Review article: intestinal lymphoid nodular hyperplasia in children--the relationship to food hypersensitivity.

BACKGROUND: Lymphoid aggregates are normally found throughout the small and large intestine. Known as lymphoid nodular hyperplasia (LNH), these aggregates are observed especially in young children and are not associated with clinical symptoms being considered 'physiological'. In children presenting with gastrointestinal symptoms the number and size of the lymphoid follicles are increased. Patients suffering from gastrointestinal symptoms (i.e. recurrent abdominal pain) should systematically undergo gastroduodenoscopy and colonoscopy. With these indications LNH, especially of the upper but also of the lower gastrointestinal tract has been diagnosed, and in some children it may reflect a food hypersensitivity (FH) condition. AIM: To review the literature about the relationship between LNH and FH, particularly focusing on the diagnostic work-up for LNH related to FH. METHODS: We reviewed literature using Pubmed and Medline, with the search terms 'lymphoid nodular hyperplasia', 'food hypersensitivity', 'food allergy' and 'food intolerance'. We overall examined 10 studies in detail, selecting articles about the prevalence of LNH in FH patients and of FH in LNH patients. RESULTS: Collected data showed a median of 49% (range 32-67%) LNH in FH patients and a median of 66% (range 42-90%) FH in LNH patients. Literature review pointed out that the most important symptom connected with LNH and/or FH was recurrent abdominal pain, followed by diarrhoea and growth retardation. Both LNH and FH are associated with an increase in lamina propria γ/δ+ T cells, but the mechanisms by which enhanced local immune responses causing gastrointestinal symptoms still remain obscure. CONCLUSIONS: When assessing FH, we rely on clinical evaluation, including elimination diet and challenge tests, and endoscopic and immunohistochemical findings. Considering the possible co-existence of duodenal and ileo-colonic LNH, upper endoscopy can be recommended in children with suspected FH, especially in those presenting with additional upper abdominal symptoms (i.e. vomiting). Likewise, lower endoscopy might be additionally performed in patients with suspected FH and LNH of the duodenal bulb, also presenting with lower abdominal symptoms (i.e. recurrent abdominal pain).

A key role for abdominal ultrasound examination in "difficult" diagnoses of celiac disease.

PURPOSE: To evaluate the usefulness of abdominal ultrasound examination (US) for the diagnostic workup of cases of suspected CD involving negative serum antibodies and difficult diagnosis. MATERIALS AND METHODS: 524 consecutive patients with symptoms of suspected CD underwent an extensive diagnostic workup. 76 (14 %) were excluded since they were positive for serum anti-tTG and/or EmA antibodies. 377 were excluded since they were diagnosed with something other than CD or did not have the alleles encoding for HLA DQ 2 or DQ 8. A diagnosis of CD with negative serum antibodies was probable in 71 patients who underwent abdominal US and duodenal biopsy for histology evaluation. RESULTS: Intestinal histology and subsequent clinical and histological follow-up confirmed the CD diagnosis in 12 patients (GROUP 1) and excluded it in 59 subjects (GROUP 2). Abdominal US showed that the presence of dilated bowel loops and a thickened small bowel wall had a sensitivity of 83 % and a negative predictive value (NPV) of 95 % in CD diagnosis. Furthermore, in 11 of the 12 CD seronegative patients there was at least one of these two abdominal US signs. Therefore, considering the presence of one of these two signs, abdominal US sensitivity increased to 92 % and NPV to 98 %. CONCLUSION: Abdominal US is useful in the diagnostic workup of patients with a high clinical suspicion of CD but with negative serology.

Haematological deficiencies in patients with recurrent aphthosis.

BACKGROUND: Recurrent aphthosis is a common oral ulcerative condition consisting also of a subset of similar ulcers, properly named 'aphthous-like' ulcers (ALU), linked to systemic diseases and among these, to iron, folic acid and vitamin B(12) deficiencies. OBJECTIVES: The main objectives of this study were: (i) to evaluate the association between recurrent aphthosis and the most common predisposing factors; (ii) to assess the frequency of ALU in recurrent aphthosis; (iii) to verify the efficacy of a replacement therapy in all ALU patients. METHODS: Thirty-two adults with recurrent aphthosis and 29 otherwise healthy controls were consecutively recruited, interviewed and subjected to haematological investigations. RESULTS: Family history of recurrent aphthosis was significantly associated (P < 0.01). The overall frequency of haematinic deficiencies was 56.2% in recurrent aphthosis patients vs. 7% in controls (P < 0.0001). All ALU patients with a negative family history showed a complete remission of the ulcerative episodes after replacement therapy, while those with a positive family history only had a reduction in frequency and severity. In the logistic regression model, only family history was associated with recurrent aphthosis (P = 0.0137). CONCLUSION: The strong association with familiarity, the unexpected higher frequency of ALU (compared with the idiopathic variant) and the good response to replacement therapy means that familiarity should always be investigated. Furthermore, routine haematological screening and tests for serum iron, folic acid and vitamin B(12) deficiencies should be assessed in all patients with recurrent aphthosis to treat any nutritional deficiency and to prevent more important related systemic manifestations.

Histomorphology of healthy oral mucosa in untreated celiac patients: unexpected association with spongiosis.

BACKGROUND: The jejunal mucosa is the major site involved in celiac disease, but modifications have also been found in the gastric, rectal and esophageal mucosa. Few studies have focused on the histomorphological features of the oral mucosa in celiac disease patients. Our objectives were: (i) to assess the presence, quality and intensity of lymphocytic infiltrate in clinically healthy oral mucosa and its relation to celiac disease severity (villous height to crypt depth ratio); and (ii) to detect any other histological features connected to celiac disease. METHODS: Twenty-one untreated celiac disease patients (age range 13-68 years) with clinically healthy oral mucosa were enrolled and compared with 14 controls. Intestinal and oral biopsies were carried out and specimens were evaluated after staining with hematoxylin and eosin. RESULTS: Intra-epithelial lymphocyte B and T infiltrates of the oral mucosa were found to be similar in both groups; likewise, intensity of the lymphocytic infiltrate in the lamina propria was similar in both groups and was not related to intestinal damage; important signs of spongiosis were found to be more significantly present in celiac disease patients compared with controls (P = 0.0002). CONCLUSIONS: Our study showed that the healthy oral mucosa of untreated patients does not reflect the intestinal damage by celiac disease, but it is unexpectedly affected by spongiosis, as being detected for the first time in the literature. This latter feature could be related to gliadin ingestion and could contribute to explain the higher susceptibility of celiac disease patients to suffering from oral mucosa lesions.

Coeliac disease: oral ulcer prevalence, assessment of risk and association with gluten-free diet in children.

AIMS: Oral mucosal lesions may be markers of chronic gastrointestinal disorders, such as those causing malabsorption. Our objectives were to assess the prevalence of recurrent oral aphthous-like ulcers in coeliac disease patients living in the Mediterranean area, and to evaluate the impact of a gluten-free diet. METHODS: A test group of 269 patients (age range 3-17 years) with coeliac disease confirmed both serologically and histologically was compared with a control group of 575 otherwise clinically healthy subjects for the presence, or a positive history of aphthous-like ulcers. Coeliac disease patients with aphthous-like ulcers were re-evaluated 1-year after starting a gluten-free diet. RESULTS: Aphthous-like ulcers were found significantly more frequently in coeliac disease, in 22.7% (61/269) of patients with coeliac disease versus 7.1% (41/575) of controls (p=<0.0001; chi-square=41.687; odds ratio=4.3123; 95% confidence interval=2.7664:6.722). Most coeliac disease patients with aphthous-like ulcers and adhering strictly to gluten-free diet (71.7%; 33/46) reported significant improvement on gluten-free diet, with no or reduced episodes of aphthous-like ulcers (p=0.0003; chi-square=13.101; odds ratio=24.67; 95% confidence interval=2.63:231.441). CONCLUSIONS: The epidemiological association found between coeliac disease and aphthous-like ulcers suggests that recurrent aphthous-like ulcers should be considered a risk indicator for coeliac disease, and that gluten-free diet leads to ulcer amelioration.

Oral pathology in untreated coeliac [corrected] disease.

BACKGROUND: Many coeliac disease patients with atypical symptoms remain undiagnosed. AIM: To examine the frequency of oral lesions in coeliac disease patients and to assess their usefulness in making coeliac disease diagnosis. PATIENTS AND METHODS: One hundred and ninety-seven coeliac disease patients and 413 controls were recruited and the oral examination was performed. RESULTS: Forty-six out of 197 coeliac disease patients (23%) were found to have enamel defects vs. 9% in controls (P < 0.0001). Clinical delayed eruption was observed in 26% of the pediatric coeliac disease patients vs. 7% of the controls (P < 0.0001). The prevalence of oral soft tissues lesions was 42% in the coeliac disease patients and 2% in controls (P < 0.0001). Recurrent aphthous stomatitis disappeared in 89% of the patients after 1 year of gluten-free diet. Multi-logistic analysis selected the following variables as the most meaningful in coeliac disease patients: dental enamel defects (OR = 2.652 CI = 1.427-4.926) and soft tissue lesions (OR = 41.667, CI = 18.868-90.909). Artificial Neural Networks methodology showed that oral soft tissue lesions have sensitivity = 42%, specificity = 98% and test accuracy = 83% in coeliac disease diagnosis. CONCLUSIONS: The overall prevalence of oral soft tissue lesions was higher in coeliac disease patients (42%) than in controls. However, the positive-predictive value of these lesions for coeliac disease diagnosis was low.

IgA anti-actin antibodies ELISA in coeliac disease: a multicentre study.

BACKGROUND: Previous studies have demonstrated that serum anti-actin antibodies are a reliable marker of intestinal damage severity in coeliac disease. AIMS: To validate in a multicentre study the clinical usefulness of serum IgA anti-actin antibody ELISA and its possible use in monitoring intestinal mucosa lesions during gluten-free diet. PATIENTS AND METHODS: Four centres recruited 205 newly diagnosed coeliac disease patients with villous atrophy, 80 healthy controls and 81 "disease" controls. Twelve coeliac disease patients on gluten-free diet but with persistent symptoms underwent serum IgA anti-actin antibody assay and intestinal histology evaluation. IgA anti-actin antibody ELISA was performed with a commercial kit. All coeliac disease patients underwent intestinal histology study. RESULTS: IgA anti-actin antibodies showed a sensitivity of 80% and a specificity of 85% in the diagnosis of coeliac disease patients with villous atrophy. The area under the receiving operator curve for anti-actin antibodies was 0.873 [95% C.I. 0.805-0.899]. Serum anti-actin antibodies values were significantly higher in coeliac disease patients than in healthy or "disease" controls (P<0.0001). Serum anti-actin antibodies were positive in 41 of the 60 coeliac disease patients with mild intestinal histology lesions (69%) and in 123 of the 145 with severe lesions (85.3%) (P<0.05). There was a significant inverse correlation between anti-actin antibody values and the villi/crypts ratio (r=-0.423; P<0.0001). In the 12 coeliac disease patients on gluten-free diet who underwent re-evaluation as they were persistently symptomatic, intestinal histology showed three cases with persistent villous atrophy: all of these were positive for serum anti-actin antibodies ELISA, whereas both serum anti-tTG and EmAs were negative. The other nine patients showed normal intestinal villi and were negative for serum anti-actin antibodies. CONCLUSIONS: Anti-actin antibodies are a reliable marker of severe intestinal mucosa damage in coeliac disease patients and a simple ELISA technique offers an accurate method for their determination. These antibodies seem to be a very reliable marker of persistent intestinal damage in coeliac disease patients.

Oral mucosa of coeliac disease patients produces antiendomysial and antitransglutaminase antibodies: the diagnostic usefulness of an in vitro culture system.

BACKGROUND: Antiendomysial (EmA) and antitransglutaminase (anti-tTG) antibodies are the most specific indirect marker of coeliac disease (CD). It is not known whether the oral mucosa of patients with CD is able to produce these antibodies or not. AIMS: To evaluate the ability of the oral mucosa of patients with CD to produce antibodies in an in vitro culture system. PATIENTS AND METHODS: Twenty-eight patients with new diagnosis of CD (15 adults and 13 children) and 14 adult subjects with other diseases (controls) were studied. All underwent oral mucosa biopsy and subsequent EmA and anti-tTG assays on the mucosa culture medium. RESULTS: Sensitivity and specificity of EmA and anti-tTG assayed in the oral mucosa culture medium for CD diagnosis were 54% and 100% and 57% and 100%, respectively. The CD clinical presentation, such as the presence of oral mucosa lesions, did not influence the results of the EmA and anti-tTG assays in the oral mucosa culture medium. There was an association between positivity of antibodies and greater severity of the oral mucosa lymphocyte infiltration. CONCLUSION: This study demonstrates that the oral mucosa contributes to EmA and anti-tTG production in untreated patients with CD.

Review article: Chronic constipation and food hypersensitivity--an intriguing relationship.

BACKGROUND: Chronic constipation is common in the general population. Some studies have shown that in children cow's milk protein hypersensitivity can cause chronic constipation unresponsive to laxative treatment. AIMS: To review the literature and summarize the data that point to a relationship between refractory chronic constipation and food hypersensitivity, and to discuss the hypothesis that the pathogenesis of constipation due to food hypersensitivity. METHODS: A search in the U.S. National Library of Medicine was performed, matching the key words 'chronic constipation, food intolerance and allergy'. RESULTS: Thirty-three papers were found but only 19 of them were related to the topic of this review. Most of the data indicated a relationship between constipation and food allergy in a subgroup of paediatric patients with 'idiopathic' constipation unresponsive to laxative treatment. There was only one study in adults that demonstrated the resolution of chronic constipation on hypoallergenic diet in four patients. CONCLUSIONS: An increasing number of reports suggest a relationship between refractory chronic constipation and food allergy in children. Similar data in adults are scarce and need to be confirmed. Further studies should be performed to obtain firmer evidence for the role of allergy in constipation and clarify the pathogenetic mechanisms involved.

Gastrointestinal symptoms in infancy: a population-based prospective study.

BACKGROUND: During the first months of life, infants can suffer from many 'minor' gastroenterological disturbances. However, little is known about the frequency of these problems and the factors which predispose or facilitate their onset. AIMS: (a) To ascertain the frequency of the most common gastrointestinal symptoms in infants during the first 6 months after birth; (b) to evaluate the influence of some variables on the onset of the symptoms. STUDY DESIGN AND PATIENTS: Each of the 150 paediatricians distributed throughout Italy followed 20 consecutive infants from birth to 6 months. 2879 infants (1422 f, 1457 m) concluded the study. The presence of the following symptoms was evaluated: constipation, diarrhoea, vomiting, regurgitation, failure to thrive and prolonged crying fits (colic). Symptoms were recorded whenever the parents requested a clinical check-up or during a set monthly examination. RESULTS: 1582/2879 (54.9%) infants suffered from one of the gastrointestinal symptoms. Regurgitation was the most common disturbance (present in 23.1% of infants), followed by colic (20.5%), constipation (17.6%), failure to thrive (15.2%), vomiting (6%) and diarrhoea (4.1%). Low birth weight was the factor most frequently associated with the onset of gastrointestinal symptoms, followed by low gestational age. Feeding habits did not influence the onset of symptoms, with the exception of constipation, which was linked to a low frequency of breast-feeding. Ninety-three infants (3.2%) were hospitalised for one or more of the gastrointestinal symptoms which were considered. During the whole study period the type of formula-milk was changed in 60% of the infants with one or more gastrointestinal symptoms, and in 15.5% of the infants who did not suffer from any gastrointestinal troubles. CONCLUSIONS: Gastrointestinal symptoms are very common in infants during the first 6 months after birth. These symptoms required hospitalisation only in a small percentage of cases, but led to the prescription of a 'dietary' milk formula in approximately 60% of the cases. Low birth weight and low gestational age were the main factors influencing the onset of the symptoms.

Ultrasound detection of abdominal lymph nodes in chronic liver diseases. A retrospective analysis.

AIM: To retrospectively evaluate the prevalence of lymph nodes of the hepato-duodenal ligament in a group of patients with chronic liver disease of various aetiologies and to investigate what clinical, aetiological and laboratory data may lead to their appearance. MATERIALS AND METHODS: One thousand and three patients (554 men, 449 women) were studied, including 557 with chronic hepatitis and 446 with liver cirrhosis. The presence of lymph nodes near the trunk of the portal vein, hepatic artery, celiac axis, superior mesenteric vein and pancreas head was investigated using ultrasound. RESULTS: Lymph nodes were detected in 394 out of the 1003 study patients (39.3%); their number ranged from one to four, with a diameter ranging between 0.8 and 4 cm. The highest prevalence was in the subgroup of patients with primary biliary cirrhosis (87.5%), followed by patients with hepatitis C virus (HCV; 42%), patients with HCV and hepatitis B virus (HBV; 41.3%), autoimmune hepatitis (40%), and HBV alone (21.2%). In the alcoholic and idiopathic subgroups prevalence was 9.5%, while in the non-alcoholic steatohepatitis and haemochromatosis subgroups it was 0%. HCV RNA was present in 97 out of 103 lymph node-positive patients and in 141 out of 168 lymph node-negative HCV-negative patients (p<0.003). Lymphadenopathy frequency increased as the liver disease worsened (chi(2) MH=74.3; p<0.0001). CONCLUSION: Despite the limitations of a retrospective study, our data indicate a high prevalence of lymphadenopathy in liver disease patients; ultrasound evidence of lymph nodes of the hepato-duodenal ligament in a given liver disease may most likely suggest a HCV or an autoimmune aetiology and a more severe histological picture.

Hemodynamic changes in splanchnic circulation after orthotopic liver transplantation in patients with liver cirrhosis.

BACKGROUND: Liver cirrhosis increases portal vein pressure and alters the splanchnic circulation. With Doppler sonography, we investigated the hemodynamic changes in the portal vein, superior mesenteric artery, hepatic and splenic arteries and spleen size in a group of patients with end-stage liver disease before and after orthotopic liver transplantation (OLT). METHODS: Ten patients (seven male, three female; mean age = 48.8 +/- 7.6 years) who underwent OLT for liver cirrhosis mainly associated with hepatitis C virus infection completed the study. The control group consisted of 10 patients matched by sex and age who had no gastroenterologic or vascular diseases. All patients underwent duplex Doppler sonography (Toshiba SSA 270A with a 3.5-MHz probe) after 24 h of fasting (baseline) and then 6 and 12 months after OLT. The following parameters, expressed as the mean of three measurements, were evaluated: portal flow velocity (PFV), pulsatility index of the superior mesenteric artery (MAPI), resistance indexes of the hepatic (HARI) and splenic (SARI) arteries, and longitudinal diameter of the spleen (LDS). RESULTS: PFV in the pre-OLT phase was significantly lower in the patients than in the controls ( p < 0.0001); it progressively and significantly increased over baseline levels at 6 and 12 months ( p < 0.0001), approaching control values. LDS in the pre-OLT phase was significantly higher than in controls ( p < 0.0001); after OLT, it decreased significantly compared with baseline values ( p < 0.005). The MAPI of patients in the pre-OLT phase was lower than that in controls ( p < 0.0001); post-OLT, it progressively increased and reached values that were significantly above baseline at 12 months ( p < 0.005). In the pre-OLT phase, the HARI and SARI were significantly higher than in controls ( p < 0.04); 6 and 12 months after OLT, those values were significantly below baseline values ( p < 0.001), and there was no significant difference from control values. CONCLUSION: These data show that many of the hemodynamic parameters typical of decompensated cirrhosis improve progressively within 12 months after transplantation.

Acute pancreatitis in children. An Italian multicentre study.

AIM: To evaluate the clinical, morphological and aetiological aspects of acute pancreatitis in children in Italy. PATIENTS: The hospital records of 50 consecutive patients with acute pancreatitis observed in 5 Italian Pediatric Departments were reviewed. RESULTS: A total of 25 males and 25 females (median age 10.5 years, range 2-17) were studied. Of these patients, 48 (96%) had abdominal pain. The pancreatitis was associated with biliary disease in 10 patients (20%); it was due to viral infection in 6 patients (12%), pancreatic duct abnormalities in 4 (8%, familial chronic pancreatitis in 3 (6%), trauma in 5 (10%) and other causes in 5 (10%); the pancreatitis was of unknown origin in 17 patients (34%). Previous attacks of the disease had occurred in 14 patients. A diagnosis of mild pancreatitis was made in 41 patients (82%) and of severe disease in 9 (18%). One patient with severe pancreatitis died from multiorgan failure. Patients with severe pancreatitis had significantly higher serum concentrations of C-reactive protein than patients with mild pancreatitis. Hospital stay was similar for patients with the mild form and those with the severe form of the disease. CONCLUSIONS: In Italian children, acute pancreatitis is of unknown origin in about one-third of the children and is recurrent in 28% of the cases. The disease is severe in 18% of the cases.

Production of anti-endomysial antibodies in cultured duodenal mucosa: usefulness in coeliac disease diagnosis.

BACKGROUND: Although anti-endomysial antibodies (EmA) have been found in the supernatants of cultured intestinal mucosa from patients with coeliac disease (CD), in no study has the clinical reliability of this new diagnostic tool been investigated. Our aims were to evaluate the clinical usefulness of the in vitro production of EmA in CD diagnosis in consecutive patients with suspected CD, and to evaluate the reliability of the in vitro challenge in CD patients on a gluten-free diet (GFD). METHODS: For the former aim, consecutive patients who were due to undergo intestinal biopsy for suspected diagnosis of CD were enrolled: according to the final diagnosis, these patients were divided into two groups: Group 1 comprised 91 newly diagnosed CD patients (40 males; age range 7 months to 84 years), Group 2 included 100 subjects with diseases other than CD (44 males; age range 9 months to 76 years). For the latter aim, we also studied 21 CD patients on a gluten-free diet after 16-123 months (8 males; age range 3-51 years), with normal intestinal architecture (Group 3) and 22 patients who served as controls (12 males; age range 4-60 years) with gastroesophageal reflux disease-like symptoms (Group 4). All patients underwent determination of serum anti-gliadin (AGA) and EmA antibodies, histology evaluation of the intestinal biopsies and EmA assay in the supernatants of in vitro gliadin-challenged duodenal mucosa. RESULTS: EmA assay in the supernatants showed a sensitivity and specificity of 96% and 100%, respectively; these were not significantly different from those observed for serum EmA (88% and 99%, respectively). However, EmA assay in the supernatants was useful in CD patients with mild intestinal histology lesions (infiltrative/hyperplastic type): in this subgroup it was positive in 9/12 of cases, but serum EmA was positive in only 2/12. As regards the reliability of the in vitro gliadin challenge, EmA production in supernatants was recorded only in 10/21 CD patients on a gluten-free diet. The patients with a positive in vitro challenge had a higher number of intra-epithelial lymphocytes than patients with a negative challenge. CONCLUSIONS: 1) EmA assay in the medium of cultured intestinal biopsy can detect gluten-sensitive enteropathy, characterized by an infiltrative/hyperplastic histological pattern, which is often associated with negative serum EmA. 2) The in vitro challenge in CD patients on a gluten-free diet detects EmA production in the culture medium only in half of the cases and other studies must be performed to evaluate whether EmA production after in vitro challenge can be considered a reliable test for confirming CD diagnosis.

Screening for autoantibodies to tissue transglutaminase reveals a low prevalence of celiac disease in blood donors with cryptogenic hypertransaminasemia.

Patients with chronic cryptogenic hypertransaminasemia are at high risk of developing celiac disease (CD). In fact, among the various serological disorders, CD patients at onset frequently present hypertransaminasemia. In this study, we evaluated usefulness and reliability of the new test for antitissue transglutaminase (tTG) in screening for CD as well as in estimating the prevalence of CD in a population of blood donors presenting unexplained hypertransaminasemia at donation. Controls were 180 consecutive healthy donors without hypertransaminasemia and 20 CD patients with known antiendomysial antibody (EmA) positivity. Out of 22,204 blood donors over a period of 2 years, we found 258 subjects (1.2%) with cryptogenic hypertransaminasemia. Four of these subjects (1.5%) were positive for anti-tTG, but only 3 of them were positive for EmA. EmA were negative in all the remaining hypertransaminasemia subjects. In the control groups, anti-tTG antibodies were negative in all the 180 healthy donors without hypertransaminasemia, but positive in all the CD patients known to be EmA positive. 3 of the 4 subjects positive for anti-tTG, including 2 who were also EmA positive, underwent biopsy of the distal duodenal mucosa which showed a picture compatible with CD only in the 2 patients with concomitant EmA positivity. After 3 months of gluten-free diet, the serum transaminase values normalized in these 2 patients. In conclusion, the prevalence of CD in our blood bank population was lower than that reported in other similar studies, but the new test for anti-tTG showed a good sensitivity and reliability, and, therefore, it can be proposed as a first-level test in screening for CD in selected populations such as subjects with hypertransaminasemia.

Glycemic homeostasis in chronic viral hepatitis and liver cirrhosis.

OBJECTIVES: This study aimed at investigating the respective impacts of virus-related chronic hepatitis (CH) and liver cirrhosis (LC) on glycemic homeostasis, with reference to grading and/or staging of liver disease and to contribution of the two main responsible viruses. MATERIAL AND METHODS: The glycometabolic features of 82 patients with CH (B-related 16, and C-related 66) and 145 with LC (B-related 24, and C-related 121) were evaluated. RESULTS: Impaired glucose tolerance (IGT) was detected in 9 (11.0%) and diabetes mellitus (DM) in 6 (7.3%) of the CH patients [(P<0.05 vs controls, in both cases; respective odds ratios (95% CI): 2.6 (1.1-6.3), and 4.0 (1.2-13.2)]. IGT was detected in 86 (59.3%) and DM in 34 (23.4%) of the LC patients [(P=0.000 vs controls, in both cases; respective odds ratios: 10.0 (7.0-14.4), and 5.5 (3.5-8.5)]. The odds ratios for the prevalence of IGT and DM in the LC patients were 11.8 (5.2-27.5) and 3.9 (1.5-10.8), compared with the CH patients. In the CH patients, glycometabolic failure was significantly related to age (P=0.026), but not to grading and staging, and in the LC patients to Pugh-Child score (P=0.037). IGT was found in 17/40 (42.5%) HBV-related patients and in 13/40 (32.5) matched HCV-related patients. DM was found in 9/40 (22.5%) HBV-related patients and in 10/40 (25.0%) HCV-related matched patients, without significant difference in the respective proportions. CONCLUSION: The prevalence of DM associated to virus-related CH is on average four times higher than in the general population, independently of the histopathological picture of disease. Virus-related LC further increases the prevalence of both IGT and DM, independently of sex and age, but in relationship with the severity of disease. HBV and HCV infections do not appear to have a different impact on glycemic homeostasis.

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.