Abstract: BACKGROUND & AIMS: Data regarding the nutritional status, antioxidant compounds and plasma fatty acid (FA) composition in inactive IBD are conflicting. We compared plasma levels of antioxidants and FA of patients with inactive IBD with active IBD and controls. METHODS: Plasma levels of vitamin C, vitamin E, carotenoids, saturated, monounsaturated and polyunsaturated FA, inflammatory markers and nutritional status were determined after an overnight fast in 132 patients with quiescent IBD (40.6+/-13.2 years, 87F/45M), 35 patients with active disease (37.9+/-12.1 years, 25F/10M) and 45 age- and BMI-matched healthy controls (38.1+/-10.5 years, 39F/6M). Results are expressed as mean+/-SD or median [25th percentile;75th percentile]. RESULTS: Body mass index (BMI) was normal in inactive (23.9+/-4.7 kg/m(2)), active IBD (22.7+/-4.2 kg/m(2)) and controls (22.3+/-1.9 kg/m(2)). Compared with controls patients with quiescent IBD showed significantly decreased plasma levels of carotenoids (1.85 [1.37;2.56] vs 1.39 [0.88;1.87] micromol/L) and vitamin C (62.3 [48.7;75.0] vs 51.0 [36.4;77.6] micromol/L), increased levels of saturated FA (3879 [3380;4420] vs 3410 [3142;3989] micromol/L) and monounsaturated FA (2578 [2258;3089] vs 2044 [1836;2434] micromol/L) and similar levels of vitamin E and polyunsaturated FA. Results in active disease were similar to inactive disease. CONCLUSION: This study shows that antioxidant status and FA profile in a larger population of IBD patients are disturbed independently from disease activity and despite normal overall nutritional status.
Abstract: OBJECTIVE: This prospective, controlled, and multicentric study evaluated nutritional status, body composition, muscle strength, and quality of life in patients with inflammatory bowel disease in clinical remission. In addition, possible effects of gender, malnutrition, inflammation, and previous prednisolone therapy were investigated. METHODS: Nutritional status (subjective global assessment [SGA], body mass index, albumin, trace elements), body composition (bioelectrical impedance analysis, anthropometry), handgrip strength, and quality of life were assessed in 94 patients with Crohn's disease (CD; 61 female and 33 male, Crohn's Disease Activity Index 71 +/- 47), 50 patients with ulcerative colitis (UC; 33 female and 17 male, Ulcerative Colitis Activity Index 3.1 +/- 1.5), and 61 healthy control subjects (41 female and 20 male) from centers in Berlin, Vienna, and Bari. For further analysis of body composition, 47 well-nourished patients with inflammatory bowel disease were pair-matched by body mass index, sex, and age to healthy controls. Data are presented as median (25th-75th percentile). RESULTS: Most patients with inflammatory bowel disease (74%) were well nourished according to the SGA, body mass index, and serum albumin. However, body composition analysis demonstrated a decrease in body cell mass (BCM) in patients with CD (23.1 kg, 20.8-28.7, P = 0.021) and UC (22.6 kg, 21.0-28.0, P = 0.041) compared with controls (25.0 kg, 22.0-32.5). Handgrip strength correlated with BCM (r = 0.703, P = 0.001) and was decreased in patients with CD (32.8 kg, 26.0-41.1, P = 0.005) and UC (31.0 kg, 27.3-37.8, P = 0.001) compared with controls (36.0 kg, 31.0-52.0). The alterations were seen even in patients classified as well nourished. BCM was lower in patients with moderately increased serum C-reactive protein levels compared with patients with normal levels. CONCLUSION: In CD and UC, selected micronutrient deficits and loss of BCM and muscle strength are frequent in remission and cannot be detected by standard malnutrition screening.
Abstract: Parenteral nutrition is a life-saving treatment for patients who have acute and chronic intestinal failure. Severe cholestasis induced by total parental nutrition (TPN-IC) is characterized by bile duct regeneration, portal inflammation, and fibrosis. Its progression could be very rapid, and in some patients liver cirrhosis may develop in few months. This article describes the definition, incidence, hepatic changes, histopathologic findings, risk factors, pathogenesis, and clinical implications of TPN-IC. The goal is to improve hospital and home management, quality of life, and prognosis of patients requiring parenteral nutrition.
Abstract: BACKGROUND & AIMS: The US Medicare indications for intestinal transplantation are based on failure of home parenteral nutrition. The American Society of Transplantation also includes patients at high risk of death from their primary disease or with high morbidity intestinal failure. A 3-year prospective study evaluated the appropriateness of these indications. METHODS: Survival on home parenteral nutrition or after transplantation was analyzed in 153 (97 adult, 56 pediatric) candidates for transplantation and 320 (262 adult, 58 pediatric) noncandidates, enrolled through a European multicenter cross-sectional survey performed in 2004. Kaplan-Meier and chi-square test statistics were used. RESULTS: The 3-year survival was 94% (95% CI, 92%-97%) in noncandidates and 87% (95% CI, 81%-93%) in candidates not receiving transplants (P = .007). Survival was 80% (95% CI, 70%-89%), 93% (95% CI, 86%-100%), and 100% in parenteral nutrition failure, high-risk primary disease, and high-morbidity intestinal failure, respectively (P = .034). Fifteen candidates underwent transplantation. Six died, including all 3 of those who were in hospital, and 25% of those who were at home at time of transplantation (P = .086). Survival in the 10 patients receiving a first isolated small bowel transplant was 89% (95% CI, 70%-100%), compared with 85% (95% CI, 74%-96%) in the candidates with parenteral nutrition failure not receiving transplants because of central venous catheter complications, or 70% (95% CI, 53%-88%) in those with parenteral nutrition-related liver failure (P = .364). CONCLUSIONS: The results confirm home parenteral nutrition as the primary therapeutic option for intestinal failure and support the appropriateness and potential life-saving role of timely intestinal transplantation for patients with parenteral nutrition failure.
Abstract: Total parenteral nutrition is a life saving therapy for patients with chronic gastrointestinal failure, being an effective method for supplying energy and nutrients when oral or enteral feeding is impossible or contraindicated. Clinical epidemiological data indicate that total parenteral nutrition may be associated with a variety of problems. Herein we reviewed data on the gastroenterological tract regarding: (i) total parenteral nutrition-related hepatobiliary complications; and (ii) total parenteral nutrition-related intestinal complications. In the first group, complications may vary from mildly elevated liver enzyme values to steatosis, steatohepatitis, cholestasis, fibrosis and cirrhosis. In particular, total parenteral nutrition is considered to be an absolute risk factor for the development of biliary sludge and gallstones and is often associated with hepatic steatosis and intrahepatic cholestasis. In general, the incidence of total parenteral nutrition-related hepatobiliary complications has been reported to be very high, ranging from 20 to 75% in adults. All these hepatobiliary complications are more likely to occur after long-term total parenteral nutrition, but they seem to be less frequent, and/or less severe in patients who are also receiving oral feeding. In addition, end-stage liver disease has been described in approximately 15-20% of patients receiving prolonged total parenteral nutrition. Total parenteral nutrition-related intestinal complications have not yet been adequately defined and described. Epidemiological studies intended to define the incidence of these complications, are still ongoing. Recent papers confirm that in both animals and humans, total parenteral nutrition-related intestinal complications are induced by the lack of enteral stimulation and are characterised by changes in the structure and function of the gut. Preventive suggestions and therapies for both these gastroenterological complications are reviewed and reported in the present review.
Abstract: BACKGROUND AND AIMS: A total of 334 stable, compensated cirrhotic patients admitted to 10 Italian Gastroenterology Units were included in a prospective study to evaluate nutritional state and energy balance in liver cirrhosis. MATERIALS AND METHODS: Nutritional state and calorie intake were examined in the total population, while adequacy of calorie intake versus measured total energy expenditure was evaluated in a comparable subpopulation and in 40 matched controls, by computing the energy balance. RESULTS: Our data demonstrated that: (i) malnutrition was present in 25% of the total patients and significantly correlated with the Child's group (A=16%; B=25%; C=44%); (ii) the type of malnutrition is influenced by mBEE: normometabolic patients exhibit a significant (p<0.005) reduction of mid-arm fat area while both hypermetabolic and hypometabolic patients show a significant (p<0.005) decline in kg of free fat mass; (iii) normometabolic and hypometabolic patients have a negative energy balance, due to a high level of physical activity (127+/-14 kJ) in the first group and a reduced energy intake/kg body weight (102+/-12 kJ) in the second; (iv) hypermetabolic patients have a positive energy balance due to decreased daily physical activity/kg body weight (108+/-28 kJ); (v) malnourished and normometabolic patients eat a significantly (p<0.05) reduced percentage of protein whereas malnourished and hypermetabolic patients eat a significantly increased percentage of fat (p<0.05). CONCLUSION: Although multivariate regression analysis confirms that the Child-Pugh's score is a better independent predictor of malnutrition, the measure of REE, TEE, calorie intake and energy balance need to be routinely performed in cirrhotic patients, in order to recognise hypermetabolic and hypometabolic patients (approximately 30%) in whom the nutritional and metabolic parameters are indispensable as a basis for designing and prescribing personalised nutritional strategies that can treat muscle malnutrition and thus improve the morbidity and mortality rates.
Abstract: Qualitative and quantitative alterations of mitochondrial DNA (mtDNA) in the skeletal muscle from two patients with cirrhosis and severe asthenia have been studied. The 4977 bp (mtDNA(4977)) and the 7436 bp (mtDNA(7436)) mtDNA deletions, as well as other mtDNA deletions, revealed by long extension PCR (LX-PCR), were found in the two patients, whereas the 10,422 bp (mtDNA(10,422)) mtDNA deletion was absent. Altogether, the qualitative alterations of mtDNA in cirrhotic patients with severe asthenia were comparable to those of age-matched healthy individuals. The mtDNA content, on the contrary, was substantially decreased in both patients with respect to control. Such mtDNA depletion might be explained by an increased, disease-related, oxidative damage to mtDNA, which probably affects the replication of the mitochondrial genome as already suggested in other oxidative stress-associated diseases.
Abstract: BACKGROUND & AIMS: The epidemiology of bone disease in home parenteral nutrition (HPN) is unknown. The aim of this paper is to evaluate the prevalence and severity of reduced bone mineral density (BMD) in long-term HPN. DESIGN: Cross-sectional, multicentre study including patients who within the last 12 months had their BMD assessed by dual-energy-X-ray absorptiometry after at least 6 months of HPN. Data on bone pain and fractures, the primary gastrointestinal diseases, nutritional and rehabilitation status and HPN regimen were reviewed. Both the T-score (no. of SD below mean BMD of young subjects) and the Z-score (no. of SD from normal BMD values corrected for sex and age) were analysed. RESULTS: A T -score <-1 at any site of assessment was observed in 84% of the 165 patients enrolled (<or= -2.5 in 41%). Bone pain occurred in 35% and bone fracture in 10% of patients. Both T - and Z-scores were significantly lower in symptomatic patients. The frequency of bone disease was higher in post-menopausal women but did not differ among the subgroups of the primary diseases. Stepwise regression analysis showed the lumbar spine Z -score positively associated with the age at starting HPN and the femoral neck Z-score positively associated with the body mass index. CONCLUSIONS: Bone disease was present in most of the patients on HPN, was of severe degree in one-half of them and symptomatic in one-third. The BMD Z-score appeared predictive of the risk of fracture. The prevalence of bone disease did not differ between the various primary diseases. Age at starting HPN and body mass index appeared to be the major factors associated with BMD Z-scores.
Abstract: AIM: To report the results of a prospective, open-label, uncontrolled study in 13 patients affected by Crohn's disease with resistance to steroids. METHODS: The patients were treated long-term with oral tacrolimus, aiming to both resolve acute attacks and maintain remission. Tacrolimus was administered at the dose of 0.1--0.2 mg.day/kg and adjusted in order to achieve levels of 5--10 ng/mL; only mesalazine was continued concomitantly. Steroids and total parenteral nutrition were tapered when appropriate. RESULTS: Median treatment was 27.3 months. Only one patient dropped out due to adverse events. Crohn's disease activity index score significantly decreased after 6 months in 11 patients; for 1 year in nine of them, and 7 years in two of them. The inflammatory bowel disease life-quality questionnaire score significantly increased over the same periods. A marked drop in hospitalizations was recorded. In three out of six patients complete closure of fistulas occurred. Tacrolimus allowed total parenteral nutrition to be withdrawn in three out of five patients. Supplementation with low-dose steroids was required in five patients. Two patients underwent surgery. CONCLUSIONS: Tacrolimus therapy appears to be associated with both short- and long-term benefits, and may represent a therapeutic option in Crohn's disease when conventional therapies fail. This study encourages its use in controlled trials.
Abstract: BACKGROUND: Nutritional status affects the course, ensuing complications and prognosis of virtually all diseases. AIMS: To define the role of nutrition in Gastroenterology Units by means of two investigations that analyse: a) availability of devices for assessing nutritional status; b) nutritional treatment in clinical practice: incidence and frequency of indications for its use, together with type of treatment adopted. PATIENTS AND METHODS: Two questionnaires were sent to Italian Academic and Hospital Gastroenterology Units, all with clinical wards. RESULTS: Results refer to 27 Units, 22 of which took part in both parts of the analysis, enrolling 547 patients during the two-week study The first analysis shows that scales and the altimeter are not available everywhere, while more specific tools, such as skinfold calipers are available in 54% of the Units, and caloric intake can be assessed in 22-41%. The second analysis reveals that nutritional treatment was necessary in 50% of patients in the series examined, and that this was taken into account and prescribed in almost all cases (91%). Of the patients treated, 69% received dietetic supplementation and 31% artificial nutrition [12% enteral, 88% parenteral), although supportive parenteral nutrition is often contraindicated in conditions where good bowel function provides the conditions for enteral nutrition. CONCLUSION: Data emerging from the investigation showed that i) artificial nutrition is commonly used in gastroenterology Units in Italy although 23% of them never consider either enteral or parenteral nutrition as medical treatment of gastrointestinal disease; ii) malnutrition is a very frequent complication (mean 27%; range 4-55%0) in Gastroenterology Unit patients albeit only 42% of malnourished patients received artificial nutrition; iii) indications for enteral and parenteral nutrition are not always respected, as there is an excessive use of parenteral nutrition and an unjustified resistance to the use of enteral nutrition; iv] nutritional treatment is often administered without adequate nutritional assessment and without a complete adherence to the standards recommended for preparation of parenteral bags, supported by suitable technology; v) only two Gastroenterology Units report admitting and following patients in a home parenteral nutrition programme; vi) this investigation probably reflects the response of those Gastroenterology Units most aware of the importance of nutritional problems. Better awareness of correct practices for nutritional support should be promoted, encouraging greater use of diagnostic and monitoring techniques and a more discerning choice of the most suitable type of artificial nutrition to be administered in gastroenterology
Abstract: A recent study, using height-standardized resistance (R/H) and reactance (Xc/H) and assuming a bivariate distribution, has proposed the "RXc graph". We applied this new approach for patients with chronic liver disease in differentiating various degrees of fluid unbalance. Our data showed that a 95% confidence ellipse of patients with chronic hepatitis (CH) overlapped that of healthy control subjects (CONTR), while those of patients with liver cirrhosis (CIR), patients with cirrhosis and ascites (ACIR), and patients with cirrhosis, edemas, and ascites (AECIR) were clearly different for both genders. A progressively shorter mean impedance vector proportional to the stage of liver disease and to the degree of fluid unbalance was found. The lower half of the 50% tolerance ellipse for the healthy population proved to be a threshold for cirrhotics, while almost all the subjects with clinically detectable edema fell outside this limit. The RXc graph was shown to be useful in monitoring the treatment of fluid unbalance and for the immediate selection of patients in whom BIA can precisely assess body composition.
Abstract: The aim of this study was to examine and compare whole-body and segmental impedance measurements in control subjects and patients with progression of liver disease and to investigate whole-body and segmental bioelectrical changes occurring during dehydration therapy or paracentesis. Males have lower resistance (R) and reactance (Xc) values than females in measurements both of the whole body and of the arm, leg, and trunk. This is not true in patients. In the three groups of patients, whole-body R and Xc were lower in each increased disease stage, suggesting that stage has a significant main effect on impedance measurements. The lower extremities were the segment most influenced by the progression of liver disease. The sum of the arm and leg R was only slightly lower than the value of whole-body resistance. The trunk has a meager influence on this parameter, as is clearly shown by the absence of variations before and immediately after paracentesis. In edematous cirrhotic patients without ascites treated with diuretics, our data also showed a significant correlation (r = .81; SEE = 1.2) between changes in body weight (BW) and in the bioelectrical evaluation of total body water (TBW). The association of a prevalent increment of Xc (approximately 40%) with a reduction of extracellular water is the most significant bioelectrical event during dehydration therapy. All these findings show that impedance measurements have a low sensitivity in detecting the volume of ascites in cirrhotic patients, whereas Xc has a clinical use in monitoring changes in extracellular water (EW).
Abstract: Despite numerous studies on the effects of bile salts therapy in chronic liver disease, there are no reports on the influence such therapy has on hepatocyte proliferation. The aim of this preliminary study was to evaluate the effect of TUDCA on hepatocyte proliferation in 5 patients with HCV-correlated chronic liver disease. All patients were treated with TUDCA (10-13 mg/day) for three months and the determination of PCNA (Proliferating Cell Nuclear Antigen) expression was used to assess the proliferative activity of hepatocytes at the beginning and at the end of treatment. TUDCA reduced both ALT and Knodell's score in the 5 patients in whom a significant increase of PCNA-LI (p < 0.05) was observed after treatment. TUDCA administration seems to stimulate hepatocyte proliferation in man.
Abstract: Progressive degrees of metabolic alterations are frequent in cirrhosis impairing peripheral tissue and body composition. Hepatocellular carcinoma worsens protein wasting and malnutrition. A normal energy production rate and an abnormal substrate oxidation rate are well-known findings in cirrhosis; however, no data are available on cirrhotic patients with hepatocellular carcinoma. The aim of this study was to measure oxidative metabolism in cirrhotic patients with and without hepatocellular carcinoma and to investigate the correlation between energy production rate, respiratory quotient and nutritional state. Thirteen male cirrhotic patients with hepatocellular carcinoma (8 well-nourished and 5 malnourished) were compared with 17 cirrhotic patients without hepatocellular carcinoma (11 well-nourished and 6 malnourished) and six controls who were age and sex matched. A diagnosis of malnutrition was made if the fat mass percentage was reduced to less than 20% of the patient's body weight. Indirect calorimetry was performed between 8 and 10 AM, after a 12-hr fast, for 30 min (with a 10-min steady-state period), and measured energy production rate was calculated according to Weir's formula. Body composition was assessed by means of the Durnin and Womersley formula. Anthropometry and bioelectric impedance analysis showed no variations in kilograms of fat-free mass in our malnourished patients. Our data show that, when the energy production rate is measured while the patient is at rest and corrected for fat-free mass, the energy requirements of cirrhotic patients and cirrhotic patients with hepatocellular carcinoma matched that of the controls, regardless of nutritional state.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: Bioelectric impedance analysis is a new, convenient and portable method used to estimate total body water and to assess body composition in healthy people. We used the tetrapolar bioelectrical impedance analysis method in 58 cirrhotic patients to assess its clinical applicability. Whole-body resistance, reactance and impedance were measured and compared with those of 30 healthy volunteers matched for age and sex. The resistance and impedance values of ascitic cirrhotic patients (resistance = 461 +/- 80 omega; impedance = 462 +/- 80 omega) and nonascitic cirrhotic patients (resistance = 487 +/- 96 omega; impedance = 489 +/- 97 omega) were comparable with the resistance (488 +/- 44 omega) and impedance (491 +/- 44 omega) of controls. However, a significant (p less than 0.05) reduction in whole body reactance was found in patients with ascites and in those without ascites (34 +/- 9 omega vs. 47 +/- 12 omega) as compared with healthy subjects (56 +/- 7 omega). In 10 ascitic patients total body water was determined both before and after paracentesis; the volume of intraperitoneal fluid removed (7.9 +/- 3.8 L) could not be fully accounted for but only detected as an average volume of 1.9 +/- 1.0 L independently of the initial volume of the ascites. Our data clearly demonstrate that tetrapolar bioelectric impedance analysis is not adequate for measuring variations of "compartmentalized" fluid in the abdomen.
Abstract: The effect of ranitidine administration upon the hepatotoxic effect produced by a multidose acetaminophen administration regimen was examined. Seventy-two dogs received three subcutaneous injections of acetaminophen (750, 200, 200 mg/kg body wt) in DMSO (600 mg/ml) at time zero, 9 hr later, and 24 hr after the first dose. Ten control animals (group I) were not given ranitidine, the remaining 62 dogs received an intramuscular injection of ranitidine 30 min before each acetaminophen dose. Three different doses of ranitidine were used (mg/kg body wt): 50 mg, group II (33 dogs); 75 mg, group III (14 dogs); 120 mg, group IV (15 dogs). Ranitidine reduced the expected acetaminophen-induced hepatoxicity in a dose-response manner. Moreover, a significant correlation was found between the ranitidine dose and the survival rate, as evidenced by transaminase levels in the serum and histology of the liver. This model of fulminant hepatic failure induced by acetaminophen and its modulation with ranitidine provides clinical investigators with a research tool that will be useful in the future investigation of putative medical and surgical therapies being investigated for use in the clinical management of fulminant hepatic failure. Because of the size of the animal used in this model, frequent and serial analyses of blood and liver were available for study to determine the effect of therapy within a given animal as opposed to within groups of animals.
Abstract: In five adult male patients undergoing a 40-60% partial hepatectomy, serum sex hormone levels before and after hepatic resection were determined. Blood was drawn immediately prior to each surgical procedure and at specified time points postoperatively. Compared to hormone levels found prior to surgery, following major hepatic resection, estradiol levels increase at 24 and 48 hr, while testosterone levels decline, being significantly reduced at 96 and 144 hr. These data demonstrate that adult males who undergo a 40-60% partial hepatectomy experience alterations in their sex hormone levels similar to those observed in male rats following a 70% hepatectomy. These changes in sex hormone levels have been associated in animals with an alteration of the sex hormone receptor status of the liver that is thought to participate in the initiation of the regenerative response. These studies suggest, but do not prove, that in man, as in the case of the rat, sex hormones may participate in the initiation of or at least modulate in part the regenerative response that occurs following a major hepatic resection.
Abstract: Psychometric tests, visual reaction time tests and electroencephalograms were performed in 26 cirrhotic patients without overt portal-systemic encephalopathy and in 26 healthy individuals. Cirrhotics performed poorly, compared with controls, on intelligence, learning and memory, perceptual motor and spatial tests. Non-alcoholic scored lower than alcoholic cirrhotics compared with controls in most tests. Visual reaction time ability was lower in cirrhotics than controls, but the etiology of the cirrhosis did not influence the test results. EEG was normal in all subjects. We conclude that psychomotor tests are the most useful tool for the detection of latent encephalopathy and in the discrimination of different cirrhosis.
