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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.

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.

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 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 sought to compare the impact upon grip strength (GS) between the Mac-2 binding protein glycosylation isomer (M2BPGi) and the Fibrosis-4 (FIB4) index in chronic liver disease (CLD) patients (n = 376: 171 males and 205 females, and 137 liver cirrhosis (LC) cases (36.4%)). Factors linked to the low GS (&lt, 26 kg in male and &lt, 18 kg in female) were also investigated using univariate and multivariate analyses. The median GS in males was 35.5 kg, while that in females was 21.1 kg. The median M2BPGi was 1.11 cutoff index, whereas the median FIB4 index was 2.069. In both male (P &lt, 0.0001) and female (P = 0.0001), GS in LC patients was significantly lower than that in non-LC patients. In males, M2BPGi (r = &minus, 0.4611, P &lt, 0.0001) and the FIB4 index (r = &minus, 0.4556, P &lt, 0.0001) significantly correlated with GS. Similarly, in females, M2BPGi (r = &minus, 0.33326, P &lt, 0.0001) and our FIB4 index (r = &minus, 0.26388, P = 0.0001) also significantly correlated with GS. In the multivariate analyses of factors linked to the low GS, independent factors were: M2BPGi (P = 0.0003) and skeletal muscle index (P = 0.0007) in males, and age (P &lt, 0.0001) and serum albumin level (P = 0.0484) in females. In conclusion, liver fibrosis markers were well-correlated with GS in CLD patients. In particular, M2BPGi can be helpful for predicting the low GS in male patients.

Association between sarcopenia, as evaluated by grip strength (GS) and skeletal muscle mass (SMM), and depression, as evaluated by Beck Depression Inventory-2nd edition (BDI-II) in chronic liver diseases (CLDs, n = 414, average age = 61.5 years), was investigated. Study subjects were classified into four groups: Group A (n = 60), lower GS and lower SMM (sarcopenia); group B (n = 44), lower GS and higher SMM; group C (n = 100), higher GS and lower SMM; group D (n = 210), higher GS and higher SMM. Factors associated with BDI-II score ≥11 were examined. BDI-II score 0−10 (normal) was found in 284 (68.6%), 11−16 (minimal) in 76 (18.4%), 17−20 (mild) in 24 (5.8%), 21−30 (moderate) in 15 (3.6%), and ≥31 (severe) in 15 (3.6%). The average ± standard deviation BDI-II score in liver cirrhosis (LC) patients (10.2 ± 9.6, n = 152) was significantly higher than that in non-LC patients (7.4 ± 7.2, n = 262) (p = 0.0058). Univariate analysis identified three factors to be significantly associated with BDI-I score ≥11: Our classification (groups of A, B, C, and D) (p = 0.0259), serum albumin (p = 0.0445), and the presence of LC (p = 0.0157). Multivariate analysis revealed that only group A (p = 0.0074, group D as a reference) was significant. In conclusion, sarcopenia can be an independent predictor for depression in CLDs.