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Objective: Despite the documented effectiveness of endoscopic ultrasound (EUS) in research studies, data on the utilization of this technology in clinical practice are scarce. The aim of this study was to assess EUS availability and accessibility as well as EUS utilization among clinicians from different European countries., Material and Methods: A direct mail survey was sent to members of the national gastroenterological associations in Sweden, Norway, Greece, and the United Kingdom., Results: Out of 2361 clinicians with valid addresses, 593 (25.1%) responded. Overall, EUS was available to 43% of clinicians within their practice but availability varied from 23% in Greece to 56% in the United Kingdom. More than 50% of respondents evaluating patients with esophageal cancer, rectal cancer, or pancreaticobiliary disorders had utilized EUS during the previous year, but utilization varied considerably among different countries, being more frequent in the United Kingdom. In logistic regression analyses, factors independently related to EUS utilization were mainly EUS availability and accessibility as well as perceived utility of EUS (p <0.05 for all). Respondents considered the lack of trained endosonographers (79%) and high cost (52%) as the main barriers to wider EUS use., Conclusions: The majority of responding clinicians use EUS but overall utilization varies considerably among different countries. There is considerable variation in EUS service availability and accessibility among countries which, together with perceived usefulness of EUS, is a major determinant of EUS utilization. A shortage of trained endosonographers and the high cost are major barriers to wider EUS use. The findings of this study might help to define policies aimed at development of EUS services.

Objective: Patients with hepatitis C have been shown to have impaired health-related quality of life (HRQoL). The aim of this study was to determine HRQoL in patients in different stages of hepatitis C virus (HCV) and to compare HRQoL in HCV cirrhosis with non-HCV-induced cirrhosis., Material and Methods: Out of 489 consecutive patients who fulfilled the inclusion criteria, 472 (96%) agreed to participate in the study: 158 patients with mild/moderate fibrosis with chronic hepatitis C (CHC group), 76 patients with HCV compensated cirrhosis (CC), 53 patients with HCV decompensated (DC) cirrhosis, 52 non-cirrhotic patients with sustained viral response (SVR), and a control group consisting of 32 patients with non-HCV CC and 101 with non-HCV DC who completed the Short Form-36 (SF-36) and EQ-5D questionnaire., Results: The CHC group had significantly lower SF-36 scores than healthy controls, with the exception of scores for the dimensions physical function and bodily pain. HCV patients with DC had lower scores in all SF-36 dimensions in comparison with those of the CHC group, as well as in physical and mental component summaries (p<0.001). In comparison with the CHC group, the HCV CC group had lower scores on the SF-36 general health dimension (p<0.05) and lower SF-36 physical component summary (PCS) scores (p<0.05). No major differences were seen in patients with HCV- and non-HCV-induced cirrhosis., Conclusions: Impairment in HRQoL in patients with HCV was associated with the severity of liver disease, patients with decompensated cirrhosis exhibiting the highest impairment in HRQoL. The etiology of liver disease does not seem to be important in determining HRQoL in cirrhosis.

Aim: To investigate the proportion of patients with alcoholic cirrhosis who abstained from alcohol after contact with a hepatology unit, the predictors for abstinence, and the role of clinical and psychosocial factors in short-term mortality in these patients., Methods: Eighty-seven consecutive patients with alcoholic cirrhosis from a transplant center were included. Data on cirrhosis severity and complications, as well as on abstinence and psychosocial factors were collected. Patients were followed up for 19 (12-25) months. Data on abstinence during follow up, alcohol abuse treatment, psychiatric contact, severity of cirrhosis, mortality, and liver transplantation were analyzed., Results: Prior to inclusion, 53/87 (61%) patients had abstained from alcohol for 24 months (interquartile range: 18-33). Twenty percent had a history of other substance abuse, 47% had undergone alcohol abuse treatment, and 21% had a previous psychiatric diagnosis. Forty-eight percent lived with a partner, 23% worked/studied, and 53% were pensioners. During follow up, 26% died, 20% received a liver transplant, 55% abstained from alcohol, 47% received alcohol abuse treatment, and 33% had psychiatric contact. In a multivariate analysis, abstinence during follow up was found to be related to abstinence upon inclusion in the study, to the model for end-stage liver disease (MELD) score at follow up, and to no abuse treatment in a detoxification unit, whereas mortality was related to index MELD and alcohol abuse treatment during follow up. Neither abstinence nor mortality was related to psychosocial factors., Conclusion: More than half of patients with alcoholic cirrhosis were found to abstain from alcohol during follow up, which was related to prior documentation of abstinence and cirrhosis severity. Cirrhosis severity (expressed as the MELD) and alcohol abuse treatment during follow up were related to short-term mortality.

Objective: To determine the clinical characteristics of patients with acute liver failure of indeterminate cause and their long-term outcome in comparison with patients with acute liver failure of obvious aetiology (acetaminophen and mushroom poisoning, Budd-Chiari syndrome, acute viral hepatitis) and other controls (idiosyncratic drug reactions, autoimmune hepatitis and Wilson's disease)., Material and Methods: All patients with acute liver failure and listed for liver transplantation in Sweden between 1984 and 2006 were included in a retrospective analysis., Results: A total of 71 patients with acute liver failure were identified, 33 with indeterminate cause (IDC group), 23 with obvious aetiology (OE group) and 15 other controls (OC group). Before admission to the transplant centre, IDC patients were hospitalized in the referring hospital for 9 days (4-15) versus 1.5 days (1-3) in the OE group (p<0.001) and 7 days (2-14) in the OC group (NS). Serum bilirubin was higher (p<0.001), whereas peak creatinine was lower (p=0.001) in the IDC group compared with the OE group but was not significantly different from the OC group. There were no significant differences in 1-, 3-, 5- and 10-year patient and graft survival rates between the IDC group and the OE or the OC group., Conclusions: Patients with acute liver failure of indeterminate cause seem to differ from those with obvious aetiology in clinical and biochemical presentation but are similar to other controls. The overall long-term outcome seems to be similar in patients with an unknown aetiology as in those with a specific aetiology.

Objective: Patients with short-bowel syndrome (SBS) have impaired health-related quality of life (QoL). However, comparisons of QoL data with the data on other chronic gastrointestinal diseases are not available. The aim of this study was to assess QoL in SBS patients compared with that in the general population and with patients with inflammatory bowel disease (IBD). The potential relation between fatigue and gastrointestinal symptoms and impaired QoL in these patients was also investigated., Material and Methods: Four validated questionnaires were used to measure aspects of QoL (SF-36), psychological distress (hospital anxiety and depression scale, HAD), fatigue (fatigue impact scale, FIS), and gastrointestinal symptoms (gastrointestinal symptom rating scale, GSRS) in 26/28 patients (93%) attending a SBS clinic (median age 62 years, 15 F/11 M) at a tertiary referral center. Persons from the general population (n=286) as well as patients with IBD (n=41) of similar age and gender distribution as the SBS group acted as controls., Results: SBS patients had significantly lower SF-36 physical and mental component summaries than those in the general population as well as significantly lower SF-36 physical (p<0.05) but not mental (p>0.05) component summaries compared with those of IBD patients. Fatigue and gastrointestinal symptoms were more severe in SBS patients than in IBD patients (p>0.05). The SF-36 physical component summary was independently related to the physical FIS dimension (beta=-0.4, p=0.004), the GSRS eating dysfunction dimension (beta=-0.31, p=0.025), and opiate use (beta=-0.28, p=0.031), regardless of diagnosis (SBS or IBD)., Conclusions: Patients with SBS show poor QoL compared with that in the general population and also impairment of mainly physical health compared with that in patients with IBD. Fatigue and gastrointestinal symptoms are more severe in patients with SBS, which has an impact on QoL.

Background/aims: Studies on animal models of hepatic encephalopathy (HE) suggest that poor nutritional status may facilitate the development of HE. Insulin resistance and diabetes mellitus have recently been reported to affect cognition in patients with hepatitis C cirrhosis awaiting liver transplantation. Our aim was to investigate the effects of malnutrition and diabetes mellitus on HE in unselected patients with liver cirrhosis., Methods: A total of 128 consecutive cirrhotic patients were prospectively evaluated for the presence of HE according to the West-Haven criteria as well as by means of two psychometric tests and fasting plasma ammonium ion concentrations. Nutritional status was assessed by anthropometry and estimation of recent weight change. Fasting plasma glucose was measured, and in a subgroup of 84 patients fasting serum insulin and insulin resistance were also determined., Results: Fifty-one (40%) cirrhotics were malnourished, 33 (26%) had diabetes and 42 (34%) had HE. Patients with vs. without malnutrition had more frequently HE (46 vs. 27%; P=0.031) but did not differ in age, aetiology or severity of liver cirrhosis (P>0.1). Multivariate analysis showed that the time needed to perform number connection test A was independently correlated to age, the Child-Pugh score, diabetes and malnutrition (P<0.05 for all). Plasma ammonium ion levels were related to insulin resistance (r=0.42, P<0.001) and muscle mass (r=0.28, P=0.003)., Conclusion: Malnutrition and diabetes mellitus seem to be related to HE in patients with liver cirrhosis. Nutritional status and insulin resistance might be implicated in the pathogenesis of HE.

Objective: Cognitive impairment is a common problem in patients with liver cirrhosis. Its pathogenesis is multifactorial and ammonia is considered to play a central role. Renal function has been shown to be important for ammonia metabolism in cirrhosis. Although renal dysfunction is common in cirrhotic patients, its effect on cognitive function is largely unexplored., Material and Methods: A total of 128 consecutive cirrhotic patients were prospectively evaluated for the presence of cognitive dysfunction according to the West-Haven criteria and by means of two psychometric tests. Serum creatinine, sodium and potassium as well as plasma ammonia concentrations were assessed. Glomerular filtration rate was also measured by (51)Cr- EDTA clearance in a subgroup of patients., Results: Forty-one patients (32%) were found to have cognitive dysfunction (clinical evaluation and/or psychometric tests). Sixteen patients (13%) found with serum creatinine levels above reference values had cognitive dysfunction more frequently than patients with creatinine within the normal range (69% versus 31%; p = 0.001), but did not differ in aetiology or severity of cirrhosis (p >0.1). Patients with loop diuretics versus without did not differ in creatinine values (p >0.1). Multivariate analysis showed that cognitive dysfunction was related to hospital admission at inclusion in the study, international normalized ratio and serum creatinine (p <0.05 for all), but not to potassium or sodium levels. Plasma ammonia concentration was related to serum creatinine (r = 0.26, p = 0.004) and the glomerular filtration rate (r = -0.44, p = 0.023)., Conclusions: Renal dysfunction seems to be related to cognitive impairment in patients with liver cirrhosis and might be implicated in the pathogenesis of hepatic encephalopathy.

Proton-pump inhibitors (PPIs) are the drugs of choice for the treatment of gastroesophageal reflux disease (GERD). Esomeprazole is the latest PPI and was developed as the S-isomer of omeprazole as an attempt to improve its pharmacokinetic properties. Esomeprazole has been reported to have a somewhat higher potency in acid inhibition than other PPIs. Despite some controversy, data from clinical trials and meta-analyses indicate that esomeprazole 40 mg od for up to 8 weeks provided higher rates of healing of erosive GERD and a greater proportion of patients with sustained resolution of heartburn, than omeprazole 20 mg, lansoprazole 30 mg, or pantoprazole 40 mg od. Esomeprazole 20 mg od has also been shown to be more effective in maintaining healing of erosive GERD compared with lansoprazole 15 mg od or pantoprazole 20 mg od. However, it is not clear whether these statistically significant differences are of major clinical importance. Esomeprazole 20 mg od is superior to placebo for treatment of non-erosive reflux disease (NERD) but clinical trials have not shown any significant differences in efficacy between esomeprazole 20 mg and omeprazole 20 mg or pantoprazole 20 mg od. Lastly, although esomeprazole treatment in GERD has been reported to result in improvement of health-related quality of life (QoL) indices, no clinical trials have evaluated the possible differential effects of different PPIs on QoL in GERD.

Background: Fatty change of the liver (FCL) is very common in dairy cattle periparturiently. Many laboratory methods have been implicated in order to assist the diagnosis., Hypothesis: To investigate whether FCL in dairy cattle could be evaluated by assessment of ornithine carbamoyl transferase (OCT) by means of an assay modified for bovine serum, other enzyme activity, serum bile acids (SBA) concentration, or other biochemical constituents., Animals: A total of 187 dairy cattle were included: 106 were suspected to have liver dysfunction and were examined after referral by veterinarians; 70 were clinically healthy with mild FCL; and 11 were clinically healthy without FCL., Methods: Blood and liver biopsy samples were obtained after clinical examination. Histologic examination by light microscopy and classification of samples according to the severity of FCL was done, and total lipid and triglyceride concentration was measured. In serum, OCT, aspartate aminotransferase (AST), alanine aminotransferase (ALT), sorbitol dehydrogenase (SDH), glutamate dehydrogenase (GDH), alkaline phosphatase (ALP), and gamma-glutamyltransferase (gamma-GT) activity as well as SBA, glucose, ketones, total bilirubin (tBIL), and nonesterified fatty acids (NEFA) concentration were measured., Results: OCT and AST activity and tBIL concentration correlate well with the degree of FCL. SBA concentration does not contribute well to FCL diagnosis. The majority of FCL cases appeared within the first 21 days-in-milk (DIM). The majority of moderate-to-severe and severe FCL cases arose in the first 7 DIM., Conclusions and Clinical Importance: Except for OCT, AST, and tBIL, none of the biochemical tests used, including SBA, had sufficient discriminatory power to differentiate reliably between mild and severe FCL because of poor sensitivity. A weak correlation between clinical signs and the extent of FCL was evident.

Background: Liver cirrhosis is associated with reduced energy intake and increased resting energy expenditure., Objective: We aimed to investigate the possible role of glucose, insulin, leptin, and ghrelin in the pathogenesis of these alterations., Design: Nutritional status, energy intake, resting energy expenditure, and fasting glucose, insulin, and leptin were assessed in 31 patients with cirrhosis. Postprandial glucose, insulin, C-peptide, leptin, and ghrelin responses were studied in a subgroup of patients after a standard meal. Ten healthy subjects served as controls., Results: Patients with cirrhosis had a lower energy intake (P < 0.05), higher resting energy expenditure (P < 0.05), higher fasting leptin (P < 0.05), and higher insulin resistance (P < 0.001) than did the healthy control subjects. In the patients with cirrhosis, fasting leptin was negatively correlated with resting energy expenditure (r = -0.38, P < 0.05) but not with energy intake. In control subjects, leptin was negatively correlated with energy intake (r = -0.72, P < 0.05) but not with resting energy expenditure. The patients with cirrhosis had higher postprandial glucose (P < 0.001) and lower ghrelin (P < 0.05) concentrations at 4 h postprandially than did the control subjects. The increase in ghrelin from its minimal postmeal value to 4 h postmeal was negatively correlated (r = -0.66, P = 0.014) with weight loss in the patients with cirrhosis. Energy intake was negatively correlated (r = -0.42, P < 0.01) with the postprandial increase in glucose., Conclusions: In cirrhosis, altered postprandial glucose and ghrelin are associated with reduced energy intake and weight loss, respectively, and the effects of leptin on energy intake and expenditure seem to be altered. Insulin resistance might be involved in these altered postprandial responses.

Objective: Altered gastric sensorimotor function is related to the symptomatology in several gastrointestinal diseases. Gastrointestinal symptoms in patients with cirrhosis may result in low energy intake contributing to malnutrition and increased morbidity. The aim of this study was to investigate gastric accommodation to a meal and sensitivity to gastric distension with reference to energy intake, nutritional status and gastrointestinal symptoms in liver cirrhosis., Material and Methods: Sixteen patients with cirrhosis and 15 healthy controls underwent a gastric barostat study to assess gastric accommodation to a meal and sensory thresholds for first perception and discomfort. The patients also underwent a slow caloric satiety drinking test. Food intake and nutritional status were also evaluated and gastrointestinal symptoms were assessed by means of a questionnaire., Results: Compared with controls, patients with cirrhosis had enhanced gastric accommodation (p<0.05) but lower daily energy intake (p<0.05). Patients with versus those without compromised nutritional status had enhanced gastric accommodation (p<0.05). Gastric accommodation was correlated to daily energy intake in controls (r=0.67, p<0.05) but not in cirrhotic patients (p>0.4). The end-point of the satiety test was inversely related to gastric volumes in cirrhotic patients. Mean post-meal balloon volumes were positively correlated to the Model for End Stage Liver Disease (MELD) score (r=0.53, p<0.05). Sensory thresholds did not differ between patients and controls but were related to gastrointestinal symptom severity and cirrhosis severity scores in the patients., Conclusions: Gastric accommodation is increased in cirrhotic patients but there seems to be some disturbance in its relation to energy intake. The satiety drinking test is not a good surrogate marker of accommodation in cirrhotic patients. In cirrhosis the severity of gastrointestinal symptoms is related to gastric sensitivity.

Objective: Gastrointestinal symptoms can lead to decreased food intake and thereby increased morbidity. There is a general lack of data on the prevalence of gastrointestinal symptoms and their potential association with malnutrition and health-related quality of life (QoL) in cirrhosis. Our aim was to prospectively evaluate gastrointestinal symptoms, malnutrition, and QoL in patients with cirrhosis., Material and Methods: Two validated questionnaires were used to measure gastrointestinal symptoms (gastrointestinal symptom rating scale (GSRS)) and health-related QoL (SF-36) in 128 consecutive cirrhotics (mean age 57 years, Child-Pugh score 8.6, MELD score 13.2) at a tertiary referral center. The results were compared with those of controls from the general population. Nutritional status was assessed by anthropometry and estimation of recent weight change., Results: Compared to controls, cirrhotic patients showed higher gastrointestinal symptom severity (total GSRS score: 1.53, 95% CI 1.50-1.55 versus 2.21, 95% CI 2.04-2.38) and profound reductions in the SF-36 physical (47.0 95% CI 45.0-49.0 versus 37.9, 95% CI 35.7-40.1) and mental component summary scores (51.0 95% CI 49.0-53.0 versus 39.2 95% CI 36.7-41.6). There were no significant differences in any GSRS domain between patients with and those without malnutrition. Multivariate analysis showed that gastrointestinal symptom severity was associated with the Child-Pugh score (beta = 0.10, r<0.05), daily lactulose use (beta = 0.65, p<0.005), and the presence of gastrointestinal comorbidities (beta = 0.51, p<0.05). Negative weight change (beta = -0.72, p<0.05) and the SF-36 physical (beta = -4.26, p<0.005) and mental (beta = -4.53, p<0.005) summaries were independently related to gastrointestinal symptom severity., Conclusions: Patients with cirrhosis show increased severity of gastrointestinal symptoms, which are associated with recent weight loss and impaired health-related QoL. The severity of gastrointestinal symptoms seems to be related to the severity of cirrhosis.

Objective: To evaluate postsurgical outcome in dairy cows with left-displaced abomasum (LDA) with regard to severity of fatty liver and assess the usefulness of preoperative determination of serum ornithine carbamoyl transferase (OCT) activity, bile acids concentration, and other variables for evaluating liver function during the postsurgical convalescence period., Design: Prospective study., Animals: 68 Holstein cows., Procedures: Blood and liver biopsy specimens were obtained during standing LDA surgery. Liver tissue was examined histologically and classified by severity of fatty change. Serum activities of liver-derived enzymes and concentrations of total lipids, triglycerides, bile acids, glucose, beta-hydroxybutyric acid, bilirubin, and nonesterified fatty acids were determined., Results: Most cows with LDA and cows with severe fatty liver were detected within the first month after calving. Postsurgical outcome was related to severity of fatty liver. All cows that died had severe fatty liver. Serum activities of OCT, aspartate aminotransferase, and glutamate dehydrogenase and serum total bilirubin concentration were sensitive indicators of fatty liver. Serum bile acids concentration was not an accurate indicator of fatty liver., Conclusions and Clinical Relevance: Postsurgical outcome of cows undergoing surgery to correct LDA was related to fatty liver severity. Assessment of serum activities of OCT, aspartate aminotransferase, and glutamate dehydrogenase and serum total bilirubin concentration is recommended for diagnosis of fatty liver in dairy cows with LDA, whereas determination of bile acids concentration is not. The strong correlation between OCT activity and degree of hepatocellular damage supports use of this enzyme for assessing severity of fatty liver and predicting postsurgical outcome in cows with LDA.

Objective: It has been suggested that increased intestinal permeability plays a pathogenic role in bacterial infections, such as spontaneous bacterial peritonitis, in patients with liver cirrhosis. The aim of this study was to assess whether intestinal permeability is altered in cirrhotic patients with and without ascites., Material and Methods: Intestinal permeability was assessed by a (51)Cr-EDTA permeability test in 20 cirrhotic patients (10 with and 10 without ascites) along with 20 age- and gender-matched healthy controls. In six patients with ascites, the test was performed before and after therapeutic paracentesis., Results: The median (IQR) 24-h urinary excretion of (51)Cr-EDTA was higher in patients with cirrhosis (1.94% (1.21-2.70%)) compared with that in controls (1.40% (1.09-1.99%); p<0.05). Patients with (2.05% (1.50-3.46%); p<0.05) but not those without ascites (1.94% (1.13-2.53%); p>0.1) had significantly higher excretion values compared with those of controls. Only one patient without ascites and a total of four patients with ascites had increased intestinal permeability ((51)Cr-EDTA excretion > 95% confidence than that of controls; p>0.1). Paracentesis did not affect urinary (51)Cr-EDTA excretion significantly (1.69% (1.16-2.86%) versus 1.30% (1.08-1.79%) before and after, respectively; p>0.1). No significant correlation was found between clinical severity scores for liver disease and intestinal permeability., Conclusions: Only a small proportion of patients with liver cirrhosis have increased intestinal permeability and it is unlikely that this plays any major role in predisposing these patients to infections.