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.

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.

Clinical implications of serum Wisteria floribunda agglutinin-positive Mac-2-binding protein in treatment-naïve chronic hepatitis B.

AIM: To examine the relationship between serum Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+ -M2BP) levels and liver histological findings for patients with treatment naïve chronic hepatitis B (CHB). METHODS: A total of 189 treatment naïve-CHB patients were analyzed. We examined the effect of pretreatment serum WFA+ -M2BP levels on histological findings compared with other laboratory markers, including aspartate aminotransferase (AST) to platelet ratio index, Fibrosis-4 index, platelet count, AST to alanine aminotransferase (ALT) ratio, and hyaluronic acid as liver fibrosis markers, and AST value, ALT value, and serum interferon-γ-inducible protein-10 level as liver inflammation markers. RESULTS: The WFA+ -M2BP value ranged from 0.3 cut-off index (COI) to 12.9 COI (median value, 1.2 COI). The degree of liver fibrosis was significantly stratified according to WFA+ -M2BP level in each group except for groups F2 and F3 and the degree of liver inflammation activity was significantly stratified according to WFA+ -M2BP level in each group. For predicting F4, WFA+ -M2BP level yielded the highest area under the receiver operating characteristic curve (AUROC) with a level of 0.87 and for predicting advanced liver fibrosis (≥F3) and significant liver fibrosis (≥F2), WFA+ -M2BP level yielded the second highest AUROCs (both, 0.77) among six fibrotic markers. For predicting severe (A3) or significant liver inflammation activity (≥A2), AUROCs of WFA+ -M2BP level were 0.78 and 0.76. CONCLUSION: The WFA+ -M2BP level can be a useful marker for assessing liver histological findings in patients with treatment-naïve CHB, although it has several limitations.

Development of a simple predictive model for decreased skeletal muscle mass in patients with compensated chronic liver disease.

AIM: To develop and validate a simple predictive model using easily obtained clinical parameters to predict decreased skeletal muscle mass (DSMM) in chronic liver disease (CLD) patients (n = 652). METHODS: Study subjects were divided into a training set (n = 326) and a validation set (n = 326). Decreased skeletal muscle mass was diagnosed based on skeletal muscle mass index measured by bioimpedance analysis. Variables significantly associated with DSMM were identified using univariate and multivariate analyses in the training set and used to construct a predictive formula. Receiver operating characteristic (ROC) curve analysis was carried out and the predictive model was validated in the validation set. Subgroup analyses were undertaken based on gender, age, or cirrhosis status of patients. RESULTS: Body mass index (BMI), age, serum albumin, and branched-chain amino acid to tyrosine ratio (BTR) were determined to be significant predictive factors for DSMM. A composite formula "BALB score" was constructed [-7.740 + (0.539 × BMI) + (-0.112 × age) + (1.358 × albumin) + (-0.264 × BTR)]. The BALB score had the best predictive characteristics among all variables in both population sets (area under the ROC curve, 0.877-0.898). Patients with DSMM were stratified into three BALB score categories (>4, 0-4, and <0). Subgroup analyses also showed that BALB scoring was predictive of DSMM irrespective of gender, age, or cirrhosis status. The BALB score significantly correlated with psoas muscle index on computed tomography (rs = 0.6083 for men; rs = 0.6814 for women). CONCLUSION: The BALB scoring system based on routinely used clinical parameters offers a convenient and non-invasive method for predicting DSMM in compensated CLD patients with high accuracy.

Prognostic significance of low skeletal muscle mass compared with protein-energy malnutrition in liver cirrhosis.

AIMS: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Proposal of a predictive model for advanced fibrosis containing Wisteria floribunda agglutinin-positive Mac-2-binding protein in chronic hepatitis C.

AIM: We aimed to construct a predictive model for advanced fibrosis containing Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+ -M2BP) level in patients with chronic hepatitis C (CHC) and to validate its accuracy in an independent cohort. METHODS: A total of 386 patients with CHC were retrospectively analyzed. For the purpose of this study, we formed a training set (n = 210) and a validation set (n = 176). In the training set, we investigated variables linked to the presence of advanced fibrosis using univariate and multivariate analyses. We constructed a formula for predicting advanced fibrosis and validated its accuracy in the validation cohort. Receiver operating characteristic curve (ROC) analysis was carried out for calculating the area under the ROC (AUROC). RESULTS: In multivariate analyses, WFA+ -M2BP (P = 0.029) and prothrombin time (PT) (P = 0.018) were found to be significant predictive factors linked to the presence of advanced fibrosis; platelet count (P = 0.098) and hyaluronic acid (P = 0.078) showed borderline statistical significance for the presence of advanced fibrosis. Using these four variables (with the initials MPPH), we constructed the following formula: MPPH score = -3.584 - (0.275 × WFA+ -M2BP) + (0.068 × platelet count) + (0.042 × PT) - (0.005 × hyaluronic acid). In the training and validation sets, MPPH score yielded the highest AUROCs (0.87 and 0.83) for predicting advanced fibrosis among eight serum liver fibrosis markers. Similarly, in the training and validation sets, MPPH score had the highest diagnostic accuracies for predicting advanced fibrosis among eight serum variables (81.4% and 74.4%). CONCLUSION: Our proposed MPPH scoring system can be useful for predicting advanced fibrosis in patients with CHC.

Impact of serum Wisteria floribunda agglutinin positive Mac-2-binding protein and serum interferon-γ-inducible protein-10 in primary biliary cirrhosis.

AIM: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Serum WFA(+) -M2BP and serum IP-10 can be useful markers for predicting histological findings in PBC patients.

Clinical significance of serum Wisteria floribunda agglutinin positive Mac-2-binding protein level and high-sensitivity C-reactive protein concentration in autoimmune hepatitis.

AIM: 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). METHODS: 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). RESULTS: 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). CONCLUSION: WFA(+) -M2BP can be a useful marker for assessing liver histological findings in AIH patients and it correlated well with hCRP concentration.

Clinical significance of serum Wisteria floribunda agglutinin positive Mac-2-binding protein level in non-alcoholic steatohepatitis.

AIM: To examine the relationship between the Wisteria floribunda agglutinin positive Mac-2-binding protein (WFA+ -M2BP) level and histological findings for patients with non-alcoholic steatohepatitis (NASH). METHODS: A total of 134 NASH patients (mean age, 51.7 years) were analyzed. We examined the effect of WFA+ -M2BP level on severity of liver fibrosis comparing with other laboratory markers, including aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio, AST to platelet ratio index (APRI), FIB-4 index, platelet count and hyaluronic acid as serum liver fibrosis markers. Receiver-operator curve (ROC) analysis was performed for calculating the area under the ROC (AUROC). RESULTS: The WFA+ -M2B P-value ranged from 0.2 cut-off index (COI) to 9.6 COI (median, 0.9). The median values in each fibrosis stage were: 0.7 COI in F1, 0.7 COI in F2, 1.2 COI in F3 and 2.4 COI in F4 (P < 0.001). For predicting liver cirrhosis (F4), WFA+ -M2BP level had the AUROC of 0.854 (sensitivity, 69.2%; specificity, 88.4%) and for predicting advanced liver fibrosis (≥F3), WFA+ -M2BP level yielded the second highest AUROC with a level of 0.842 (sensitivity, 73.7%; specificity, 80.2%) and for predicting significant liver fibrosis (≥F2), WFA+ -M2BP level yielded the highest AUROC with a level of 0.663 (sensitivity, 47.2%; specificity, 78.6%) among six liver fibrosis markers. The median values in patients with ballooning scores 1 (n = 58) and 2 (n = 76) were 0.6 and 1.1 COI, respectively (P < 0.001). CONCLUSION: Serum WFA+ -M2BP level can be useful for assessing liver histological findings in patients with NASH.

Comparison of sleep disorders in chronic hepatitis C patients treated with interferon-based therapy and direct acting antivirals using actigraphy.

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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Clinical implication of serum Wisteria floribunda agglutinin positive Mac-2-binding protein level on hepatitis B e-antigen loss or seroconversion in hepatitis B e-antigen positive patients.

AIM: To examine the impact of pretreatment Wisteria floribunda agglutinin positive Mac-2-binding protein (WFA+ -M2BP) level on hepatitis B e-antigen (HBeAg) loss or HBeAg seroconversion (SC) for patients with nucleoside/nucleotide analog (NUC) therapy naive HBeAg positive chronic hepatitis B (CHB). METHODS: A total of 57 patients were analyzed. All subjects were initially treated with NUC. We examined the impact of pretreatment WFA+ -M2BP level on HBeAg loss and HBeAg SC using univariate and multivariate analyses. RESULTS: There were 36 men and 21 women (median age, 39 years). The WFA+ -M2BP cut-off index (COI) level ranged 0.43-12.9 (median, 1.55). WFA+ -M2BP level in patients with F3 or F4 was significantly higher than that with F0-F2. WFA+ -M2BP level in patients with A2 or 3 was significantly higher than that with A0 or 1. For all cases, the 1- and 3-year cumulative HBeAg loss rates were 10.5% and 34.4% and the corresponding cumulative HBeAg SC rates were 8.8% and 29.0%, respectively. In the multivariate analysis, in terms of HBeAg loss, pretreatment HBV DNA of 5 log copies/mL or more and pretreatment WFA+ -M2BP level of more than 1.55 COI tended to be significant factors linked to loss of HBeAg, while in terms of HBeAg SC, pretreatment HBV DNA of 5 log copies/mL or more was an independent predictor and pretreatment WFA+ -M2BP level of more than 1.55 COI tended to be a significant factor. CONCLUSION: Pretreatment WFA+ -M2BP level may be a useful predictor for HBeAg loss or SC after NUC therapy for patients with HBeAg positive CHB.

Impact of Wisteria floribunda Agglutinin-Positive Mac-2-Binding Protein in Patients with Hepatitis C Virus-Related Compensated Liver Cirrhosis.

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.

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.

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.

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.

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.

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.