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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

AIM We sought to create a prediction model for intrahepatic covalently closed circular DNA (IH-cccDNA) level in chronic hepatitis B (CHB) patients and to validate the model's predictive accuracy. METHODS Patients who did not receive previous nucleoside analogue (NA) therapy were assigned to the training cohort (n = 57), and those who received previous NA therapy were assigned to the validation cohort (n = 69). Factors linked to IH-cccDNA levels in the training cohort were analyzed and a formula to predict IH-cccDNA levels was constructed. Next, the reproducibility of that formula was assessed. RESULTS In the multivariate analysis for the prediction of IH-cccDNA level in the training cohort, fasting blood sugar (FBS) (P = 0.0227), hepatitis B e antigen (HBeAg) (P = 0.0067) and log10 (HB surface antigen [HBsAg]) (P = 0.0497) were significant, whereas HB core-related antigen (HBcrAg) tended to be significant (P = 0.0562). The formula was constructed and named the FBS-cres score based on the variables used (FBS, HBcrAg, HBeAg, and HBsAg). The FBS-cres score was calculated as: 3.1686 - (0.0148 × FBS) + (0.1982 × HBcrAg) + (0.0008168 × HBeAg) + (0.1761 × log10 (HBsAg)). In the training cohort, a significant correlation was noted between HBcrAg and IH-cccDNA levels (P

Aims 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). DSMM 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 performed and the predictive model was validated in the validation set. Subgroup analyses were performed 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)]. 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

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.

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.

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.

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 naive chronic hepatitis B (CHB). Methods A total of 189 treatment naive-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-naive CHB, although it has several limitations.

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.

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

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

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