Severity of liver fibrosis using shear wave elastography is influenced by hepatic necroinflammation in chronic hepatitis patients, but not in cirrhotic patients.

AIM: Shear wave elastography (SWE) in patients with chronic liver diseases is a noninvasive useful method for the diagnosis of liver fibrosis severity, which can be an alternative to liver biopsy. However, the liver stiffness measurement using SWE can be affected by various factors including hepatic inflammation, extrahepatic cholestasis, heart failure, and underlying liver diseases. The aim of this study is to clarify the correlation between liver stiffness using SWE and hepatic necroinflammation serologically and pathologically. METHODS: A total of 843 patients with chronic liver disease who received liver biopsy were analyzed. Liver stiffness measurement using transient elastography (TE) and virtual touch quantification (VTQ) were carried out on the same day as the liver biopsy. The correlation between SWE and hepatic inflammation was analyzed serologically and pathologically. RESULTS: The liver stiffness values increased significantly with the progression of liver fibrosis and inflammation (overall p < 0.001). In patients with F0-1, F2, and F3, TE and VTQ values of A2 or A3 were significantly higher than those of A0 or A1 (p value, all <0.05), but not in patients with F4. The median alanine aminotransferase (ALT) values increased significantly with the progression of liver inflammation (p < 0.001). Moreover, TE and VTQ in patients with ALT ≥70 IU/L were significantly higher than those in patients with ALT <70 IU/L (p < 0.01), but not in patients with F4. CONCLUSION: Shear wave elastography can be affected by hepatic necroinflammation in F0-F3 fibrosis, but not in F4.

Usefulness of Attenuation Imaging with an Ultrasound Scanner for the Evaluation of Hepatic Steatosis.

We investigated the diagnostic capability of the proprietary attenuation imaging (ATI) modality found on some Canon Medical Systems Corp. ultrasound scanners to detect histologically diagnosed steatosis in 148 patients. ATI values increased significantly with increasing steatosis grade (p < 0.001). The diagnostic values (area under the receiver operating characteristic curve) of ATI for steatosis grades ≥ 1 (5%-33% of hepatocytes), ≥ 2 (33%-66% of hepatocytes) and 3 (> 66% of hepatocytes) were 0.85, 0.91 and 0.91. In addition, ATI values increased significantly with increasing steatosis grades (p = 0.002) even in obese patients (n = 41). The diagnostic values of ATI for steatosis grades ≥ 1, ≥ 2 and 3 in obese patients were 0.72, 0.72 and 0.78. Furthermore, ATI values increased significantly with increasing steatosis grade (p < 0.001) in patients with non-alcoholic fatty liver disease (NAFLD) (n = 38). The diagnostic values of ATI for steatosis grades ≥ 1, ≥ 2 and 3 in NAFLD patients were 0.77, 0.88 and 0.86. In conclusion, the ATI method showed good diagnostic capability for the detection of hepatic steatosis.

Liver fibrosis markers as assessed by ultrasound elastography and serum samples: A large comparative study in hepatitis virus B and C liver diseases.

AIM: We aimed to compare the well-established liver fibrosis (LF) markers in Japanese patients with chronic hepatitis B (CHB, n = 331) and chronic hepatitis C (CHC, n = 886) and to discuss possible causes of differences in results between CHB patients and CHC patients. METHODS: Virtual touch quantification (VTQ) in acoustic radiation force impulse, Fibrosis-4 (Fib-4) index, aspartate aminotransferase to platelet ratio index (APRI), and hyaluronic acid (HA) were compared between the two cohorts. As an additional investigation, total collagen proportional area (TCPA, %) was tested using liver pathological samples (n = 83). RESULTS: Significant LF (F2 or greater) and advanced LF (F3 or greater) were identified in 153 (46.2%) and 76 (23.0%) patients in the CHB cohort and 579 (65.3%) and 396 (44.7%) patients in the CHC cohort. The median VTQ, Fib-4 index, APRI, and HA values in the CHB cohort were 1.20 m/s, 1.36, 0.44, and 25 ng/mL; those in the CHC cohort were 1.32 m/s, 2.60, 0.74, and 65.5 ng/mL (P-values, all <0.0001). Similar tendencies were noted by F stage-based stratification. The median TCPA in the CHB cohort and the CHC cohort were 8.5% and 12.7% (P < 0.0006). The TCPA values in the CHC cohort were higher than those in the CHB cohort regardless of LF stage. CONCLUSION: Values of LF markers in CHB patients can differ from those in CHC patients even in the same LF stage. Difference in total amount of collagen fiber in CHB and CHC appears to be linked to the difference.

Comparison of liver stiffness assessment by transient elastography and shear wave elastography using six ultrasound devices.

AIM: Transient elastography (TE) is the gold standard for measurement of liver stiffness. The usefulness of shear wave elastographies (SWE) is well accepted. However, the measurement values cannot be equivalently compared because cut-off values for the diagnosis of liver fibrosis are different among those devices. We aimed to clarify correlations, to generate the regression equations between TE and SWEs, and to compare the diagnostic ability of each device to diagnose liver fibrosis. METHODS: A total of 109 patients with chronic liver disease who underwent liver biopsy and same-day evaluation of liver stiffness using six ultrasound devices were analyzed. The diagnostic ability of liver stiffness from each ultrasound device and correlations between TE and each SWE were analyzed. RESULTS: Liver stiffness measured by all six ultrasound devices increased significantly as liver fibrosis stage advanced (P < 0.001). Receiver operating characteristic (ROC) curve analysis for predicting significant fibrosis (≥F2) and cirrhosis yielded area under the ROC curve (AUROC) values based on TE of 0.830 (95% confidence interval [CI], 0.755-0.905) and 0.959 (95% CI, 0.924-0.995), respectively. The AUROCs for predicting significant fibrosis (≥F2) and cirrhosis (F4) based on SWE from all five ultrasound devices were over 0.8 and 0.9, respectively. Furthermore, the correlation coefficients between TE values and SWE values from five ultrasound devices were all over 0.8, indicating a strong relationship. CONCLUSION: Our study showed strong correlations between TE and SWEs with high correlation coefficients. The regression equations between TE and SWEs demonstrated the ability to compare the measurement values in each device equivalently.

Extracellular Water to Total Body Water Ratio in Viral Liver Diseases: A Study Using Bioimpedance Analysis.

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 ≥0.4). RESULTS: The median ECW/TBW in the HCV group was 0.388 (range, 0.365⁻0.433), while that in the HBV group was 0.381 (range, 0.363⁻0.425) (p < 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 ≥0.4. In patients with FIB-4 index <2, ECW/TBW in the HCV group was significantly higher than that in the HBV group (p = 0.0188), while in patients with 2 ≤ FIB-4 index <4 and FIB-4 index ≥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.

Amplification of bacterial genomic DNA from all ascitic fluids with a highly sensitive polymerase chain reaction.

Due to varying positive rates of polymerase chain reaction (PCR) amplification, interpretation of conventional PCR results for non­infectious ascites remains problematic. The present study developed a highly sensitive PCR protocol and investigated the positive rate of PCR for the 16S ribosomal (r)RNA gene in non­infectious ascites. Following the design of a new PCR primer pair for the 16S rRNA gene (800F and 1400R), the sequences of PCR products were analyzed and the lower limit for bacterial DNA detection evaluated. The positive rate of PCR for 16S rRNA gene in non­infectious ascites was also evaluated. PCR with the primer pair amplified the genomic DNA of 16S rRNA genes of major disease­causing bacterial strains. Additionally, PCR with this primer pair provided highly sensitive detection of bacterial genomic DNA (lower limit, 0.1 pg of template DNA). When DNA samples isolated from ascites were used, the 16S rRNA gene was amplified independently of the presence of bacterial infection. PCR products contained the genomic DNA fragments of multiple bacterial species. Bacterial genomic DNA can be amplified from all ascitic fluids using a highly sensitive PCR protocol. Careful attention is required to interpret the results based on simple amplification of 16S rRNA gene with conventional PCR.

Clinical impact of physical exercise on sleep disorder as assessed by actigram in patients with chronic pancreatitis: a study protocol for a randomised controlled trial.

INTRODUCTION: In most chronic pancreatitis (CP) cases, malabsorption, pain, and weight loss are the leading clinical symptoms, which significantly worsen the quality of life (QOL) and decreased QOL in patients with CP can cause sleep disorder. There is a growing body of evidence that recognises the favourable effects of physical exercise (PE), however, there are limited data currently available concerning patients with CP undergoing PE. Actigram is a device for gathering objective sleep/awake data in the natural sleeping surroundings over an extended time period. In this study, we will aim to prospectively investigate the effect of PE on sleep disorder as assessed by actigram in patients with CP. METHODS AND ANALYSIS: This study is a non-double-blind randomised controlled trial. Study participants will be randomised into the PE group and the control group. When registering patients, precise assessment for nutritional status and daily physical activities will be undertaken in each study patient. In the PE group, physical activities equal to or higher than walking for 60 min/day should be strongly recommended. Sleep quality using actigram will be prospectively compared in the two groups. The primary endpoint is the activity index in actigram at 12 weeks. ETHICS AND DISSEMINATION: Ethical approval for the study was granted by the Institutional Review Board at Hyogo College of Medicine (approval number 2767). Results will be presented at relevant conferences and submitted to an appropriate journal following trial closure and analysis. TRIAL REGISTRATION NUMBER: UMIN000029265 (https://upload.umin.ac.jp/); Pre-results.

Effect of exercise therapy on sarcopenia in pancreatic cancer: a study protocol for a randomised controlled trial.

INTRODUCTION AND PURPOSE: Sarcopenia 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 ANALYSIS: All 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 DISSEMINATION: The 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 NUMBER: UMIN000029271; Pre-results.

Implication of exercise interventions on sleep disturbance in patients with pancreatic cancer: a study protocol for a randomised controlled trial.

INTRODUCTION AND PURPOSE: Patients with pancreatic cancer (PC) have long been known to have high rates of depression. Depression in patients with PC can be linked to sleep disturbance. The American College of Sports Medicine notes that physical exercise is safe for most patients with cancer and physical inactivity should be avoided. However, clinical impacts of exercise interventions (EIs) on patients with PC have been poorly investigated. We aim to prospectively examine the effect of EIs on sleep disturbance in patients with PC using actigraphy, which is an objective measurement of motor activity and sleep. METHODS AND ANALYSIS: This trial is a non-double blind randomised controlled trial. Standard therapy for each patient with PC will be allowed. When registering study subjects, a thorough assessment of the nutritional status and the daily physical activities performed will be undertaken individually for each participant. Study subjects will be randomly assigned into two groups: (1) the EI and standard therapy group or (2) the standard therapy group. In the EI and standard therapy group, physical activities equal to or higher than walking for 60 min/day will be strongly recommended. The primary outcome measure is the sleep-related variable using actigraphy (activity index) at 12 weeks. ETHICS AND DISSEMINATION: The trial received approval from the Institutional Review Board at Hyogo College of Medicine (approval no. 2769). Final data will be publicly announced. A report releasing the study findings will be submitted for publication to an appropriate peer-reviewed journal. TRIAL REGISTRATION NUMBER: UMIN000029272; Pre-results.

Changes in liver stiffness and steatosis among patients with hepatitis C virus infection who received direct-acting antiviral therapy and achieved sustained virological response.

AIM: Whether direct-acting antiviral (DAA) therapy can reduce liver fibrosis and steatosis in patients with chronic hepatitis C virus (HCV) infection remains unclear. We evaluated sequential changes in liver stiffness and steatosis using transient elastography (TE) and the TE-based controlled attenuation parameter (CAP) in patients with HCV who received DAA therapy. PATIENTS AND METHODS: A total of 57 patients with HCV who received DAA therapy and achieved sustained virological response (SVR) were analyzed. Liver stiffness as evaluated with TE, steatosis as evaluated with CAP, and laboratory data were assessed before treatment (baseline), at end of treatment (EOT), 24 weeks after EOT (SVR24), and 48 weeks after EOT (SVR48). RESULTS: Alanine aminotransferase levels, corresponding to the presence of necroinflammatory activity, significantly decreased overall, with significant differences between baseline and EOT, EOT, and SVR24, and baseline and SVR48. However, alanine aminotransferase levels showed no significant changes between SVR24 and SVR48. Median (interquartile range) liver stiffness values at baseline, EOT, SVR24, and SVR48 were 8.3 (5.0-14.8), 7.4 (4.6-14.7), 5.3 (4.1-11.8), and 5.4 (4.0-13.4) kPa, respectively (baseline vs. EOT, P=0.044; EOT vs. SVR24, P=0.011; and SVR24 vs. SVR48, P=0.054). In patients with fatty liver (CAP≥236 dB/m, n=14), CAP values at baseline and SVR48 were 253 (245-278) and 229 (209-249) dB/m, respectively (P=0.020). CONCLUSION: Liver stiffness at SVR24 might reflect liver fibrosis in the patients who received DAA therapy and achieved SVR. In addition, liver steatosis reduces in the same cohort with fatty liver.

Clinical influence of exercise therapy on sarcopenia in patients with chronic pancreatitis: a study protocol for a randomised controlled trial.

INTRODUCTION AND PURPOSE: Chronic pancreatitis (CP) involves progressive inflammatory changes to the pancreas and can lead to permanent structural damage and impairment of both endocrine and exocrine functions. Current reports highlight a rise in the incidence and prevalence of CP. However, there is limited data currently available concerning patients with CP undergoing exercise therapy (ET). We aim to prospectively examine the influence of ET on sarcopenia in patients with CP. METHODS AND ANALYSIS: A detailed evaluation of the nutritional condition and the daily physical activities of each participant will be conducted prior to entering the study. Our patients will be randomly allocated to either: (1) the ET group or (2) the control group. In the ET group, our patients with CP will receive nutritional guidance once a month. The patients with CP will also 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 >23 mets/week. The primary end point will be an improvement in sarcopenia, defined as an increase in muscle mass and muscle strength, at 3 months postrandomisation. A comparison of the amelioration of sarcopenia in the two groups will be undertaken. ETHICS AND DISSEMINATION: The Institutional Review Board at Hyogo College of Medicine approved this study protocol (approval no. 2766). Final data will be publicly announced. A report releasing the study results will be submitted for publication to an appropriate journal. TRIAL REGISTRATION NUMBER: UMIN000029263; Pre-results. No patient is registered at the submission of our manuscript.

Association of the Body Mass Index with the Presence of Gastroesophageal Varices in Compensated Cirrhotic Patients with Hepatitis C Viral Infection.

Obesity is regarded as a risk factor for various benign and malignant diseases. We evaluated whether or not the body mass index (BMI) was associated with the presence of gastroesophageal varices in asymptomatic hepatitis C virus (HCV)-related compensated cirrhosis (Child-Pugh grade A status). Among a total of 794 patients of HCV-related chronic liver disease, 90 had histologically-proven cirrhosis, and 63 were classified as having compensated cirrhosis (30 had varices, and the remaining 33 did not). The values of prothrombin time (%) and platelet count were significantly lower in the patients with varices than in those without (P=0.042 and P=0.013, respectively). In addition to the abovementioned variables, the BMI was significantly higher in the patients with varices than in those without (P=0.031). In a multivariate analysis, only an increased BMI (odds ratio 1.205, 95% confidence interval 1.009-1.486, P=0.039) was independently associated with the presence of varices. In asymptomatic HCV-related compensated cirrhosis with a Child-Pugh A status, an increased BMI is suggested to be related to the presence of gastroesophageal varices.

Effect of physical exercise on sarcopaenia in patients with overt hepatic encephalopathy: a study protocol for a randomised controlled trial.

INTRODUCTION: Limited data are currently available for patients with overt hepatic encephalopathy (OHE)) receiving physical exercise (PE). The aim of the current study is to prospectively examine the effect of PE on sarcopaenia in patients with OHE. METHODS AND ANALYSIS: At the time of patient recruitment, a precise assessment for nutritional status and daily physical activities will be performed in each subject. Study participants will be randomly assigned into two groups: (1) the PE group and (2) the control group. In the PE group, we will conduct guidance to study participants once a month at the outpatient nutrition guidance room. We will also instruct them to do exercise with >3 metabolic equivalents (mets; energy consumption in physical activities/resting metabolic rate) for 60 min per day and to do exercise >23 mets per week. Improvement of sarcopaenia as defined by muscle mass and muscle strength at 3 months after the randomisation will be the primary endpoint. Sarcopaenia will be defined based on the current Japanese guidelines. We prospectively compared the improvement of sarcopaenia in the two groups. ETHICS AND DISSEMINATION: This study has received approval from the Institutional Review Board at Hyogo college of medicine (approval no. 2768). Final data will be publicly disseminated irrespective of the study results. A report releasing study results will be submitted for publication in an appropriate journal after completion of data collection. TRIAL REGISTRATION NUMBER: UMIN000029248; Pre-results. No patient is registered at the submission of our manuscript.

Effect of nalfurafine hydrochloride in patients with chronic liver disease with refractory pruritus on sleep disorders: a study protocol for single-arm, prospective, interventional study.

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.

Efficacy of capsule endoscopy in patients with cirrhosis for the diagnosis of upper gastrointestinal lesions and small bowel abnormalities: a study protocol for prospective interventional study.

INTRODUCTION AND AIMS: The 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 ANALYSIS: The 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 DISSEMINATION: This 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 NUMBER: UMIN000028433 (https://upload.umin.ac.jp/).

Effect of pretreatment psoas muscle mass on survival for patients with unresectable pancreatic cancer undergoing systemic chemotherapy.

To the best of our knowledge, there are few previous studies that have investigated the effect of decreased skeletal muscle mass (DSMM) on survival in patients with unresectable advanced pancreatic cancer (APC) who are undergoing systemic chemotherapy. Thus, the present study aimed to investigate the impact of DSMM, as determined by the psoas muscle index (PMI) following computed tomography and prior to systemic chemotherapy, on the outcomes of patients with unresectable APC (n=61). The primary endpoint used was the overall survival (OS) rate. The OS rates in the PMI-High group (exceeds the median PMI value in each gender) were retrospectively compared with those in the PMI-Low group (below the median PMI value in each gender), and factors associated with OS were investigated using univariate and multivariate analyses. The study cohort included 31 male and 30 female patients with a median age of 72 years, 13 of whom were stage IVA, and 48 were stage IVB. The median PMI in males was 4.3 cm2/m2 (range, 1.6-8.2 cm2/m2), while that in females was 2.3 cm2/m2 (range, 0.7-6.1 cm2/m2). The proportion of patients with performance status 0 in the PMI-High group was significantly high, compared with that in the PMI-Low group [83.3% (25/30) vs. 58.1% (18/31); P=0.0486]. Body mass index in the PMI-High group was significantly higher compared with that in the PMI-Low group (P=0.0154). The 1-year cumulative survival rate was 43.3% in the PMI-High group and 12.9% in the PMI-Low group (P=0.0027). Following multivariate analysis, PMI (P=0.0036), prothrombin time (P=0.0044) and carbohydrate antigen 19-9 (P=0.0451) were identified to be significant predictors of OS. In conclusion, DSMM, as determined by the PMI, could be a significant predictor of prognosis in patients with unresectable APC who are receiving systemic chemotherapy.

Predictors Associated with Increase in Skeletal Muscle Mass after Sustained Virological Response in Chronic Hepatitis C Treated with Direct Acting Antivirals.

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.

Implication of Psoas Muscle Index on Survival for Hepatocellular Carcinoma Undergoing Radiofrequency Ablation Therapy.

Aims We aimed to retrospectively examine the impact of pretreatment psoas muscle index (PMI) as determined by computed tomography on survival for treatment naïve hepatocellular carcinoma (HCC) patients who underwent percutaneous radiofrequency ablation (RFA) therapy (n=182; 111 males and 71 females with median age of 70 years). Patients and methods Optimal cut-off points of PMI in male and female were calculated by receiver operating characteristic analysis for survival. We investigated parameters associated with overall survival (OS) in the univariate and multivariate analyses. Results The median follow-up period in this study was 4.28 years. For all cases, the 5-year cumulative OS rate after initial RFA was 69.2%. The median (range) value in PMI for male was 6.03 (1.63-9.90) cm2/m2 whereas that for female was 4.06 (1.21-7.32) cm2/m2. Maximum tumor size ranged from 0.7 cm to 3.5 cm (median, 1.5cm). There were 145 patients with single nodule and 37 with multiple nodules. The optimal cut-off point for PMI was 6.31 cm2/m2 in male and 3.91 cm2/m2 in female. The 5-year cumulative OS rates were 51.5% in the decreased PMI group (n=90) and 86.5% in the non-decreased PMI group (n=92) (P<0.0001). In patients with Child-Pugh A (n=137) and Child-Pugh B or C (n=45), similar results were obtained. In the multivariate analysis, presence of decreased PMI (P<0.0001), total bilirubin ≥1.2 mg/dl (P=0.0015) and des-γ-carboxy prothrombin ≥34 mAU/ml (P=0.0089) were found to be significant adverse predictors related to OS. Conclusion PMI can be useful for predicting outcomes in HCC patients undergoing percutaneous RFA therapy.

Effect of dexmedetomidine in the prophylactic endoscopic injection sclerotherapy for oesophageal varices: a study protocol for prospective interventional study.

BACKGROUND: Dexmedetomidine (DEX) is a novel, highly selective α2-adrenoceptor agonist that elicits sedative, amnestic, sympatholytic and analgesic effects in patients. Several Japanese investigators have reported the clinical usefulness of DEX for sedation in endoscopic therapies for gastrointestinal malignancies; however, there have been limited data regarding the usefulness and safety of DEX for sedation during endoscopic procedures for oesophageal varices (OVs), such as endoscopic injection sclerotherapy (EIS). In this prospective, single-arm interventional study, we aimed to elucidate these issues. METHODS: Patients who require two or more sessions of prophylactic EIS for the treatment of OVs will be enrolled in this prospective interventional study. EIS procedures include two methods: (1) sedation during endoscopic procedures will be performed using conventional methods (pentazocine (PNZ) and midazolam (MDZ)), and (2) sedation during endoscopic procedures will be performed using PNZ, low-dose MDZ and DEX. These two methods were randomly assigned in the first and second EIS. The effect and safety of these two procedures with respect to patient sedation are to be compared with the degree of sedation evaluated using the Bispectral Index monitoring system (Aspect Medical Systems, Norwood, Massachusetts, USA). ETHICS AND DISSEMINATION: This study received approval from the Institutional Review Board at Hyogo College of Medicine (approval no. 2324). The authors are committed to publishing the study results as widely as possible in peer-reviewed journals, and to ensuring that appropriate recognition is provided to everyone who is working on this study. TRIAL REGISTRATION NUMBER: UMIN000026688; Pre-results.

Comparison of Prognostic Impact between the Child-Pugh Score and Skeletal Muscle Mass for Patients with Liver Cirrhosis.

AIMS: To investigate the influence of skeletal muscle mass index (SMI) as determined by bioimpedance analysis (BIA) (appendicular skeletal muscle mass/(height)²) on survival by comparing the Child-Pugh score in patients with liver cirrhosis (LC, n = 383, average age = 65.2 years). PATIENTS AND METHODS: In terms of comparison of the effects of SMI and other markers on survival, we used time-dependent receiver operating characteristics (ROC) analysis. RESULTS: The average SMI for male was 7.4 cm²/m² whereas that for female was 6.0 cm²/m² (p < 0.0001). As for the Child-Pugh score, five points were in the majority, both in males (51.7%, (106/205)) and females (44.9%, (80/178)). For both genders, the survival curve was well stratified according to SMI (p < 0.0001 for males and p = 0.0056 for females). In the multivariate analysis for survival, SMI and Child-Pugh scores were found to be significant both in males and females. In time-dependent ROC analyses, all area under the ROCs (AUROCs) for SMI in each time point were higher than those for Child-Pugh scores in males, while in females AUROCs for Child-Pugh scores at each time point were higher than those for SMI. CONCLUSION: SMI using BIA can be helpful for predicting outcomes, at least in male LC patients.