Biomedical subjects

Akinobu Kato

Publications and source records attributed to Akinobu Kato.

13 recordsLinked to original sources

PubMed2006

Overweight and obesity increase the risk for liver cancer in patients with liver cirrhosis and long-term oral supplementation with branched-chain amino acid granules inhibits liver carcinogenesis in heavier patients with liver cirrhosis.

We conducted a multicenter, randomized, controlled trial to investigate the effect of long-term oral supplementation with branched-chain amino acids (BCAA) on the event-free survival in 622 patients with decompensated cirrhosis. In the present study, the development of liver cancer was analyzed as an endpoint in particular. Subjects received either treatment with BCAA at 12g/day or dietary therapy containing the matched daily energy and protein intake. A Cox regression analysis was carried out to estimate the hazard ratios for different background factors stratified by treatment group. Liver cancer was noted in 89 patients. The risk for liver cancer was significantly higher for males, patients with concurrent diabetes mellitus, patients with an alpha-fetoprotein (AFP) level of 20ng/mL or higher, patients with higher body mass index (BMI), and patients with lower serum albumin levels. When the BCAA group and the diet group were compared for factors that interacted with the treatment arms, the risk for liver cancer was significantly reduced in the BCAA group with a BMI of 25 or higher and with an AFP level of 20ng/mL or higher. Oral supplemental treatment with BCAA may reduce the risk of liver cancer in cirrhotic patients with these specific factors.

Journal Article↗

PubMed2006

Fasting plasma ghrelin levels reflect malnutrition state in patients with liver cirrhosis.

BACKGROUND AND AIM: Ghrelin plays an important role in controlling the feeding and nutritional states by signaling hypothalamic centers. However, the role of ghrelin in cirrhotic patients in the malnutrition state remains unclear. SUBJECTS AND METHODS: Thirty-four patients with liver cirrhosis (LC) and 10 healthy controls (normal controls, NC) were enrolled in this study. Fasting plasma ghrelin levels (desacyl form) were measured using a newly developed ELISA and the relationship among biochemical parameters including plasma leptin, body composition and energy metabolism were evaluated using an indirect calorimeter. RESULTS: Plasma ghrelin levels were slightly but not significantly elevated in patients with LC when compared with NC. Plasma ghrelin levels showed a negative correlation (r=-0.432, p<0.01) with plasma leptin levels and positive correlations with blood urea nitrogen (BUN), creatinine, white blood cell count and C-reactive protein. No correlation with the severity of liver damage based on the classification of Child-Pugh was noted. Plasma ghrelin levels were significantly correlated with body mass index (BMI), arm muscular circumference (AMC), triceps skinfold thickness (TSF) (BMI, r=-0.389, p<0.05; AMC, r=-0.416, p<0.05; TSF, r=-0.459, p<0.01, respectively) and the substrate oxidation rates of glucose (%CHO), fat (%FAT) and non-protein respiratory quotients (npRQ) (%CHO, r=-0.391, p<0.05; %FAT, r=0.438, p<0.01; npRQ, r=-0.411, p<0.05, respectively). Four factors (npRQ, TSF, total bilirubin, BUN) associated with plasma ghrelin levels were identified by multiple regression analysis. CONCLUSIONS: These data suggest that fasting plasma ghrelin levels may be a useful indicator reflecting malnutrition in patients with LC, although renal failure and inflammatory status are also closely associated with plasma ghrelin levels.

Journal Article↗

PubMed2005

Clinical comparison of branched-chain amino acid (l-Leucine, l-Isoleucine, l-Valine) granules and oral nutrition for hepatic insufficiency in patients with decompensated liver cirrhosis (LIV-EN study).

This multicenter study compared the effects of branched-chain amino acid granules (Livact((R)) Granules, LIV) and an enteral nutrient for chronic hepatic failure (Aminoleban((R)) EN, EN) on serum albumin in patients with decompensated liver cirrhosis. This study enrolled "patients with decompensated liver cirrhosis associated with hepatic encephalopathy who were suffering from hypoalbuminemia in spite of adequate food intake," a condition for which both drugs are indicated. Enrolled patients were randomized to the two groups according to the central registration method. This study continued for 24 weeks. Selected foods were supplied to each patient in principle so that caloric and protein intakes were standardized between the two groups. A total of 281 patients were enrolled. LIV was not inferior to EN concerning the primary efficacy endpoint changes in serum albumin.

Journal Article↗

PubMed2005

Effects of oral branched-chain amino acid granules on event-free survival in patients with liver cirrhosis.

BACKGROUND & AIMS: Nutritional intervention with branched-chain amino acid (BCAA) is reported to increase serum albumin concentration in patients with decompensated cirrhosis. However, a definite conclusion on whether it can improve patients' survival has not yet been reached. The present study aimed to test possibilities of improving survival of patients with decompensated cirrhosis by using a BCAA preparation that is suitable for long-term oral administration. METHODS: A multicenter, randomized, and nutrient intake-controlled trial on the comparative effects of BCAA orally administered at 12 g/day for 2 years versus diet therapy with defined daily food intake (1.0-1.4 g protein kg(-1) day(-1) including BCAA preparation and 25-35 kcal kg(-1) day(-1)) was conducted in 646 patients with decompensated cirrhosis. The primary end point was a composite of death by any cause, development of liver cancer, rupture of esophageal varices, or progress of hepatic failure (event-free survival). The secondary end points were serum albumin concentration and health-related quality of life (QOL) measured by Short Form-36 questionnaire. RESULTS: The incidence of events comprising the primary end point significantly decreased in the BCAA group as compared with the diet group (hazard ratio, 0.67; 95% confidence interval, 0.49-0.93; P = .015; median observation period, 445 days). Serum albumin concentration increased significantly in the BCAA group as compared with the diet group (P = .018). The "general health perception" domain in Short Form-36 measures was also improved (P = .003). Patients' adherence to the prescription was favorable. CONCLUSIONS: Oral supplementation with a BCAA preparation that can be administered for a long period improves event-free survival, serum albumin concentration, and QOL in patients with decompensated cirrhosis with an adequate daily food intake.

Administration, Oral↗

PubMed2005

Low incidence of vascular complications in patients with diabetes mellitus associated with liver cirrhosis as compared with type 2 diabetes mellitus.

We compared clinical features and vascular complications of patients with diabetes mellitus associated with liver cirrhosis versus patients with type 2 diabetes mellitus. Subjects were 19 patients (LC-DM group) in whom diabetes was diagnosed after development of liver cirrhosis. Control consisted of 38 patients with type 2 diabetes (T2DM group) matched for sex, age, duration of diabetes, body mass index, treatment, and degree of glycemic control, which was determined by glycoalbumin. The LC-DM group had significantly more smokers, higher serum insulin levels, more insulin resistance calculated by homeostasis model assessment, lower blood counts (white and red blood cells, hemoglobin, and platelets), and lower serum levels of total cholesterol, triglyceride, low density lipoprotein cholesterol and lipoprotein (Lp)(a) than the T2DM group. The incidence of diabetic retinopathy and cerebrovascular disease was significantly lower in the LC-DM group compared to the T2DM group. Logistic regression analysis indicated that Lp(a) and the diabetes duration were significant predictors for the retinopathy, while Lp(a) was a significant predictor for the cerebrovascular complication. In diabetes associated with liver cirrhosis, the incidence of diabetic retinopathy and cerebrovascular disease is lower than in type 2 diabetes mellitus in this study, probably because of lower levels of serum Lp(a).

Aged↗

PubMed2004

Branched-chain amino acid treatment in patients with liver cirrhosis.

We discuss branched-chain amino acid (BCAA) treatment for the management of hepatic encephalopathy (HE) and protein-energy malnutrition (PEM) in patients with liver cirrhosis (LC). PEM is closely associated with the prognosis of patients with LC independently of liver function. Therefore, adequate protein and energy intake is a fundamental management to improve the status of PEM in patients with LC. However, it is difficult to maintain good nutritional status with diet therapy alone in patients with LC, because the majority of these patients have disturbances of the nutritious metabolism including urea synthesis in the liver, together with the existence of portal-systemic shunt which is related with the pathogenesis of HE. BCAA enriched amino acid solution was administered at first to treat chronic HE based on amino acid imbalance and neurotransmitter theory. Furthermore, recent studies have suggested that the supplement of BCAA enriched oral mixture and BCAA granules with diet therapy might improve the status of PEM in patients with LC. However, as the effects of these BCAA supplements are basically related to the severity of liver damage, further investigations are required to identify the efficacy of these treatments.

Journal Article↗

PubMed2004

How to select BCAA preparations.

In Japan, oral branched-chain amino acid (BCAA) preparations are used in nutritional therapy for correcting disorders of protein and amino acid metabolism in patients with liver cirrhosis. There are two forms of oral BCAA preparations: enteral nutrition products for liver failure (or elemental nutrition products for liver cirrhosis) and oral BCAA granular products. Granular products are indicated for patients with uncompensated liver cirrhosis who have no dietary restriction and hypoproteinemia. Enteral nutrition products are indicated for patients who have a history of hepatic encephalopathy and exhibit protein intolerance. In clinical practice, the existence of protein intolerance in patients with uncompensated liver cirrhosis should be determined based on a history of hepatic encephalopathy and blood ammonia concentration. When patients exhibit protein intolerance, they are given a low protein diet (approximately 0.5-1.0g/kg/day) with enteral nutrition products for liver failure. However, when patients consume adequate amounts of a well-balanced diet and ammonia concentration does not increase, it is possible to control their condition with granular products. However, when patients cannot achieve an adequate dietary intake, it is recommended that enteral nutrition products should be used in order to improve nutritional status, even if these patients do not have a history of encephalopathy.

Journal Article↗

PubMed2004

Brain glutamine and glutamate levels in patients with liver cirrhosis: assessed by 3.0-T MRS.

Background/Objectives: Magnetic resonance spectroscopic (MRS) studies have revealed abnormal metabolism in the brain of patients with liver cirrhosis, including an increase in total brain glutamine (Gln) and glutamate (Glu) levels (Glx). However, with conventional MRS techniques, it was difficult to separate the Glx signals. Using a high-magnetic field MR equipment and a newly developed data processing method, we attempted to separate the Glx signals on an MRS. Subjects and Methods: Twenty-three patients with liver cirrhosis and 11 healthy adults were enrolled in this study. After designating a region of interest in the occipital lobe gray matter of each subject, [Formula: see text] (proton)-MRS was performed using 3.0-T MR equipment. Results: MRS conducted using the 3.0-T MR equipment allowed Gln signals in the brain to be distinguished from the Glx signals. The brain signal intensity of Gln was found to be significantly higher in the liver cirrhosis group (0.658 +/- 0.23) than in the control group (0.473 +/- 0.08) (P < 0.05). Neither the Glu nor the Gln signal intensity showed any correlation with the blood ammonia level. Conclusion: High-magnetic field MRS allowed us to separate the Glx signals in the brain and revealed that the increase in the total brain Glu and Gln levels in patients is solely attributable to an increase in the level of Gln.

Journal Article↗

PubMed2004

Development of quantitative neuropsychological tests for diagnosis of subclinical hepatic encephalopathy in liver cirrhosis patients and establishment of diagnostic criteria-multicenter collaborative study in Japanese.

At present, there are no generally accepted diagnostic criteria or methods for subclinical hepatic encephalopathy (SHE) associated with liver cirrhosis. We therefore developed an easily conducted computer-aided quantitative neuropsychiatric function test system for use in routine medical practice. We established normal values in healthy Japanese subjects and determined differences between healthy persons and liver cirrhosis patients without clinical encephalopathy in a multi-center clinical trial. The test system consists of eight tests: number connection tests A and B, a figure position test, a digit symbol test, a block design test, and reaction time tests A, B and C. The test results were affected by age, but not by gender or facility. No learning effect was noted. The results were therefore reported by 5-year quartile ranges and differences were evaluated between 542 healthy subjects and 292 cirrhotic patients. When the cut-off value was set at the 10th/90th percentile of the results in healthy subjects, the results of each of the 8 tests were abnormal in about 25% of cirrhotic patients, and at least 1 of the 8 tests gave values greater than the 10th/90th percentile cut-off value in 58.2% of the 292 liver cirrhosis patients. SHE patients were thought to be included in these 58.2% of patients. The developed test makes it possible to quantitatively assess neuropsychiatric function, and the results obtained can be used as a basis for the diagnosis of SHE.

Journal Article↗

PubMed2004

Plasma and urine levels of urinary trypsin inhibitor in patients with chronic liver diseases and hepatocellular carcinoma.

BACKGROUND AND AIM: Because urinary trypsin inhibitor (UTI) is synthesized by hepatocytes and excreted into the urine, plasma and urine levels of UTI may alter in liver diseases. However, there are few reports on the changes in these levels in chronic liver diseases and hepatocellular carcinoma (HCC). The aim of the present study was to evaluate the relationships between plasma and urine UTI levels and the severity of liver damage or progression of HCC in patients with chronic liver diseases and HCC. METHODS: Plasma and urine UTI levels were measured by a newly developed enzyme-linked immunosorbent assay in 16 patients with chronic hepatitis (CH), 19 patients with liver cirrhosis (LC) and 39 patients with HCC. RESULTS: Plasma UTI level exhibited a significant positive correlation with the urine UTI level. Plasma and urine UTI levels significantly decreased in LC patients compared with those of normal controls. In contrast, the plasma UTI level in HCC patients was higher than that in LC patients, but there was no difference between the groups in the urine UTI level. Plasma and urine UTI levels in LC and HCC patients were significantly correlated with the degree of liver damage according to the Child-Pugh classification. Although neither the plasma nor urine level of UTI in HCC patients were related to the clinical stage of HCC, both levels were closely associated with the level of protein induced by vitamin K absence or antagonist-II. CONCLUSIONS: The present findings indicate that the levels of plasma and urine UTI in patients with LC reflect the severity of liver damage. In HCC patients, these levels may also reflect progression of HCC, although further study is required.

Adult↗

PubMed2003

Intravenous nicorandil in conjunction with coronary reperfusion therapy is associated with better clinical and functional outcomes in patients with acute myocardial infarction.

The aim of this retrospective study was to assess whether intravenous nicorandil, a hybrid of NO and a KATP channel opener, in conjunction with percutaneous coronary intervention (PCI) improves the long-term prognosis in patients with acute myocardial infarction (AMI). Intravenous nicorandil has already been shown to improve the in-hospital prognosis of patients with anterior AMI. The study population consisted of 272 patients with a reperfused AMI who were admitted during a similar time interval, before (control; n=114) and after nicorandil treatment (n=158). In the nicorandil group, a 4 mg bolus injection was given, followed by 6 mg/h infusion for 24 h and then oral nicorandil at 15 mg/day for at least 1 month. In the patients with an anterior AMI, left ventricular (LV) function was better and the frequency of LV remodeling was lower after 3 months in the nicorandil group; however, in those with a non-anterior AMI, there were no differences in functional outcome and the frequency of LV remodeling between the 2 groups. The frequency of cardiac events was significantly lower in the nicorandil group, and the use of nicorandil was derived as a potential factor related to freedom from cardiac events (p<0.01, odds ratio = 0.27). Nicorandil treatment was associated with better myocardial perfusion and a better functional and clinical outcome than PCI alone, and this beneficial effect was maintained for a long time, particularly in patients with anterior AMI.

Aged↗

PubMed2002

Executive dysfunction and clinical outcome in chronic alcoholics.

BACKGROUND: The purpose of this study was to investigate which of 12 neuropsychological tests predict alcoholic patients' alcohol-specific and/or alcoholic-nonspecific outcome. Our hypothesis was that the ecologically valid neuropsychological tests that measure executive function are better predictors of alcoholics' functional outcome. METHODS: We administered 12 neuropsychological tests to chronic alcoholics. Included in the tests were tasks of Reaction Time, Symbol Digit Modalities, Figure Position, Digit Span, Block Design, Trail Making, and six subtests of a battery called the Behavioral Assessment of the Dysexecutive Syndrome (BADS). Previous investigators have suggested that the BADS has ecological validity. Twenty-two male alcoholics were compared with 15 nonalcoholic control subjects on these neuropsychological measures 7 weeks after detoxification. Two functional outcome indices, i.e., resumption of drinking and occupation, were evaluated 18 months after discharge. RESULTS: The total profile score and the score on three of the six subtests of the BADS were lower in alcoholics than in nonalcoholic controls. Alcoholics' performance on the BADS predicted alcohol-nonspecific outcome (occupation) but not alcohol-specific (drinking) outcome. In contrast, other neuropsychological tests did not predict either of the two outcome indices. CONCLUSIONS: The BADS total profile score is related to alcohol-nonspecific outcome but not to alcohol-specific outcome.

Alcoholism↗

PubMed2001

Serum leptin concentrations in liver cirrhosis: relationship to the severity of liver dysfunction and their characteristic diurnal profiles.

Liver cirrhosis is often associated with malnutrition status, and while leptin, which reduces food intake, appears to contribute to it, there have been few detailed studies of serum leptin concentrations in cases of liver cirrhosis. We therefore measured serum leptin concentrations in liver cirrhosis and investigated its relationship with gender, body composition analysis, and the severity of liver dysfunction and the patterns of diurnal profiles in serum leptin. There were no significant differences between the serum leptin concentrations in the healthy controls and patients with liver cirrhosis. The serum leptin concentrations in liver cirrhosis cases were significantly higher in females than in males. Significant positive correlations were observed between the serum leptin and the body composition analysis data such as body mass index (BMI), arm circumference (AC), and triceps skin fold thickness (TSF). There was no correlations between BMI and arm muscle circumference (AMC). No changes in leptin levels were observed in association with the progression of liver dysfunction, according to the Child-Pugh classification. The diurnal profiles showed different patterns in liver cirrhosis and diabetes mellitus. In diabetes, a nocturnal rise was seen beginning around 21:00, but in liver cirrhosis, the rise in serum leptin started around 12:00, peaked at 13:00, and remained elevated until 03:00 in the morning. No associations were observed between the variations in serum leptin concentrations and variations in blood glucose or plasma insulin levels. In summary, serum leptin concentrations in liver cirrhosis are higher in women, positively correlated with the body composition analysis data, but not correlated with the severity of liver dysfunction. The diurnal profiles in serum leptin concentrations in liver cirrhosis also showed a different pattern from the profiles in diabetes with the values starting to increase earlier, during the daytime. Further study regarding the relation of leptin to nutrition and metabolic abnormalities in liver cirrhosis appears to be necessary.

Journal Article↗