Hepatic arterial infusion of autologous CD34+ cells for hepatitis C virus-related decompensated cirrhosis: A multicenter, open-label, exploratory randomized controlled trial.

Introduction: In this multicenter clinical study, we aimed to investigate the efficacy and safety of the transhepatic arterial administration of granulocyte-colony stimulating factor (G-CSF)-mobilized autologous peripheral blood (PB)-CD34+ cells compared with standard therapy in patients with decompensated cirrhosis type C. Methods: Patients were randomly assigned (2:1) to the CD34+ cell transplant (CD34+ cell) or standard-of-care (SOC) group and followed up for 52 weeks. The primary endpoints were the non-progression rate of Child-Pugh (CP) scores at 24 weeks post-enrollment and the safety of the protocol treatment. Results: Fourteen patients (CD34+ cell group: 10; SOC group: 4) were enrolled. CP scores at 24 weeks had a non-progression rate of 90% in the CD34+ cell group and 100% in the SOC group, with no significant difference between groups. Importantly, 4 out of 10 patients in the CD34+ cell group exhibited an improvement from decompensated to compensated cirrhosis, whereas all patients in the SOC group remained in decompensated cirrhosis. With regard to secondary endpoints, a trend toward increased serum albumin levels in the CD34+ cell group was noted. Serious adverse events (SAEs) occurred in three patients in the CD34+ cell group and in one patient in the SOC group. No causal relationship was observed between all SAEs and G-CSF, leukapheresis, or cell transplantation in the CD34+ cell group. No patients died and no hepatocellular carcinoma occurred within the study period. Conclusions: PB-CD34+ cell infusion therapy may have the potential to circumvent the decompensated stage of cirrhosis, thus avoiding the need for liver transplantation.

Dynapenia Rather Than Sarcopenia Is Associated with Metabolic Syndrome in Patients with Chronic Liver Diseases.

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 < 0.0001; C vs. D, p = 0.0081; A vs. C, p = 0.0867; A vs. D, p = 1.000, B vs. D, p < 0.0001; overall p value < 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.

Factors Associated With Longitudinal QOL Change in Patients With Chronic Liver Diseases.

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 (ΔPCS and ΔMCS). 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: Δalbumin (p=0.0325) and ΔGS (p<0.0001) were independent factors linked to ΔPCS Δalbumin (p=0.0005) and ΔBMI (p=0.0232) were independent factors linked to ΔMCS Conclusion: Significance of serum albumin level, muscle strength and body composition on health-related QOL in CLD patients should be emphasized.

Combined grip strength and calf circumference as a useful prognostic system in patients with liver diseases: a large cohort study.

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/m2 in men and 5.7 kg/m2 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<0.0001), presence of liver cirrhosis (LC) (P<0.0001), presence of hepatocellular carcinoma (HCC) (P<0.0001), low-GS (P<0.0001), low-CC (P<0.0001), serum albumin (P=0.0355), estimated glomerular filtration rate (P=0.0461), hepatitis B virus (P=0.0044) and hepatitis C virus (P<0.0001) were significant factors contributing to the OS by the multivariate analysis. The study subjects were classified into the 4 groups (combined GS-SMI system): (I) low-GS and low-SMI (sarcopenia, n=73); (II) low-GS and high-SMI (n=65); (III) high-GS and low-SMI (n=110); and (IV) high-GS and high-SMI (n=383). The cumulative OS rates were well stratified among 4 groups (overall P<0.0001, AIC =360.895). The study subjects were also classified into the 4 groups (combined GS-CC system): (I) low-GS and low-CC (n=60); (II) low-GS and high-CC (n=78); (III) high-GS and low-CC (n=70); and (IV) high-GS and high-CC (n=423). The cumulative OS rates were also well stratified among 4 groups (overall P<0.0001, AIC =349.521). In receiver operating characteristic (ROC) curve analysis for CC based on the OS, the optimal cutoff point in men was 34.6 cm [area under the ROC (AUC) =0.70, sensitivity =0.558, specificity =0.842], and that in women was 32.8 cm (AUC =0.72, sensitivity =0.619, specificity =0.787). CONCLUSIONS: CC can be an alternative marker for muscle mass in CLD patients. Our proposed combined GS-CC system can be helpful in the community settings without special equipment for muscle mass measurement.

Reduced grip strength is associated with progression of depressive status in chronic liver diseases.

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 BDI-II 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.

Clinical impact of the finger-circle test in patients with liver diseases.

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 (<26 kg for men and <18 kg for women) and skeletal muscle index (SMI) decline (<7.0 kg/m2 in men and <5.7 kg/m2 in female) were diagnosed as sarcopenia. RESULTS: Liver cirrhosis was found in 56 patients (27.7%). The proportions of bigger, just-fits, and smaller in liver cirrhosis versus non-liver cirrhosis patients were 51.8%, 21.4%, and 26.8% versus 77.4%, 11.4%, and 8.2% (p < 0.01). The proportions of grip strength decline in patients with bigger, just-fits, and smaller were 12.0% (77/142), 21.2% (7/33), and 40.7% (11/27; overall p < 0.01). The proportions of SMI decline in patients with bigger, just-fits, and smaller were 9.9% (14/142), 45.5% (15/33), and 77.8% (21/27; overall p < 0.01). The proportions of sarcopenia in patients with bigger, just-fits, and smaller were 3.5% (5/142), 18.2% (6/33), and 33.3% (9/27; overall p < 0.01). In both sexes, arm circumference, triceps skinfold thickness, calf circumference, and waist circumference were significantly stratified according to the finger-circle test. In the multivariate analysis, smaller was an independent predictor for SMI decline (p < 0.01, risk ratio 8.188, bigger as a reference), and body mass index was an independent predictor for both SMI decline and sarcopenia. CONCLUSION: The finger-circle test can be helpful for the screening of sarcopenia in chronic liver disease and is closely linked to body composition.

Predictors for Grip Strength Loss in Patients With Chronic Liver Diseases.

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 <0 kg/year. RESULTS: The median ΔGS in patients with non-LC, Child-Pugh A (n=70) and Child-Pugh B (n=17) were 0.3, -0.2 and -1.6 kg/year (overall p<0.0001). In the multivariate analysis of factors linked to the GSL for all cases, extracellular water (ECW) to total body water (TBW) ratio was significant (p=0.0007). In the multivariate analysis in male, no significant factor was found, while in female, ECW to TBW ratio was significant (p=0.0024). CONCLUSION: Liver functional parameters can be closely linked to the GSL especially in female CLD patients.

Calf Circumference as a Useful Predictor of Sarcopenia in Patients With Liver Diseases.

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<0.0001) and female (r=0.83, p<0.0001). Among the above mentioned 7 anthropometry parameters, CC had the highest area under the receiver operating characteristics curve (AUC) for sarcopenia both in males (AUC=0.88) and females (AUC=0.86). CONCLUSION: CC can be helpful for predicting sarcopenia in CLDs.

Sarcopenia and Frailty in Chronic Liver Damage: Common and Different Points.

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.

Frailty and Sleep Disorder in Chronic Liver Diseases.

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 < 0.0001 between any two groups and overall p < 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 < 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.

Anthropometric Measurements and Frailty in Patients with Liver Diseases.

There have been scarce data regarding the relationship between frailty and anthropometry measurements (AMs) in patients with chronic liver diseases (CLDs). We aimed to elucidate the influence of AMs on frailty in CLDs (median age = 66 years, 183 men and 192 women). AMs included arm circumference, triceps skinfold thickness, calf circumference (CC), waist circumference, and body mass index. Frailty assessment was done by using five phenotypes (body weight loss, exhaustion, decreased muscle strength, slow walking speed, and low physical activity). Robust (frailty point 0), prefrail (frailty point 1 or 2), and frailty (frailty point 3 or more) were observed in 63 (34.4%), 98 (53.6%), and 22 (12.0%) of males, respectively, and 63 (32.8%), 101 (52.6%), and 28 (14.6%) of females, respectively. In receiver operating characteristics (ROC) curve analyses for the presence of frailty, CC had the highest area under the ROC (AUC) both in male (AUC = 0.693, cutoff point = 33.7 cm) and female (AUC = 0.734, cutoff point = 33.4 cm) participants. In the multivariate analysis associated with frailty, for the male participants, only the presence of liver cirrhosis (p = 0.0433) was identified to be significant, while among the female participants, serum albumin (p = 0.0444) and CC (p = 0.0010) were identified to be significant. In conclusion, CC can be helpful for predicting frailty, especially in female CLD patients.

Close Correlation between Frailty and Depressive State in Chronic Liver Diseases.

BACKGROUND AND OBJECTIVES: Few data with regard to the relevance between depression and frailty in chronic liver disease (CLD) patients are currently available. We aimed to elucidate the relationship between frailty and depression as evaluated by the Beck Depression Inventory-2nd edition (BDI-II) in CLD patients (n = 340, median age = 65.0 years). METHODS: Frailty was defined as a clinical syndrome in which three or more of the following criteria were met: body weight loss, exhaustion, muscle weakness, slow walking speed and low physical activity. Depressive state was defined as BDI-II score 11 or greater. RESULTS: Robust (frailty score = zero), prefrail (frailty score = one or two) and frailty were identified in 114 (33.5%), 182 (53.5%) and 44 (12.9%). The median BDI-II score was five. Depressive state was identified in 84 patients (24.7%). The median BDI-II scores in patients with robust, prefrail and frail traits were 2, 7 and 12.5 (robust vs. prefrail, p < 0.0001; prefrail vs. robust, p = 0.0003; robust vs. frail, p < 0.0001; overall p < 0.0001). The proportions of depressive state in patients with robust, prefrail and frail traits were 3.51%, 30.77% and 54.55% (robust vs. prefrail, p < 0.0001; prefrail vs. robust, p = 0.0046; robust vs. frail, p < 0.0001; overall p < 0.0001). BDI-II score significantly correlated with frailty score (rs = 0.5855, p < 0.0001). CONCLUSIONS: The close correlation between frailty and depression can be found in CLD. Preventing frailty in CLD should be approached both physiologically and psychologically.

Possible Relevance of PNPLA3 and TLL1 Gene Polymorphisms to the Efficacy of PEG-IFN Therapy for HBV-Infected Patients.

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 = 1.0×10-4). 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.

Serum Zinc Level Is Associated with Frailty in Chronic Liver Diseases.

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: <26 kg in men and <18 kg in women), slow walking speed (<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 µg/dL, 72.8 µg/dL, and 76.9 µg/dL, respectively (p-values: frailty vs. prefrail, p < 0.0001; prefrail vs. robust, p = 0.0063; frailty vs. robust, p < 0.0001; overall p < 0.0001). For all cases, variables with absolute values of correlation coefficient with frailty score (0-5) ≥ 0.3 were age (rs = 0.3570, p < 0.0001), serum albumin (rs = -0.3212, p < 0.0001), extracellular water to total body water ratio using bioimpedance analysis (rs = 0.4386, p < 0.0001), and serum Zn level (rs = -0.3406, p < 0.0001). In conclusion, decreased serum Zn level in patients with CLDs can be closely associated with the presence of frailty.

Health-Related Quality of Life and Frailty in Chronic Liver Diseases.

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: <26 kg in men and <18 kg in women), slow walking speed (<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 < 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.

Grip Strength: A Useful Marker for Composite Hepatic Events in Patients with Chronic Liver Diseases.

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 <26 kg in men and <18 kg in women, while a skeletal muscle mass index (SMI) decrease was defined as <7.0 kg/m2 in men and <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.

Serum Zinc Level Grading System: A Useful Model for Composite Hepatic Events in Hepatitis C Virus-Associated Liver Cirrhosis.

We aimed to clarify the impact of the serum zinc (Zn) level grading system proposed by the Japanese society of clinical nutrition (JSCN: 80 µg/dL < serum Zn level <130 µg/dL (type A), 60 µg/dL < serum Zn level <80 µg/dL (type B), and serum Zn level <60 µg/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-Pugh (C-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-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 < 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.

Serum Zinc Level and non-Protein Respiratory Quotient in Patients with Chronic Liver Diseases.

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 <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 µg/dL. The median npRQ in patients with non-LC, Child-Pugh A, Child-Pugh B and Child-Pugh C were 0.89, 0.85, 0.83 and 0.82 (overall p < 0.0001)). The median serum Zn level in patients with npRQ <0.85 (58 µg/dL) was significantly lower than that in patients with npRQ ≥ 0.85 (68 µg/dL) (p < 0.0001). The correlation coefficient (r) between npRQ level and serum Zn level for all cases was 0.40 (p < 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-Pugh C (n = 22, r = 0.69). In ROC analyses for npRQ <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.

Walking Speed: Japanese Data in Chronic Liver Diseases.

We aim to clarify the impact of walking speed (WS) and analyze factors linked to WS decline in patients with chronic liver diseases (CLDs, 165 males and 191 females, 137 liver cirrhosis patients). The WS decline is defined as <0.8 m/second (m/s), referring to the guidelines. The median (range) WS was 1.3 m/s (0.2-2.02 m/s). There were 17 patients with WS <0.8 m/s (4.8%). The WS value was significantly correlated with the handgrip strength value both in males (r2 = 0.252, p < 0.0001) and females (r2 = 0.256, p < 0.0001). In the multivariate analysis of factors associated with WS decline, only the extracellular water (ECW) to total body water (TBW) ratio using bioimpedance analysis was an independent predictor (p = 0.0398). Extracellular fluid excess was categorized as follows: normal condition (ECW to TBW ratio <0.390), mild overhydrated condition (ECW to TBW ratio 0.390-0.399), and moderate to severe overhydrated condition (ECW to TBW ratio ≥0.400). The WS value was well stratified according to the ECW to TBW ratio (normal vs. mild, p = 0.0001; mild vs. moderate to severe, p < 0.0001; normal vs. moderate to severe, p < 0.0001; overall p-value <0.0001). In conclusion, the ECW to TBW ratio can be closely linked to WS decline in CLD patients.

Serum zinc concentration and quality of life in chronic liver diseases.

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.