Hypozincemia is associated with human hepatocarcinogenesis in hepatitis C virus-related liver cirrhosis.

AIM: Hypozincemia is associated with the progression of chronic liver diseases, but it is unknown whether hypozincemia promotes human hepatocarcinogenesis. Our aim is to evaluate the serum zinc levels in liver cirrhosis (LC) patients and clarify the relationship between the serum zinc levels and the development of hepatocellular carcinoma (HCC). METHODS: Cirrhotic patients without HCC (n = 299) were enrolled from 14 medical institutes in Japan as a multicenter prospective study (No. 2028). Of the 299 patients, 157 were included in the present study based on reliable and consistent serum zinc levels and no history of oral zinc supplementation. Clinical parameters associated with the development of HCC were determined. Furthermore, the cumulative incidence of HCC was analyzed using Kaplan-Meier methods and was calculated using the log-rank test. A Cox regression analysis was utilized for the multivariate analysis to evaluate the predictors of hepatocarcinogenesis. RESULTS: Thirty of 157 patients (19.1%) developed HCC during an observation period of 3 years. Serum zinc levels were significantly decreased in hepatitis C virus-related LC (C-LC) patients with HCC (0.0180). The risk factors for incidence of HCC were hypozincemia (0.0014), high α-fetoprotein (0.0080), low branched chain amino acids-to-tyrosine ratio (0.0128), or female sex (0.0228). Hypozincemia (hazard ratio 1.61, 0.0324) was the only significant predictor of hepatocarcinogenesis by multivariate Cox regression analysis. CONCLUSIONS: Hypozincemia is associated with hepatocarcinogenesis in C-LC patients.

Updating the neuropsychological test system in Japan for the elderly and in a modern touch screen tablet society by resetting the cut-off values.

AIM: Covert hepatic encephalopathy is frequently seen in cirrhotic patients. This condition can be diagnosed by a computerized neuropsychological test system (NPT); however, NPT has not been updated for approximately two decades in Japan. The aim of this study is to update the NPT to be more suitable for both the elderly and modern society by resetting of cut-off values. METHODS: We enrolled 367 healthy subjects aged between 40 and 79 years old between 2003 and 2010. The NPT consists of the following eight tests: number connection tests (NCT)-A and -B, a figure position test, a digit symbol test, a block design test, and reaction time tests (RTT)-A, -B, and -C. All subjects were classified into eight groups (5-year quartile ranges from 40 to 79 years old), and the cut-off value for each test was compared to the former cut-off value (NPT version 1). RESULTS: In all eight tests, most of the cut-off values were different from those in NPT version 1. The difference was minimal in RTT-A, RTT-B, and RTT-C. However, the difference was evident in the NCT-A, NCT-B, digit symbol test, and block design test. In particular, a 57.8-s decrease in the cut-off value was seen in the 65-69-year-old group for the NCT-B test (71.3 s vs. 129.1 s). CONCLUSIONS: We updated the NPT by covering subjects aged 40-79 years and resetting the cut-off values. Thus, the updated NPT is an elderly and modern subject-compliant application. This update may improve the diagnostic ability of covert hepatic encephalopathy in contemporary cirrhotic patients.

Brain metabolism in minimal hepatic encephalopathy assessed by 3.0-Tesla magnetic resonance spectroscopy.

AIM: To examine whether the brain exhibits metabolic disorder prior to overt hepatic encephalopathy in patients with liver cirrhosis (LC), the intracerebral glutamine and myo-inositol levels were determined using 3.0-Tesla (T)(1) H (proton) magnetic resonance spectroscopy (MRS). METHODS: We tested 21 LC patients, including seven patients with minimal hepatic encephalopathy (MHE). RESULTS: No significant differences were noted between the two patient groups in terms of the severity of LC, levels of blood ammonia or levels of blood or liver enzymes. In the MHE group, the levels of brain glutamine were significantly higher than those in the non-MHE group, whereas the levels of brain myo-inositol were significantly lower. This demonstrated that MHE patients were already exhibiting metabolic disorder in the brain, similar to those observed during overt hepatic encephalopathy. CONCLUSION: A quantitative analysis of this phenomenon using MRS may contribute to an early and objective diagnosis of MHE.

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.

The nutritional management of hepatic encephalopathy in patients with cirrhosis: International Society for Hepatic Encephalopathy and Nitrogen Metabolism Consensus.

UNLABELLED: Nitrogen metabolism plays a major role in the development of hepatic encephalopathy (HE) in patients with cirrhosis. Modulation of this relationship is key to the management of HE, but is not the only nutritional issue that needs to be addressed. The assessment of nutritional status in patients with cirrhosis is problematic. In addition, there are significant sex-related differences in body composition and in the characteristics of tissue loss, which limit the usefulness of techniques based on measures of muscle mass and function in women. Techniques that combine subjective and objective variables provide reasonably accurate information and are recommended. Energy and nitrogen requirements in patients with HE are unlikely to differ substantially from those recommended in patients with cirrhosis per se viz. 35-45 kcal/g and 1.2-1.5g/kg protein daily. Small meals evenly distributed throughout the day and a late-night snack of complex carbohydrates will help minimize protein utilization. Compliance is, however, likely to be a problem. Diets rich in vegetables and dairy protein may be beneficial and are therefore recommended, but tolerance varies considerably in relation to the nature of the staple diet. Branched chain amino acid supplements may be of value in the occasional patient intolerant of dietary protein. Increasing dietary fiber may be of value, but the utility of probiotics is, as yet, unclear. Short-term multivitamin supplementation should be considered in patients admitted with decompensated cirrhosis. Hyponatremia may worsen HE; it should be prevented as far as possible and should always be corrected slowly. CONCLUSION: Effective management of these patients requires an integrated multidimensional approach. However, further research is needed to fill the gaps in the current evidence base to optimize the nutritional management of patients with cirrhosis and HE.

Nutritional management contributes to improvement in minimal hepatic encephalopathy and quality of life in patients with liver cirrhosis: A preliminary, prospective, open-label study.

AIM: Problems in patients with minimal hepatic encephalopathy (MHE) include episodes such as falls and deficient driving skills, without any recognition of neurophysiological dysfunction. Patients with MHE are also more likely to develop overt hepatic encephalopathy. However, there is not yet any interventional strategy for MHE involving nutritional management. We conducted a preliminary study to investigate the proportion of positive MHE and the effects of nutritional management on MHE. METHODS: Patients with viral liver cirrhosis and abnormal neuropsychological tests were included. Nutritional consultations were conducted periodically by a dietitian, who recommended 30-35 kcal with 1.0-1.5 g of protein/kg of ideal bodyweight/day. The primary end-point was to evaluate the proportion of patients who recovered from MHE. The secondary end-point was to evaluate the improvement in the patients' quality of life (QOL). RESULTS: Thirty-two (30.1%) of 106 patients were diagnosed with MHE. Nineteen patients were enrolled in the study. Eleven of 19 patients became non-MHE after 4 weeks, and 13 of 19 patients (68.4%, P < 0.001) after 8 weeks. The mental summary scores were significantly improved at 8 weeks (P = 0.0413). Changes in albumin levels from week 0 to week 8 were 0.15 ± 0.16 g/dL in the improved MHE group and -0.28 ± 0.33 g/dL in the non-improved MHE group, which differ significantly (P = 0.0130). CONCLUSION: Periodical nutritional management improved MHE and QOL. Improving the patient's nutritional condition may be one approach to treating MHE.

Recent Progress of Nutritional Management for Liver Cirrhosis.

Evidence-based Clinical Practice Guidelines for Liver Cirrhosis were updated in 2021 by The Japanese Society of Gastroenterology/Japan Society of Hepatology. In the guidelines, the flowchart for nutritional therapy was revised based on accumulated evidence. In particular, sarcopenia is incorporated as an assessment for nutritional status. In addition, late evening snack is repositioned as a 1st-line nutritional therapy. Furthermore, recent study demonstrated unforeseen pharmacological actions of branched-chain amino acids including improving sarcopenia and prognosis. In this mini-review, we summarize the updated points for nutritional therapy for patients with liver cirrhosis.

Effects of branched-chain amino acid-enriched nutrient for patients with hepatocellular carcinoma following radiofrequency ablation: a one-year prospective trial.

BACKGROUND AND AIM: This prospective control study examined whether supplementation with branched-chain amino acid (BCAA)-enriched nutrients can help maintain and improve residual liver function and nutritional status in cirrhotic patients with hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA). METHODS: Subjects were 49 patients with hepatitis C-related HCC who underwent RFA. Two groups were formed: BCAA group (BCAA-enriched nutrient, aminoleban EN) and controls (standard diet only). Event-free survival rate, liver function tests, and Short Form (SF)-8 scores were evaluated in both groups before and one year after RFA. Energy metabolism using indirect calorimetry was measured before and after 3 months. RESULTS: Complete data were obtained from 35 patients (BCAA group, n = 20; controls, n = 15). Six events (death, recurrence of HCC, rupture of esophageal varices and liver failure) occurred during the observation period, but frequencies of these events did not differ between groups. Event-free survival rate tended to be higher in the BCA group than in controls. Among the parameters of liver function, serum albumin level was only significantly increased over 6 months, and remained at similar values for one year (P < 0.05). SF-8 scores for general health, physical functioning, and social functioning were significantly elevated in the BCAA group (P < 0.05). Non-protein respiratory quotient was significantly improved in the BCAA group (P < 0.01). CONCLUSION: Supplementation with BCAA-enriched nutrients for one year in cirrhotic patients with HCC after RFA therapy can perform safety and improve both nutritional state and quality of life.

Radiotracer imaging studies in hepatic encephalopathy: ISHEN practice guidelines.

There is lack of consensus on radiotracer usage in hepatic encephalopathy (HE). We have focused our attention on three main areas: (i) radiotracer imaging in animal models of HE, (ii) methodological issues of radiotracer imaging in HE and (iii) radiotracer imaging studies on the pathophysiology and (new) therapies in HE. We suggest the following: 1. Positron emission tomography (PET) and single photon emission computed tomography lend themselves to the study of animal models of HE, but the models that are suitable depend on the specific research question. Magnetic resonance imaging (MRI) may be a useful alternative technique. 2. Owing to the cost of the technique, there is a need for multicentre human PET studies to overcome the problem of underpowered small studies being undertaken in individual research centres. There should be a unified PET protocol with central, anonymised data analysis in one centre, using validated methodology, on behalf of all participating centres. Such studies would be useful for the assessment of early intervention in patients with subtle neuropsychiatric symptoms, or for clarification of the effect of liver transplantation on HE. 3. While radiotracer imaging modalities remain useful research tools for the study of pathogenesis and for the assessment of treatment effects, there is no consensus on the use of imaging in routine clinical practice for diagnosis and prognosis. The most promising objective tools appear to be magnetic resonance spectroscopy (MRS) and volumetric MRI, which can be performed in multiple centres without the difficulties that radiotracer imaging entail.

Diagnosis of sub-clinical hepatic encephalopathy by Neuropsychological Tests (NP-tests).

AIM: At present, there are no generally accepted diagnostic criteria or methods for sub-clinical hepatic encephalopathy (SHE) associated with liver cirrhosis. We therefore developed an easily conducted computer-aided quantitative neuropsychological function test system for use in routine medical practice. METHODS: The system was used prepare basic values according to age in 542 healthy subjects, and the results were compared with 292 liver cirrhosis patients. The software is composed of eight tests: NCT-A, NCT-B, Figure Design Test, Digit Symbol Test, Block Design Test, and the Reaction Time-A, Reaction Time-B, and Reaction Time-C. RESULTS: Performance time is approximately 15 to 20 min. There is no need to select a specific test location and it is convenient to use even without a professional examiner. When the top and bottom 10%, which correspond to the outlier values statistically in the healthy subjects, were used as the cutoff values abnormal results were observed in approximately 25% of the liver cirrhosis patients. Moreover, 58% of the patients had abnormal values according to the results of at least one of the tests. CONCLUSION: It is expected that this test will be used to further assess the diagnosis and pathology of SHE and that it will be utilized as a routine method of diagnosis.

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.

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.

Asymptomatic acute hepatitis E in a female patient with ulcerative colitis.

We present a 60-year-old female patient with asymptomatic acute hepatitis E that was fortuitously detected during the course of ulcerative colitis (UC). She was admitted to hospital on October 30, 2015. Endoscopy and histological examination of the colon showed typical findings of UC. All parameters of liver function tests were normal on this date. Combination therapy with oral prednisolone and mesalazine was started and intravenous administration of infliximab once every 8 weeks was added later. Her symptoms gradually improved after these treatments, and she was discharged on February 7, 2016. In a periodic check-up on July 7, 2016, high levels of serum transaminases were detected in liver function tests. Although drug-induced liver injury was first suspected, anti-hepatitis E virus (HEV) immunoglobulin A was positive. The genotype and subgenotype of this HEV are 3 and 3a, respectively, although the infectious route of the HEV was unclear. Within 2 weeks after the onset of acute liver injury, the HEV viremia disappeared and her liver function tests improved. Examination of serum anti-HEV immunoglobulin A should be added at the time of abnormal liver function tests in patients with UC receiving immunosuppressive and biological drugs.

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.

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.

Evidence-based clinical practice guidelines for liver cirrhosis 2015.

The Japanese Society of Gastroenterology revised the evidence-based clinical practice guidelines for liver cirrhosis in 2015. Eighty-three clinical questions were selected, and a literature search was performed for the clinical questions with use of the MEDLINE, Cochrane, and Igaku Chuo Zasshi databases for the period between 1983 and June 2012. Manual searching of the latest important literature was added until August 2015. The guidelines were developed with use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. This digest version in English introduces selected clinical questions and statements related to the management of liver cirrhosis and its complications. Branched-chain amino acids relieve hypoalbuminemia and hepatic encephalopathy and improve quality of life. Nucleoside analogues and peginterferon plus ribavirin combination therapy improve the prognosis of patients with hepatitis B virus related liver cirrhosis and hepatitis C related compensated liver cirrhosis, respectively, although the latter therapy may be replaced by direct-acting antivirals. For liver cirrhosis caused by primary biliary cirrhosis and active autoimmune hepatitis, urosodeoxycholic acid and steroid are recommended, respectively. The most adequate modalities for the management of variceal bleeding are the endoscopic injection sclerotherapy for esophageal varices and the balloon-occluded retrograde transvenous obliteration following endoscopic obturation with cyanoacrylate for gastric varices. Beta-blockers are useful for primary prophylaxis of esophageal variceal bleeding. The V2 receptor antagonist tolvaptan is a useful add-on therapy in careful diuretic therapy for ascites. Albumin infusion is useful for the prevention of paracentesis-induced circulatory disturbance and renal failure. In addition to disaccharides, the nonabsorbable antibiotic rifaximin is useful for the management of encephalopathy. Anticoagulation therapy is proposed for patients with acute-onset or progressive portal vein thrombosis.

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.

Impact of Remnant Lipoprotein on Coronary Plaque Components.

AIM: Intravascular ultrasound (IVUS) is a useful modality for visualizing atherosclerotic lesions in coronary arteries, not only for the degree of arterial luminal stenosis but also for the plaque composition within the vessel walls. We aimed to determine the relationship between the clinical parameters and coronary plaque characteristics evaluated by IVUS in patients with stable angina under medical treatment. METHODS: Plaque measurements within the coronary arteries were collected by coronary angiography and iMAP-IVUS in 40 men with stable angina. The serum remnant-like cholesterol (RemL-C) was measured using homogeneous assays and serum adiponectin and omentin-1 levels were measured by enzyme-linked immunosorbent assays. RESULTS: The iMAP-IVUS analysis of the coronary arteries demonstrated that the plaque cross-sectional area (CSA) was 11.0±3.5 mm(2). Plaque CSA positively correlated with body mass index and negatively correlated with the serum adiponectin levels. Both areal and volumetric analyses of the plaque characteristics demonstrated that the serum RemL-C level was a positive determinant for %Necrosis and the negative determinant for %Fibrosis of the plaques. Neither serum high-density lipoprotein cholesterol nor low-density lipoprotein cholesterol levels correlated with the proportion of any plaque components. Additionally, the RemL-C/triglyceride ratio positively correlated with %Lipid significantly in the areal analysis. CONCLUSION: Elevation of the serum RemL-C levels in the patients with stable angina may link to coronary plaque vulnerability, which is characterized by high necrotic and low fibrotic components.

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.

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.