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ABSTRACT: Clinical impact of protein-energy malnutrition (PEM) on the outcome of liver cirrhosis is well documented. As a candidate interventional modality to improve PEM in cirrhosis, effects of branched-chain amino acid (BCAA) supplementation on event-free survival and quality of life (QOL) was first reported by Yoshida et al. in 1989. Although critical arguments still continue regarding the effects of BCAA, several randomized trials in the last 5 years have brought positive results, and seem to have settled the discussion in a favorable direction for the efficacy of BCAA in liver cirrhosis. Actually, The European Society for Clinical Nutrition and Metabolism (ESPEN) upgraded the recommendation of BCAA supplementation in decompensated liver cirrhosis in the latest revision of its guidelines in 2006, by referring to the literatures from Italy and Japan. Particularly in these two long-term randomized studies with 1-2 years-supplementation, event-free survival was estimated by employing composite endpoints such as aggravation of hepatic failure (ascites, peripheral edema, hepatic encephalopathy, and jaundice), rupture of esophageal or gastric varices, development of liver cancer, and death from any cause. Both trials agreed on the effect of BCAA to reduce the incidence of hepatic failure, thus contributing to the rise in the event-free survival. Quality of life is another essential marker of outcome survey. Marchesini, Muto, and Nakaya reported the improved QOL in cirrhotics with BCAA supplementation. In particular, quantitative analysis of QOL measured by Short Form 36 (SF-36) questionnaire demonstrated a significant recovery of general heath perception score in BCAA supplemented patients in a randomized trial. In this article, the long-term outcome of BCAA treatment in liver cirrhosis will be reviewed with its action mechanisms. In addition, the effects of BCAA treatment on the incidence of liver cancer in obese patients with type C liver cirrhosis, significance of obesity as a risk factor for type C liver cancer, and a possible role of Body Mass Index to estimate the histological grade of fat deposition in the liver will be briefly discussed.
Hepatology Research 12/2008; 38 Suppl 1:S102-6. · 2.20 Impact Factor
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Gastrointestinal Endoscopy 06/2008; 67(6):988-90. · 4.88 Impact Factor
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Toshitatsu Wakahara,
Makoto Shiraki,
Kayoko Murase, Hideki Fukushima,
Katsuhiko Matsuura,
Ayumi Fukao,
Sachiko Kinoshita,
Naoko Kaifuku,
Naoe Arakawa,
Takashi Tamura,
Junpei Iwasa,
Nobuo Murakami,
Takashi Deguchi,
Hisataka Moriwaki
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ABSTRACT: Nutritional status is an important factor that determines hospital stay, and the Subjective Global Assessment (SGA) is a candidate tool for nutritional screening on admission. However, the significance of the SGA has not been evaluated well in the ward for digestive diseases. We conducted the present study to test whether the SGA predicts hospital stay of these patients.
Two hundred sixty-two patients with digestive diseases were consecutively enrolled between July 2004 and April 2005. They consisted of 145 males and 117 females and included 110 patients with cancer. Disease category was gastrointestinal in 94, hepatic in 111, and biliary/pancreatic in 57. The SGA was performed by a certified dietician. Effects of SGA and other nutritional parameters on hospital stay were examined by simple and multiple regression analysis.
Among tested variables, simple regression analysis identified the SGA, disease category, presence of malignancy, serum albumin level, percent triceps skinfold thickness, and percent arm muscle circumference as significant predictive parameters for hospital stay. Multiple regression analysis revealed that the SGA had the best predictive power, followed by the presence of malignancy and disease category.
The SGA is a simple and reliable predictor for hospital stay in patients with digestive diseases.
Nutrition 10/2007; 23(9):634-9. · 3.03 Impact Factor
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ABSTRACT: Aim: Branched-chain amino acid (BCAA) supplementation improves hypoalbuminemia in decompensated cirrhotics. Recently, it was clarified that the ratio of oxidized albumin within total albumin rises with progression of liver cirrhosis. We conducted a feasibility study to investigate whether BCAA supplementation might improve this ratio. Methods: Seven cirrhotic patients (age: 70 +/-> 6 years; M/F = 4/3; etiology: hepatitis C in six and non-B/non-C hepatitis virus in one; Child-Pugh classification: A in six and B in one) were enrolled consecutively in this study in October 2004 to March 2005. Patients were given 4 g BCAA after each meal for 8 weeks. Serum total, oxidized and reduced albumin, plasma amino acids, glutathione, zinc, selenium, and lipid peroxide concentrations were measured every 2 weeks. Results: Low total albumin, high oxidized albumin, and low reduced albumin levels were observed at entry. After 8 weeksBCAA supplementation, the ratio of oxidized albumin within total albumin decreased significantly and that of reduced albumin increased significantly (P < 0.05, respectively). Total albumin tended to rise and lipid peroxide concentrations tended to fall, but not significantly. Conclusion: BCAA supplementation improved the oxidized/reduced state of serum albumin. This intervention is effective to maintain the quality of serum albumin in cirrhotic patients.
Hepatology Research 09/2007; 37(9):765-70. · 2.20 Impact Factor
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ABSTRACT: While lower serum albumin concentration is often found in the elderly, a relation between serum albumin and age has not been fully elucidated. We conducted population-based cross-sectional and 5-y longitudinal study to examine the relation. A total of 22,705 male and 40,149 female, aged 65 y and older, living in Gifu, participated in the health check service conducted by Gifu City Medical Association. They were self-supported in the activity of daily living and 3,438 of them were followed up every year from 1999 to 2003. Serum albumin levels decreased with age in both men and women. In the cross-sectional study, median value declined from 4.3 g/dL in males aged 65-69 y to 3.9 g/dL in 90< or = y, and 4.3 g/dL to 4.0 g/dL in females. Incidence of hypoalbuminemia (serum albumin < or =3.5 g/dL) increased in parallel with age from 1.2% (65-69 y) to 6.6% (85-89) in males, and 0.6% to 4.1% in females. In the longitudinal study, regression analysis showed a significant decline in serum albumin of 0.015 g/dL per year (r= -0.716) in males, and 0.012 g/ dL per year (r= -0.794) in females. Relative reduction of serum albumin in 5 y was larger in advanced age; 1.2% in females aged 65-69 y and 3.1% in 85-89 y (p<0.05), but not in males. In conclusion, a fall in serum albumin concentration in community-dwelling, self-supported elderly persons was associated significantly with aging.
Journal of Nutritional Science and Vitaminology 03/2007; 53(1):37-42. · 1.20 Impact Factor
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ABSTRACT: Patients with chronic liver disease (CLD) often develops glucose intolerance. We explored the prevalence of diabetes mellitus in viral CLD, and analyzed factors profoundly affecting the diabetic angiopathies. 229 CLD patients (124 chronic hepatitis and 105 liver cirrhosis) entered the study. The diagnosis of diabetes was made with the criteria by World Health Organization. Laboratory investigation included serum asparate aminotransferase, alanine aminotransferase, albumin, fasting blood sugar, hemoglobin A1c (HbA1c), fasting immunoreactive insulin, and HOMA-R (FBS*IRI/405). The incidence of macro- and microangiopathy were also examined. Forty (17.5%) CLD patients were diagnosed diabetes, giving a significantly higher incidence than that of general cohort (5.3%) (p<0.001). Among them, 12 (30%) had the triopathy, significantly lower than that in a matched group of diabetic patients without CLD (65%) (p<0.001). Significantly increased levels of HbA1c and HOMA-R were observed in diabetic CLD with angiopathy compared with diabetic CLD without. Incidence of diabetes was increased in viral CLD patients. The rate of diabetic angiopathies in CLD, however, was relatively low, this could be explained by low coagulability in these patients. Poor control of hyperglycemia, partly due to insulin resistance, might explain the onset of angiopathy in diabetic CLD.
Journal of Clinical Biochemistry and Nutrition 03/2007; 40(2):116-22. · 1.98 Impact Factor
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ABSTRACT: Elderly people at nursing homes often suffer from malnutrition, which is characterized by a loss of muscle mass and hypoalbuminemia. This malnourished state is closely associated with an impaired activity of daily living (ADL). We analyzed the nutritional state of such elderly individuals longitudinally over 3 years by anthropometry, serum albumin, and muscle and fat volume as estimated by MRI.
The subjects consisted of 16 elderly women aged 83 +/- 7 (mean +/- SD) years who resided at a nursing home in an urban area of central Japan. We determined their ADL levels using the Barthel Index (BI) at entry. Seven women belonged to group A (BI; 65-100), thus implying either a mild or no decline in ADL, while the other 9 were in group B (BI; 0-60) and they demonstrated a severe decline in ADL. We measured the following parameters every year from 2000 to 2003; anthropometry including height, body weight, arm circumference (AC), and arm muscle circumference (AMC), thigh muscle and fat volume as estimated by MRI [thigh muscle volume (TMV) and thigh fat volume (TFV)], serum albumin, and plasma amino acid levels by blood biochemistry. The anthropometric values were converted into percentages of the age- and sex-matched reference values for Japanese.
In all subjects, the TMV, %AMC, and serum albumin level decreased significantly during the three-year period (p<0.05, respectively). The change in TMV correlated significantly with those in the %AC and %AMC (p<0.05, respectively). Group B showed significantly larger decreases in the %AMC and serum albumin level than group A.
Both the muscular and visceral protein levels were found to decrease with aging in the subjects at the nursing home. This decrease depends partly on the ADL level of each subject.
Internal Medicine 01/2006; 45(20):1113-20. · 0.94 Impact Factor
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Katsuhisa Toda,
Yoshiyuki Miwa,
Shoko Kuriyama, Hideki Fukushima,
Makoto Shiraki,
Nobuo Murakami,
Makoto Shimazaki,
Yoichiro Ito,
Toshiyuki Nakamura,
Jun'ichi Sugihara,
Eiichi Tomita,
Chisato Nagata,
Kazutomo Suzuki,
Hisataka Moriwaki
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ABSTRACT: In patients with chronic liver disease (CLD), quality of life is generally accepted as poor, especially for physical function. However, sufficient data regarding erectile function has not been shown in patients with CLD. The international index of erectile function (IIEF) is widely used to assess erectile function, and a short form of the IIEF was recently developed (IIEF-5). Using this questionnaire, we evaluated erectile dysfunction (ED) in patients with CLD.
A total of 117 Japanese patients (64 with chronic hepatitis [CH] and 53 with liver cirrhosis [LC]) were analyzed. The etiologies were hepatitis B virus (HBV) in 21, HCV in 94, and non-B non-C in 2. The IIEF-5 and Medical Outcomes Study Short Form 36 (SF-36) were administered to the patients, and biochemical analyses for items serum albumin, prothrombin time, bilirubin, and ammonia were also performed.
The incidence of ED was 85% in the total cohort with CLD, 78% in those with CH, and 92% in those with LC (P < 0.05 between CH and LC). ED was found in 50% of CLD patients under age 50 years, in 79% aged 50-59, and in 100% aged over 60 (P, overall <0.001). The scores for ED severity correlated with increasing grades of a modified Child-Pugh classification (P < 0.05). Simple regression analysis showed age (P < 0.01), physical function (P < 0.001), role physical (P < 0.001), and social functioning (P < 0.05) on the SF-36, and serum albumin (P < 0.001) as significant determinants of ED. Multiple regression analysis identified age (P < 0.001) and serum albumin (P < 0.001) as independent significant factors that determined ED.
These data clearly demonstrate that liver disease is the cause of ED in patients with CLD, and serum protein status could be relevant to this condition in these patients.
Journal of Gastroenterology 09/2005; 40(9):894-900. · 4.16 Impact Factor
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ABSTRACT: Tumor necrosis factor-alpha (TNFalpha) promotes oxidation of branched-chain amino acids (BCAA). BCAA catabolism is regulated by branched-chain alpha-keto acid dehydrogenase (BCKDH) complex, which is regulated by phosphorylation-dephosphorylation of the E1alpha subunit at Ser293. BCKDH kinase is responsible for inactivation of the complex by phosphorylation. In the present study, we examined the effects of TNFalpha administration on hepatic BCKDH complex and kinase in rats. Rats were intravenously administered with 25 or 50 microg TNFalpha/kg body weight 4 h prior to sacrifice. The TNFalpha treatment at both doses elevated the activity state (percentage of the active form) of BCKDH complex from 22% to 69% and 86%, respectively, and the amount of phospho-Ser293 on the E1alpha subunit in each group of rats corresponded inversely to the activity state of BCKDH complex. The TNFalpha treatment of rats significantly decreased the activity as well as the bound form of BCKDH kinase. These results suggest that the decrease in the bound form of kinase is involved in the mechanism responsible for TNFalpha-induced activation of the BCKDH complex.
Biochemical and Biophysical Research Communications 04/2005; 328(4):973-8. · 2.48 Impact Factor
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Nippon rinsho. Japanese journal of clinical medicine 01/2005; 62 Suppl 12:138-40.
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ABSTRACT: Protein-energy malnutrition (PEM) is a common manifestation in cirrhotic patients with reported incidences as high as 65-90%. PEM affects largely the patients' quality of life and survival. Thus, diagnosis of and intervention for PEM is important in the clinical management of liver cirrhosis. Supplementation with branched-chain amino acids (BCAA) is indicated to improve protein malnutrition. As an intervention for energy malnutrition, frequent meal or late evening snack has been recently recommended. Plasma amino acid analysis characterizes the patients with liver cirrhosis to have decreased BCAA. Such reduction of BCAA is explained by enhanced consumption of BCAA for ammonia detoxication and for energy generation. Supplementation with BCAA raises in vitro the synthesis and secretion of albumin by cultured rat hepatocytes without affecting albumin mRNA expression. BCAA recover the impaired turnover kinetics of albumin both in rat cirrhotic model and in cirrhotic patients. Longer-term supplementation with BCAA raises plasma albumin, benefits quality of life issues, and finally improves survival in liver cirrhosis. Recent interests focused on the timing of administration of BCAA, since daytime BCAA are usually consumed by energy generation for physical exercise of skeletal muscles. Nocturnal BCAA seem to be more favorable as a source of protein synthesis by giving higher nitrogen balance. This minireview focuses on the basic and clinical aspects of BCAA as a pharmaco-nutritional source to control PEM in liver cirrhosis.
Biochemical and Biophysical Research Communications 02/2004; 313(2):405-9. · 2.48 Impact Factor
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ABSTRACT: In an attempt to optimize oral branched-chain amino acid (BCAA) administration to improve serum albumin in cirrhotic patients, we compared the effects of nocturnal and daytime BCAA administration on protein metabolism in cirrhotic patients.
Twelve cirrhotic patients were enrolled in a short-term study. Patients were administered either conventional daytime BCAA granule or nocturnal BCAA for a week, and metabolic analyses were performed, followed by a crossover study in the next week. Another 12 patients, who showed no improvement of serum albumin level with previous daytime BCAA administration, were randomly assigned to either a nocturnal or a daytime BCAA administration group in a long-term study.
Low Fischer's ratio, reduced respiratory quotient, and low serum albumin were observed at entry in cirrhotic patients. Whereas daytime BCAA administration improved nitrogen balance and Fischer's ratio, these 2 were further significantly improved after nocturnal BCAA administration. There were no changes in parameters of energy metabolism throughout the study. In the 3-month follow-up, a significant increase in serum albumin was observed in patients administered nocturnal BCAA but not in those administered daytime BCAA.
Nocturnal BCAA administration improved serum albumin in cirrhotic patients who showed no improvement in serum albumin level with daytime BCAA administration. This effect could be partly caused by the improved protein sparing with this administration method.
Journal of Parenteral and Enteral Nutrition 27(5):315-22. · 3.29 Impact Factor
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ABSTRACT: Tumor necrosis factor-α (TNFα) promotes oxidation of branched-chain amino acids (BCAA). BCAA catabolism is regulated by branched-chain α-keto acid dehydrogenase (BCKDH) complex, which is regulated by phosphorylation–dephosphorylation of the E1α subunit at Ser293. BCKDH kinase is responsible for inactivation of the complex by phosphorylation. In the present study, we examined the effects of TNFα administration on hepatic BCKDH complex and kinase in rats. Rats were intravenously administered with 25 or 50 μg TNFα/kg body weight 4 h prior to sacrifice. The TNFα treatment at both doses elevated the activity state (percentage of the active form) of BCKDH complex from 22% to 69% and 86%, respectively, and the amount of phospho-Ser293 on the E1α subunit in each group of rats corresponded inversely to the activity state of BCKDH complex. The TNFα treatment of rats significantly decreased the activity as well as the bound form of BCKDH kinase. These results suggest that the decrease in the bound form of kinase is involved in the mechanism responsible for TNFα-induced activation of the BCKDH complex.
Biochemical and Biophysical Research Communications.
