Noriko Ishii

Elevated serum myostatin level is associated with worse survival in patients with liver cirrhosis

We aimed to elucidate the relationship between serum myostatin levels and other markers including skeletal muscle mass and to investigate the influence of serum myostatin levels on survival for patients with liver cirrhosis (LC).

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.

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

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).

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.

Effect of psoas muscle mass after endoscopic therapy for patients with esophageal varices

Abstract We aimed to investigate the impact of decrease of muscle mass on survival after eradication of esophageal varices (EVs) treated by endoscopic therapies as a primary prophylaxis in patients with liver cirrhosis (LC). In all, 177 LC individuals with EVs undergoing endoscopic therapies were analyzed. We retrospectively examined the impact of muscle mass decrease as determined by psoas muscle mass (PMM) at the third lumber on computed tomography (depletion of PMM [DPMM]) on survival as compared with serum sodium combined Model for End-stage Liver Disease (MELD-Na). In comparison of the effects of these parameters, we used time-dependent receiver-operating characteristics (ROC) analysis. We also investigated parameters related to overall survival in the univariate and multivariate analyses. This study included 116 males and 61 females with a median age of 66 years. The median follow-up periods were 2.7 years (range 0.1–9.6 years). In all, 110 patients (62.1%) had DPMM. The median MELD-Na score was 7.200 (range −3.451 to 30.558). The MELD-Na score in patients with DPMM (median 7.685) was significantly higher than that in patients without DPMM (median 6.235) (P = .0212). In the multivariate analysis, presence of hepatocellular carcinoma (P < .0001), presence of DPMM (P < .0001), and MELD-Na ≥7.2 (P = .0438) were revealed to be significant predictors related to overall survival. In time-dependent ROC analyses, all area under the ROCs for DPMM in each time point were higher than those for MELD-Na in the entire cohort and in patients without hepatocellular carcinoma at baseline (n = 133). In conclusion, for LC patients treated by endoscopic therapies for EVs, DPMM had stronger prognostic impact than MELD-Na.

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

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).

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.

Impact of Virtual Touch Quantification in Acoustic Radiation Force Impulse for Skeletal Muscle Mass Loss in Chronic Liver Diseases

Background and aims: We sought to clarify the relationship between virtual touch quantification (VTQ) in acoustic radiation force impulse and skeletal muscle mass as assessed by bio-electronic impedance analysis in patients with chronic liver diseases (CLDs, n = 468, 222 males and 246 females, median age = 62 years). Patients and methods: Decreased skeletal muscle index (D-SMI) was defined as skeletal muscle index (SMI) <7.0 kg/m2 for males and as SMI <5.7 kg/m2 for females, according to the recommendations in current Japanese guidelines. We examined the correlation between SMI and VTQ levels and investigated factors linked to D-SMI in the univariate and multivariate analyses. The area under the receiver operating curve (AUROC) for the presence of D-SMI was also calculated. Results: In patients with D-SMI, the median VTQ level was 1.64 meters/second (m/s) (range, 0.93–4.32 m/s), while in patients without D-SMI, the median VTQ level was 1.11 m/s (range, 0.67–4.09 m/s) (p < 0.0001). In the multivariate analysis, higher VTQ was found to be an independent predictor linked to the presence of D-SMI (p < 0.0001). In receiver operating characteristic analysis, body mass index had the highest AUROC (0.805), followed by age (0.721) and VTQ (0.706). Conclusion: VTQ levels can be useful for predicting D-SMI in patients with CLDs.

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.