Search

To investigate the impact of low skeletal muscle mass (LSMM) on survival as compared with protein-energy malnutrition (PEM) in patients with liver cirrhosis (LC).A total of 206 individuals with LC were analyzed. We retrospectively examined the impact of LSMM, as defined by psoas muscle mass at the third lumber on computed tomography, on survival as compared with PEM. In terms of comparison of the effects of LSMM and PEM on survival, we used time-dependent receiver operating characteristics (ROC) analysis.Our study cohort included 115 men and 91 women with a median age of 67 years. There were 140 patients with Child-Pugh A, 62 with Child-Pugh B, and 4 with Child-Pugh C. A total of 117 patients (56.8%) had LSMM and 52 patients (25.2%) had PEM. The proportion of PEM in patients with LSMM (31.62%, 37/117) was significantly higher than in patients without LSMM (16.85%, 15/89) (P = 0.0229). In the multivariate analysis for the entire cohort, the presence of hepatocellular carcinoma, lower body mass index, presence of LSMM, lower triglyceride value, poorer renal function, and higher des-γ-carboxy prothrombin value were found to be significant adverse predictors linked to overall survival, while presence of PEM tended to be significant. In the time-dependent ROC analysis, all area under the ROCs for survival in LSMM at each time point were higher than those in PEM except for Child-Pugh B patients.In this comparison of LSMM and PEM on clinical outcomes in LC patients, it was shown that LSMM may have stronger prognostic impact than PEM.

We created a predictive model using serum-based biomarkers for advanced fibrosis (F3 or more) in patients with chronic hepatitis B (CHB) and to confirm the accuracy in an independent cohort. A total of 249 CHB patients were analyzed. To achieve our study aim, a training group (n = 125) and a validation group (n = 124) were formed. In the training group, parameters related to the presence of advanced fibrosis in univariate and multivariate analyses were examined, and a formula for advanced fibrosis was created. Next, we verified the applicability of the predictive model in the validation group. Multivariate analysis identified that gamma-glutamyl transpeptidase (GGT, P = 0.0343) and platelet count (P = 0.0034) were significant predictors of the presence of advanced fibrosis, while Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+-M2BP, P = 0.0741) and hyaluronic acid (P = 0.0916) tended to be significant factors. Using these 4 parameters, we created the following formula: GMPH score = −0.755 − (0.015 × GGT) − (0.268 × WFA+-M2BP) + (0.167 × platelet count) + (0.003 × hyaluronic acid). In 8 analyzed variables (WFA+-M2BP, aspartate aminotransferase-to-platelet ratio index, FIB-4 index, prothrombin time, platelet count, hyaluronic acid, Forns index, and GMPH score), GMPH score had the highest area under the receiver operating characteristic (AUROC) curve for advanced fibrosis with a value of 0.8064 in the training group and in the validation group, GMPH score also had the highest AUROC (0.7782). In all subgroup analyses of the hepatitis B virus (HBV) status (HB surface antigen quantification, HBV-DNA quantification, and HBe antigen seropositivity), GMPH score in F3 or F4 was significantly lower than that in F0 to F2. In the above mentioned 8 variables, differences between the liver fibrosis stages (F0 to F1 vs F2, F2 vs F3, F3 vs F4, F0 to F1 vs F3, F0 to F1 vs F4, and F2 vs F4) for the entire cohort (n = 249) were all significant only in GMPH score. In conclusion, the GMPH scoring system may be helpful for detecting advanced liver fibrosis in patients with CHB.

We aimed to examine the effect of Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+-M2BP) level on survival comparing with other laboratory liver fibrosis markers in hepatitis C virus (HCV)-related compensated liver cirrhosis (LC) (n = 165). For assessing prognostic performance of continuous fibrosis markers, we adapted time-dependent receiver operating characteristics (ROC) curves for clinical outcome. In time-dependent ROC analysis, annual area under the ROCs (AUROCs) were plotted. We also calculated the total sum of AUROCs in all time-points (TAAT score) in each fibrosis marker. WFA+-M2BP value ranged from 0.66 cutoff index (COI) to 19.95 COI (median value, 5.29 COI). Using ROC analysis for survival, the optimal cutoff point for WFA+-M2BP was 6.15 COI (AUROC = 0.79348, sensitivity = 80.0%, specificity = 74.78%). The cumulative five-year survival rate in patients with WFA+-M2BP ≥ 6.15 COI (n = 69) was 43.99%, while that in patients with WFA+-M2BP < 6.15 COI (n = 96) was 88.40% (p < 0.0001). In the multivariate analysis, absence of hepatocellular carcinoma (p = 0.0008), WFA+-M2BP < 6.15 COI (p = 0.0132), achievement of sustained virological response (p < 0.0001) and des-γ-carboxy prothrombin < 41 mAU/mL (p = 0.0018) were significant favorable predictors linked to survival. In time-dependent ROC analysis in all cases, WFA+-M2BP had the highest TAAT score among liver fibrosis markers. In conclusion, WFA+-M2BP can be a useful predictor in HCV-related compensated LC.

Serum hyaluronic acid (HA) is a well-established marker of fibrosis in patients with chronic liver disease (CLD). However, the relationship between serum HA level and protein-energy malnutrition (PEM) in patients with CLD is an unknown. We aimed to examine the relationship between serum HA level and PEM in patients with chronic hepatitis C (CHC) compared with the relationships of other serum markers of fibrosis. A total of 298 CHC subjects were analyzed. We defined patients with serum albumin level of ≤3.5 g/dL and nonprotein respiratory quotient

Nonalcoholic fatty liver disease has been suggested to be associated with alanine aminotransferase (ALT) elevation in hepatitis B virus (HBV)-infected patients with HBe antigen (HBeAg)-negativity and a low HBV-DNA level. However, few studies have evaluated the association according to histological findings of the liver. Among a total of 198 HBV-infected patients who received a percutaneous liver biopsy, we studied the histological and laboratory findings of HBeAg-negative patients without receiving nucleoside/nucleotide analogues treatment (N = 70) in order to evaluate whether hepatic steatosis and its related metabolic disorders were associated with an elevation in ALT levels in HBeAg-negative patients. In HBeAg-negative patients with a high serum HBV-DNA level (≥2000 IU/mL), the level of HBV-DNA was the only significant factor related to ALT elevation. However, in HBeAg-negative patients with a low HBV-DNA level, the serum ferritin level, and histologically observed hepatic steatosis were significantly associated factors with ALT elevation. When we evaluated 2 metabolic variables (serum ferritin and fasting insulin) that are suggested to be relevant to the presence of progressive disease in Japanese patients, we found that the rate of metabolic disorders was significantly higher among patients with a high ALT level and a low HBV-DNA level than it was among those with other conditions. The triglyceride level and the frequency of moderate or severe hepatic steatosis were significantly higher in patients with a low HBV-DNA level than in those with a high HBV-DNA level. Histologically proven hepatic steatosis and its related metabolic disorders are suggested to be involved in the elevation of aminotransferases of HBeAg-negative patients, particularly those with low HBV-DNA levels.

This study aimed to establish a new scoring system that combined several risk factors, including virtual touch quantification (VTQ) values and fasting plasma glucose (FPG) levels, for predicting the development of hepatocellular carcinoma (HCC) in patients with chronic liver disease. A total of 1808 chronic liver disease patients who underwent VTQ measurement were analyzed. Risk factors for developing HCC were selected by multivariate Cox proportional hazards models. VTQ (>1.33 m/s), FPG (≥110 mg/dl), sex (male), age (≥55 years), and α-fetoprotein (AFP) level (≥5 ng/ml) were independently selected as risk factors for HCC development by multivariate analysis. Using these parameters, we established a new scoring system (0 to 5 points), based on VTQ, FPG, sex, age, and AFP level, named VFMAP. As compared with the low VFMAP score group (0 or 1 point), the hazard ratio for the incidence of HCC was 17.37 [95 % confidence interval (CI), 2.35–128.40] in the intermediate-score group (2 or 3 points) and 66.82 (95 % CI, 9.01–495.80) in the high-score group (4 or 5 points). The area under the receiver operating characteristic curve of the VFMAP score for predicting HCC development within 5 years was 0.82 (95 % CI, 0.76–0.87), indicating a moderate diagnostic value. A VFMAP cutoff value of 3 excluded HCC within 5 years with a high negative predictive value (98.2 %). The VFMAP score accurately predicted HCC in patients with chronic liver disease.

The aims of the present study were to examine the relationship between serum B-cell activating factor belonging to the tumor necrosis factor family (BAFF) levels and serum interferon-γ-inducible protein-10 (IP-10) levels in patients with autoimmune hepatitis (AIH). A total of 80 corticosteroid therapy naive AIH patients were analyzed in this analysis. First, we examined the relationship between pretreatment serum BAFF and IP-10 levels and liver histological findings. Next, we investigated the relationship of pretreatment serum BAFF and IP-10 levels and aspartate aminotransferase value (AST), alanine aminotransferase value, and serum Immunoglobulin G (IgG) level as serum liver inflammation markers. Our study included 14 men and 66 women with the median (range) age of 64 (21–83) years. The serum BAFF levels ranged from 122.5 to 7696.0 pg/mL (median value, 1417.8 pg/mL), whereas the serum IP-10 levels ranged from 142.0 to 4198.7 pg/mL (median value, 640.1 pg/mL). The serum BAFF levels were significantly stratified in each 2 liver inflammation stage. Similarly, the serum IP-10 levels were significantly stratified in each 2 liver inflammation stage. Among 3 serum inflammation markers, AST value had the highest rs value in terms of the relationship with BAFF level (rs = 0.511, P

Aim Sonazoid is a new contrast agent for ultrasonography (US). Contrast-enhanced ultrasonography (CEUS) using Sonazoid enables Kupffer imaging, which improves the sensitivity of hepatocellular carcinoma (HCC) detection. However, there are no studies on the cost-effectiveness of HCC surveillance using Sonazoid. Methods We constructed a Markov model simulating the natural history of HCV-related liver cirrhosis (LC) patients, and compared three strategies (no surveillance, US surveillance and CEUS surveillance). The transition probability and cost data were obtained from published data. The simulation and analysis were performed using TreeAge pro 2009 software. Results When compared to the no surveillance group, the US and CEUS surveillance groups increased the life expectancy by 1.67 and 1.99 quality-adjusted life-years (QALY), respectively, and the incremental cost effectiveness ratio (ICER) were 17 296 $US/QALY and 18 384 $US/QALY, respectively. These results were both less than the commonly-accepted threshold of $US 50 000/QALY. Even if the CEUS surveillance group was compared with the US surveillance group, the ICER was $US 24 250 and thus cost-effective. Sensitivity analysis showed that the annual incidence of HCC and CEUS sensitivity were two critical parameters. However, when the annual incidence of HCC is more than 2% and/or the CEUS sensitivity is more than 80%, the ICER was also cost-effective. Conclusions Contrast-enhanced ultrasonography surveillance for HCC is a cost-effective strategy for LC patients and gains their longest additional life years, with similar degree of ICER in the US surveillance group. CEUS surveillance using Sonazoid is expected to be used not only in Japan, but also world-wide.

Background & Aims Despite the importance of identifying the causative pathogen(s), ascitic fluid cultures are occasionally negative in patients with spontaneous bacterial peritonitis (SBP). A novel strategy using the in situ hybridization (ISH) method was introduced to detect the bacterial genomic DNA phagocytized in the blood of patients with sepsis. In the present study, we developed a new ISH probe to detect global bacterial DNA (named as GB probe) and evaluated its utility for detecting the phagocytized bacterial DNA in SBP ascites. Methods Hybridization of bacterial DNA with the GB probe was examined by dot-blot and ISH tests. In addition, the utility of the ISH method to detect the bacterial DNA in the leukocytes of SBP ascites was evaluated. Results The GB probe hybridized with the genomic DNA of all 59 bacterial strains tested (59 species of 36 genus). Eleven of 51 patients with ascites (out of total 542 cirrhotic inpatients) were categorized as SBP. The ISH tests showed positive results in 10 of 11 SBP cases. However, the ISH tests all showed negative results in the 40 non-SBP ascitic samples. Therefore, the ISH tests yielded highly sensitive and specific results for detecting the phagocytized bacterial DNA in the leukocytes of SBP ascites. Moreover, all of the ISH test results were obtained within only one day. Conclusions Our newly established ISH method was found to provide both a rapid and sensitive detection of bacterial DNA in SBP ascites, thus suggesting its utility for providing early and direct evidence of bacterial infection in SBP ascites.

Aims: To investigate the relationship between extracellular water to total body water ratio (ECW/TBW) in bioimpedance analysis (BIA) and clinical parameters in hepatitis viruses related to liver diseases. Methods: ECW/TBW was compared in patients with hepatitis B virus (HBV, n = 85) and hepatitis C virus (HCV, n = 440) related liver diseases. We also examined factors linked to mild to severe overhydrated state (ECW/TBW &ge, 0.4). Results: The median ECW/TBW in the HCV group was 0.388 (range, 0.365&ndash, 0.433), while that in the HBV group was 0.381 (range, 0.363&ndash, 0.425) (p &lt, 0.0001). In all cases (n = 525), for predicting F3 or more, ECW/TBW yielded the area under the receiver operating characteristics (AUROC, 0.74912) and for predicting F4, ECW/TBW yielded the AUROC (0.75517). Multivariate analysis showed that age, prothrombin time, serum albumin, and alanine aminotransferase were significant factors linked to ECW/TBW &ge, 0.4. In patients with FIB-4 index &lt, 2, ECW/TBW in the HCV group was significantly higher than that in the HBV group (p = 0.0188), while in patients with 2 &le, FIB-4 index &lt, 4 and FIB-4 index &ge, 4, the difference in the two groups did not reach significance. Conclusion: ECW/TBW can be different according to hepatitis viruses. Overhydrated status can easily occur in the HCV group even in the non-LC status compared with the HBV group.

Introduction and purposeSarcopenia is defined as a decrease in muscle mass and muscle strength, and it has been demonstrated to be an adverse predictor in numerous types of cancers. Exercise therapy (ET) carries multiple health benefits in several diseases. Despite these clinical benefits, there are limited data available regarding patients with pancreatic cancer (PC) undergoing ET. We aim to prospectively examine the effect of ET on sarcopenia in patients with PC.Methods and analysisAll clinical stages of PC can be included. When registering study subjects, a precise evaluation of the nutritional status and the daily physical activities performed will be undertaken individually, for each participant. Study participants will be randomly allocated into two groups: (1) the ET and standard therapy group and (2) the standard therapy group. Amelioration of sarcopenia at 3 months postrandomisation will be the primary endpoint. Muscle mass will be calculated using bioimpedance analysis. Sarcopenia will be defined based on the current Asian guidelines. Participants will be instructed to perform exercises with>3 metabolic equivalents (mets; energy consumption in physical activities/resting metabolic rate) for 60 min/day and to perform exercises with>23 mets/week. In the ET group, physical activities equal to or greater than walking for 60 min/day will be strongly recommended.Ethics and disseminationThe Institutional Review Board at Hyogo College of Medicine has approved this study protocol (approval no. 2772). The final data will be publicly announced. A report releasing the study results will be submitted for publication.Trial registration numberUMIN000029271; Pre-results.

Aim: Vitamin K2 has been reported to inhibit the growth of human hepatocellular carcinoma (HCC) in vitro and suppress hepatocarcinogenesis in vivo. However, its inhibitory mechanism has not yet been clarified. Methods: Different concentrations of vitamin K2 (30, 10, 1, 0.1 and 0.01 μM) were added to the HCC cell line HepG2 to assess effects on cell growth. The effect of vitamin K2 on cell cycle progression was determined by flow-cytometric analysis. The expression of cell cycle regulatory proteins p21 and p27 was then examined by Western blot. Whether vitamin K2 regulates the gene expression through action on the p21 promoter region was investigated by luciferase assay. Results: Vitamin K2 inhibited the growth of HepG2 cells dose-dependently, and its inhibitory rate reached approximately 50% at the dose of 30 μM after 96 h treatment. After treatment with vitamin K2, the proportion of cells in G0–G1 phase increased, and in S phase decreased. Apoptotic cells were not detected. The expression of cell cycle regulatory protein p21 was induced by vitamin K2 treatment, but p27 was not. By the luciferase assay, vitamin K2 significantly activated the promoter of p21. Knock-down of p21 by siRNA reversed the growth inhibition of HepG2 cells by vitamin K2. Conclusions: The findings suggest that vitamin K2 suppresses the proliferation of HCC cells by blocking the cell cycle G1/S progression through the transcriptional induction of p21.

Background: In patients with chronic liver diseases (CLDs), hepatitis C virus (HCV) infection in particular may cause various metabolic disorders. We previously reported that the value of the ratio of branched-chain amino acids to tyrosine (BTR) decreased with the progression of liver fibrosis. Objectives: We investigated the changes in clinical variables during interferon (IFN) treatment and assessed whether HCV eradication improved the amino acid imbalance in HCV infected patients. Patients and Methods: We retrospectively collected the clinical data of HCV-related CLD patients whose BTR values had been measured both pre- and post-IFN treatment. A total of 17 patients with a sustained viral response (SVR) (mean observational period: 1085.0 days) and 19 patients without an SVR (Non-SVR) (mean observational period: 1002.5 days) were studied. Results: In patients with an SVR, the serum levels of aminotransferases were decreased after HCV eradication. Although general liver functional tests (albumin and total bilirubin) did not significantly change, the BTR values significantly increased. However, in patients without an SVR, an improvement in the BTR value was not observed after IFN treatment. Conclusions: HCV eradication can improve the amino acid imbalance in HCV infected patients.

This study aimed to compare the severity of sleep problems between chronic hepatitis C (CHC) patients treated with interferon (IFN)-based triple therapy (pegylated [Peg]-IFN plus ribavirin [RBV] plus simeprevir [SMV]) and those who received IFN-free direct-acting antiviral (DAA) therapy.Our study included 31 patients in group A (Peg-IFN/RBV/SMV combination therapy) and 41 patients in the group B (IFN-free DAA therapy). We prospectively compared the effect of each antiviral treatment regimen on sleep conditions between the two groups adding actigraphy data. Five parameters detected by actigraphy (objective assessment) and scores of the Pittsburgh Sleep Quality Index (subjective assessment, n = 30 [group A] and 35 [group B]) were estimated. The causal effect of each therapy on sleep disturbances was evaluated at baseline and at 4 weeks after commencement of therapy.In terms of baseline characteristics, no significant differences between groups were found, except for hepatitis C virus genotype. In group A, sustained virological response 12 rate was 83.9% (26/31), whereas in group B it was 95.1% (39/41). In group A, each score of waking after sleep onset, activity index, wake episodes, and Pittsburgh Sleep Quality Index at 4 weeks significantly increased compared to those evaluated at baseline. In group B, scores of all variables except for sleep episodes at 4 weeks did not significantly change compared to those at baseline.Interferon-based triple therapy in patients with CHC may cause significant sleep disturbances. Interferon-free DAA therapy is less likely to deteriorate sleep conditions in patients with CHC.

Hepatoma-derived growth factor (HDGF) is a growth factor of various malignant diseases. However, the in vivo effects of HDGF suppression targeting for hepatocellular carcinoma (HCC) have not been clarified to date.We stably transfected HDGF shRNA into SK-HEP-1 human HCC cells and investigated the effects of HDGF reduction on HCC growth using a cell proliferation assay and a murine xenograft model. The effects of HDGF reduction on VEGF expression and in vivo angiogenesis were also investigated with real-time PCR and immunostaining analyses, respectively.HDGF reduction resulted in a decreased proliferative activity of SK-HEP-1 cells both in vitro and in vivo. The in vivo anti-tumor effects of HDGF were particularly higher than that expected in vitro. HDGF-reduction suppressed VEGF expression in SK-HEP-1 cells and in vivo angiogenesis of developed tumors.These findings suggest that targeted inhibition of HDGF may be a novel anti-HCC therapy.

To examine the relationship between serum Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFAA total of 189 treatment naïve-CHB patients were analyzed. We examined the effect of pretreatment serum WFAThe WFAThe WFA

Background. In hepatitis B virus- (HBV-) positive patients, the relationship between the metabolic variables and histological degree of liver fibrosis has been poorly investigated. Methods. A total of 176 HBV-positive patients were assessed in whom the ratios of glycated albumin-to-glycated hemoglobin (GA/HbA1c) were calculated in order to investigate the relationship with the degree of liver fibrosis. Results. The GA/HbA1c ratio increased in association with the severity of fibrosis (METAVIR scores: F0-1: 2.61 ± 0.24, F2: 2.65 ± 0.24, F3: 2.74 ± 0.38, and F4: 2.91 ± 0.63). The GA/HbA1c ratios were inversely correlated with four variables of liver function: the prothrombin time (PT) percentage (P0.0001), platelet count (P0.0001), albumin value (P0.0001), and cholinesterase value (P0.0001). The GA/HbA1c ratio was positively correlated with two well-known markers of liver fibrosis, FIB-4 (P0.0001) and the AST-to-platelet ratio index (APRI) (P0.0001). Furthermore, the GA/HbA1c showed better correlations with two variables of liver function (PT percentage and cholinesterase value) than did FIB-4 and with all four variables than did the APRI. Conclusion. The GA/HbA1c ratio is associated with the degree of liver fibrosis in HBV-positive patients.

To examine the impact of pretreatment Wisteria floribunda agglutinin positive Mac-2-binding protein (WFAA total of 57 patients were analyzed. All subjects were initially treated with NUC. We examined the impact of pretreatment WFAThere were 36 men and 21 women (median age, 39 years). The WFAPretreatment WFA

To examine the relationship between the Wisteria floribunda agglutinin positive Mac-2-binding protein (WFAA total of 134 NASH patients (mean age, 51.7 years) were analyzed. We examined the effect of WFAThe WFASerum WFA

We aimed to examine the relationship between the Wisteria floribunda agglutinin positive Mac-2-binding protein (WFA(+) -M2BP) level and high-sensitivity C-reactive protein (hCRP) concentration and liver histological findings for patients with autoimmune hepatitis (AIH).A total of 84 AIH patients (median age, 64 years) were analyzed. We examined the effect of pretreatment WFA(+) -M2BP level and hCRP concentration on histological findings of liver fibrosis and liver inflammation activity comparing with other laboratory markers. Receiver-operator curve (ROC) analysis was performed for calculating the area under the ROC (AUROC).The median WFA(+) -M2BP values in each fibrosis stage were: 1.5 cut-off index (COI) in F1, 2.1 in F2, 3.3 in F3 and 9.8 in F4 (P 0.001). The median WFA(+) -M2BP values in each liver inflammation stage were: 1.6 COI in A1, 2.5 in A2 and 5.4 in A3 (P 0.001). For predicting liver cirrhosis (F4), WFA(+) -M2BP yielded the highest AUROC (0.853). For predicting advanced liver fibrosis (F3 or F4), WFA(+) -M2BP, FIB-4 index and hyaluronic acid yielded the highest AUROC (0.747). For predicting severe liver inflammation activity (A3), WFA(+) -M2BP yielded the highest AUROC (0.739). The hCRP concentration in patients with A3 (median, 2230 ng/mL) was significantly higher than that in patients with A1 or A2 (median, 854.5 ng/mL) (P 0.01). WFA(+) -M2BP level significantly correlated with hCRP concentration (rs = 0.461, P 0.001).WFA(+) -M2BP can be a useful marker for assessing liver histological findings in AIH patients and it correlated well with hCRP concentration.

We aimed to examine the relationship between serum Wisteria floribunda agglutinin positive Mac-2-binding protein (WFA(+) -M2BP) levels and serum interferon-γ-inducible protein-10 (IP-10) levels and liver histological findings for patients with primary biliary cirrhosis (PBC) compared with other laboratory fibrotic or inflammatory parameters.A total of 57 PBC patients were analyzed. Receiver-operator curve (ROC) analysis was performed for calculating the area under the ROC (AUROC) for WFA(+) -M2BP, IP-10 and four serum fibrosis markers for the presence of liver cirrhosis (F4) or advanced fibrosis (F3 or F4). Similarly, ROC analysis of WFA(+) -M2BP, IP-10, aspartate aminotransferase and alanine aminotransferase for the presence of severe inflammation activity (A3) was performed.There were eight men and 49 women (median age, 59 years). As for histological findings, F4 was observed in five patients, F3 in 11, F2 in 17, F1 in 24 and F0 in zero, whereas A3 was observed in seven patients, A2 in 27, A1 in 19 and A0 in four. The WFA(+) -M2BP levels ranged from 0.5 cut-off index (COI) to 13.6 COI (median, 1.8), while serum IP-10 levels ranged 121.9-1835.9 pg/mL (median, 571.5). For predicting liver cirrhosis, WFA(+) -M2BP yielded the highest AUROC (0.97, P 0.01). For predicting severe liver inflammation activity (A3), WFA(+) -M2BP and serum IP-10 yielded the highest AUROC with a level of 0.87. WFA(+) -M2BP levels significantly correlated with serum IP-10 levels (rs = 0.55, P 0.0001).Serum WFA(+) -M2BP and serum IP-10 can be useful markers for predicting histological findings in PBC patients.

In this study, a design of an energy harvesting damper for low-frequency applications, such as energy harvesting from long period infrastructures, tanks and pipings, and maritime and offshore structures, is presented. In this design, the low-frequency relative motion of the damper is transformed into a high-frequency motion of a piezoelectric cantilever beam by a mechanical switching mechanism, referred to as “plucking” mechanism that couples and decouples the cantilever to the damper rod so that the input energy into the damper is converted to electric energy with high efficiency. In this paper, the energy harvesting efficiency is theoretically calculated for the harvesters with and without plucking mechanism and the optimized maximum performance is derived. Then the electrical switching circuit for the enhancement of the electromechanical conversion efficiency, referred to as “SSHI” interface is introduced. Numerical case studies suggest that the harvester with an ideally implemented parallel SSHI circuit can retrieve over 70 % energy of the maximum mechanical work input on the damper rod.Copyright © 2015 by ASME

Wireless sensor networks need energy harvesting from vibrational environment for their power supply. The conventional resonance type vibration energy harvesters, however, are not always effective for low frequency application. The purpose of this paper is to propose a high efficiency energy harvester for low frequency application by utilizing plucking and SSHI techniques, and to investigate the effects of applying those techniques in terms of the energy harvesting efficiency. First, we derived an approximate formulation of energy harvesting efficiency of the plucking device by theoretical analysis. Next, it was confirmed that the improved efficiency agreed with numerical and experimental results. Also, a parallel SSHI, a switching circuit technique to improve the performance of the harvester was introduced and examined by numerical simulations and experiments. Contrary to the simulated results in which the efficiency was improved from 13.1% to 22.6% by introducing the SSHI circuit, the efficiency obtained in the experiment was only 7.43%. This would due to the internal resistance of the inductors and photo MOS relays on the switching circuit and the simulation including this factor revealed large negative influence of it. This result suggested that the reduction of the switching resistance was significantly important to the implementation of SSHI.

The HFE, H ferritin, TFR2, and ferroportin 1 genes of a Japanese patient diagnosed as having hemochromatosis were amplified by PCR and sequenced. A novel mutation in the ferroportin 1 was found in the patient. It was located in the noncoding region of the ferroportin 1; nucleotide 117 adenine was changed to guanine, 7 nucleotides downstream the iron responsive element (IRE) region. This mutation was not found in the patient's son or daughter, or in 50 healthy individuals. It was suggested that the mutation in the ferroportin 1 may be related to hemochromatosis of this patient.

Dispersion polymerization of vinyl acetate (VAc) was studied in a mixed solvent of ethanol and water using poly(vinyl alcohol) (PVA) with a low degree of hydrolysis as a steric stabilizer. Six compositions were chosen from a homogeneous phase before the polymerization. In a composition with the highest solubility parameter, 450 nm particles with a size distribution close to monodispersity were obtained. With decreasing solubility parameters of the compositions, the particles became polydisperse. In the compositions with solubility parameter lower than 17.1, particles were not formed even at 100 % conversion. Degrees of polymerization obtained in this homogeneous phase were less than 100 and close to calculated values. With increasing solubility parameters of the system, degrees of polymerization increased but were still less than 200. Grafting of VAc onto PVA and grafted PVA were very small, indicating the presence of a competing reaction to the grafting. Copyright © 2004 Society of Chemical Industry

Aims: We aimed to examine changes in skeletal muscle mass in chronic hepatitis C (CHC) patients undergoing interferon (IFN)-free direct acting antivirals (DAAs) therapy who achieved sustained virological response (SVR). Patients and methods: A total of 69 CHC patients treated with DAAs were analyzed. We compared the changes in skeletal muscle index (SMI) using bio-impedance analysis at baseline and SMI at SVR. SMI was calculated as the sum of skeletal muscle mass in upper and lower extremities divided by height squared (cm2/m2). Further, we identified pretreatment parameters contributing to the increased SMI at SVR. Results: SMI in males at baseline ranged from 6.73 to 9.08 cm2/m2 (median, 7.65 cm2/m2), while that in females ranged from 4.45 to 7.27 cm2/m2 (median, 5.81 cm2/m2). At SVR, 36 patients (52.2%) had increased SMI as compared with baseline. In the univariate analysis, age (p = 0.0392), hyaluronic acid (p = 0.0143), and branched-chain amino acid to tyrosine ratio (BTR) (p = 0.0024) were significant pretreatment factors linked to increased SMI at SVR. In the multivariate analysis, only BTR was an independent predictor linked to the increased SMI at SVR (p = 0.0488). Conclusion: Pretreatment BTR level can be helpful for predicting increased SMI after SVR in CHC patients undergoing IFN-free DAAs therapy.

Introduction Chronic liver disease (CLD)-related pruritus manifests as cholestasis symptoms, which can cause severe itches in the whole body and significantly decrease quality of daily activities and sleep. The actigram, which documents movement by means of an accelerometer, has been demonstrated to be useful for assessing sleep quality. Nalfurafine hydrochloride, which is a selective κ-opioid receptor agonist, exerts its antipruritic efficacies through a novel mechanism. We aimed to prospectively examine the effect of nalfurafine hydrochloride on sleep quality for patients with CLD with pruritus utilising actigram. Methods and analysis This study will be a single-centre, prospective, interventional, single-arm study. Our study participants are subjects whose pruritus was confirmed to be uncontrollable by antihistamines or antiallergics within 6 months before informed consent (IC). Evaluation time points using actigram will be (1) before administration of testing drug; (2) after 1 week; (3) after 4 weeks (primary endpoint); and (4) every 4 weeks thereafter. The follow-up period will be 6 months. We will prospectively assess and compare changes in sleep quality in patients with CLD with pruritus undergoing nalfurafine hydrochloride therapy using actigram. Quantitative variables will be compared by paired t-test. Ethics and dissemination This study has received approval from the Institutional Review Board at Hyogo College of Medicine (approval no 2325). The study protocol, IC form and other documents were reviewed and approved. Final data will be publicly disseminated regardless of the results. A report releasing study results will be submitted in an appropriate journal. Trial registration number UMIN000028161; Pre-results.

Introduction and aimsThe role of capsule endoscopy (CE) in patients with liver cirrhosis (LC) has yet to be established; however, it is likely that it will remain a valuable diagnostic modality in several groups of patients with LC. The primary aims of the current prospective interventional study are to examine the prevalence for small bowel lesions and transit time of CE in the gastrointestinal tract in patients with LC with oesophageal varices (EVs) requiring endoscopic therapies.Methods and analysisThe current study will be a single-centre prospective interventional study. Our study participants are LC subjects with portal hypertension who were determined to be necessary for prophylactic endoscopic therapies for EVs. From the view point of safety, patients with gastrointestinal obstruction or fistula or those being suspected of having gastrointestinal obstruction or fistula will be excluded from our study. Patients with implanted medical devices will be also excluded. CE will be performed prior to prophylactic endoscopic therapies in the same hospitalisation and relevant images will be analysed after 8 hours by expert endoscopists. This study will continue to recruit until 50 participants.Ethics and disseminationThis study has received approval from the Institutional Review Board at Hyogo College of Medicine (approval no. 2680). The study protocol, informed assent form and other submitted files were reviewed and acknowledged. Final data will be publicly scattered regardless of the study results. A report releasing study results will be submitted for publication in a suitable journal after being finished in data collection.Trial registration numberUMIN000028433 (https://upload.umin.ac.jp/).

To the best of our knowledge, no available data with regard to changes in skeletal muscle mass for liver cirrhosis (LC) patients with esophageal varices (EVs) undergoing endoscopic therapy as a primary prophylaxis could exist. As endoscopic therapies, such as endoscopic injection sclerotherapy or endoscopic band ligation for EVs, accompany invasive procedure and patients with EVs receiving endoscopic therapies mostly rest in bed during hospitalization, clarifying these issues are clinically of importance. The purposes of this study were therefore to examine changes in skeletal muscle mass for LC patients with EVs undergoing endoscopic therapy as a primary prophylaxis and to identify pretreatment predictors which are associated with the amelioration in skeletal muscle mass. This is a subgroup analysis in our previous randomized controlled trial. A total of 51 LC patients with EVs were analyzed. Skeletal muscle mass was assessed using bioimpedance analysis (BIA). Skeletal muscle index (SMI) was defined as sum of skeletal muscle mass in body trunk and upper and lower extremities divided by height squared (cm2/m2) using data for BIA. We compared the changes in SMI at baseline and SMI at Day 50 after endoscopic treatment for EVs. Our study cohort included 33 males and 18 females with median (range) age of 62 (29–81) years. There were 31 patients with Child–Pugh A and 20 with Child–Pugh B. The median SMI for the entire cohort at baseline was 8.96 cm2/m2 (range, 5.87–13.11 cm2/m2), while the median SMI for the entire cohort at Day 50 was 8.83 cm2/m2 (range, 5.59–12.29 cm2/m2) (P = .9995). In baseline characteristics, prealbumin (P = .0477), branched-chain amino acid to tyrosine ratio (BTR) (P = .0056), and retinol-binding protein (P = .0296) in the increased SMI group (n = 15) were significantly higher than those in the nonincreased SMI group (n = 36). Multivariate analysis for the above 3 significant factors showed that only BTR was a significant prognostic pretreatment factor linked to the presence of increased SMI (P = .0235). In conclusion, pretreatment BTR level can be helpful for predicting increased SMI after endoscopic therapy as a primary prophylaxis for LC patients with EVs.

Although the development of anti-interferon (IFN)-α neutralizing antibodies (NAbs) is likely to be a common clinical problem for patients with various diseases treated with IFN, anti-IFN-α NAb has been exceptionally considered to have no clinical significance in the treatment of chronic hepatitis C with pegylated IFN-α (Peg-IFN-α). However, we recently clarified that the presence of NAb was associated with a non-response to the Peg-IFN plus ribavirin (RBV) therapy. In this study, we used the HCV-replicon system with genotype 1b, and investigated the role of anti-IFN-α NAb in the response to telaprevir (TVR)-containing new antiviral therapy for hepatitis C virus (HCV). Anti-IFN-α NAb-positive sera specifically inhibited the anti-HCV effects of IFN-α, without any effect on the activity of IFN-β in vitro. The NAb-positive sera also inhibited the IFN-α-dependent induction of interferon-stimulated genes, MxA and OAS-1, in a dose-dependent manner. Although TVR monotherapy decreased the HCV-RNA in vitro, the HCV-RNA was increased again with the development of TVR-resistant mutations. When IFN-α was administrated with TVR, the replication of HCV was continuously suppressed for more than a month. However, in the presence of anti-IFN-α NAb-positive sera, even when IFN-α was combined with TVR, the levels of HCV-RNA exhibited a time-course similar to that with TVR monotherapy, and HCV with TVR-resistant mutations emerged. In conclusion, our findings suggest that the presence of IFN-α NAb decreases the antiviral effects of IFN-α and may be related to the development of TVR-resistant mutated viruses.

Background. In hepatitis B virus- (HBV-) positive patients, the relationship between the metabolic variables and histological degree of liver fibrosis has been poorly investigated.Methods. A total of 176 HBV-positive patients were assessed in whom the ratios of glycated albumin-to-glycated hemoglobin (GA/HbA1c) were calculated in order to investigate the relationship with the degree of liver fibrosis.Results. The GA/HbA1c ratio increased in association with the severity of fibrosis (METAVIR scores: F0-1: 2.61 ± 0.24, F2: 2.65 ± 0.24, F3: 2.74 ± 0.38, and F4: 2.91 ± 0.63). The GA/HbA1c ratios were inversely correlated with four variables of liver function: the prothrombin time (PT) percentage (P<0.0001), platelet count (P<0.0001), albumin value (P<0.0001), and cholinesterase value (P<0.0001). The GA/HbA1c ratio was positively correlated with two well-known markers of liver fibrosis, FIB-4 (P<0.0001) and the AST-to-platelet ratio index (APRI) (P<0.0001). Furthermore, the GA/HbA1c showed better correlations with two variables of liver function (PT percentage and cholinesterase value) than did FIB-4 and with all four variables than did the APRI.Conclusion. The GA/HbA1c ratio is associated with the degree of liver fibrosis in HBV-positive patients.Corrigendum to “An Increased Ratio of Glycated Albumin to HbA1c Is Associated with the Degree of Liver Fibrosis in Hepatitis B Virus-Positive Patients”

In chronic liver disease associated with hepatitis C virus (HCV), a low platelet count is a major obstacle in carrying out interferon (IFN) treatment. We used a questionnaire to clarify the extent to which splenectomy/partial splenic embolization (PSE) is performed before IFN treatment, as well as the efficacy and complications thereof.Two questionnaires were distributed to 413 medical institutes in Japan specializing in the treatment of liver diseases, and responses were obtained from 204 institutes. Furthermore, a more detailed questionnaire was completed by 10 institutes that experienced cases of death.In patients with HCV genotype 1b and a high viral load (HCV1b/High), the sustained viral response (SVR) rate was 28% for the splenectomy group and 22% for the PSE group, with no significant difference between these groups. In patients that were not HCV1b/High, the SVR rate was higher in those that underwent splenectomy (71%) compared to the PSE group (56%; P = 0.025). There were cases of death in seven of 799 splenectomy cases (0.89%) and four of 474 PSE cases (0.84%). Infectious diseases were involved in nine of 11 cases of death, with a peculiar patient background of Child-Pugh B (6/10) and an age of 60 years or greater (7/11).The application of splenectomy/PSE before IFN treatment should be avoided in patients with poor residual hepatic function and/or elderly patients. In HCV1b/High patients, splenectomy/PSE should be performed only after selecting those in which IFN treatment should be highly effective.

Introduction: Hematological complete remission (CR) is the evident prognostic factor of allogeneic hematopoietic stem cell transplantation (HSCT) in patients with Acute Myeloid Leukemia (AML). CR with incomplete blood cell count recovery (CRi) after induction therapy was identified as independent prognostic factor for inferior long-term outcomes in patients with AML achieving remission (Chen et al, JCO 2015). There is a paucity of data regarding the impact of response (CR vs. CRi) prior to allogeneic HSCT. Here we examined whether CRi provide prognostic information on the transplant outcomes. Methods: We retrospectively analyzed 73 consecutive adults with AML who received first allogeneic HSCT between 2008 and 2015. All clinical data were collected from medical records. CRi were defined CR with absolute neutrophil count < 1,000/mm3 and/or platelet count < 100,000/mm3. CR and CRi were confirmed just prior to allogeneic HSCT in bone marrow and peripheral blood. Cytogenetic risk group was assigned based on CIBMTR criteria. Chemotherapy regimens prior to allogeneic HSCT defined as follows; standard-dose (cytarabine plus anthracycline), high-dose (cytarabine at individual dose ≥ 1g/m2 with or without other drugs), low-dose (azacitidine or low dose cytarabine). Categorical and continuous variables were analyzed using Fisher's exact test and Mann-Whitney U test, respectively. Overall survival (OS) and relapse free survival (RFS) were estimated by Kaplan-Meiyer method. Cumulative incidence of relapse (CIR), non-relapse mortality (NRM), engraftment rate and cumulative infectious events were calculated using Grayfs method. Multivariate analysis was performed using the Fine-gray proportional hazard regression model for NRM and cumulative infectious events. Results: A total of 48 (66%) were in CR and 25 (34%) in CRi. The characteristics of the study population, donors and transplants stratified by blood count recovery pre-HSCT are summarized in Table 1. There were several statistically differences between patients in CR and CRi. More patients in CR had longer time from final chemotherapy to HSCT, lower HCT-CI and a higher proportion of major ABO mismatch donor. Median follow-up from allogeneic HSCT was 18 months (range, 1 to 80 months) in the patients still alive. Patients in CR and CRi had a similar 2-year OS (63% vs. 60%, p = 0.29), 2-year RFS (58% vs. 54%, p = 0.42) and 2-year CIR (30% vs. 19%, p = 0.64). 2-year NRM was significantly higher for patients in CRi (17% vs. 34%, p = 0.046) (Figure 1). Ten patients in CRi (40%) died after allogeneic HSCT. One patient died from relapse of AML. Causes of NRM were infection (n=2), veno-occlusive disease (n=3), respiratory failure (n=3) and chronic graft-versus-host disease (n=1). The median time of neutrophil engraftment was 15 days for patients in CR (range, 10 to 25 days) and 18 days for patients in CRi (range, 11 to 49 days). Engraftment rate of neutrophil for patients in CR and CRi was 96% and 92%, respectively. 2 patients in CRi died before neutrophil engraftment. Engraftment rate of neutrophil within 30 days after allogeneic HSCT was significantly lower for patients in CRi (96% vs 84%, p = 0.037). The median time of platelet engraftment was 22 days for patients in CR (range, 10 to 77 days) and 26 days for patients in CRi (range, 12 to 164 days). Engraftment rate of platelet for patients in CR and CRi was 92% and 80%, respectively. 3 patients in CRi died before platelet engraftment. Engraftment rate of platelet within 60 days after allogeneic HSCT was lower for patients in CRi (85% vs. 65%, p = 0.093). To assess the effect of delayed engraftment, we examined infectious events, including bacteria, fungus and virus, within 60 days after allogeneic HSCT. Significantly more patients in CRi had higher cumulative infectious events (46% vs. 72%, p = 0.0086) (Figure 2). There was no bleeding event within 60 days after allogeneic HSCT. Multivariate analysis demonstrated that CRi was an independent risk factor of early infection after allogeneic HSCT (hazard ratio: HR 2.65, 95% CI: 1.37-5.08, p = 0.0037) without a difference in NRM (HR 1.21, 95% CI: 0.26-5.59, p = 0.81). Conclusion: Our data, although retrospectively collected, show that incomplete blood count prior to allogeneic HSCT is a predictable marker of early infection after HSCT in patients with AML. This suggests that we need to develop prophylactic strategies for early infection after allogeneic HSCT based on risk assessments. Disclosures Maeda: Mundipharma KK: Research Funding.

Introduction: The creatinine clearance rate (Ccr) is a more accurate indicator of renal function than serum creatinine. There remains a paucity date of prognostic value of mild to severe renal impairment calculated by Ccr for patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Herein, we evaluated the transplant outcome of patients with mild to severe renal dysfunction and compared to those without renal dysfunction. Patients and methods: A total of 186 patients (118 male and 68 female; median age, 50 years; range 15-70 years) with hematological malignancies who underwent first allo-HSCT in our institution between 2008 and 2015 were retrospectively collected from medical records. Transplant outcomes were compared with regard to renal function before allo-HSCT. The threshold of renal dysfunction was 60 ml/min (Ccr < 60) calculated by Ccr. Overall survival (OS) was estimated by Kaplan-Meiyer. Engraftment rate, cumulative incidence of relapse (CIR), non-relapse mortality (NRM), acute graft-versus-host disease (aGVHD), chronic GVHD and acute kidney injury (AKI) within 100 days after alo-HSCT were calculated using Grayfs method. Factors associated with significance (p < 0.1) on univariate analyses were subjected to multivariate analysis. Multivariate analysis was performed using the Cox proportional hazards regression model for OS and Fine-gray proportional hazard regression model for NRM and CIR. Results: Among the 186 patients, renal dysfunction (Ccr < 60) was observed in 30 patients (16%) before conditioning regimen. We observed no significant difference between Ccr < 60 group and Ccr ≥ 60 group in terms of clinical characteristics including gender, HLA disparity, stem cell source, disease risk, comorbidity, performance status at allo-HSCT and GVHD prophylaxis. However, compared to Ccr ≥ 60 group, patients with Ccr < 60 group were significantly older (p = 0.0008), lower estimated GFR (p < 0.0001), higher serum creatinine (p < 0.0001), more cases diagnosed non-Hodgkin lymphoma (p = 0.0003) and more cases received reduced intensity conditioning regimen (p = 0.002). All but one patient with CCr < 60 group achieved neutrophil engraftment median 15 days (range, 9-24) after transplantation (engraftment rate 97%) and 1 patient died before engraftment. Regarding the transplantation outcome, no significant difference was observed in OS, CIR, NRM, aGVHD, cGVHD and AKI after allo-HSCT between 2 groups (Ccr < 60 vs. CCr ≥ 60; 2-year OS, 45% vs. 49%, p = 0.6, 2-year CIR, 41% vs. 30%, p = 0.3, 2-year NRM, 23% vs. 26%, p = 0.6, day-100 AKI, 57% vs. 63%, p = 0.6, Figure 1). Multivariate analysis demonstrated that Ccr < 60 before allo-HSCT was not an independent prognostic factor for OS, CIR and NRM (Table 1). To investigate the impact of mild to severe renal failure on the transplant outcome, we next explored the clinical results of 30 patients with renal failure more in detail. Of them, 13 patients (43%) had estimated GFR < 60 ml/min/1.73m2 and only 5 patients (17%) had a serum creatinine level > 1.2mg/dl. Two patients (7%) developed end-stage renal failure requiring dialysis. Eighteen patients (60%) died at a median 194.5 (range, 15-859) days after allo-HSCT. Relapse of the primary disease was the leading cause of death (n=9) and cause of NRM were infection (n=3), veno-occlusive disease (n=2), respiratory failure (n=2), cGVHD (n=1) and central nervous system complication (n=1). No patients died from renal failure. All patients with severe renal dysfunction defined as Ccr < 40ml/min (Ccr; 13.4 ml/min, 36 ml/min and 36 ml/min) died 17, 15 and 72 days after allo-HSCT, respectively. Conclusion: Our cohorts with total 186 patients underwent allo-HSCT showed that mild renal dysfunction defined as Ccr < 60 ml/min before allo-HSCT did not affect adversely for transplant outcomes. In line with previous reports, Ccr could detect renal impairment that could not identified by GFR estimated from serum creatinin. On the other hand, no patients with severe renal dysfunction could survive after allo-HSCT. To our knowledge, the current study includes the largest number of patients with Ccr < 60ml/min. However, our small experience clearly desires larger series patients for evaluating the real impact of mild to severe renal dysfunction before transplantation. Disclosures No relevant conflicts of interest to declare.

This paper treats an inverse problem for estimating the magnitude and direction of an impact force acting on a body of arbitrary shape. It is shown that three directional components of the impact force vector can be estimated from responses measured at more than three points of the body by means of deconvolution. It is pointed out that the impact force cannot always be estimated satisfactorily since the inverse problem is ill-posed and/or ill-conditioned in some situations. For improving the estimation accuracy, the singular value decomposition technique is adopted. The validity of the present method is demonstrated through an experiment in which an impact force acting on a simply supported beam is estimated from strain responses measured by strain gages.

We aimed to elucidate the incidence of protein-energy malnutrition (PEM) in patients with chronic liver disease and to identify factors linked to the presence of PEM.A total of 432 patients with chronic liver disease were analyzed in the current analysis. We defined patients with serum albumin level of ≤3.5 g/dL and nonprotein respiratory quotient (npRQ) value using indirect calorimetry less than 0.85 as those with PEM. We compared between patients with PEM and those without PEM in baseline characteristics and examined factors linked to the presence of PEM using univariate and multivariate analyses.There are 216 patients with chronic hepatitis, 123 with Child-Pugh A, 80 with Child-Pugh B, and 13 with Child-Pugh C. Six patients (2.8%) had PEM in patients with chronic hepatitis, 17 (13.8%) in patients with Child-Pugh A, 42 (52.5%) in patients with Child-Pugh B, and 10 (76.9%) in patients with Child-Pugh C (P < 0.001). Multivariate analysis revealed that Child-Pugh classification (P < 0.001), age ≥64 years (P = 0.0428), aspartate aminotransferase (AST) ≥40 IU/L (P = 0.0023), and branched-chain amino acid to tyrosine ratio (BTR) ≤5.2 (P = 0.0328) were independent predictors linked to the presence of PEM. On the basis of numbers of above risk factors (age, AST, and BTR), the proportions of patients with PEM were well stratified especially in patients with early chronic hepatitis or Child-Pugh A (n = 339, P < 0.0001), while the proportions of patients with PEM tended to be well stratified in patients with Child-Pugh B or C (n = 93, P = 0.0673).Age, AST, and BTR can be useful markers for identifying PEM especially in patients with early stage of chronic liver disease.

BACKGROUND/AIMS The development of esophageal varices depends on the progression of liver fibrosis. However, it has not yet been sufficiently clarified whether biomarkers of liver fibrosis can be used to predict the incidence of varices in cirrhotic patients with a well-maintained liver function (Child-Pugh class A). METHODOLOGY Three established markers of liver fibrosis, including AST-to-ALT ratios (AAR), FIB-4 and AST-to-platelet ratio indices (APRI), were analyzed in HCV-positive cirrhotic patients with Child-Pugh class A status, and the relationships between these markers and the risk of variceal bleeding were investigated. RESULTS The values of AAR and FIB-4 in the patient with varices with a high risk of hemorrhage were significantly higher than those in the patients without high-risk varices, whereas the value of APRI was not found to be related to the risk of variceal bleeding. Of all the parameters examined, the values of AAR were the most significantly different between the two (with or without high-risk varices) groups. In addition, the values of AAR increased in line with variceal severity. CONCLUSIONS The value of AAR is related to the severity and risk of variceal bleeding in patients with HCV-related compensated cirrhosis.

The ultrasonography contrast agent Sonazoid provides parenchyma-specific contrast imaging (Kupffer imaging) based on its accumulation in Kupffer cells. This agent also facilitates imaging of the fine vascular architecture in tumors through maximum intensity projection (MIP). We examined the clinical utility of the malignancy grading system for hepatocellular carcinoma (HCC) using a combination of 2 different contrast-enhanced ultrasonography images.We studied 121 histologically confirmed cases of HCC (well-differentiated, 45; moderately differentiated, 70; poorly differentiated, 6). The results of Kupffer imaging were classified as (1) iso-echoic pattern or (2) hypo-echoic pattern. The MIP patterns produced were classified into one of the following categories: fine, tumor vessels were not clearly visualized and only fine vessels were visualized; vascular, tumor vessels were visualized clearly; irregular, tumor vessels were thick and irregular. Based on the combined assessment of Kupffer imaging and the MIP pattern, the samples were classified into 4 grades: Grade 1 (iso-fine/vascular), Grade 2 (hypo-fine), Grade 3 (hypo-vascular), and Grade 4 (hypo-irregular).The distribution of moderately and poorly differentiated HCCs was as follows: Grade 1, 4 % (1/24); Grade 2, 52 % (15/29); Grade 3, 85 % (44/52); and Grade 4, 100 % (16/16). The grading system also predicted portal vein invasion in 72 resected HCCs: Grade 1, 0 % (0/4); Grade 2, 13 % (1/8); Grade 3, 23 % (11/48); and Grade 4, 67 % (8/12).This new malignant grading system is useful for estimation of histological differentiation and portal vein invasion of HCC.

Sonazoid is a new contrast agent for ultrasonography (US). Contrast-enhanced ultrasonography (CEUS) using Sonazoid enables Kupffer imaging, which improves the sensitivity of hepatocellular carcinoma (HCC) detection. However, there are no studies on the cost-effectiveness of HCC surveillance using Sonazoid. We constructed a Markov model simulating the natural history of HCV-related liver cirrhosis (LC) patients, and compared three strategies (no surveillance, US surveillance and CEUS surveillance). The transition probability and cost data were obtained from published data. The simulation and analysis were performed using TreeAge pro 2009 software. When compared to the no surveillance group, the US and CEUS surveillance groups increased the life expectancy by 1.67 and 1.99 quality-adjusted life-years (QALY), respectively, and the incremental cost effectiveness ratio (ICER) were 17 296 $US/QALY and 18 384 $US/QALY, respectively. These results were both less than the commonly-accepted threshold of $US 50 000/QALY. Even if the CEUS surveillance group was compared with the US surveillance group, the ICER was $US 24 250 and thus cost-effective. Sensitivity analysis showed that the annual incidence of HCC and CEUS sensitivity were two critical parameters. However, when the annual incidence of HCC is more than 2% and/or the CEUS sensitivity is more than 80%, the ICER was also cost-effective. Contrast-enhanced ultrasonography surveillance for HCC is a cost-effective strategy for LC patients and gains their longest additional life years, with similar degree of ICER in the US surveillance group. CEUS surveillance using Sonazoid is expected to be used not only in Japan, but also world-wide.

We report a case of hepatocellular carcinoma (HCC) in association with autoimmune hepatitis (AIH). In May 2003, a 66- year-old man was admitted to our hospital because of acute liver dysfunction. He was diagnosed with AIH, and his liver function was normalized by oral administration of the corticosteroid. In July 2007, when he was admitted for the treatment of bacterial pneumonia, two liver tumors (S4: ø4 cm and S2: ø1 cm) were revealed by abdominal CT scan, and the serum level of AFP was high. According to the findings of imaging diagnosis and laboratory data, the patient was diagnosed as having HCC. Since the standard invasive therapies of HCC were not accepted by the patient and his family, he was treated by oral administration of UFT-E (tegafur/uracil: 200 mg/day). Three months after the initiation of administration, CT scan showed a remarkable reduction of the tumors, and his serum AFP level was decreased to the normal range. This case shows that HCC develops in an AIH patient even if liver function is maintained in the normal range. It also suggests the clinical usefulness of UFT-E in the management of HCC given the difficulty of treatment by the standard therapies.

This study investigates the usefulness of long-term interferon (IFN) therapy following radiofrequency ablation (RFA) for HCV-associated hepatocellular carcinoma (HCC).This is a retrospective observational study. Patients underwent pegylated IFN-α/ribavirin combination therapy for 48 weeks and then were maintained on IFN-α administration on average for 68 weeks (mean total duration 116 weeks). Patients who underwent IFN monotherapy were maintained on IFN administration on average for 78 weeks.There were biases in the background factors between the IFN and non-IFN groups. Therefore, a covariate adjustment was performed using the propensity score. An analysis of 20-matched patients from each group showed the 5-year cumulative survival rate was higher in the IFN group than in the non-IFN group (100 and 76%, respectively), and the 3-year cumulative recurrence rate was significantly lower in the IFN group than in the non-IFN group (38.0 and 64.2%, respectively). In 14 patients (i.e., IFN responders), the serum alanine aminotransferase (ALT) level remained normalized at 30 IU/mL or lower, regardless of disappearance of serum HCV RNA. In these patients, the cumulative recurrence rate was low, the hazard ratio was 0.158 (95% confidence interval = 0.045-0.561, P = 0.004), and the serum albumin level was retained.These results show the importance of maintaining the liver function and suggest that long-term IFN administration after RFA inhibits recurrence and contributes to an improved outcome in patients (in particular, IFN responders) who initially develop HCC.