounted for by other risk factors.