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Background The causal relationship between sarcopenia and depression in chronic liver disease (CLD) patients is unclear. To elucidate these issues, we aimed to investigate the impacts of muscle strength as assessed by grip strength (GS) and muscle mass as assessed by bioelectrical impedance analysis (BIA) on the progression of depression in CLD patients (n=189, 49 cirrhotic cases, and 87 males). Methods The Beck Depression Inventory-2nd edition (BDI-II) was used for the evaluation of depression. Time interval from the date of baseline BDI-II and the first confirmed date of elevation of BDI-II score was calculated in each subject. We analyzed factors associated with the elevation of BDI-II score. Results The baseline mean BDI-II score was 8.4 (median value, 7). Depression (BDI-II score >11) was found in 63 patients (33.33%). GS decline at baseline was found in 13 male patients (14.9%) and 37 female patients (36.3%). Skeletal muscle index (SMI) by BIA decline at baseline was found in 25 male patients (28.7%) and 40 female patients (39.2%). During the follow-up period, 84 patients (44.4%) had the elevation of BDIII score. For all cases, the 1-, 2- and 3-year cumulative elevation rates of BDI-II score were 39.2%, 46.6% and 54.9%. In patients with GS decline at baseline, the 1-, 2- and 3-year cumulative elevation rates of BDI-II score were 53.1%, 67.8% and 77.9%, while in patients with GS non-decline at baseline, the 1-, 2- and 3-year cumulative elevation rates of BDI-II score were 34.4%, 39.8% and 47.4% (P=0.0006). In patients with SMI decline at baseline, the 1-, 2- and 3-year cumulative elevation rates of BDI-II score were 43.5%, 50.8% and 62.1%, while in patients with SMI non-decline at baseline, the 1-, 2- and 3-year cumulative elevation rates of BDI-II score were 36.9%, 44.5% and 51.0% (P=0.2487). As per the multivariate analyses, only lower GS at baseline (P=0.0022) was identified to be a significant factor associated with the elevation of BDI-II score. Conclusions Reduced GS rather than loss of muscle mass can be independently associated with an elevated risk for the progression of depression.

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

Background/Aim: To elucidate factors associated with secular changes of grip strength (GS) in patients with chronic liver diseases (CLDs) (n=241, 102 males, median age=63 years, 87 liver cirrhosis cases). Materials and Methods: ΔGS (kg/year) was defined as [GS value (second time) – GS value (first time)]/[time interval between the first and second time]. GS loss (GSL) was defined as ΔGS

Aim To elucidate the common and different points between sarcopenia and frailty in chronic liver damage (CLD). Patients and methods Patients with both grip strength decline and skeletal muscle index decline were regarded as sarcopenia. Frailty was defined as a syndrome in which 3 or more of the following criteria were met: i) exhaustion, ii) body weight loss, iii) slow walking speed, iv) muscle weakness, and v) low physical activity. Results Sarcopenia and frailty were identified in 52 patients (15.2%) and 46 (13.5%), respectively. The prevalence of sarcopenia and frailty was well stratified according to age and the liver cirrhosis (LC) status. In the multivariate analysis, we identified significant factors for sarcopenia: i) age, ii) LC, iii) body mass index and iv) extracellular water (ECW) to total body water (TBW) ratio, while only the ECW to TBW ratio was significant for frailty. Conclusion Sarcopenia and frailty in CLD should be separately evaluated.

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 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

AIM The pathogenic process underlying the development of hepatocellular carcinoma (HCC) is not yet clear in patients with chronic hepatitis C virus who receive direct-acting antiviral therapy and achieve sustained virological response. This study investigated two risk factors for HCC in these patients; specifically, hepatic fibrosis and steatosis. METHODS A total of 355 patients in whom hepatitis C virus was eradicated by direct-acting antiviral were evaluated. Fibrosis and steatosis were assessed using transient elastography (TE) and the controlled attenuation parameter (CAP). Inverse probability weighting was applied to patient age, sex, albumin-bilirubin, α-fetoprotein, history of HCC, TE, or CAP. RESULTS The 12-, 24-, and 36-month cumulative incidence rates of HCC were 0.9%, 2.4%, and 4.1%, respectively. Univariate analysis with the Cox proportional hazards model showed that whereas a high TE value (≥10 kPa) was significantly associated with HCC development (HR 7.861, 95% CI 2.126-29.070; p = 0.002), CAP was not. Additionally, univariate analysis with the Cox proportional hazards model adjusted by inverse probability weighting showed that a high TE value was significantly associated with HCC development (HR 3.980, 95% CI, 1.036-15.290; p = 0.044), whereas CAP was not. The cumulative inverse probability weighting-adjusted incidence of HCC rates at 12, 24, and 36 months were 0.0%, 0.5%, and 1.7%, respectively, in patients with a low TE value, and 2.5%, 5.1%, and 7.6%, respectively, in those with a high TE value. CONCLUSION A high TE value was a risk factor for HCC in hepatitis C virus patients who received direct-acting antiviral therapy and achieved sustained virological response.

The aim of the study described here was to clarify the diagnostic value of the fluttering sign, a new sign that characterizes hepatic hemangiomas in gray-scale ultrasonography (US). It refers to a phenomenon in which the speckled echogenicity inside the hemangioma changes continuously and seems to be moving. A total of 172 hemangiomas diagnosed with contrast-enhanced US were evaluated. The fluttering sign was found in 123 of 172 hemangiomas (71.5%). Its prevalence was significantly higher than that of the marginal strong echo (89/172, 51.7%, p < 0.001), posterior acoustic enhancement (103/172, 59.9%, p = 0.031) and chameleon sign (100/172, 58.1%, p = 0.013). In addition, the fluttering sign was observed significantly more frequently in mixed or hypo-echoic tumors than in hyper-echoic tumors (p < 0.001), relatively large tumors (p < 0.001) and tumors that were less than 5 cm from the body surface (p = 0.015). The fluttering sign in gray-scale US has great potential to be a new complementary sign for the diagnosis of hemangioma.

Background/Aim: To elucidate the influence of calf circumference (CC) on sarcopenia in patients with chronic liver damages (CLDs, n=525, 255 men). Patients and Methods: Anthropometry parameters including arm circumference, arm muscle circumference, CC, arm muscle area, triceps skinfold thickness, waist circumference and body mass index were measured. Patients with both grip strength (GS) decline and skeletal muscle index (SMI) decline were diagnosed as sarcopenic. Results: Liver cirrhosis was identified in 103 cases (40.4%) in males and 87 cases (32.2%) in females. Sarcopenia was identified in 23 male patients (9.0%) and 38 female patients (14.1%). CC had the strong positive correlation with SMI both in male (r=0.79, p

We sought to examine the serum zinc (Zn) level and frailty in patients with chronic liver diseases (CLDs, n = 285, 107 liver cirrhosis cases, median age = 66 years). Frailty was defined as a clinical syndrome in which three or more of the following criteria were met (frailty score 3, 4, or 5): unintentional body weight loss, self-reported exhaustion, muscle weakness (grip strength: &lt, 26 kg in men and &lt, 18 kg in women), slow walking speed (&lt, 1.0 m/s), and low physical activity. Robust (frailty score 0), prefrail (frailty score 1 or 2), and frailty were found in 90 (31.6%), 157 (55.1%), and 38 (13.3%), respectively. The median serum Zn levels in patients with frailty, prefrailty, and robust were 59.7 &mu, g/dL, 72.8 &mu, g/dL, and 76.9 &mu, g/dL, respectively (p-values: frailty vs. prefrail, p &lt, 0.0001, prefrail vs. robust, p = 0.0063, frailty vs. robust, p &lt, overall p &lt, 0.0001). For all cases, variables with absolute values of correlation coefficient with frailty score (0&ndash, 5) &ge, 0.3 were age (rs = 0.3570, p &lt, 0.0001), serum albumin (rs = &minus, 0.3212, p &lt, 0.0001), extracellular water to total body water ratio using bioimpedance analysis (rs = 0.4386, p &lt, 0.0001), and serum Zn level (rs = &minus, 0.3406, p &lt, 0.0001). In conclusion, decreased serum Zn level in patients with CLDs can be closely associated with the presence of frailty.

Lifestyle changes have led to an increase in the number of patients with nonalcoholic fatty liver disease (NAFLD). However, the effects of NAFLD-associated single-nucleotide gene polymorphisms (SNPs) in HBV-infected patients have not been adequately investigated. Methods: We investigated the association of the NAFLD-related SNPs patatin-like phospholipase domain-containing protein 3 (PNPLA3, rs738409), transmembrane 6 superfamily member 2 (TM6SF2, rs58542926), 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13, rs72613567, rs6834314 and rs62305723), membrane-bound O-acyltransferase domain containing 7 (MBOAT7, rs641738) and glucokinase regulatory protein (GCKR, rs1260326) with the presence of histologically proven hepatic steatosis (HS) in HBV-infected patients (n = 224). We also investigated tolloid-like 1 (TLL1) SNP (rs17047200), which has been reported to be involved in the disease progression in Japanese NAFLD patients, and evaluated the association of HS and various SNPs with the treatment efficacy of pegylated-interferon (PEG-IFN) monotherapy following nucleotide/nucleoside (NA) treatment (NA/PEG-IFN sequential therapy, n = 64). Among NAFLD-associated SNPs evaluated, only the PNPLA3 SNP was significantly associated with the presence of hepatic steatosis in a total of 224 HBV-infected patients (P = 1.0&times, 10-4). Regarding the sequential therapy, PNPLA3 SNP and TLL1 SNP were related to the treatment efficacy, and patients without minor alleles of these SNPs showed favorable results with a high virologic response and significant reduction in their HBsAg titer. A multivariate analysis showed that HBeAg positivity (odds ratio 5.810, p = 0.016) and the absence of a risk allele in PNPLA3 and TLL1 SNPs (odds ratio 8.664, p = 0.0042) were significantly associated with treatment efficacy. The PNPLA3 SNP might be associated with the presence of HS, and the combination of the PNPLA3 and TLL1 SNPs might be related to the efficacy of PEG-IFN monotherapy following NA treatment.

We aimed to clarify the impact of the serum zinc (Zn) level grading system proposed by the Japanese society of clinical nutrition (JSCN: 80 &mu, g/dL &lt, serum Zn level &lt, 130 &mu, g/dL (type A), 60 &mu, 80 &mu, g/dL (type B), and serum Zn level &lt, 60 &mu, g/dL (type C)) in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC) on the incidence of composite hepatic events (Com-HEs) compared with Child&ndash, Pugh (C&ndash, P) classification or albumin-bilirubin (ALBI) grade. (n = 275, median age = 67 years). The Akaike information criterion (AIC) was compared among three prognostic models. Factors associated with the incidence of Com-HEs were also studied. The first incidence of any HE was confirmed in 112 patients (40.7%). The AIC value for Com-HEs by the Zn level grading system was the lowest among the three prognostic models (AIC: 301.788 in Zn level grading system, 303.372 in ALBI grade, and 333.953 in C&ndash, P classification). In the multivariate analysis, male (p = 0.0031), ALBI grade 3 (p = 0.0041), type B (p = 0.0238), type C (p = 0.0004), and persistent viremia (p &lt, 0.0001) were significant factors associated with the incidence of Com-HEs. In conclusion, the serum Zn level grading system proposed by JSCN can be helpful for estimating the incidence of Com-HEs in HCV-related LC patients.

We sought to clarify the correlation between non-protein respiratory quotient (npRQ) in indirect calorimetry and serum zinc (Zn) level in chronic liver diseases (CLDs, n = 586, 309 liver cirrhosis (LC) patients, median age = 63 years). Clinical parameters potentially linked to npRQ &lt, 0.85 (best cutoff point for the prognosis in LC patients) were also examined in receiver operating characteristic curve (ROC) analyses. The median npRQ was 0.86. The median serum Zn level was 64 &mu, g/dL. The median npRQ in patients with non-LC, Child&ndash, Pugh A, Child&ndash, Pugh B and Child&ndash, Pugh C were 0.89, 0.85, 0.83 and 0.82 (overall p &lt, 0.0001)). The median serum Zn level in patients with npRQ &lt, 0.85 (58 &mu, g/dL) was significantly lower than that in patients with npRQ &ge, 0.85 (68 &mu, g/dL) (p &lt, 0.0001). The correlation coefficient (r) between npRQ level and serum Zn level for all cases was 0.40 (p &lt, 0.0001). Similar tendencies were observed in all subgroup analyses. The highest correlation coefficient between serum Zn level and npRQ was found in patients with Child&ndash, Pugh C (n = 22, r = 0.69). In ROC analyses for npRQ &lt, 0.85, serum Zn level had the highest area under the ROC (AUC) among baseline laboratory parameters (AUC = 0.69). In conclusion, serum Zn level can be helpful for npRQ in patients with CLDs.

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

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.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).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).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.

Background 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). Methods A total of 198 LC subjects were analysed in this study. Myostatin levels were measured using stored sera. We retrospectively investigated the relationship between myostatin level and other markers, and the influence of myostatin level on overall survival (OS). Assessment of skeletal muscle mass was performed using the psoas muscle index (PMI) on computed tomography images at baseline. PMI indicates the sum of bilateral psoas muscle mass calculated by hand tracing at the lumber three level on computed tomography images divided by height squared (cm2/m2). The study cohort was divided into two groups based on the median myostatin value in each gender. Results Our study cohort included 108 male and 90 female patients with a median age of 67.5 years. The median (range) myostatin level for male patients was 3419.6 pg/mL (578.4–12897.7 pg/mL), whereas that for female patients was 2662.4 pg/mL (710.4–8782.0 pg/mL) (P = 0.0024). Median (range) serum myostatin level for Child–Pugh A patients (n = 123) was 2726.0 pg/mL (578.4–12667.2 pg/mL), whereas that for Child–Pugh B or C patients (n = 75) was 3615.2 pg/mL (663.3–12897.7 pg/mL) (P = 0.0011). For the entire cohort, the 1-, 3-, 5-, and 7-year cumulative OS rates were 93.94%, 72.71%, 50.37%, and 38.47%, respectively, in the high-myostatin group and 96.97%, 83.27%, 73.60%, and 69.95%, respectively, in the low-myostatin group (P = 0.0001). After excluding hepatocellular carcinoma patients (at baseline) from our analysis (n = 158), the 1-, 3-, 5-, and 7-year cumulative OS rates were 96.0%, 77.93%, 52.97%, and 39.08%, respectively, in the high-myostatin group and 96.39%, 87.58%, 77.63%, and 73.24%, respectively, in the low-myostatin group (P = 0.0005). Higher age (P = 0.0111) and lower PMI (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.

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

We aimed to clarify the relationship between sustained virological response (SVR) and gastroesophageal varices (GEVs) progression among hepatitis C virus (HCV)-related liver cirrhosis (LC) patients treated with interferon (IFN)-based therapies (n = 18) and direct-acting antiviral (DAA)-based therapies (n = 37), and LC patients with no SVR (n = 71) who had already developed GEVs. Factors influencing GEVs progression were also examined. During the follow-up period, GEVs progression was observed in 50 patients (39.7%). The 3-year cumulative GEVs progression rates in the DAA-SVR group, the IFN-SVR group, and the non-SVR group were 32.27%, 5.88%, and 33.76%, respectively (overall p value = 0.0108). Multivariate analysis revealed that sex (p = 0.0430), esophageal varices (EVs) F2 or more (p &lt, 0.0001), and DAA-SVR (p = 0.0126, IFN-SVR as a reference) and non-SVR (p = 0.0012, IFN-SVR as a reference) were independent predictors for GEVs progression. The proportion of GEVs progression in patients with no or F1 EVs was significantly lower than that in patients with F2 or F3 EVs (33.9% (38/112) vs. 85.7% (12/14), p = 0.0003). In conclusion, IFN-based therapies can have a favorable impact for preventing GEVs progression in HCV-related LC patients with GEVs. Clinicians should be aware of a point of no return where SVR is no longer capable of avoiding GEVs progression.

We aimed to compare the impact on survival among albumin-bilirubin (ALBI) grade, modified ALBI (mALBI) and our proposed combined ALBI grade and Mac-2 binding protein glycosylation isomer (M2BPGi) or FIB4 index grading system in chronic hepatitis C (CHC) related compensated liver cirrhosis (n = 165, 93 men and 72 women, median age = 67 years). Patients with ALBI grade 1, 2, and 3 were allocated a score of 1, 2, and 3 points, respectively. Patients with mALBI grade 1, 2A, and 2B were allocated a score of 1, 2, and 3 points, respectively. Patients with a high or low M2BPGi were allocated a score of 1 and 0 point. Patients with a high or low FIB4 index were allocated a score of 1 and 0 point. Sum of the point of ALBI (1, 2, or 3) and M2BPGi (0 or 1) or FIB4 index (0 or 1) was defined as ALBI-M2BPGi grade or ALBI-FIB4 grade. Prognostic accuracy was compared using the Akaike information criterion (AIC) value and time dependent receiver operating characteristics (ROC) curve analysis. The median follow-up duration was 5.422 years. AIC value for survival by ALBI-M2BPGi grade was the lowest among 4 prognostic models (AIC: 205.731 in ALBI grade, 200.913 in mALBI grade, 189.816 in ALBI-M2BPGi grade, and 204.671 in ALBI-FIB4 grade). All area under the ROC curves of ALBI-M2BPGi grade in each time point were higher than those of ALBI grade, mALBI grade, and ALBI-FIB4 grade. In conclusion, our proposed ALBI-M2BPGi grading system seems to be helpful for estimating prognosis in patients with CHC related compensated LC.

Currently, the Japanese society of clinical nutrition (JSCN) defines serum zinc (Zn) level &lt, 60 &mu, g/dL as Zn deficiency and 60 &mu, g/dL &le, serum Zn level &lt, 80 &mu, g/dL as subclinical Zn deficiency, and 80 &mu, 130 &mu, g/dL as normal Zn range. We aimed to elucidate the prognostic impact of this Zn classification system in patients with liver cirrhosis (LC) compared to the Child&ndash, Pugh classification and the albumin&ndash, bilirubin (ALBI) grading system (n = 441, median age = 66 years). The Akaike information criterion (AIC) with each evaluation method was tested in order to compare the overall survival (OS). The median serum Zn level was 65 &mu, g/dL. There were 56 patients with normal Zn level, 227 with subclinical Zn deficiency and 158 with Zn deficiency. OS was well stratified among three groups of serum Zn level (p &lt, 0.0001). The AIC value for survival by the Zn classification system was the lowest among three prognostic models (AIC: 518.99 in the Child&ndash, Pugh classification, 502.411 in ALBI grade and 482.762 in the Zn classification system). Multivariate analyses of factors associated with OS revealed that serum Zn classification by JSCN was an independent factor. In conclusion, the serum Zn classification proposed by JSCN appears to be helpful for estimating prognosis in LC patients.

We sought to elucidate the relationship between albumin-bilirubin (ALBI) grade and non-protein respiratory quotient (npRQ) calculated by indirect calorimetry in chronic liver disease (CLD) patients (n = 601, median age = 63 years). Factors linked to npRQ &lt, 0.85, which is reported to be an optimal cutoff point for the prognosis in liver cirrhosis (LC) patients, were also investigated using univariate and multivariate analyses. The median npRQ for all cases was 0.86. In total, 253 patients (42.1%) had npRQ &lt, 0.85. The proportions of patients with npRQ &lt, 0.85 in LC and non-LC patients were 51.9% (166/320) in LC patients and 31.0% (87/281) in non-LC patients (p &lt, 0.0001). The median npRQ in ALBI grades 1, 2, and 3 for all cases were: 0.89, 0.85, and 0.82 (overall p &lt, 0.0001). The proportions of patients with npRQ &lt, 0.85 were 31.0% (71/229) in ALBI grade 1, 46.34% (152/328) in ALBI grade 2, and 68.18% (30/44) in ALBI grade 3 (overall p &lt, 0.0001). In multivariate analyses of factors linked to npRQ &lt, 0.85, ALBI grade 3 (p = 0.0095, hazard ratio = 3.242, ALBI grade 1 as a reference) was an independent predictor along with prothrombin time (p = 0.0139). In conclusion, ALBI grade can be a useful marker for npRQ in patients with CLDs.

We sought to investigate the influence of serum zinc (Zn) concentration on sarcopenia in chronic liver diseases (CLDs, n = 372, median age = 65 years, 147 liver cirrhosis (LC) cases (39.5%)). Sarcopenia was defined by low grip strength and low skeletal muscle mass. Study subjects were divided into the following three groups (High-, Intermediate-, and Low-Zn groups) based on the baseline serum Zn level. The impacts of serum Zn concentration on sarcopenia were examined. The median (interquartile range) serum Zn concentration for all cases was 72.85 (63.7, 81.45) &mu, g/dL. The proportions of sarcopenia in the High-Zn, Intermediate-Zn, and Low-Zn groups were 10.75% (10/93), 11.23% (21/187), and 27.17% (25/92), respectively (P = 0.9046 (High vs. Intermediate), P = 0.0007 (Intermediate vs. Low), P = 0.0044 (High vs. Low), overall P value = 0.0009). The median serum Zn concentrations in patients with sarcopenia, pre-sarcopenia, and control were 66.35, 73.1 and 73.8 &mu, g/dL, respectively (P = 0.0234 (sarcopenia vs. pre-sarcopenia), P = 0.2116 (pre-sarcopenia vs. control), P = 0.0002 (sarcopenia vs. control), overall P value = 0.0016). In the multivariate analyses of factors linked to the presence of sarcopenia, Low-Zn was an independent predictor for all cases (P = 0.0236) and LC cases (P = 0.0082). In conclusion, Zn deficiency can be an independent predictor for sarcopenia in patients with CLDs.

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 (p0.001). 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 (p0.001) 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.

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.

Background: Helicobacter pylori ( H. pylori ) infection is associated with a low platelet count in patients with immune thrombocytopenic purpura (ITP). While eradication of H. pylori is an established therapy for increasing the platelet count in ITP patients, it is unclear whether or not eradication will similarly affect the platelet counts in patients with chronic liver diseases (CLDs). We herein examined the effect of H. pylori eradication on the platelet counts in hepatitis C virus (HCV)-related CLD patients. Methods: A total of 65 patients were enrolled, and the H. pylori -positive patients were treated to eradicate H. pylori . The eradication of H. pylori was assessed using a 13 C-urea breath test 4 weeks after the completion of the therapy. In addition to the general laboratory variables of HCV-infected patients, including platelet counts, the prothrombin time (PT), and liver function markers (AST, ALT, total bilirubin, alkaline phosphatase, and albumin), we also investigated the presence of splenomegaly via ultrasonography. The platelet counts were measured at 1, 3, and 6 months after the final eradication therapy in order to assess the success of H. pylori eradication. Results: Of the 65 patients with HCV-related CLD, 30 were found to be H. pylori -positive. The oral treatment regimen succeeded in eliminating H. pylori in 19 patients. These H. pylori -eradicated patients included eight males and 11 females, and 15 (78.9%) had liver cirrhosis. Regarding the patients who failed to achieve H. pylori eradication, their platelet counts did not markedly differ between pre- and post-treatment. Regarding the patients with H. pylori eradication, the platelet counts tended to increase 6 months after the treatment (9.2 ± 2.9 × 10 3 /μL vs. 10.1 ± 3.7 × 10 3 /μL, P = 0.085). We also found that the platelet count was significantly increased after the eradication in patients without splenomegaly (9.8 ± 2.8 ×10 3 /μL vs. 11.0 ± 3.7 ×10 3 /μL, P = 0.040). Regarding the seven patients whose platelet count increased by more than 20 × 10 3 /μL after anti- H. pylori treatment, most (6/7, 85.7%) did not have splenomegaly. Conclusion: H. pylori eradication may increase the platelet count in HCV-positive patients, particularly those without splenomegaly. J Clin Med Res. 2016;8(12):854-858 doi: http://dx.doi.org/10.14740/jocmr2725w

We sought to examine the relationship between frailty and health-related quality of life as evaluated using the 36-item Short-Form Health Survey (SF-36) questionnaire in Japanese chronic liver disease (CLD) patients (n = 341, 122 liver cirrhosis cases, median age = 66 years). Frailty was defined as a clinical syndrome in which three or more of the following criteria were met (frailty score 3, 4, or 5): unintentional body weight loss, self-reported exhaustion, muscle weakness (grip strength: &lt, 26 kg in men and &lt, 18 kg in women), slow walking speed (&lt, 1.0 m/s), and low physical activity. Robust (frailty score 0), prefrail (frailty score 1 or 2), and frailty were found in 108 (31.7%), 187 (54.8%), and 46 (13.5%) patients, respectively. In all eight scales of the SF-36 (physical functioning, role physical, bodily pain, general health perception, vitality, social functioning, role emotion, and mental health), and the physical component summary score and mental component summary score, each score was well stratified according to the frailty status (all p &lt, 0.0001). In the multivariate analysis, age (p = 0.0126), physical functioning (p = 0.0005), and vitality (p = 0.0246) were independent predictors linked to the presence of frailty. In conclusion, Japanese CLD patients with frailty displayed poorer conditions, both physically and mentally.

Here we sought to clarify the prognostic impact of sarcopenia-related markers (grip strength (GS), muscle mass using bioimpedance analysis and patient quality of life as assessed by the 36-Item Short-Form Health Survey (SF36)) in patients with chronic liver diseases (CLDs, n = 411, 160 liver cirrhosis patients, median age, 64 years) on the incidence of composite hepatic events (CHEs). A GS decrease was defined as &lt, 26 kg in men and &lt, 18 kg in women, while a skeletal muscle mass index (SMI) decrease was defined as &lt, 7.0 kg/m2 in men and &lt, 5.7 kg/m2 in women based on the current guidelines. The physical and metal component summary scores on the SF36 were also included into the analysis. Sixty-two patients (15.1%) had the first incidence of CHEs. The three-year cumulative incidence rates of CHEs in patients with GS decrease or non-decrease were 24.51% and 12.44% (p = 0.0057). The three-year cumulative incidence rates of CHEs in patients with an SMI decrease or non-decrease were 19.65% and 12.99% (p = 0.0982). Multivariate analysis revealed that GS decrease (p = 0.0350) and prothrombin time (p = 0.0293) were significantly associated with the incidence of CHEs. In conclusion, GS can be an independent predictor for CHE development in patients with CLDs.

Health related quality of life (HRQOL) in chronic liver disease (CLD) patients has been attracting much attention these days because it is closely associated with clinical outcomes in CLD patients. HRQOL has become established as an important concept and target for research and practice in the fields of medicine. A critique of HRQOL research is the lack of conceptual clarity and a common definition of HRQOL. Using a clear definition of HRQOL may increase the conceptual understanding. In this study, we aimed to elucidate the association between serum zinc (Zn) level and HRQOL as assessed by the Beck Depression Inventory-2nd edition (BDI-II), Pittsburgh Sleep Quality Index Japanese version (PSQI-J) and the 36-Item Short Form Health Survey (SF-36) in CLD patients (n = 322, median age = 65 years, 121 liver cirrhosis (LC) patients (37.6%)). The median serum Zn level for all cases was 73.2 μg/dl. The median BDI-II score and PSQI-J score were 6 and 5, respectively. Patients with higher BDI-II score tended to have lower serum Zn level compared with those with lower BDI-II score. Similar tendencies were observed in patients with higher PSQI-J score. In the SF-36, physical functioning, role physical and physical component summary score significantly correlated with serum Zn level regardless of age, liver disease etiology and the LC status. While mental health and mental component summary score did not significantly correlate with serum Zn level regardless of age, liver disease etiology and the LC status. In conclusion, serum Zn level can be a useful marker for decreased HRQOL in patients with CLDs, especially for physical components.

We sought to investigate the influence of sarcopenia as defined by muscle strength and skeletal muscle mass (SMM) on sleep disturbance as evaluated by the Japanese version of Pittsburgh Sleep Quality Index (PSQI-J) in chronic liver diseases (CLDs) (n = 419). Muscle strength and muscle mass were determined by grip strength (GS) and SMM using bioimpedance analysis. Patients were classified into four types: type A (n = 61), decreased GS and decreased SMM, type B (n = 45), decreased GS and non-decreased SMM, type C (n = 102), non-decreased GS and decreased SMM, and type D (n = 211), non-decreased GS and non-decreased SMM. Factors associated with PSQI-J score 6 or more were examined. PSQI-J score 0&ndash, 5 (normal) was found in 253 (60.4%), 6&ndash, 8 (mild) in 97 (23.2%), 9&ndash, 11 (moderate) in 45 (10.7%) and 12 or more (severe) in 24 (5.7%). Univariate analysis identified three factors to be significantly associated with PSQI-J score 6 or more: presence of liver cirrhosis (LC) (P = 0.0132), our classification of type A, B, C and D (P &lt, 0.0001) and serum albumin level (P = 0.0041). Multivariate analysis showed that type A (P = 0.0021) and type B (P = 0.0220) were significant independent factors. In conclusion, sarcopenia in CLDs appears to be closely associated with sleep disturbance mainly due to muscle strength decline.

We sought to examine the influence of hand grip strength (HGS) and skeletal muscle mass (SMM) on the health-related quality of life (H-QOL) as evaluated by the 36-Item Short-Form Health Survey (SF-36) questionnaire in chronic liver diseases (CLDs, 198 men and 191 women). Decreased HGS was defined as HGS &lt, 26 kg for men and &lt, 18 kg for women. Decreased SMM was defined as SMM index &lt, 7.0 kg/m2 for men and &lt, 5.7 kg/m2 for women, using bioimpedance analysis. SF-36 scores were compared between groups stratified by HGS or SMM. Between-group differences (decreased HGS vs. non-decreased HGS) in the items of physical functioning (PF), role physical (RP), bodily pain, vitality (VT), social functioning (SF), role emotional (RE), and physical component summary score (PCS) reached significance, while between-group differences (decreased SMM vs. non-decreased SMM) in the items of PF, SF and RE were significant. Multivariate analyses revealed that HGS was significantly linked to PF (p = 0.0031), RP (p = 0.0185), and PCS (p = 0.0421) in males, and PF (p = 0.0034), VT (p = 0.0150), RE (p = 0.0422), and PCS (p = 0.0191) in females. HGS had a strong influence especially in the physiological domains in SF-36 in CLDs.

Aims: To identify the relationship between the Controlling Nutrition Status (CONUT) score and clinical parameters among adults with hepatitis C virus (HCV)-related liver cirrhosis (LC) (n = 264, 141 males and 123 females). Methods: The relationship between the CONUT score and clinical variables such as Child-Pugh classification were investigated. We also examined factors linked to poor nutritional state as determined by CONUT score. Results: According to the CONUT score, normal nutritional state was found in 57 patients, mild malnutrition state in 132, moderate malnutrition state in 68 and severe malnutrition state in 7. The CONUT score ranged from 0 to 9 (median = 2) in Child-Pugh A (n = 198), 0 to 10 (median = 6) in Child-Pugh B (n = 62) and 6 to 9 (median = 7.5) in Child-Pugh C (n = 4) (overall, p &lt, 0.00001). Multivariate analysis revealed that FIB-4 index, branched-chain amino acid to tyrosine ratio and extracellular water to total body water ratio in bioimpedance analysis were significant for both CONUT score 2 or more, and 5 or more. FIB-4 index had the highest predictability for both CONUT score 2 or more and 5 or more among three parameters. Conclusion: The CONUT score well reflects liver functional reserve among adults with HCV-related LC. FIB-4 index can be useful for malnutrition.

We aimed to elucidate the relationship between serum liver fibrosis markers (Mac-2 binding protein glycosylation isomer (M2BPGi), FIB-4 index, aspartate aminotransferase to platelet ratio index and hyaluronic acid), and skeletal muscle mass and to investigate factors linked to skeletal muscle mass loss (SMML) in patients with chronic hepatitis C (CHC, n = 277, median age = 64 years). We defined patients with psoas muscle index [PMI, sum of bilateral psoas muscle mass calculated by manual trace method at the lumber 3 level on the computed tomography images divided by height squared (cm2/m2)] less than 6.36 cm2/m2 for male and 3.92 cm2/m2 for female as those with SMML based on the recommendations in current guidelines. Receiver operating curve (ROC) analysis was performed for predicting SMML in 4 liver fibrosis markers and parameters linked to SMML were also investigated in the univariate and multivariate analyses. In terms of liver fibrosis stages, F4 was observed in 115 patients, F3 in 67, F2 in 38, F1 in 53, and F0 in 4. The median (range) PMI for male and female were 6.198 (2.999–13.698) and 4.100 (1.691–7.052) cm2/m2, respectively. There were 72 male patients with SMML (55.4%) and 58 female patients with SMML (39.5%) (P = .0112). In both male and female, a significant inverse correlation between PMI and levels of liver fibrosis markers was observed in all liver fibrosis markers. ROC analyses for predicting SMML revealed that FIB-4 index had the highest area under the ROC (AUC = 0.712), followed by M2BPGi (AUC = 0.692). In the multivariate analysis of factors linked to SMML, gender (P = .0003), body mass index (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

Background. Only a few biomarkers based on metabolic parameters for evaluating liver fibrosis have been reported. The aim of this study was to investigate the relevance of an index obtained from three metabolic variables (glycated albumin: GA, glycated hemoglobin: HbA1c, and branched-chain amino acids to tyrosine ratio: BTR) to the degree of liver fibrosis in hepatitis C virus virus- (HCV-) positive patients.Methods. A total of 394 HCV-positive patients were assessed based on the values of a new index (GA/HbA1c/BTR). The index findings were used to investigate the relationship with the degree of liver fibrosis.Results. The new index showed an association with the stage of fibrosis (METAVIR scores: F0-1: 0.42 ± 0.10, F2: 0.48 ± 0.15, F3: 0.56 ± 0.22, and F4: 0.71 ± 0.30). The index was negatively correlated with three variables of liver function: the prothrombin time percentage (P<0.0001), albumin level (P<0.0001), and cholinesterase level (P<0.0001). The new index showed a higher correlation related to liver function than FIB-4 and the APRI did. In addition, the index showed a higher AUROC value than that of FIB-4 and the APRI for prediction of liver cirrhosis.Conclusion. The new metabolism-related index, GA/HbA1c/BTR value, is shown to relate to the degree of liver fibrosis in HCV-positive patients.

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.

Introduction and purposeChronic 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 analysisA 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 disseminationThe 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 numberUMIN000029263; Pre-results. No patient is registered at the submission of our manuscript.

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)

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.

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

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.

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.

The aim of this study was to examine the effect of nonprotein respiratory quotient (npRQ), as assessed using indirect calorimetry, on clinical outcomes in patients with liver cirrhosis (LC). A total of 244 LC patients were evaluated in this study. For the univariate analysis, for each continuous variable, the optimal cutoff value that maximized the sum of sensitivity and specificity was selected using receiver operating curve (ROC) analysis for survival. There were 137 men and 107 women with the median (range) age of 67 (25–90) years. Indirect calorimetry indicated that 54 patients (22.1%) had hepatocellular carcinoma (HCC) on radiological findings and 59 patients (24.2%) had protein energy malnutrition, as defined by npRQ

The relationships between the serum mineral concentrations and the endoscopic findings of esophageal varices have been poorly investigated. In this study, we investigated hepatitis virus-positive patients who had undergone a liver biopsy (n = 576) and 75 patients with compensated cirrhosis in order to evaluate the association of the zinc value with the severity of liver fibrosis and esophageal varices. The mean zinc values decreased with the progression of fibrosis (METAVIR score; F0-1: 71.3 ± 11.3, F2: 68.9 ± 11.7, F3: 66.3 ± 11.8, F4: 63.9 ± 15.0). In the hepatitis virus-related compensated cirrhosis, the mean zinc value decreased with the severity of varices (patients without varices: 66.3 ± 12.6, patients with low-risk varices: 62.5 ± 13.7, patients with high-risk varices: 55.6 ± 13.0). The zinc value was significantly lower in patients with varices than in those without varices (59.3 ± 13.6 vs 66.3 ± 12.6, p

Background The usefulness of branched-chain amino acid (BCAA) granules and BCAA-enriched nutrient mixtures for patients with liver cirrhosis is often reported. However, no randomized controlled studies have investigated the usefulness of these supplements in the nutritional intervention of cirrhotic patients receiving endoscopic treatment for esophageal varices. Methods Patients without BCAA before endoscopic treatment were divided into study 1, and those who received BCAA were divided into study 2. In study 1, 44 eligible patients were divided into a control group (n = 13), a general liquid nutrient (snack) group (n = 15), and a BCAA-enriched nutrient mixture (BCAA-EN) group (n = 16). In study 2, 48 eligible patients were divided into a BCAA group (n = 24) and a BCAA-EN group (n = 24). The nutritional status including non-protein respiratory quotient (NPRQ) levels, weight gain, and albumin were evaluated on days 0, 7, and 50. Results In study 1, the BCAA-EN group showed significant improvement in NPRQ levels on day 7 as compared with the snack group. In study 2, the BCAA-EN group showed significant improvement in NPRQ levels on day 7 and in weight levels on day 50 relative to the BCAA group, while the BCAA group showed improved serum albumin levels on day 7 compared to the BCAA-EN group. Conclusions The BCAA-enriched nutrient mixture maintained NPRQ and weight in cirrhotic patients. Our findings suggest that supplements including both BCAA and a nutritional energy supplement would be beneficial for cirrhotic patients undergoing endoscopic treatment for esophageal varices. Electronic supplementary material The online version of this article (doi:10.1007/s00535-014-0950-2) contains supplementary material, which is available to authorized users.