Yoshiyuki Miwa

Prognostic Value of Energy Metabolism in Patients With Viral Liver Cirrhosis

The effect of energy malnutrition on survival in patients with non-alcoholic viral liver cirrhosis has not been well defined. We characterized energy metabolism at study entrance and prospectively analyzed its effect on subsequent survival in cirrhotics. One hundred nine consecutive patients with viral liver cirrhosis and 22 healthy control subjects participated in the study. By indirect calorimetry after overnight bedrest and fasting, resting energy expenditure (REE) was measured and non-protein respiratory quotient (npRQ) was calculated. Survival of cirrhotics were followed for up to 8 y. Survival rate was estimated with the Kaplan-Meier method. REE at entrance was significantly higher than the predicted basal metabolic rate (BMR) in cirrhotics (P < 0.001). NpRQ was significantly lower in cirrhotics than in controls (P < 0.001). Survival rate was significantly lower in patients with low npRQ ( < 0.85) than in patients with scores above 0.85 (P < 0.01) and was significantly higher in normal metabolic patients (0.9 < REE/BMR < 1.1) than in hypometabolic (REE/BMR < 0.9) or hypermetabolic (1.1 < REE/BMR) patients (P < 0.05). The proportional hazards model showed that npRQ (relative risk = 0.0003, 95% confidence interval = 0.0000-0.0970), REE/BMR (0.0199, 0.0007-0.5652), prothrombin time, and ammonia were independent significant factors determining survival. Thus evaluation of energy metabolism can be used to predict survival in patients with viral liver cirrhosis.

Improvement of fuel metabolism by nocturnal energy supplementation in patients with liver cirrhosis.

Aims: patients with liver cirrhosis exhibit abnormal fuel metabolism, including increased fat and decreased glucose oxidation. Such altered energy metabolism is similar to that observed after starvation and could lead to malnutrition. We therefore studied whether nocturnal energy supplementation might improve the fuel metabolism in cirrhotic patients. Methods: 12 cirrhotic patients and 14 healthy controls participated in this study. Subjects in the two groups ate isonitrogenous (1.2 g/kg/day) and isocaloric (35 kcal/day) diets for 1 week before and during the study. On day 1 of the study, indirect calorimetry was carried out in the morning after an overnight fast. The next morning, the same measurement was performed after the patients took a liquid nutrient (Ensure Liquid(R), 250 kcal) at 23:00 on day 1. Respiratory quotient (RQ), resting energy expenditure (REE), and substrate oxidation rates of glucose (% CHO), fat (% FAT) and protein were estimated from measured VO(2), VCO(2) and urinary nitrogen. Results: Significant decreases in RQ, and % CHO and a significant increase in % FAT were observed at baseline in cirrhotic patients as compared with controls. After the nocturnal energy supplementation, RQ, % CHO and % FAT in cirrhotic patients were significantly recovered, ending at levels close to normal. Conclusions: These results suggest that nocturnal energy supplementation could be useful to correct abnormal fuel metabolism and to prevent malnutrition in cirrhosis.

Nocturnal branched-chain amino acid administration improves protein metabolism in patients with liver cirrhosis: Comparison with daytime administration

BACKGROUND 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. METHODS 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. RESULTS Low Fischers ratio, reduced respiratory quotient, and low serum albumin were observed at entry in cirrhotic patients. Whereas daytime BCAA administration improved nitrogen balance and Fischers 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. CONCLUSIONS 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.

Oral branched‐chain amino acid supplementation improves the oxidized/reduced albumin ratio in patients with liver cirrhosis

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.

Erectile dysfunction in patients with chronic viral liver disease: its relevance to protein malnutrition

BackgroundIn 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.MethodsA 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.ResultsThe 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.ConclusionsThese 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.

Elevated serum tumor necrosis factor-α and soluble tumor necrosis factor receptors correlate with aberrant energy metabolism in liver cirrhosis

OBJECTIVE Protein-energy malnutrition is frequently observed in patients with liver cirrhosis and is associated with their poor prognosis. Tumor necrosis factor-alpha (TNF-alpha) is elevated in those patients and may contribute to the alterations of energy metabolism. Our aim was to characterize the aberrant energy metabolism in cirrhotic patients with regard to TNF-alpha. METHODS Twenty-four patients (mean age 65 +/- 6 y) with viral liver cirrhosis who did not have hepatocellular carcinoma or acute infections were studied. Twelve healthy volunteers were recruited after matching for age, gender, and body mass index with the patients and served as controls (59 +/- 8 y). Serum levels of TNF-alpha, soluble 55-kDa TNF receptor (sTNF-R55), soluble 75-kDa TNF receptor (sTNF-R75), and leptin were determined by immunoassay. Substrate oxidation rates of carbohydrate and fat were estimated by indirect calorimetry after overnight bedrest and fasting. RESULTS In cirrhotic patients, serum levels of TNF-alpha, sTNF-R55, and sTNF-R75 were significantly higher than those in the controls and correlated with the increasing grade of disease severity as defined by Child-Pugh classification. Serum leptin concentration was not different between cirrhotics and controls but correlated with their body mass index. The decrease in substrate oxidation rate of carbohydrate and the increase in substrate oxidation rate of fat significantly correlated with serum TNF-alpha, sTNF-R55, and sTNF-R75 concentrations. CONCLUSION Tumor necrosis factor-alpha might be associated with the aberrant energy metabolism in patients with liver cirrhosis.

Validation of a portable indirect calorimeter (Metavine®) for measuring energy expenditure in an elderly population

1. The aim of the present study was to evaluate the usefulness and reliability of a portable indirect calorimeter (Metavine; Vine, Tokyo, Japan).1. The present study was performed in order to determine the reliability of the portable calorimeter. 2. Resting energy expenditure (REE) was measured by two different apparatuses: one was the typical gas analyser, the other was the portable calorimeter. 3. Although there are differences among individuals, unless the subject has been exposed to severe physical activity prior to the measurement, a suitable resting time prior to the measurement of resting metabolic rate is 10 min. 4. For the measurement of resting metabolic rate, fluctuations in respiratory quotient (RQ) are extremely small; there is greater fluctuation due to variations in respiration. Therefore, for the screening of energy consumption, the use of a fixed value for RQ is sufficient when measuring only oxygen uptake. 5. Respiratory fluctuations vary from person to person and it is not possible to make stable measurements in 1 or 2 min. Therefore, a suitable measurement time for resting metabolic rate is from 3 to approximately 6 min. 6. The results indicate that this portable calorimeter is a useful apparatus for measuring REE in the field.

Prevalence of Diabetes and Incidence of Angiopathy in Patients with Chronic Viral Liver Disease

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.

Both insulin sensitivity and glucose sensitivity are impaired in patients with non-diabetic liver cirrhosis.

Background: Careful nutritional support is required in patients with liver cirrhosis due to their glucose intolerance. To elucidate the mechanism of glucose intolerance in cirrhotics, we measured insulin secretion, whole body insulin sensitivity (SI), and glucose sensitivity (SG) in non-diabetic cirrhotics.Methods: Eight patients with compensated cirrhosis who showed normal fasting blood glucose levels and non-diabetic curves on a 75 g oral glucose tolerance test participated in this study. Four normal volunteers were selected as controls. After an overnight fast, glucose was injected intravenously at 300 mg kg(-1) in 2 min followed 20 min later by intravenous insulin at 0.02 U kg(-1) in 5 min. Sequential blood samples were drawn from 20 min before the glucose injection to 3 h post-injection, and plasma glucose and insulin levels were determined. Plasma glucose and insulin disappearance curves were analyzed using the minimal compartment model, and kinetic parameters, including glucose clearance (KG), insulin secretion, SI and SG, were estimated.Results: KG was slower in cirrhosis than in controls, although not significant (P=0.051). Insulin secretion was not different between the two groups. However, SI was significantly lower in cirrhotics (0.814x10(-4) min(-1) pM(-1); 0.572-1.403x10(-4) min(-1) pM(-1)) as compared to controls (1.643x10(-4) min(-1) pM(-1); 0.678-2.085x10(-4) min(-1) pM(-1)) (P=0.029). SG was also lower in the cirrhosis (0.0154 min(-1); 0.0071-0.0208 min(-1)) than in the control group (0.0211 min(-1); 0.0184-0.0260 min(-1)) (P=0.026).Conclusion: Both SI and SG are already impaired in non-diabetic cirrhotic patients even when KG is minimally delayed and insulin secretion has not yet been affected.

Energy Metabolism in Liver Cirrhosis: Its Characteristics, Clinical Significance, and Possible Intervention

A large proportion of patients with liver cirrhosis have protein and energy malnutrition. Our recent research revealed that approximately 30% of the patients had protein-energy malnutrition, 40% protein malnutrition, and 10% energy malnutrition, while 20% were in a normal nutritional state. Since both protein and energy malnutrition determine survival of patients with cirrhosis, careful nutritional support for such patients is required. Supplementation with branched-chain amino acids improves chronic liver failure and protein nutritional state and, subsequently, prolongs survival. In contrast, therapeutic modalities for energy malnutrition have not been fully elucidated yet and await further studies. In this article, we focus on energy metabolism in cirrhotic patients and show its basal characteristics and impact on outcome. In addition, we describe our clinical experience with intervention for energy malnutrition, in particular late evening energy supplementation, in patients with cirrhosis and review recent literature on this subject.