Rumi Mifuji-Moroka

Branched-chain amino acid supplementation reduces oxidative stress and prolongs survival in rats with advanced liver cirrhosis.

Long-term supplementation with branched-chain amino acids (BCAA) is associated with prolonged survival and decreased frequency of development of hepatocellular carcinoma (HCC) in patients with liver cirrhosis. However, the pharmaceutical mechanism underlying this association is still unclear. We investigated whether continuous BCAA supplementation increases survival rate of rats exposed to a fibrogenic agent and influences the iron accumulation, oxidative stress, fibrosis, and gluconeogenesis in the liver. Further, the effects of BCAA on gluconeogenesis in cultured cells were also investigated. A significant improvement in cumulative survival was observed in BCAA-supplemented rats with advanced cirrhosis compared to untreated rats with cirrhosis (P<0.05). The prolonged survival due to BCAA supplementation was associated with reduction of iron contents, reactive oxygen species production and attenuated fibrosis in the liver. In addition, BCAA ameliorated glucose metabolism by forkhead box protein O1 pathway in the liver. BCAA prolongs survival in cirrhotic rats and this was likely the consequences of reduced iron accumulation, oxidative stress and fibrosis and improved glucose metabolism in the liver.

Sarcopenia and Sarcopenic Obesity Are Prognostic Factors for Overall Survival in Patients with Cirrhosis

OBJECTIVE Although the prognosis is known to be poor in cirrhosis patients associated with sarcopenia, the relationships among skeletal muscle, visceral fat, and the liver have not yet been thoroughly investigated. Therefore, the prognosis and its associations with body composition and the severity of liver disease were examined in patients with cirrhosis. METHODS The skeletal muscle mass and visceral fat area were measured in 161 patients with cirrhosis, the effects of body composition on the prognosis were analyzed, and any factors that contribute to changes in body composition were assessed. RESULTS During the mean observation period of 1,005 days, 73 patients died. Patients with sarcopenia or sarcopenic obesity had a poor prognosis, and this difference was pronounced in the subset of patients classified as Child-Pugh class A. A decreased skeletal muscle mass was strongly correlated with decreased serum albumin levels. Sarcopenia is a common feature of advanced cirrhosis, and transitions were observed from normal body composition to sarcopenia and from obese to sarcopenic obesity. CONCLUSION The body composition is a prognostic factor for cirrhosis, and a better body composition may be advantageous for obtaining a long-term survival in patients with cirrhosis.

Nutrition therapy using a multidisciplinary team improves survival rates in patients with liver cirrhosis

OBJECTIVES Very few reports thus far have clinically elucidated the advantages of a nutrition support team (NST) in the field of liver diseases. The present study retrospectively analyzed whether nutrition therapy for liver cirrhosis (LC), performed by a multidisciplinary team that includes registered dieticians, improves survival rates. METHODS In study 1, we compared survival rates between two groups of patients with LC to elucidate the effects of nutrition management by registered dieticians. The first group was comprised of 101 patients that received no dietary counseling from a dietician, and the second group was comprised of 133 patients that received nutritional counseling following nutrition assessment. In study 2, we split the patients who received nutritional counseling in study 1 into two groups and compared their survival rates with the objective of investigating the effects of a multidisciplinary team approach on survival rate. The first group was comprised of 51 patients that, in addition to regular nutritional counseling given by a dietician, regularly attended courses on liver disease given every 3 to 6 mo. The second group was comprised of 82 patients that did not attend the liver-disease courses. RESULTS During study 1, 34 patients in the first group and 20 patients in the second group died, representing a significant difference (P < 0.05). This difference was even more pronounced in the subset of patients classified as Child-Pugh class A (P < 0.01), but no differences were seen among patients in classes B and C (P = 0.378). During study 2, four patients in the first group and 15 patients in the second group died, representing a significant difference (P < 0.05). CONCLUSIONS This study showed that nutritional intervention using a multidisciplinary team during the treatment of LC improves survival rates and quality of life of the patients.

Regional reduction in gray and white matter volume in brains of cirrhotic patients: voxel-based analysis of MRI

Chronic hepatic encephalopathy is a characteristically reversible neuropsychiatric disorder that occurs mainly in patients with liver cirrhosis. The brain regions critically involved in the pathophysiology of cirrhosis are not clear. Magnetic resonance imaging (MRI) with voxel-based morphometry (VBM) is a valuable tool for evaluating structural brain changes in many neurodegenerative diseases. We performed an MRI scan on 18 patients with liver cirrhosis and 16 age-matched healthy controls. We evaluated brain regional structural changes, regional differences and the relationship of these changes with the blood levels of ammonia and the results of neuropsychological tests in patients with cirrhosis. The VBM showed reduction in the volume of gray matter in the cerebellum and occipital lobe and in the volume of white matter in the cingulate, parietal, temporal, occipital lobe and precentral area in cirrhotic patients compared with controls. There were significant correlations between the volume of these regions with the plasma levels of ammonia and the results of neuropsychological tests. Voxel-based analysis of MRI revealed evidence for structural abnormalities of brain in patients with cirrhosis. Abnormal function in the above regions may account for the ammonia-mediated changes and neuropsychological deficits in hepatic encephalopathy.

Elevation of branched-chain amino acid levels in diabetes and NAFL and changes with antidiabetic drug treatment.

Diabetes mellitus (DM), non-alcoholic fatty liver (NAFL), and obesity are associated with elevated branched-chain amino acid (BCAA) levels, but the mechanism and significance of this has not been elucidated. Eighty-four subjects were enrolled including 43 with DM. Serum BCAA levels were positively correlated with waist-hip ratio and ALT. Serum BCAA levels in subjects with DM were higher than non-DM and those in subjects with NAFL were also higher than non-NAFL. Treatment with pioglitazone and alogliptin (19 of 43 DM subjects) improved serum haemoglobin A1c and decreased BCAA levels. The decrease in BCAAs with improved glucose metabolism suggests that abnormal glucose metabolism is also a factor in elevated BCAA levels.

Evaluation and prognosis of sarcopenia using impedance analysis in patients with liver cirrhosis

Dear Editor, We recently read an interesting article on sarcopenia in liver cirrhosis (LC) by Hayashi et al. in Hepatology Research. They evaluated sarcopenia based on skeletal muscle mass (SMM) using impedance analysis and measurement of handgrip strength, and reported that sarcopenia in LC patients was associated with physical inactivity and insufficient dietary intake. Sarcopenia has received attention as an important predictor of prognosis in LC. Evaluation of sarcopenia has included anthropometry of upper arm circumference, dual-energy X-ray absorption, and measurement of SMM using trunk computed tomography. Impedance analysis has been used more recently as a convenient modality that does not involve radiation exposure. Hayashi et al. used SMM / height as an index. Multifrequency impedance analysis enables separate calculation of SMM at different sites, such as the arms, trunk and legs. The influence of edema of the lower extremities in LC can thus be eliminated. We therefore evaluated the usefulness of measuring SMM at different sites in LC, and also examined the influence on prognosis of sarcopenia. Participants in our study comprised 137 patients with LC (80 men, 57 women; mean age, 66 1 9 years; mean Child–Pugh score, 6.7 1 3.0). SMM was measured at different sites using a body composition analyzer (InBody 720; Biospace, Seoul, Korea) and compared with SMM in 554 patients with type 2 diabetes mellitus (DM) (323 men, 231 women; mean age, 65 1 9 years). In the DM group, exclusion criteria were as follows: positive test results for hepatitis B surface antigen or hepatitis C virus RNA; significant thrombocytopenia (platelet count <10 × 10/μL); or ultrasonographic features of cirrhosis. Measurement of SMM included arm index (arm SMM / height), leg index (leg SMM / height) and appendicular index (appendicular SMM / height). The prognosis of LC with sarcopenia was then analyzed using Kaplan–Meier analysis. Appendicular SMM / height tended to be lower in LC than in DM, but the difference was not significant (men: LC, 7.37 1 1.06 kg/m; DM, 7.52 1 0.92 kg/m; women: LC, 6.31 1 0.88 kg/m; DM, 6.48 1 1.12 kg/m). In particular, arm index was significantly lower in LC (men: LC, 1.87 1 0.32 kg/m; DM, 2.00 1 0.32 kg/m; P < 0.01; women: LC, 1.50 1 0.31 kg/m; DM, 1.63 1 0.37 kg/m; P < 0.05). In this study, sarcopenia was defined based on the result of the arm index. Values less than −1 standard deviation from the mean values in the DM group, namely, less than 1.7 kg/m in men and 1.2 kg/m in women, were considered to be indicative of sarcopenia. Comparison of patient background characteristics between the groups with and without sarcopenia showed a significantly greater proportion of men in the group with sarcopenia (23 men, seven women) than in the group without sarcopenia (57 men, 50 women; P < 0.05), but no significant differences in mean age (68 1 9 vs 66 1 9 years). Child–Pugh score was higher (men, 6.9 1 1.7 vs 6.5 1 1.7; women, 8.1 1 2.7 vs 6.7 1 1.6) and hepatic functional reserve was lower in LC with than in LC without sarcopenia. In addition, analysis of prognosis with stratification for arm index showed that prognosis was significantly poorer in the arm index subgroup with lower values (Fig. 1, P < 0.05). Sarcopenia may coexist in LC, particularly in LC with decreased hepatic functional reserve, and measurement of arm SMM can be useful in evaluation. LC patients should be monitored for sarcopenia using arm SMM, because nutritional therapy can readily improve the prognosis.

Seasonal variation in visceral fat and blood HbA1c in people with type 2 diabetes

Seasonal variations in hemoglobin A1c (HbA1c) levels among patients with either type 1 or type 2 diabetes have been reported [1–4]. This phenomenon has been explained in part by weight gain due to increases in food intake and decreases in exercise during winter. Visceral fat accumulation also has been shown to have a negative impact on glycemic control in persons with diabetes [5]. However, there is no study showing the relationship between HbA1c and visceral fat area (VFA) in type 2 diabetes. We investigated the relationship between seasonal changes in body composition, especially visceral fat, and blood HbA1c levels in patients with type 2 diabetes to determine the factor that significantly contributes to the aggravation of HbA1c levels. There were 140 patients with type 2 diabetes (70 males, 70 females; mean age 60.2 12.2 years). All patients had achieved stable plasma glucose control for >2 years. Venous blood samples were drawn to determine HbA1c (Japan Diabetes Society) every 1–3 months for 2 years. % body fat (%BF), VFA, lean body mass (LBM) were determined every 1–3 months by the whole body 8-electrode approach using a multifrequency impedance analyzer (InBody 720, Seoul, Korea). Control by a

Visceral fat volume predicts new-onset type 2 diabetes in patients with chronic hepatitis C

Ninety seven patients with chronic hepatitis C (CHC) and 72 with non-alcoholic fatty liver disease (NAFLD) were enrolled. Increased visceral fat area (VFA) was associated with high values of HbA1c. The variables associated with a high risk of new-onset diabetes had a VFA>101 cm(2) in CHC, but not in NAFLD.

Protein S exacerbates alcoholic hepatitis by stimulating liver natural killer T cells

Alcohol consumption is a major cause of liver injury but the mechanisms are not completely understood. Protein S (PS) is an anticoagulant glycoprotein with multiple functions. The role of PS in liver injury is unknown.

The Associations between Circulating Bile Acids and the Muscle Volume in Patients with Non-alcoholic Fatty Liver Disease (NAFLD)

Objective Non-alcoholic fatty liver disease (NAFLD) is frequently associated with obesity, dyslipidemia and type-2 diabetes mellitus. Bile acids (BAs) bind to the farnesoid X receptor (FXR) and G protein-coupled receptor 5 (TGR5), which are involved in lipid and glucose metabolism and energy expenditure. The present study aimed to determine associations between the circulating BAs and the skeletal muscle volume (SMV), and lipid and glucose metabolism in patients with NAFLD. Methods Serum BAs and metabolic parameters were measured in 55 patients with NAFLD (median age, 55 years). The changes (Δ) in serum BA (ΔBA) and metabolic parameters were determined in 17 patients (male, n=10; female, n=7) who received nutritional counseling for 12 months. Results Spearmans test revealed that the levels of 12α-hydroxysterol (12α-OH) BAs, including deoxycholic acid (DCA), were inversely correlated with the SMV of the upper and lower limbs and the total SMV. A multivariate analysis revealed that the level of DCA was correlated with a reduced total SMV, whereas non-12α-OH BAs, including chenodeoxycholic acid (CDCA), were correlated with an increased SMV of the lower limbs. Changes in CDCA were positively correlated with the ΔSMV of the lower limbs, and inversely correlated with the Δwaist-hip ratio and Δtotal cholesterol. Changes in the total non-12α-OH BA level were positively correlated with the ΔSMV of the lower limbs. Conclusion Circulating BAs were associated with SMV. The 12α-OH BAs, including DCA were associated with reduced SMV levels, whereas non-12α-OH BAs including CDCA were associated with increased SMV levels. The molecular mechanisms underlying the association between the BA levels and the SMV remain to be explored.