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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.

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 examine the relationship between longitudinal quality of life (QOL) change, as assessed by the 36-Item Short Form Health Survey (SF-36), sarcopenia-related factors and body composition in patients with chronic liver diseases (CLDs). Patients and Methods: Data from patients with CLDs (n=184) were retrospectively analyzed, focusing on factors associated with the difference of physical and mental component summary score (PCS and MCS) in SF-36 between the two visits (Δ(PCS) and Δ(MCS)). The difference of serum albumin level, body mass index (BMI), arm circumference, arm muscle circumference, grip strength (GS), skeletal muscle index, extracellular to total body water ratio between the two visits were included into the multiple regression analysis. Results: Δ(albumin) (p=0.0325) and Δ(GS) (p

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 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

BACKGROUND: Sarcopenia and body composition can be associated with mortality in chronic liver diseases (CLDs). We sought to identify predictors in CLD patients (n=631, 309 males) and create a prognostic model using easily available indexes. METHODS: Reference values for low-grip strength (GS) were 26 kg in men and 18 kg in women. Reference values for low-skeletal muscle index (SMI) were 7.0 kg/m(2) in men and 5.7 kg/m(2) in women using bioelectrical impedance analysis (BIA). Reference values for low-calf circumference (CC) were 34 cm in men and 33 cm in women. Reference values for high-waist circumference were 85 cm in men and 90 cm in women. Using significant factors in the multivariate analysis contributing to the overall survival (OS), we created a simple predictive model. Akaike information criterion (AIC) was compared. RESULTS: Men (P

AIM To elucidate the relationship between the finger-circle test (Yubi-wakka [in Japanese] test; three levels of bigger, just-fits, and smaller) and sarcopenia-related factors and anthropometric parameters in patients with chronic liver disease (n = 202, 99 men, mean age 61 years). METHODS Patients with both grip strength decline (

Background and aims: The causal relationship between sarcopenia and sleep disorder in patients with chronic liver disease (CLDs) is unclear. We aimed examine the influence of sarcopenia-related factors (grip strength (GS) and muscle mass) on the progression of sleep disorder in patients with chronic liver disease (n=182, 46 cirrhotic cases, median age=64 years). Methods: Sleep quality was evaluated by the Japanese version of Pittsburgh Sleep Quality Index (PSQI-J). PSQI-J >6 points was defined as sleep disorder. In all analyzed patients, evaluation using PSQI-J questionnaire was performed twice or more during the follow-up period. Time interval from the date of baseline PSQI-J and the first confirmed date of elevation of PSQI-J score was calculated. Our primary endpoint was the elevation of PSQI-J score compared to the baseline PSQI-J score. GS decline was diagnosed with a GS of 6 points at baseline was found in 83 patients (45.6%). In patients with GS decline (n=48), the 3-year cumulative elevation rate of PSQI-J score was 82.4%, while in patients with GS non-decline, that was 36.2% (P

We aimed to investigate the association in frailty and sleep disorder as assessed by the Japanese version of Pittsburgh Sleep Quality Index (PSQI-J) in patients with chronic liver diseases (CLDs, n = 317, 141 males). Frailty was determined using the following five phenotypes: unintentional body weight loss, self-reported exhaustion, muscle weakness, slow walking speed, and low physical activity. Sleep disorder was defined as patients with PSQI-J score 6 or greater. Robust (phenotype, 0), prefrail (1 or 2 phenotypes) and frailty (3 phenotypes or greater) were observed in 101 (31.9%), 174 (54.9%) and 42 (13.2%), respectively. The median (interquartile range (IQR)) PSQI-J score was 4 (3, 7). Sleep disorder was found in 115 patients (36.3%). The median (IQR) PSQI-J scores in patients of the robust, prefrail, and frail groups were 3 (2, 5), 5 (3, 7), and 8 (4.75, 10.25), respectively (P &lt, 0.0001 between any two groups and overall P &lt, 0.0001). The ratios of sleep disorder in patients with robust, prefrail and frailty were 15.8% (16/101), 39.1% (68/174), and 73.8% (31/42), respectively (overall P &lt, 0.0001). In conclusion, CLD patients with frailty can involve poorer sleep quality. As sleep disorder in CLDs is potentially remediable, future frailty-preventive strategies must take sleep complaints into account.

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.

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.

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.

We aimed to examine the association between sarcopenia-related factors and metabolic syndrome (Met-S) in patients with chronic liver diseases (CLDs, n = 582, average age = 59.5 years, 290 males, 168 liver cirrhosis cases). Met-S was determined based on the Japanese criteria. Sarcopenia was determined based on grip strength (GS) and skeletal muscle index (SMI) by bioelectrical impedance analysis. Our cohort was divided into the four groups: (A) sarcopenia (n = 44), (B) dynapenia (n = 45), (C) presarcopenia (n = 112), and (D) the control (n = 381). Impacts of GS and SMI on Met-S were investigated. In males, waist circumference (WC) ≥ 85 cm was observed in 199 patients (68.6%), while in females, WC ≥ 90 cm was observed in 94 patients (32.2%). Met-S was identified in 109 patients (18.7%). The proportion of Met-S in the group A, B, C and D were 18.2%, 48.9%, 8.0%, and 18.4% (A vs. B, p = 0.0033, B vs. C, p &lt, 0.0001, C vs. D, p = 0.0081, A vs. C, p = 0.0867, A vs. D, p = 1.000, B vs. D, p &lt, overall p value &lt, 0.0001). Multivariate analysis revealed that age, gender, and group B (dynapenia) were significant factors linked to the presence of Met-S. In conclusion, dynapenia rather than sarcopenia is associated with Met-S in CLD patients.

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 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.

Obesity is regarded as a risk factor for various benign and malignant diseases. We evaluated whether or not the body mass index (BMI) was associated with the presence of gastroesophageal varices in asymptomatic hepatitis C virus (HCV)-related compensated cirrhosis (Child-Pugh grade A status). Among a total of 794 patients of HCV-related chronic liver disease, 90 had histologically-proven cirrhosis, and 63 were classified as having compensated cirrhosis (30 had varices, and the remaining 33 did not). The values of prothrombin time (%) and platelet count were significantly lower in the patients with varices than in those without (

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.

We compared Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+ -M2BP) levels between patients with chronic hepatitis B (n=249) and chronic hepatitis C (n=386) based on the degree of liver fibrosis. We examined WFA+ -M2BP levels in patients with F4 (cirrhosis), F3 or more (advanced fibrosis) and F2 or more (significant fibrosis) in the two groups. We further examined the relationship between five fibrosis markers and the degree of fibrosis. The WFA+ -M2BP values ranged from 0.25 cut-off index (COI) to 12.9 COI in patients with hepatitis B and 0.34-20.0 COI in patients with hepatitis C (P

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.