l-carnitine supplementation vs cycle ergometer exercise for physical activity and muscle status in hemodialysis patients: A randomized clinical trial.

Serum carnitine is decreased in hemodialysis patients, which induces muscle atrophy. Thus, we examined the different effects of l-carnitine and exercise on exercise activity and muscle status in hemodialysis patients. Twenty patients were divided into l-carnitine and cycle ergometer groups and were followed for 3 months. Muscle and fat mass, physical activities, and muscle status were evaluated by an impedance, physical function test, and magnetic resonance imaging, respectively. The l-carnitine significantly increased muscle mass (P = .023) and thigh circumference (P = .027), decreased fat mass (P = .007), and shortened chair stand-up time (P = .002) and 10-m walk test (P = .037). The fat fraction was improved by the l-carnitine (P = .047). Compared with the exercise group, l-carnitine improved the changes in 10-m walk test (P = .026), chair stand-up time (P = .014), and thigh circumference (P = .022). Baseline fibroblast growth factor-21 and myostatin levels predicted the l-carnitine-associated changes in exercise activities. l-carnitine, rather than exercise, improved physical activity and muscle status in hemodialysis patients.

Identification of heterozygous p.Y150C and p.V274M mutations in the HJV gene in a Japanese patient with a mild phenotype of juvenile hemochromatosis: A case report.

Juvenile hemochromatosis (JH) is known as a progressive iron-storage disease, and causes severe organ impairments, including cardiomyopathy and liver cirrhosis. However, JH is a rare genetic disorder, and information for genetic mutations and phenotypes is limited. Here, we report a case of JH with heterozygous p.Y150C and p.V274M mutations in the HJV gene. A 39-year-old Japanese man was referred to Kurume University Hospital, Kurume, Japan, for fatigue and liver injury, which first appeared at the age of 25 years. There was no history of alcohol abuse and medication, and viral hepatitis, autoimmune liver diseases, and Wilson's disease were absent. However, transferrin saturation, serum ferritin, and fasting serum hepcidin levels were 98.4%, 6421 ng/mL, and 7.4 ng/mL, respectively. Furthermore, a marked reduction in signal intensity of the liver in T1/T2-weighted magnetic resonance images was seen and the R2* maps showed hepatic iron overload. Family history of hemochromatosis and severe organ impairment, such as cardiac dysfunction and diabetes mellitus, were negative. In addition, the HFE and HAMP genes did not show any mutation. However, we identified novel heterozygous p.Y150C and p.V274M mutations in the HJV gene in the patient. The p.Y150C and p.V274M mutations were seen in his mother and father, respectively. After phlebotomy, fatigue disappeared and serum transaminase levels were normalized. Furthermore, R2* maps showed a reduction of hepatic iron concentration. We first demonstrated heterozygous p.Y150C and p.V274M mutations in the HJV gene of patients with a mild JH phenotype. Thus, genetic testing should be considered even in patients with a mild phenotype of hemochromatosis.

The Value of MRI and Clinical Features in Differentiating Between Cellular and Fibrous Solitary Fibrous Tumors.

OBJECTIVE: The purpose of this study is to evaluate the usefulness of MRI in differentiating between fibrous and cellular solitary fibrous tumors (SFTs). MATERIALS AND METHODS: This retrospective study included 17 patients with histopathologically confirmed SFTs, including 10 patients with fibrous SFTs and seven patients with cellular SFTs. We evaluated the differences between fibrous and cellular SFTs with regard to clinical data and MRI findings, such as tumor margin definition, signal intensity, heterogeneity on T1- and T2-weighted images, presence of capsules, intratumoral cystic changes, flow signal void, perilesional edema, enhancement pattern on dynamic contrast-enhanced MRI (DCE-MRI), and mean apparent diffusion coefficient (ADC) values. RESULTS: Statistically significant differences in fibrous and cellular SFTs were noted with respect to signal intensity on T2-weighted images (p = 0.044, by Fisher exact test) and enhancement patterns on DCE-MRI (p = 0.005, by Fisher exact test). Specifically, on T2-weighted images, five of the fibrous SFTs had high signal intensity, and the other five had signal isointensity, whereas all seven cellular SFTs had high signal intensity. On DCE-MRI, fibrous SFTs tended to show a gradual increase in enhancement, whereas cellular SFTs showed a rapid initial enhancement pattern. The mean (± SD) ADC value for cellular SFTs was 1.39 ± 0.35 × 10-3 mm2/s, whereas that for fibrous SFTs was 1.37 ± 0.48 × 10-3 mm2/s, with no statistically significant difference noted between the two (p = 0.755, by Fisher exact test). CONCLUSION: Fibrous SFTs have nonspecific findings with regard to signal intensity on T2-weighted MR images and enhancement patterns on DCE-MRI, whereas cellular SFTs show high signal intensity on T2-weighted images and rapid initial enhancement on DCE-MRI.

Diffusion-weighted magnetic resonance imaging predicts malignant potential in small hepatocellular carcinoma.

BACKGROUND: Poor differentiation and microvascular invasion are indicators of poor outcome after hepatectomy for patients with small hepatocellular carcinoma (HCC). AIMS: We investigated whether gadoxetic acid-enhanced and diffusion-weighted magnetic resonance imaging (MRI) could predict these factors before hepatectomy. METHODS: Between July 2008 and April 2012, 75 patients who underwent hepatectomy for small HCCs (diameter: ≤3cm, tumor number: ≤3) were consecutively enrolled. In gadoxetic acid-enhanced MRI, the signal intensity in the tumor was corrected to that in the paraspinous muscles, and the relative enhancement was calculated. In diffusion-weighted imaging, we measured the apparent diffusion coefficient (ADC). We then investigated the correlations between relative enhancement or ADC and histological grade, microvascular invasion and recurrence-free survival. RESULTS: Poorly differentiated HCCs showed significantly lower ADC than well-differentiated and moderately differentiated HCCs. There was no significant difference in the hepatobiliary phase. Only ADC was an independent predictor of microvascular invasion, and the best cut-off point of its prediction was 1.175×10(-3)mm(2)/s. Additionally, the recurrence-free survival was significantly shorter in low-ADC group than in high-ADC group. CONCLUSION: ADC is useful for predicting poorly differentiated HCCs and microvascular invasion, and low ADC is associated with increased recurrence risk for small HCCs after hepatectomy.

Efficacy of peritoneovenous shunt for treating tolvaptan-resistant refractory ascites in a cirrhotic patient with portal vein thrombosis: A case report.

Peritoneovenous shunt is normally used for the treatment of refractory ascites. However, its efficacy in treating tolvaptan-resistant refractory ascites has not been reported thus far. In addition, the impact of peritoneovenous shunt on the prognosis of cirrhotic patients remains controversial. In the present report, a case of tolvaptan-resistant refractory ascites associated with liver cirrhosis and portal vein thrombosis is described. The male patient was diagnosed with hepatitis C virus-related liver cirrhosis at the age of 51 years. At the age of 56 years, the patient developed portal vein thrombosis, resulting in the development of refractory ascites. Since the ascites was resistant to treatment with a low-sodium diet and diuretics such as tolvaptan, a peritoneovenous shunt was implanted upon obtaining consent. The shunt immediately increased the urine volume, and the ascites was markedly decreased. The patient's body weight decreased from 62.7 to 57.1 kg in 2 days, and his ascites symptom inventory-7 score decreased from 23 to 0 points in 31 days. Although the patient succumbed to sepsis on day 486 following the shunt implant, his activities of daily living were preserved until 8 days prior to mortality. Thus, the present case supports the efficacy of peritoneovenous shunt for the treatment of tolvaptan-resistant refractory ascites associated with liver cirrhosis and portal vein thrombosis. Furthermore, the present case suggests that peritoneovenous shunt may prolong the survival of cirrhotic patents with refractory ascites.

Serum albumin level is a notable profiling factor for non-B, non-C hepatitis virus-related hepatocellular carcinoma: A data-mining analysis.

AIM: Various factors are underlying for the onset of non-B, non-C hepatitis virus-related hepatocellular carcinoma (NBNC-HCC). We aimed to investigate the independent risk factors and profiles associated with NBNC-HCC using a data-mining technique. METHODS: We conducted a case-control study and enrolled 223 NBNC-HCC patients and 669 controls from a health checkup database (n = 176 886). Multivariate analysis, random forest analysis and a decision-tree algorithm were employed to examine the independent risk factors, factors distinguishing between the case and control groups, and to identify profiles for the incidence of NBNC-HCC, respectively. RESULTS: In multivariate analysis, besides γ-glutamyltransferase (GGT) levels and the Brinkman index, albumin level was an independent negative risk factor for the incidence of NBNC-HCC (odds ratio = 0.67; 95% confidence interval = 0.60-0.70; P < 0.0001). In random forest analysis, serum albumin level was the highest-ranked variable for distinguishing between the case and control groups (98 variable importance). A decision-tree algorithm was created for albumin and GGT levels, the aspartate aminotransferase-to-platelet ratio index (APRI) and the Brinkman index. The serum albumin level was selected as the initial split variable, and 82.5% of the subjects with albumin levels of less than 4.01 g/dL were found to have NBNC-HCC. CONCLUSION: Data-mining analysis revealed that serum albumin level is an independent risk factor and the most distinguishable factor associated with the incidence of NBNC-HCC. Furthermore, we created an NBNC-HCC profile consisting of albumin and GGT levels, the APRI and the Brinkman index. This profile could be used in the screening strategy for NBNC-HCC.

Infantile hemangioma of the liver in an adult: a case report and review of the literature.

Infantile hemangioma (IH), a representative vascular liver tumor, usually occurs in infancy or early childhood but rarely in adults. In this study, we describe a case of IH in a 47-year-old female and we also review the literature. A plain computed tomography (CT) image revealed five hypoattenuating masses in the liver. A dynamic study revealed the masses appeared to be well-enhanced in the arterial phase, and were considered to be high-flow hemangiomas. The tumors appeared as hypointense tumors on the T1-weighted images and as hyperintensities on fat-suppression T2-weighted images. Following the administration of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA), tumors appeared to be well-enhanced in the arterial phase. In the portal phase, tumors demonstrated isointensity compared with the surrounding liver parenchyma, and hypointensity in the equilibrium and hepatobiliary phases. The apparent diffusion coefficient (ADC) values ranged from 2.0 to 2.4x10(-3) mm2/sec. Microscopically, the tumors were composed of numerous capillary-like small vessels lined with plump endothelial cells, arranged in a single layer without mitoses, and small bile ducts were trapped and scattered within the tumor. These findings were considered to be characteristic of IH. To the best of our knowledge, this case is the third report on IH in adults.

Quantification of hepatic iron concentration in chronic viral hepatitis: usefulness of T2-weighted single-shot spin-echo echo-planar MR imaging.

OBJECTIVE: To investigate the usefulness of single-shot spin-echo echo-planar imaging (SSEPI) sequence for quantifying mild degree of hepatic iron stores in patients with viral hepatitis. METHODS: This retrospective study included 34 patients with chronic viral hepatitis/cirrhosis who had undergone histological investigation and magnetic resonance imaging with T2-weighted gradient-recalled echo sequence (T2-GRE) and diffusion-weighted SSEPI sequence with b-factors of 0 s/mm(2) (T2-EPI), 500 s/mm(2) (DW-EPI-500), and 1000 s/mm(2) (DW-EPI-1000). The correlation between the liver-to-muscle signal intensity ratio, which was generated by regions of interest placed in the liver and paraspinous muscles of each sequence image, and the hepatic iron concentration (µmol/g dry liver), which was assessed by spectrophotometry, was analyzed by linear regression using a spline model. Akaike information criterion (AIC) was used to select the optimal model. RESULTS: Mean ± standard deviation of the hepatic iron concentration quantified by spectrophotometry was 24.6 ± 16.4 (range, 5.5 to 83.2) µmol/g dry liver. DW-EPI correlated more closely with hepatic iron concentration than T2-GRE (R square values: 0.75 for T2-EPI, 0.69 for DW-EPI-500, 0.62 for DW-EPI-1000, and 0.61 for T2-GRE, respectively, all P<0.0001). Using the AIC, the regression model for T2-EPI generated by spline model was optimal because of lowest cross validation error. CONCLUSION: T2-EPI was sensitive to hepatic iron, and might be a more useful sequence for quantifying mild degree of hepatic iron stores in patients with chronic viral hepatitis.

CD14 expression and Kupffer cell dysfunction in non-alcoholic steatohepatitis: superparamagnetic iron oxide-magnetic resonance image and pathologic correlation.

BACKGROUND AND AIM: Kupffer cell (KC) function and CD14 expression contributes to pathogenesis of non-alcoholic steatohepatitis (NASH). However, these relationships remain unclear. We investigated the relationship of KC function with superparamagnetic iron oxide-enhanced magnetic resonance imaging (SPIO-MRI), histopathological severity of NASH, and number of CD14-positive KCs in NASH. METHODS: This retrospective study included 32 patients (24 with NASH and eight with simple steatosis) who had previously undergone SPIO-MRI with T2-weighted gradient-recalled echo sequence. All subjects were diagnosed pathologically and were evaluated for necroinflammation grade, fibrosis stage, and number of CD14-positive KCs. Patients with NASH and simple steatosis were compared by using the Mann-Whitney test to determine differences in percent reduction of liver-to-muscle signal intensity ratio (reduction-%LMR), as a surrogate parameter of KC function, and number of CD14-positive KCs. Kruskal-Wallis test and Pearson's correlation coefficient were used to analyze relation among reduction-%LMR, histopathological severity and number of CD14-positive KCs. RESULTS: There were statistically significant differences in reduction-%LMR and number of CD14-positive KCs between NASH and simple steatosis patients (Mann-Whitney test, P < 0.001 for all comparisons). Reduction-%LMR decreased with an increase in necroinflammation grade or fibrosis stage. The number of CD14-positive KCs increased with an increase in necroinflammation grade and fibrosis stage (Kruskal-Wallis test, both, P < 0.001). A high correlation was seen between number of CD14-positive KCs and reduction-%LMR (Pearson r = 0.81; P < 0.001). CONCLUSIONS: KC phagocytic function evaluated with SPIO-MRI correlated with histopathological severity and number of CD14-positive KCs. These results support the concept that KC phagocytic dysfunction contributes to the pathogenesis of NASH.

Periostin, a matrix protein, has potential as a novel serodiagnostic marker for cholangiocarcinoma.

Differentiating intrahepatic cholangiocarcinoma (CCA) from other hepatic malignancies is crucial in deciding on treatment modalities and predicting clinical outcomes in patients. Periostin is a secreted protein from stromal cells and regulates the development of cancer cells through interaction with the extracellular matrix. Given that proliferation of fibrous stromal cells is a pathological feature of CCA, we examined the potential use of periostin as a serodiagnostic marker for this disease. Our study enrolled a total of 79 patients including liver cirrhosis (n=26), hepatocellular carcinoma (HCC, n=24), CCA (n=8), other hepatic malignancies (n=13) and histologically normal livers (normal control, n=8). Periostin expression was evaluated using immunohistochemistry and serum periostin level was determined via enzyme-linked immunoassay. The diagnostic performance of serum periostin levels for distinguishing CCA patients from others was also assessed. Strong expression of periostin was noted only in the fibrous stroma of CCA tissue. Serum periostin levels (median) were significantly higher in patients with CCA (513 ng/ml) compared to those patients with normal liver, liver cirrhosis, HCC and other malignancies (120, 146, 155, 213 ng/ml, respectively, all P<0.05). The area under receiver operating characteristics curve of serum periostin level was 0.94 [95% confidence interval (CI), 0.85-1.00, P<0.001]. With optimal cut-off value of 302 ng/ml, diagnostic performances for CCA were as follows: sensitivity, 0.88 (95% CI, 0.47-0.99); specificity, 0.92 (0.83-0.96); accuracy, 0.91 (0.83-0.96); positive predictive value, 0.54 (0.25-0.81); negative predictive value, 0.98 (0.92-0.99); positive-likelihood ratio, 10.4 (4.8-13.4); and negative-likelihood ratio, 0.13 (0.03-0.49). We demonstrated increased expression of periostin in the stroma of CCA tissue. Serum periostin levels were significantly elevated in patients with CCA and enable distinction between CCA and other hepatic malignancies.

Evaluation of the mean and entropy of apparent diffusion coefficient values in chronic hepatitis C: correlation with pathologic fibrosis stage and inflammatory activity grade.

PURPOSE: To determine whether mean and entropy apparent diffusion coefficient (ADC) values obtained at diffusion-weighted (DW) magnetic resonance (MR) imaging can help detect and stage histopathologic liver fibrosis and grade inflammation activity in patients with chronic hepatitis C. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board, and the requirement for informed consent was waived. The study included 55 patients with focal hepatic lesions and either chronic hepatitis C (n = 43) or normal hepatic function (control subjects) (n = 12). Mean and entropy of volume histograms were generated in four cubic regions of interest placed in the right hepatic lobe of ADC map images, which were obtained at echo-planar DW MR imaging (gradient factor b values of 0 and 1000 sec/mm(2)). These two parameters (mean and entropy ADC) were compared by using METAVIR histopathologic liver fibrosis and inflammatory activity scores. Statistical analysis was performed with the Kruskal-Wallis test and receiver operating characteristic curves. RESULTS: The mean ADC decreased with an increase in the fibrosis stage or inflammatory activity grade, and the entropy ADC increased with an increase in the fibrosis stage or inflammatory activity grade (P < .001 for all comparisons, Kruskal-Wallis test). The area under the receiver operating characteristic curve (A(z)) for the mean ADC was statistically significant in the differentiation of fibrosis stage or inflammatory activity grade (A(z), 0.807-0.926; P < .001 for all comparisons). Entropy of ADC was helpful for classifying normal from abnormal fibrosis stage or inflammatory activity grade (A(z) for both parameters, 0.937; P < .001). CONCLUSION: Assessment of a combination of mean ADC and entropy ADC in patients with chronic hepatitis C is more accurate for predicting pathologic hepatic fibrosis stage and inflammatory activity grade and helpful for detecting early fibrotic or inflammatory activity when compared with assessment of mean ADC alone.

Correlation of Kupffer cell function and hepatocyte function in chronic viral hepatitis evaluated with superparamagnetic iron oxide-enhanced magnetic resonance imaging and scintigraphy using technetium-99m-labelled galactosyl human serum albumin.

Kupffer cells contribute to the pathogenesis of liver injury in chronic liver disease, yet it is difficult to assess Kupffer cell function either ex vivo or in vivo, since supporting data are limited. The aim of this study was to clarify the relation between Kupffer cell function and hepatocyte function by analyzing the correlation between conventional indices of hepatic functional reserve and both superparamagnetic iron oxide-enhanced MRI (SPIO-MRI) and technetium-99m-galactosyl human serum albumin scintigraphy (Tc-99m-GSA) in patients with chronic viral hepatitis. Consecutive 46 patients (16 patients with chronic hepatitis and 30 patients with cirrhosis) who underwent both SPIO-MRI and Tc-99m-GSA were examined. The patients were aged 46-83 years (median 70) and included 29 men and 17 women. Spearman correlation coefficient was used to analyze the correlations between functional reserve indices and both reduction percentages of liver-to-muscle signal intensity ratio (reduction-%LMR), as a surrogate parameter of Kupffer cell function and Tc-99m-GSA parameters. The usefulness of each parameter as a marker to differentiate Child-Pugh A from Child-Pugh B/C was evaluated using receiver operating characteristic (ROC) analysis. The reduction-%LMR correlated more closely with Child-Pugh score (r=0.77; P<0.001) than did Tc-99m-GSA parameters. For predicting Child-Pugh B/C, ROC analysis revealed that reduction-%LMR (AUC=0.91, P<0.001) was the most useful parameter and at a cutoff value of 50% or less, sensitivity, specificity, positive and negative predictive values were 0.79, 0.91, 0.94 and 0.71, respectively. SPIO-MRI may be a helpful non-invasive method for the evaluation of hepatic functional reserve, and this study suggests that Kupffer cell function is closely correlated with hepatocyte function in patients with chronic viral hepatitis.

Chronic hepatitis and cirrhosis on MR imaging.

This article focuses on the current role of magnetic resonance imaging in the detection and characterization of chronic hepatitis and cirrhosis. In particular, the characteristic MR imaging features of morphologic changes and focal manifestations of chronic liver disease are highlighted.

Diffusion-weighted imaging of soft tissue tumors: usefulness of the apparent diffusion coefficient for differential diagnosis.

PURPOSE: We evaluated the efficacy of using the apparent diffusion coefficient (ADC) to differentiate soft tissue tumors. MATERIALS AND METHODS: We examined 88 histologically proven tumors (44 benign, 8 intermediate, 36 malignant) using diffusion-weighted magnetic resonance images. Images of the tumors were obtained using a single-shot, spin-echo type echo-planar imaging sequence. The tumors were classified histologically as myxoid or nonmyxoid. We then compared the ADC values of the myxoid and nonmyxoid tumors; the benign and malignant myxoid tumors; and the benign, intermediate, and malignant nonmyxoid tumors. RESULTS: The mean ADC value of the myxoid tumors (2.08 +/- 0.51 x 10(-3) mm(2)/s) was significantly greater than that of the nonmyxoid tumors (1.13 +/- 0.40 x 10(-3) mm(2)/s) (P < 0.001). There was no significant difference in the mean ADC values between benign myxoid tumors (2.10 +/- 0.50 x 10(-3) mm(2)/s) and malignant myxoid tumors (2.05 +/- 0.58 x 10(-3) mm(2)/s). The mean ADC value of benign nonmyxoid tumors (1.31 +/- 0.46 x 10(-3) mm(2)/s) was significantly higher than that of malignant nonmyxoid tumors (0.94 +/- 0.25 x 10(-3) mm(2)/s) (P < 0.001). CONCLUSION: The ADC value might be useful for diagnosing the malignancy of nonmyxoid soft tissue tumors.

Supplement improves nutrition and stresses caused by examination-associated fasting in patients with liver cirrhosis.

AIM: Cirrhotic patients tend to develop malnutrition by fasting, yet the importance of nutritional care during examination-associated fasting has not been investigated. This study aimed to examine the effects of a nutritional supplement on nutrition and stresses caused by examination-associated fasting in cirrhotic patients. METHODS: Twenty-nine cirrhotic patients were enrolled in this study. No energy was supplied to patients in the fasting group (n = 11) prior to computed tomography or magnetic resonance imaging examination. A supplement of 200 kcal was given to the patients in the supplement group (n = 18) prior to computed tomography or magnetic resonance imaging examination. The effect of the supplement on stresses was evaluated by self-rating questionnaire. Changes in biochemical parameters were also investigated before and after computed tomography or magnetic resonance imaging examinations. RESULTS: There were no significant differences in age, sex, body mass index, or liver function tests between the two groups at the start of the study. In the supplement group, stress scores for physical symptoms (thirst and light-headedness) and mental symptoms (hunger, hypodynamia and fatigue) were significantly lower compared to those in the fasting group. Also in the supplement group, peripheral 3-hydroxybutyric acid and free fatty acids levels were significantly decreased compared to those in the fasting group, to within normal ranges. In addition, a decrease in prothrombin time was significantly inhibited by intake of the supplement. CONCLUSION: We demonstrated that a nutritional supplement improved nutrition and reduced both the physical and mental stresses associated with examination-associated fasting in cirrhotic patients.

Evaluation of small (

PURPOSE: To evaluate the detectability and signal intensities of small (