Short-latency reaction time and accuracy are impaired in patients with cirrhosis: An international multicenter retrospective study.

AIM: The inability to quickly react to an external event can lead to an increased risk for accidents (e.g., falls, car crashes) in patients with cirrhosis. The aim of this study was to determine whether a novel clinically feasible measure of simple reaction time (SRT) and reaction accuracy (RA)-a go/no-go task occurring within 400 ms-could differentiate patients with cirrhosis from controls. METHODS: This retrospective study included 160 patients with cirrhosis and 160 controls assessed between January 2010 and October 2022. SRT and RA were evaluated using a ruler drop paradigm and compared using propensity score matching. Factors distinguishing patients with cirrhosis from controls were assessed using logistic regression and receiver operating characteristics curve (ROC) analyses. RESULTS: Propensity score matching identified 112 participants in each group with comparable baseline characteristics. As compared with controls, patients with cirrhosis exhibited significantly prolonged SRT (200 vs. 174 ms; P < 0.001) and diminished total RA (63% vs. 73%; P < 0.001). After adjustment for confounding factors, SRT and RA independently identified patients with cirrhosis. ROC analyses showed that SRT more effectively identified patients with cirrhosis than did the number-connection test/trail-making test-B (area under the curve, 0.87 vs. 0.60; P < 0.001). CONCLUSIONS: Patients with cirrhosis demonstrated impairments in short-latency cognitive function. Given that SRT and RA are associated with balance, falls, and response to perturbation, these parameters may present a task-specific method to identify patients with cirrhosis at high risk of falls and motor vehicle crashes. Geriatr Gerontol Int 2024; 24: 25-31.

Novel Clean End-to-End Anastomosis Method, Without Opening the Stomach Lumen, in Totally Laparoscopic or Robotic Pylorus-Preserving Gastrectomy.

PURPOSE: Intra-abdominal infection is a common postoperative complication of laparoscopic pylorus-preserving gastrectomies (PPGs). Many studies have reported that intra-abdominal infectious complications after gastrectomy adversely affect patient survival outcomes. To prevent gastric fluid leakage into the abdominal cavity, we developed a novel anastomosis method in which the stomach lumen is not opened (termed the non-opened clean end-to-end anastomosis method [NoCEAM]) and evaluated its feasibility. MATERIALS AND METHODS: Subsequent to lymphadenectomy, the oral and anal resection lines were sutured using an intraoperative endoscope. After closing the stomach circumferentially with clips, the specimen was rolled outward like a "donut." We resected the specimen circumferentially using a linear stapler, and anastomosis was completed simultaneously. We examined the feasibility of this procedure ex vivo, using three porcine stomachs, and in vivo, using one pig. Subsequently, we applied the procedure to 13 consecutive patients with middle-third early gastric cancer utilizing laparotomic, laparoscopic, and robotic PPG. RESULTS: NoCEAM was completed in all porcine models and human cases. In the human cases, the mean operation time (±standard deviation) was 279±51 minutes, and mean blood loss volume was 22±45 mL. The mean number of linear staples used was 5.06±0.76. None of the patients had complications, and all were discharged on the eighth postoperative. The serum total protein, serum albumin, and hemoglobin levels did not change significantly after surgery. CONCLUSIONS: NoCEAM is feasible and safe for performing totally laparoscopic or robotic PPG. It may reduce postoperative complications, such as intra-abdominal infections.

Identification of candidates for driver oncogenes in scirrhous-type gastric cancer cell lines.

Scirrhous-type gastric cancer (SGC) is one of the most intractable cancer subtypes in humans, and its therapeutic targets have been rarely identified to date. Exploration of somatic mutations in the SGC genome with the next-generation sequencers has been hampered by markedly increased fibrous tissues. Thus, SGC cell lines may be useful resources for searching for novel oncogenes. Here we have conducted whole exome sequencing and RNA sequencing on 2 SGC cell lines, OCUM-8 and OCUM-9. Interestingly, most of the mutations thus identified have not been reported. In OCUM-8 cells, a novel CD44-IGF1R fusion gene is discovered, the protein product of which ligates the amino-terminus of CD44 to the transmembrane and tyrosine-kinase domains of IGF1R. Furthermore, both CD44 and IGF1R are markedly amplified in the OCUM-8 genome and abundantly expressed. CD44-IGF1R has a transforming ability, and the suppression of its kinase activity leads to rapid cell death of OCUM-8. To the best of our knowledge, this is the first report describing the transforming activity of IGF1R fusion genes. However, OCUM-9 seems to possess multiple oncogenic events in its genome. In particular, a novel BORCS5-ETV6 fusion gene is identified in the OCUM-9 genome. BORCS5-ETV6 possesses oncogenic activity, and suppression of its message partially inhibits cell growth. Prevalence of these novel fusion genes among SGC awaits further investigation, but we validate the significance of cell lines as appropriate reagents for detailed genomic analyses of SGC.

The Prevalence and Implication of Zinc Deficiency in Patients With Chronic Liver Disease.

BACKGROUND: Patients with liver cirrhosis often exhibit zinc deficiency. Although zinc is involved in many bioactivities, many aspects of clinical implications of zinc deficiency in liver cirrhosis remain unclear. We aimed to reveal the prevalence and implications of zinc deficiency in liver cirrhosis by assessing associations with parameters such as clinical symptoms and laboratory data. METHODS: In 235 cirrhosis patients enrolled at multiple medical institutions in 2009, we assessed how blood zinc levels were associated with their clinical symptoms, patients characteristics, and liver function test results. RESULTS: Blood zinc levels were most strongly correlated with blood albumin levels among the study parameters (r = 0.587, P < 0.0001). When blood albumin levels were ≤ 3.5 g/dL, blood zinc levels were < 70 µg/dL in 88% of patients. Additionally, significant correlations were observed with age (r = -0.253, P = 0.0014), aspartate aminotransferase levels (r = -0.254, P = 0.0020), total bilirubin levels (r = -0.222, P = 0.0053), prothrombin time (r = -0.255, P = 0.0029), branched-chain amino acid to tyrosine ratio (r = 0.357, P < 0.0001), Child-Pugh score (r = 0.469, P < 0.0001), ammonia levels (r = -0.246, P = 0.0028), and total cholesterol levels (r = 0.314, P < 0.0001). Blood zinc levels were significantly lower in patients with edema/ascites (P < 0.0001), those with hepatic encephalopathy (P = 0.0215), those receiving oral diuretics (P = 0.0045), and those receiving oral branched-chain amino acids (P < 0.0001) than in those without these conditions. CONCLUSIONS: Zinc deficiency is prevalent in cirrhosis patients, whereas nitrogen metabolic disorders, particularly hypoalbuminemia, can be an indicator of zinc deficiency. Thus, cirrhosis patients exhibiting a nitrogen metabolic disorder should be examined for the presence of zinc deficiency.

Divergent clinical outcomes of alpha-glucosidase enzyme replacement therapy in two siblings with infantile-onset Pompe disease treated in the symptomatic or pre-symptomatic state.

Pompe disease is an autosomal recessive, lysosomal glycogen storage disease caused by acid α-glucosidase deficiency. Infantile-onset Pompe disease (IOPD) is the most severe form and is characterized by cardiomyopathy, respiratory distress, hepatomegaly, and skeletal muscle weakness. Untreated, IOPD generally results in death within the first year of life. Enzyme replacement therapy (ERT) with recombinant human acid alpha glucosidase (rhGAA) has been shown to markedly improve the life expectancy of patients with IOPD. However, the efficacy of ERT in patients with IOPD is affected by the presence of symptoms and cross-reactive immunologic material (CRIM) status. We have treated two siblings with IOPD with ERT at different ages: the first was symptomatic and the second was asymptomatic. The female proband (Patient 1) was diagnosed with IOPD and initiated ERT at 4 months of age. Her younger sister (Patient 2) was diagnosed with IOPD at 10 days of age and initiated ERT at Day 12. Patient 1, now 6 years old, is alive but bedridden, and requires 24-hour invasive ventilation due to gradually progressive muscle weakness. In Patient 2, typical symptoms of IOPD, including cardiac failure, respiratory distress, progressive muscle weakness, hepatomegaly and myopathic facial features were largely absent during the first 12 months of ERT. Her cardiac function and mobility were well-maintained for the first 3 years, and she had normal motor development. However, she developed progressive hearing impairment and muscle weakness after 3 years of ERT. Both siblings have had low anti-rhGAA immunoglobulin G (IgG) antibody titers during ERT and have tolerated the treatment well. These results suggest that initiation of ERT during the pre-symptomatic period can prevent and/or attenuate the progression of IOPD, including cardiomyopathy, respiratory distress, and muscle weakness for first several years of ERT. However, to improve the long-term efficacy of ERT for IOPD, new strategies for ERT for IOPD, e.g. modifying the enzyme to enhance uptake into skeletal muscle and/or to cross the blood brain barrier (BBB), will be required.

Gut wall replacing type of gastrointestinal stromal tumor presenting as a perforation of the ileal diverticulum.

Gastrointestinal stromal tumors (GISTs) usually form a well-circumscribed mass. Very rarely, however, sporadic GISTs show gut-wall replacing growth, similar to the diffuse hyperplasia of interstitial cells of Cajal (ICC) observed in patients with neurofibromatosis type 1 (NF1) and hereditary GIST. Here we describe a patient with ileal perforation caused by this unusual type of GIST. An 82-year-old man was admitted to the emergency department with sudden abdominal pain. Following a provisional diagnosis of perforation of Meckel's diverticulum, he underwent segmental resection of the small intestine. Macroscopic examination revealed a diverticulum-like structure 2.5cm in size near the site of mesenteric attachment of the ileum. Histological examination showed diffuse and nodular proliferation of spindle cells positive for c-KIT and CD34 that had replaced the muscularis propria of the small intestine. Mutational analyses of the lesions revealed monoclonality of proliferating cells with a somatic mutation in c-kit exon 11 (p.Leu576Pro). Gut-wall replacing type of GIST should be recognized as a specific type of GIST causing diverticulum-like structures of the gastrointestinal tract.

Branched-chain amino acids prevent hepatocarcinogenesis and prolong survival of patients with cirrhosis.

BACKGROUND & AIMS: Although a low plasma level of branched-chain amino acids (BCAAs) is a marker of cirrhosis, it is not clear whether BCAA supplements affect disease progression. We performed a multicenter study to evaluate the effects of BCAA supplementation on hepatocarcinogenesis and survival in patients with cirrhosis. METHODS: We enrolled 299 patients from 14 medical institutions in Japan in a prospective, multicenter study in 2009; 267 patients were followed through 2011. Patients were given BCAA supplements (5.5-12.0 g/day) for more than 2 years (n = 85) or no BCAAs (controls, n = 182). The primary end points were onset of hepatocellular carcinoma (HCC) and death. Factors associated with these events were analyzed by competing risk analysis. RESULTS: During the study period, 41 of 182 controls and 11 of 85 patients given BCAAs developed HCC. On the basis of the Cox and the Fine and Gray models of regression analyses, level of α-fetoprotein, ratio of BCAA:tyrosine, and BCAA supplementation were associated with development of HCC (relative risk for BCAAs, 0.45; 95% confidence interval, 0.24-0.88; P = .019). Sixteen controls and 2 patients given BCAAs died. Factors significantly associated with death were Child-Pugh score, blood level of urea nitrogen, platelet count, male sex, and BCAA supplementation (relative risk of death for BCAAs, 0.009; 95% confidence interval, 0.0002-0.365; P = .015) in both regression models. CONCLUSIONS: On the basis of a prospective study, amino acid imbalance is a significant risk factor for the onset of HCC in patients with cirrhosis. BCAA supplementation reduces the risk for HCC and prolongs survival of patients with cirrhosis.

A large-scale nationwide multicenter prospective observational study of triple therapy using rabeprazole, amoxicillin, and clarithromycin for Helicobacter pylori eradication in Japan.

BACKGROUND: In recent years in Japan, the rate of clarithromycin (CAM) resistance in Helicobacter pylori has risen to around 30%, and the eradication rate with triple therapy [proton pump inhibitor + amoxicillin (AMPC) + CAM] has been trending downward to around 70%. In 2007, rabeprazole (RPZ)-based triple therapy (RPZ + AMPC + CAM: RAC therapy) was approved in Japan, and a large-scale nationwide study was therefore initiated to evaluate the efficacy and safety of RAC therapy in clinical practice. METHODS: Patients with H. pylori-positive gastric/duodenal ulcer (including ulcer scars) were administered triple therapy comprising RPZ 10 mg, AMPC 750 mg, and CAM 200 mg (or 400 mg), twice daily for 7 days. RESULTS: The eradication rate was 80.7% (2,551/3,162). The results of multivariate analysis indicated the following as factors affecting the eradication rate: sex, treatment compliance, history of H. pylori treatment, presence of urologic disease, presence of respiratory disease, and year of starting treatment. The incidence of adverse drug reactions (such as diarrhea and dysgeusia) was 4.4% (166/3,789). The results of multivariate analysis indicated the following as factors affecting the incidence of adverse drug reactions: sex, daily CAM dose, and history of allergies. CONCLUSION: In a large-scale nationwide study of use in clinical practice, RAC therapy was confirmed to be effective and safe.

A case of nemaline myopathy with associated dilated cardiomyopathy and respiratory failure.

Nemaline myopathy is a representative form of congenital myopathy, and is characterized by nemaline bodies in muscle fibers. Here we report a 47-year-old man with congenital nemaline myopathy complicated with dilated cardiomyopathy-related heart failure, and restrictive respiratory failure. The complication of dilated cardiomyopathy in nemaline myopathy has rarely been reported. In this case, nemaline bodies were detected in the cardiac muscle fibers, demonstrating the presence of underlying disease-related myocardial degeneration. The patient responded to the combination of conventional therapy for heart failure including ß-blocker and noninvasive continuous positive-pressure ventilation for respiratory failure. His general condition has been stable during a 10-month follow up period.

Elevated serum tumor necrosis factor-alpha 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.

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. 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.

Relationship between serum albumin level and aging in community-dwelling self-supported elderly population.

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.

BCAA-enriched snack improves nutritional state of cirrhosis.

OBJECTIVE: A late evening snack improves the catabolic state in patients with advanced liver cirrhosis. We tested whether long-term (3 mo) late evening snacking that included a branched-chain amino acid (BCAA)-enriched nutrient mixture produces a better nutritional state and better quality of life than ordinary food in patients with hepatitis C virus-positive liver cirrhosis. METHODS: In a multicenter, randomized study, 48 patients with liver cirrhosis received late-evening supplementation with the BCAA-enriched nutrient mixture or ordinary food, such as a rice ball or bread, for 3 mo. During the study period, each patient was instructed on energy and protein intake. Blood biochemical data, nitrogen balance, respiratory quotient, and health-related quality of life (Short Form 36 questionnaire) were evaluated at baseline and at the end of the study. RESULTS: Total and late-evening energy intakes were similar in the two groups at 3 mo. Serum albumin level, nitrogen balance, and respiratory quotient were significantly improved by the BCAA mixture but not by ordinary food. The parameters of the Short Form 36 did not statistically significantly improve over 3 mo in either group. CONCLUSION: Long-term oral supplementation with a BCAA mixture is better than ordinary food in a late evening snack at improving the serum albumin level and the energy metabolism in patients with cirrhosis.

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.

A longitudinal study on the nutritional state of elderly women at a nursing home in Japan.

OBJECTIVE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Automatic positioning of a microinjector in mouse ES cells and rice protoplasts.

A 2-channel (2C) microinjector was prepared by pulling a glass capillary with a theta-shaped cross section. One channel was used as a potential measuring electrode (MeaE) and the other was used as an electrophoretic introduction electrode (IntE). The 2C microinjector was propelled by an oil pressure manipulator driven by a pulse motor, while the MeaE output was recorded continuously. When the 2C microinjector penetrated the cell membrane of a mouse ES cell or a rice protoplast, the output potential changed sharply. The differential of this potential change was used as a stop signal for the pulse motor. Thus, the microinjector was correctly positioned in the cell without losing cell viability. Its success rate was 73% and 84% for ES cells and rice protoplasts, respectively. After the positioning of the microinjector in the cell, Lucifer yellow (LY) was introduced via IntE. Under these conditions, the rate of viable cells was 16% and 62% for ES cells and rice protoplasts, respectively.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Activation of hepatic branched-chain alpha-keto acid dehydrogenase complex by tumor necrosis factor-alpha in rats.

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.

Nocturnal energy and BCAA supplementation in patients with liver cirrhosis.

Patients with liver cirrhosis have protein-energy malnutrition (PEM) and run short of proteins and energy. Protein deficiency leads to hypoalbuminemia, which induces peritoneal effusion and edema. Energy deficiency decreases fat and muscle mass and causes muscle weakness, which decreases the QOL of these patients. A decrease in triceps skinfold thickness (TSF) and arm muscle circumference (AMC), which are indicators of hypoalbuminemia and energy deficiency, and a decrease in respiratory quotient (RQ) affect the prognosis of these patients. Therefore, appropriate nutritional assessment should be performed in order to detect PEM in these patients, and necessary proteins or energy should be supplied. TSF, AMC and RQ are improved by increasing the energy supply to correct its deficiency and by dividing daily food intake (in some cases, adding nocturnal supplementation). Serum albumin levels increase when branched-chain amino acids (BCAAs) are administered after every meal or at bedtime. Consequently, nutritional assessment on PEM, and nutritional therapy based on this assessment are essential for improving the QOL and prognosis of patients with liver cirrhosis.