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Aim: Cognitive dysfunction (CD) is frequently observed in cirrhotic patients. However, the biochemical profiles associated with CD remain unclear. We investigated the biochemical profiles associated with the incidence of CD in cirrhotic patients by using multivariate analyses, including a decision-tree algorithm. Methods: In this study, 27 viral cirrhotic patients were enrolled. All subjects underwent neuropsychiatric tests; two or more abnormal results were defined as CD. A logistic regression model was used for multivariate stepwise analysis. A decision-tree algorithm was constructed, and the categorical differences based on the decision-tree model were analyzed by χ2-tests. Results: Multivariate stepwise analysis showed the levels of total bilirubin, triglycerides and free fatty acids (FFA) as independent bioparameters associated with the incidence of CD in cirrhotic patients. The decision-tree algorithm showed that among patients with FFA of 514 mEq/L or more, 77.8% had CD. Meanwhile, among patients with FFA of less than 514 mEq/L and triglycerides of 106 mg/dL or more, 20.0% had CD. The sensitivity, specificity and accuracy for the incidence of CD using the lipid profile (FFA >514 mEq/L or triglycerides

A 67-year-old Asian woman was referred to Kurume University Hospital due to abnormal liver function tests. She was diagnosed with nonalcoholic fatty liver disease (NAFLD). NAFLD was treated by diet therapy with medication of metformin and pioglitazone; however, NAFLD did not improve. Subsequently, the patient was administered sitagliptin. Although her energy intake and physical activity did not change, her hemoglobin A1c level was decreased from 7.8 to 6.4% 3 months after treatment. Moreover, her serum insulin level and homeostasis model assessment-insulin resistance value were also improved, as was the severity of hepatic steatosis. These findings indicate that sitagliptin may improve insulin resistance and steatosis in patients with refractory NAFLD.

Summary. Ischaemic colitis is known to be a severe emergency complication of interferon (IFN) therapy. However, as ischaemic colitis is an infrequent complication of IFN therapy, limited information is available regarding the safety of resuming IFN therapy after resolution of ischaemic colitis and subsequent recurrence. Here, we report two cases of ischaemic colitis during IFN therapy for chronic hepatitis C. Ischaemic colitis was fully healed within 1 week after its onset and IFN withdrawal, and IFN therapy was resumed following patients’ wishes to do so. Ischaemic colitis did not recur after the resumption of IFN therapy, and sustained virological response was achieved in both patients. In this report, we also summarize the findings of 11 cases of IFN-associated ischaemic colitis (nine previously published cases plus our two cases) and review the clinical characteristics of ischaemic colitis during IFN therapy in patients with chronic hepatitis C.

Summary Background & aims Serum albumin exists in oxidized and reduced forms. Although oxidation of albumin affects some functions of albumin, the involvement of oxidized albumin in disease progression and water retention in patients with chronic liver disease remains unclear. The aim of this study was to determine whether there is an association between oxidized albumin and water retention in patients with chronic liver disease. Methods Seventy-nine patients with chronic viral liver diseases and 31 cirrhotic patients with hypoalbuminemia were enrolled. The oxidized albumin percentage was determined by high-performance liquid chromatography. Water retention was assessed by the extra cellular fluid/total body fluid ratio (ECF/TBF) using a bioelectrical impedance analyzer. Results The oxidized albumin percentage was significantly increased according to disease progression (chronic hepatitis; 28.3 ± 1.1, Child A; 33.5 ± 1.2, Child B and C; 37.8 ± 1.3, P Conclusions Oxidized albumin was related to disease progression and water retention in patients with chronic liver disease.

Background and Aim: The pathogenesis of hepatitis C virus (HCV)-associated glucose intolerance remains unclear. Glucagon-like peptide-1 (GLP-1), a gut hormone, synthesizes hepatic glycogen and is inactivated by dipeptidyl peptidase IV (DPPIV). The aims of this study were to investigate the alterations in the expression of GLP-1 and DPPIV in HCV-associated glucose intolerance. Methods: We enrolled patients with HCV- or hepatitis B virus (HBV)-related liver disease (n = 94 and 37, respectively), patients with inflammatory bowel disease (IBD; n = 14) as disease controls, and healthy controls (n = 48). The serum or tissue GLP-1 and DPPIV expression levels were determined by enzyme immunoassay, immunoblotting, or immunostaining. The hepatic glycogen content was assayed by periodic acid–Schiff staining. Results: The serum GLP-1 levels were significantly decreased in the HCV group (4.9 ± 0.3 ng/mL) than those in the controls (7.5 ± 0.6 ng/mL), the HBV group (7.0 ± 0.5 ng/mL), or the IBD group (10.8 ± 1.0 ng/mL, P

This study looked at the intestinal permeability and the immune response to enteric bacterial antigens in patients with inflammatory bowel disease (IBD). They were evaluated by using a lactulose tolerance test and measuring blood anti-lipid A antibody concentrations, respectively. The lactulose tolerance tests were performed 22 times in 14 patients with Crohn's disease (CD), 19 times in 12 patients with ulcerative colitis (UC), and 12 times in 12 healthy controls. Blood lactulose concentrations were measured after oral administration every two hours for eight hours, also blood C reactive protein concentrations and anti-lipid A antibody concentrations were measured just before lactulose administration. Blood lactulose concentrations were significantly higher in patients with CD than in the controls from two to eight hours after administration, while in UC they were significantly higher than in the controls from six to eight hours. Maximum blood lactulose concentrations in each tolerance test in patients with the active phase significantly exceeded those in the inactive phase of either CD or UC. A significant correlation was also seen between the maximum blood lactulose concentrations and the C reactive protein concentrations. Blood anti-lipid A antibody concentrations in patients with CD were significantly higher than in the controls as well as in patients with UC in immunoglobulin (Ig) A class and IgG class. In UC they were significantly higher than in the controls in IgA class. But, they were not related to the severity of the disease of either CD or UC, and not correlated significantly with the maximum blood lactulose concentrations in either CD or UC. The intestinal permeability and the immune response to enteric bacterial antigens in patients with inactive CD were significantly increased over those in the controls as well as in patients with inactive UC. These findings suggest that an increase of the intestinal permeability and that of producing antibodies to enteric bacterial antigens are both important for the pathogenesis of IBD, and that the characteristics of CD and UC differ.

Although branched chain amino acid (BCAA) supplementation improves malnutrition in cirrhotic patients, patient compliance with the administration of BCAA-rich supplements is poor due to their bitter taste. Since temperature is an important factor affecting taste, we examined the effect of heating on the stability of BCAAs and on the compliance of patients with liver cirrhosis with BCAA-rich supplement administration. A thermal denaturation test was first conducted, in which the BCAA-rich supplement Aminoleban® EN was heated to 37, 60, or 80°C for 30 or 60 min. The concentration of three amino acids, L-valine, L-leucine and L-isoleucine, was subsequently measured. The nutritional status of the cirrhotic patients was also evaluted. Patients presenting liver failure with a Child-Pugh class of A (n=2), B (n=2) or C (n=2) were hospitalized at Kurume University Hospital. Six patients with liver cirrhosis (HCV, n=3; HBV, n=1; alcohol, n=2) were enrolled. Venous blood samples were drawn in the morning after a 12-h overnight fast. The BCAA-rich supplement was administered to patients at room temperature (25°C) or heat loaded at 60°C for 10 min, with the temperature maintained above 45°C. Each patient was interviewed by a nationally registered dietitian regarding food consumption and intake of the BCAA-rich supplement immediately after each meal. Nutritional status was evaluated according to serum albumin levels, blood hemoglobin, prothrombin time and total lymphocyte count. No significant decrease was noted in valine, leucine or isoleucine levels following the heating of the BCAAs to 80°C. The caloric intake of the BCAA-rich supplement was significantly higher with administration after heating to 60°C, compared to caloric intake with administration at 25°C. In addition, heating of the BCAA-rich supplement significantly increased blood lymphocyte counts. In conclusion, heating did not affect the stability of the BCAAs, and may improve compliance with BCAA-rich supplement administration. As a result, the nutritional status of cirrhotic patients may be improved.

Liver cirrhosis is frequently accompanied by malnutrition and hypoalbuminemia, which in turn commonly induces ascites in patients with liver cirrhosis. Ascites leads to abdominal distention and appetite loss, resulting in a deteriorated quality of life (QOL). Administration of branched-chain amino acid (BCAA)-rich supplements reduces hepatic encephalopathy and malnutrition. In addition, BCAAs by themselves up-regulate albumin synthesis through an increase in Fisher's ratio. Thus, in patients with liver cirrhosis, BCAA-rich supplements seem to be effective at reducing ascites and improving the QOL. Here, we report the case of a 58-year-old Japanese man with liver cirrhosis with severe ascites and peripheral edema. The hepatic function of the patient was classified as Child-Pugh grade C. To reduce protein-energy malnutrition, BCAA-rich supplements were administered as a late evening snack as part of a regimen including 2000 kcal/day (32.5 kcal/kg/day) of total energy and 83.5 g/day (1.3 g/kg/day) of total protein intake. Eight weeks after admission, ascites and edema had decreased. Nutritional status also improved from the time of admission to discharge; the serum BCAA level increased from 365.4 to 450.2 µmol/l. Furthermore, the ratio of BCAAs to tyrosine (BTR) increased from 1.70 to 3.65. We also evaluated the effects of nutritional therapy on the patient's QOL using the Medical Outcomes Study 36-Item Short-Form Health Survey upon admission and at discharge. All subscores showed marked improvement and reached a level greater than the Japanese norm with nutritional treatment. In conclusion, BCAA supplementation not only reduced ascites, but also improved the QOL in a patient with liver cirrhosis.

Background and aims Subjective global assessment (SGA) is useful for screening malnourished patients with several diseases, although it has been indicated to underestimate nutritional status for patients with liver disease. Accordingly, the aim of this study was to examine the usefulness of SGA as a nutritional screening tool for patients with liver disease, compared to patients with gastroenterological disease, without bias of personal ability and experience. Methods SGA was performed on 129 of hospitalized patients (86 with liver disease and 43 with gastroenterological disease). Nutritional status was categorized as well-nourished or malnourished status, based on nutritional indicators from laboratory data. Results The SGA screening ratio (sensitivity) for malnourished patients with liver disease was significantly lower than gastroenterological disease, while specificity or efficiency was not significantly different. In nutritional indicators from laboratory data, the difference between SGA-positive and SGA-negative patients with liver disease was significant but not so remarkable compared with the difference between those with other diseases. The positive number of SGA components per patient for the liver disease group was significantly less than gastroenterological disease group. Conclusions SGA for patients with liver diseases was not sufficient as a nutritional screening tool because malnutrition induced by defective hepatic metabolism was not characterized fully.

Interleukin-6, a cytokine produced by various cell types, has a major role in inflammatory and immunological reactions. To define its potential role in inflammatory bowel disease, its concentrations in endoscopic biopsy samples from patients with ulcerative colitis and Crohn's disease were measured. The involved colonic mucosa from active disease was found to contain significantly larger amounts of interleukin-6 than that from inactive disease or normal controls. Colonic mucosal interleukin-6 levels correlated well with the grade of macroscopic inflammation, especially in patients with ulcerative colitis. The levels of interleukin-6 decreased in parallel with clinical improvement following the start of therapy in patients with both forms of inflammatory bowel disease. Mucosal interleukin-6 is thus concluded to accurately reflect the degree of colonic inflammation and may be importantly associated with inflammatory and immunological phenomena seen in inflammatory bowel disease.

Aim: Cirrhotic patients tend to develop malnutrition by fasting, yet the importance of nutritional care during examination-associated fasting has not been investigated. This study aimed to examine the effects of a nutritional supplement on nutrition and stresses caused by examination-associated fasting in cirrhotic patients. Methods: Twenty-nine cirrhotic patients were enrolled in this study. No energy was supplied to patients in the fasting group (n = 11) prior to computed tomography or magnetic resonance imaging examination. A supplement of 200 kcal was given to the patients in the supplement group (n = 18) prior to computed tomography or magnetic resonance imaging examination. The effect of the supplement on stresses was evaluated by self-rating questionnaire. Changes in biochemical parameters were also investigated before and after computed tomography or magnetic resonance imaging examinations. Results: There were no significant differences in age, sex, body mass index, or liver function tests between the two groups at the start of the study. In the supplement group, stress scores for physical symptoms (thirst and light-headedness) and mental symptoms (hunger, hypodynamia and fatigue) were significantly lower compared to those in the fasting group. Also in the supplement group, peripheral 3-hydroxybutyric acid and free fatty acids levels were significantly decreased compared to those in the fasting group, to within normal ranges. In addition, a decrease in prothrombin time was significantly inhibited by intake of the supplement. Conclusion: We demonstrated that a nutritional supplement improved nutrition and reduced both the physical and mental stresses associated with examination-associated fasting in cirrhotic patients.

Introduction: Orthotopic liver transplantation (OLT) is a life-saving procedure for children with end-stage liver disease. Advances in surgical techniques have made OLT in children younger than one year of age increasingly feasible. Previous studies have suggested that infants may experience high operative complications, difficult post-operative courses, and poor graft and patient survival. Many transplant centers have required infants to reach a specific weight or age prior to OLT to minimize morbidity and mortality. As a result, many children have died or experienced significant decompensation while awaiting the required weight or age, thereby making them worse candidates for the procedure. Aim: To review our single center experience with OLT in children younger than one year of age at the time of transplantation. Methods: We retrospectively reviewed the charts of patients 365 days of age and younger that underwent OLT at Morgan Stanley Children's Hospital of NewYork Presbyterian from 1998 to 2014. We specifically reviewed data related to intraoperative course, length of hospitalization, duration of stay in intensive care unit (ICU), duration of mechanical ventilation, post-transplant complications within 90 days and 90-day and 1year patient and graft survival. Results: Data for 65 of 116 eligible patients were included in this interim analysis (median age:240 days, range:21-365 days; median weight:5.9 kg, range:2.0-8.5 kg). The most common indications for OLT were biliary atresia (n= 51, 78.5%) and cryptogenic cirrhosis (n=5, 7.7%). Forty-three patients (66.2%) received deceased donor grafts, of which 55.8% were whole organs. Mean duration of transplant surgery was 7.2 hours. Intra-operatively, 53 patients (89.8%) required blood transfusions (mean:72 mL/kg), 32 patients (55.2%) required fresh frozen plasma (mean:48 mL/kg) and 6 patients (11.8%) required platelet transfusions (mean:13 mL/kg). Median post-transplant hospitalization was 17 days, ICU stay was 8 days, and mechanical ventilation duration was 2 days. Posttransplant complications included bile leak (26.2%), acute rejection (18.5%), hepatic artery thrombosis (13.8%), portal vein thrombosis (13.8%), wound dehiscence (13.8%), abdominal compartment syndrome (9.2%), and bleeding (9.2%). The reoperation rate was 49.2%. Four patients required re-transplantation, 2 of whom died. Patient survival was 93.8% at both 90 days and 1 year. Graft survival was 90.8% at 90 days and 89.2% at 1 year. Conclusion: Infants can have excellent outcomes after OLT with acceptable operative complications and high survival rates in a center of excellence. The use of partial or whole grafts can yield patient and graft survivals approaching that of children greater than 1 year of age. OLT should not be delayed in infants merely because of low weight or young age, reducing pretransplant morbidity and mortality.

A case of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) producing gastric cancer with multiple liver metastasis is reported. The simultaneous presence of Borrmann I gastric cancer and IIa aggregating type gastric cancer was noted. Borrmann I gastric cancer was a poorly differentiated adenocarcinoma, while IIa aggregating type gastric cancer was a moderately differentiated adenocarcinoma. Plasma levels of AFP and DCP were 247 000 ng/ml and 320 000 mAU/ml, respectively. Immunohistochemical staining confirmed the production of these two proteins in Borrmann I gastric cancer.

Body cell mass (BCM) is a nutritional parameter, however, changes in BCM in patients with non-ascitic liver cirrhosis (LC) in comparison to patients with other malnutritional diseases remains unclear. We investigated the difference in BCM between patients with LC and malnourished gastrointestinal disease controls (M.CON), and examined the relationship between BCM and the severity of LC. Results demonstrated that serum nutritional parameters were not significantly different between the LC (n=56) and M.CON groups (n=25), whereas BCM%BW was significantly lower in the LC group than in the M.CON group (50.9+/-4.6 vs. 54.4+/-7.1%, P=0.018). Furthermore, BCM%BW negatively correlated with the model for end-stage liver disease (MELD) score (P=0.04). In concluson, BCM showed a significant decrease and a negative correlation with the MELD score in the LC group. BCM may be a useful parameter for assessing malnutrition and severity of LC.