Akinobu Kato

The nutritional management of hepatic encephalopathy in patients with cirrhosis: International society for hepatic encephalopathy and nitrogen metabolism consensus

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. (Hepatology 2013)

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).

Regional differences in cerebral glucose metabolism in cirrhotic patients with subclinical hepatic encephalopathy using positron emission tomography.

Although it is recognized that abnormalities of glucose metabolism occur substantially throughout the brain in cirrhotic patients with subclinical hepatic encephalopathy (SHE), little attention has been paid to these abnormalities in situ due to technical difficulties. The aim of this study is to clarify the regional differences of cerebral glucose metabolism (CMRglu) in patients with or without SHE using positron emission tomography (PET). Fifteen patients with posthepatitic cirrhosis and 13 control subjects underwent PET imaging of the brain using 2-[18F]fluoro-2-deoxy-D-glucose. Neurological tests included the digit symbol and block design subtests from the Wechsler Adult Intelligence Scale. Auditory brain stem reaction and electroencephalogram were also used in diagnosis of SHE. Regions were defined as frontal, parietal, occipital, basal ganglia, and the white matter. The CMRglu value in the grey matter of SHE is lower than that of control, particularly in the frontal and temporal regions and basal ganglia (P<0.05, respectively). The CMRglu values in the grey matter of non-SHE and control are almost the same, excepting the basal ganglia. The CMRglu value in the basal ganglia of non-SHE is higher than that of control and SHE. The CMRglu value in the grey matter of SHE is depressed as compared to both non-SHE and control. These data suggest that the abnormalities of cerebral glucose metabolism may be a contributing factor in SHE.

Alterations in expression of genes coding for proteins of the neurovascular unit in ischemic liver failure

There is evidence to suggest that integrity of the neurovascular unit may be compromised in acute liver failure (ALF). In order to address this issue from a molecular standpoint, expression of an array of genes coding for key cerebrovascular endothelial cell and tight junction proteins were measured by reverse transcription-polymerase chain reaction in cerebral cortex of rats with ischemic liver failure resulting from hepatic devascularization (portacaval anastomosis followed 24h later by hepatic artery ligation) compared to appropriate sham-operated controls. Expression of P-glycoprotein, endothelin-1, von Willebrand factor, caveolin-1, occludin, and the endothelial nitric oxide synthase isoform (eNOS) were measured in brain extracts from rats with ALF at coma/edema stages of encephalopathy. The effects of mild hypothermia (35 degrees C) sufficient to prevent cerebral edema in ALF animals on the expression of these genes were also studied. Brain edema and hepatic coma in normothermic ALF rats was accompanied by selective increases in expression of eNOS. Expression of occludin and von Willebrand factor mRNAs were decreased at coma/edema stages of encephalopathy in ALF rats whereas, expression of other cerebrovascular endothelial cell markers endothelin-1, P-glycoprotein, and caveolin-1 were unaffected. Mild hypothermia led to normalization of brain water content and of eNOS mRNA. However, the correlation between increased eNOS expression and encephalopathy/edema grade was poor suggesting the existence of additional mechanisms. These findings underscore the multifactorial nature of brain edema/encephalopathy mechanisms in ALF and question the role of BBB breakdown as a major pathogenetic factor.

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

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.

Guidelines on nutritional management in Japanese patients with liver cirrhosis from the perspective of preventing hepatocellular carcinoma

Aim:  The Japanese Nutritional Study Group for Liver Cirrhosis (JNUS) was assembled in 2008 with the support of a Health Labor Sciences Research Grant from the Ministry of Health, Labor and Welfare of Japan. The goal of the study group was to propose new nutritional guidelines for Japanese patients with liver cirrhosis (LC), with the aim of preventing hepatocellular carcinoma.

Effect of zinc on liver cirrhosis with hyperammonemia: A preliminary randomized, placebo-controlled double-blind trial

OBJECTIVE To our knowledge, no randomized study has shown whether zinc replacement therapy is effective for hyperammonemia in liver cirrhosis; therefore, we performed a double-blind, placebo-controlled trial to examine efficacy and safety of the zinc replacement therapy. METHODS Patients with liver cirrhosis and hyperammonemia (at or above the institutional reference value) and hypozincemia (≤65 μg/dL) were enrolled in the outpatient units of the participating institutions and were randomly divided to receive placebo (P group) or zinc acetate preparation at a dose of 3 capsules/d for a total zinc content of 150 mg/d (Z group) by the envelope method. Of the 18 enrolled patients, 6 dropped out; thus, the analyses included 12 patients (5 in the P group and 7 in the Z group). Variations in blood concentrations of zinc and ammonia as well as liver function test results were compared. RESULTS Blood zinc levels significantly increased in the Z group (P = 0.0037; Friedman test) but not the P group. Blood ammonia levels significantly decreased in the Z group (P = 0.0114; Friedman test) but not the P group. The percent change in blood ammonia level also revealed significant reduction at the eighth week in the Z group (P = 0.0188: Mann-Whitney test). No serious adverse events attributable to the zinc preparation were noted. CONCLUSION Although this study is preliminary and includes a small sample, it is, to our knowledge, the first randomized controlled trial to show that zinc supplementation for 3 mo seems effective and safe for treating hyperammonemia in liver cirrhosis. Studies with a larger sample size are needed to confirm our findings.

Validity of 13C-phenylalanine breath test to evaluate functional capacity of hepatocyte in patients with liver cirrhosis and acute hepatitis

Background : No definitive method for quantitative evaluation of hepatic function has as yet been established.

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.

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.