Low serum manganese as a noninvasive marker predicting the presence of myosteatosis among hospitalized patients with cirrhosis.

Emerging evidence expands on a close connection between trace elements and muscular abnormalities, mostly focusing on sarcopenia. We hypothesized an association between concentrations of serum trace elements and myosteatosis, given that myosteatosis has a more pronounced clinical implication relative to sarcopenia, but there is a paucity of data in patients with cirrhosis. Consecutive patients were hospitalized for cirrhosis-associated complications. Serum trace elements (zinc, copper, manganese [Mn], magnesium, calcium, and iron) were measured by inductively coupled plasma mass spectrometry. The presence of myosteatosis was defined according to computed tomography-demarcated intramuscular adipose tissue content. In total, the 295 patients with cirrhosis analyzed had a median age of 63 years and 53.6% were male. Among them, 42 patients presented with myosteatosis (14.2%) and concomitant higher Model for End-stage Liver Disease-Sodium and triglyceride concentrations and lower neutrophil counts and serum Mn concentrations (all P < .05). No differences were found regarding other 5 trace elements in patients with versus without myosteatosis. The median serum Mn concentrations were 1.16 µg/L, and this population was categorized into high-Mn and low-Mn groups. The proportion of myosteatosis was significantly lower in high-Mn group than that in low-Mn group (8.1% vs 20.4%, P < .001). Univariable binary logistic regression indicated that low Mn was associated with myosteatosis (odds ratio, 2.906; 95% confidence interval, 1.424-5.932; P = .003) in the context of cirrhosis. This result was validated according to multivariable analysis by adjusting for confounding factors. In conclusion, low serum Mn can be predictive of myosteatosis, a novel muscular abnormality representing more clinical relevance and close relation to inferior outcomes among cirrhosis.

Association Between Quality of Life Defined by EuroQol Group 5 Dimension and Composite Inferior Outcome Among Inpatients with Cirrhosis.

Purpose: The utility of the EuroQol Group 5 Dimension (EQ-5D) measuring health-related quality of life (HRQoL) has been verified; however, knowledge gaps remain concerning predictive performance in cirrhosis. We aimed to identify the optimal threshold for risk stratification and the pronounced domain in the EQ-5D linked to inferior outcomes. Patients and Methods: The X-tile project was used to obtain a threshold, considering the composite outcome of 1-year all-cause mortality or readmission. A restricted cubic spline (RCS) was performed to test the non-linear relationship between the EQ-5D utility value and the primary outcome. Six multivariate Cox regression models incorporating EQ-5D utility value and each of the five domains were constructed. Setting/Participants: Totally, 420 patients with cirrhosis were recruited. Results: The median utility value of the study population was 0.77 and 59.8% reported impairment in minimal one EQ-5D domain. RCS indicated a linear relationship between the utility value and composite inferior outcome. X-tile pinpointed a utility value of 0.59 stratifying populations into high- and low-risk groups based on the outcome. Inpatients with cirrhosis and deteriorated HRQoL (utility value ≤0.59) were at higher risk of death or readmission (adjusted HR: 2.18, P < 0.001). Furthermore, mobility and usual activities were the most pronounced domains associated with composite inferior outcome. Conclusion: A utility value ≤0.59 can identify cirrhotic inpatients exhibiting compromised HRQoL and mortality/readmission risk. It is tempting to reverse the decreased HRQoL by applying longitudinal measurements and keeping surveillance on utility value, while interventions appear to mainly focus on improving mobility and usual activities.

Health-related quality of life and frailty in liver cirrhosis.

BACKGROUND AND OBJECTIVES: There is limited evidence concerning the predictive value of health-related quality of life (HRQoL) on the presence of frailty in the context of cirrhosis. We aimed to elucidate the relationship between HRQoL and multidimensional frailty and to determine which HRQoL dimension independently impacted frail phenotype in our established cohort. METHODS: This was a prospective observational study by consecutively enrolling 355 patients with cirrhotic with decompensated signs in China. The HRQoL and frail phenotype were evaluated by the EuroQol-5D (EQ-5D) Questionnaire and Frailty Index, respectively. The relationship between EQ-5D utility index, as well as respective EQ-5D dimension, and Frailty Index was analysed according to the multiple linear regression analyses. RESULTS: More than half of the patients (56.3%) reported problems in any dimension of the EQ-5D, suggestive of impaired HRQoL. Moreover, the proportion of patients experiencing some/extreme problems significantly increased across all five dimensions (all p<0.001) in correspondence to transition from the robust to frail phenotype. Multiple linear regression analyses demonstrated that age, ascites and hepatic encephalopathy were positively associated with Frailty Index, while EQ-5D utility index (standardised ß coefficient= -0.442, p<0.001) negatively associated with Frailty Index. Notably, usual activities, self-care and mobility were the most influencing predictors associated with frailty. CONCLUSIONS: Our results support a rapid HRQoL assessment via EQ-5D may assist in predicting multidimensional frailty, and usual activities, self-care and mobility tend to be remediable targets while taking their effect on frail phenotype into consideration among patients with cirrhosis.

Reduced muscle strength is closely linked to computed tomography-defined myosteatosis among inpatients with cirrhosis.

BACKGROUND: Myosteatosis indicates pathological fat infiltration in muscles and is regarded as a distinct disease from sarcopenia. This muscular condition exhibits a link to muscle fiber disarrangement coinciding with disrupted muscle contractility and weakened mechanical action, mirrored as decreased muscle quality. However, the relationship between handgrip strength (HGS) and computed tomography-defined myosteatosis among cirrhosis is unclear. We aimed to investigate the association between HGS and myosteatosis and determine gender-specific cutoffs regarding HGS to identify myosteatotic subjects. METHODS: We prospectively recruited 221 cirrhotic patients. The presence of myosteatosis was determined according to intramuscular adipose tissue content. The relationship between HGS and myosteatosis was evaluated according to Spearman correlation coefficient, area under the ROC curve, and multivariate logistic regression analysis. Moreover, a model based on the classification and regression tree method was generated. RESULTS: Our results showed that HGS exhibits modestly negative correlation with intramuscular adipose tissue content in the entire cohort (rs = -0.269, P < .001) and across diverse subgroups precluding extremely deteriorating conditions. After controlling for multiple clinical features and biochemical parameters, HGS (odds ratio = 0.921, P = .010) was independently associated with myosteatosis in addition to age and body mass index. On applying the Japan Society of Hepatology-recommended cutoffs, an area under the ROC curve of HGS was 0.627 with a sensitivity of 77.4% and a specificity of 47.9%. The decision tree including body mass index and low HGS correctly classified ~85% of the cases in development and validation sets. CONCLUSIONS: HGS was in close relation to myosteatosis among inpatients with cirrhosis.

Coexistent GLIM-Defined Malnutrition and Sarcopenia Increase the Long-Term Mortality Risk in Hospitalized Patients with Decompensated Cirrhosis.

INTRODUCTION: The synergistic impact of coexistent malnutrition and sarcopenia on morality in hospitalized patients with decompensated cirrhosis remains elusive. This prospective cohort study aimed to delineate the prevalence concerning coexistence of malnutrition and sarcopenia and the prognosticating role on long-term mortality among cirrhosis. METHODS: Adult cirrhotic patients with decompensated episodes between 2019 and 2021 were consecutively enrolled. Malnutrition and sarcopenia were diagnosed according to the Global Leadership Initiative on Malnutrition (GLIM) criteria and the European Working Group on Sarcopenia in Older People (EWGSOP2) algorithm, respectively. The entire cohort was divided into three groups: non-malnutrition and non-sarcopenia (NN), malnutrition or sarcopenia, and coexistent malnutrition and sarcopenia (MS). Log-rank test and multivariate Cox regression model were utilized to evaluate survival status and independent risk factors for mortality, respectively. RESULTS: Our findings indicated that malnutrition manifested in 44.6% of inpatients with decompensated cirrhosis, while sarcopenia presented in 16.4% of the entire cohort, indicative of a prevalence of 14.7% regarding coexistent malnutrition and sarcopenia. The Kaplan-Meier graphic demonstrated a significant difference regarding survival curves among the three groups, referring to the MS group presented with the lowest survival rate (log-rank test: p < 0.001). Moreover, coexistent malnutrition and sarcopenia were associated with nearly 4 times higher mortality risk (model 1: hazard ratio [HR] = 3.31, 95% confidence interval [CI]: 1.20-9.13, p = 0.020; model 2: HR = 4.34, 95% CI: 1.52-12.4, p = 0.006) in comparison with patients without any condition (NN group). CONCLUSIONS: Malnutrition and sarcopenia had superimposed negative impacts on inpatients with decompensated cirrhosis. It is imperative to identify this vulnerable subset to provide prompt therapeutic intervention for better prognosis.

Association between serum trace elements and sleep disturbance in patients with decompensated cirrhosis.

Background: Sleep disturbance and trace elements imbalance are common features in patients with decompensated cirrhosis, partially sharing similar mechanistic contributors and linking to adverse outcomes. However, there is a paucity of data concerning their relationship. Objectives: To investigate the association between serum trace elements levels and sleep quality in the context of cirrhosis. Design: Cross-sectional study. Methods: We consecutively enrolled 160 patients with decompensated cirrhosis. The sleep disturbance was determined by the Pittsburgh Sleep Quality Index (PSQI > 5). Serum trace elements [magnesium, calcium, iron, copper (Cu), zinc (Zn), lead, and manganese] was measured by inductively coupled plasma mass spectrometry. Association of examined trace elements levels and sleep disturbance was analyzed by multiple linear (global PSQI scores) and multivariate logistic (dichotomized PSQI categories) regression models, respectively. Results: In total, 91 patients (56.88%) represented PSQI-defined sleep disturbance, characterized by female preponderance, lower body mass index levels, and higher serum Cu levels (all p < 0.05). Looking into its clinical relevance with debilitating conditions, we showed that Cu/Zn ratio (CZr) is significantly higher in cirrhosis with poor sleep quality (1.77 versus 1.48, p = 0.003). Diagnostic performance analysis indicated CZr > 1.62 to exhibit better discrimination relative to respective Cu. Both multiple linear (ß = 0.355, p < 0.001) and multivariate logistic regression (odds ratio = 2.364, p = 0.019) identified higher CZr as an independent risk factor associated with sleep disturbance. Conclusion: Our findings implied an association between higher CZr and the presence of sleep disturbance in patients with decompensated cirrhosis.

Dissecting the potential role of ferroptosis in liver diseases: an updated review.

Ferroptosis is a novel form of cell death, manifested by iron-dependent, non-apoptotic manner resulting from the intracellular accumulation of large clusters of reactive oxygen species (ROS) and lipid peroxides due to abnormal iron metabolism. Since the liver is the main organ of human body for storing iron, it is essential to perform in-depth investigation on the role and mechanistic basis of ferroptosis in the context of divergent liver diseases. We previously summarized the emerging role of ferroptosis among various liver diseases, however, the past few years have been a surge in research establishing ferroptosis as the molecular basis or treatment option. This review article concentrated on the accumulating research progress of ferroptosis in a range of liver diseases such as acute liver injury/failure (ALI/ALF), immune-mediated hepatitis, alcoholic liver disease (ALD), nonalcoholic fatty liver disease and liver fibrosis. Ferroptosis may be a promising target for the prevention and treatment of various liver diseases, providing a strategy for exploring new therapeutic avenues for these entities.

Handgrip strength is a substitutive metric to the GLIM criteria-defined malnutrition and predicts long-term mortality among hospitalized patients with cirrhosis.

BACKGROUND: Hospitalized patients with cirrhosis are prone to debilitating health conditions and fluid fluctuations, posing barriers to accurately obtain anthropometric measures and physical examinations as surrogates for muscle mass within the Global Leadership Initiative on Malnutrition (GLIM). We hypothesize the handgrip strength (HGS) would serve as a substitutive metric, by comparing the diagnostic consistency and prognostic accuracy with computed tomography-demarcated skeletal muscle index (SMI)-defined malnutrition according to the GLIM criteria. METHODS: Patients with cirrhosis underwent a two-step approach involving nutrition risk screening and those fulfilling GLIM consensus were further diagnosed. The evaluation of muscle mass as one constituent contained in the GLIM criteria was conducted by SMI and HGS, respectively. Consistency test, Kaplan-Meier curve, and multivariate Cox regression were used to assess the performance of GLIM-SMI and GLIM-HGS. RESULTS: Among 184 hospitalized patients with cirrhosis, 63 (34.2%) and 78 (42.4%) were diagnosed with malnutrition following GLIM-SMI and GLIM-HGS criteria, respectively. Considering the GLIM-SMI a gold standard, GLIM-HGS had a sensitivity of 87.3% and a specificity of 81.0%. GLIM-HGS criteria denoted good agreement (κ value = 0.858, P < 0.001) as compared with GLIM-SMI. Both criteria were independently associated with 1-year all-cause mortality, whereas GLIM-SMI showed slightly higher hazard ratios. Moreover, HGS positively correlated with SMI in the population alongside more pronounced correlation among patients at nutrition risk. CONCLUSION: HGS may serve as a substitutive metric of muscle mass contained in the GLIM criteria to diagnose malnutrition and predict long-term mortality among patients with cirrhosis.

Malnutrition according to the Global Leadership Initiative on Malnutrition criteria is associated with in-hospital mortality and prolonged length of stay in patients with cirrhosis.

OBJECTIVES: Malnutrition is prevalent and negatively affects patients with cirrhosis, but a generally accepted consensus pertaining to its diagnosis is lacking. Recently, a framework called the Global Leadership Initiative on Malnutrition (GLIM) has been proposed to diagnose malnutrition, but there is scant evidence regarding its validity. We aimed to investigate associations of malnutrition according to the GLIM criteria, as well as its individual indicator with in-hospital adverse outcomes. METHODS: This was a prospective, observational study of consecutively hospitalized patients with cirrhosis. The malnutrition diagnosis was built on a stepwise GLIM process with initial screening, followed by fulfillment of at least one phenotypic and one etiologic criterion. Patients were followed up for a combined endpoint of in-hospital mortality and prolonged length of stay (LOS). Covariates compromise malnutrition according to the GLIM criteria and its indicators in separation. Logistic regression analyses were implemented to determine predictive validity. RESULTS: A total of 387 cirrhotic patients were assessed. Malnutrition was diagnosed in 28.7% of patients according to the GLIM criteria, and increased the risk of in-hospital mortality and prolonged LOS by 2.166 and 1.767 times, respectively, adjusting for age, sex, biochemical parameters, and clinical scores of disease severity. When analyzing separate criteria, all constituents were independently associated with in-hospital adverse outcomes, adjusting for model for end-stage liver disease sodium score. CONCLUSIONS: Malnutrition according to the GLIM criteria was considerably prevalent among hospitalized patients with cirrhosis, and associated with approximately two times greater probability of in-hospital mortality and prolonged LOS. These diagnostic criteria may be implemented and disseminated during daily practice considering their predictive validity.

The relationship between patient-reported health-related quality of life and malnutrition risk in cirrhosis: an observational cohort study.

Patients with cirrhosis experience worse health-related quality of life (HRQoL), and attempts are warranted further exploration of modifiable factors to improve HRQoL. Data on the impact of malnutrition risk on HRQoL among cirrhosis are limited; thus, we aimed to strengthen understanding by clarifying the relationship between nutritional status and low HRQoL in patients with decompensated cirrhosis. Consecutive inpatients with cirrhosis attending our department within a tertiary hospital were studied. Generic health profiles and malnutrition risk were evaluated by the EuroQol-5D (EQ-5D) and Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT) score, respectively. Multiple linear regression analysis was used to determine association of malnutrition risk with low HRQoL. In this cohort of 364 patients with median age of 64 years and 49·5 % male, 55·5 % of the study population reported impairment pertinent to HRQoL in at least one dimension in terms of the EQ-5D. Moreover, malnutrition risk (RFH-NPT score: ß coefficient = -0·114, P = 0·038) was proved to be independently associated with poor HRQoL in multiple analysis, after adjustment for significant variables like age, BMI and markers of decompensation. Notably, we found that health dimensions representing physical function (i.e. mobility, self-care and usual activities) are substantially affected, while malnourished patients reported less frequencies of complaints in other domain such as anxiety/depression. In conclusion, the risk of malnutrition assessed by the RFH-NPT score is independently associated with low HRQoL. It is operational to improve HRQoL by identifying patients at high malnutrition risk and providing timely nutrition treatment.

Dissecting the Contributing Role of Divergent Adipose Tissue to Multidimensional Frailty in Cirrhosis.

Background and Aims: Emerging evidence has demonstrated that abnormal body composition may potentiate the development of frailty, whereas little work focuses on the role of divergent adipose tissue. Therefore, we aimed to determine the potential contribution of adipose tissue distribution to multidimensional frailty in decompensated cirrhosis. Methods: We conducted a retrospective cohort study. Divergent adipose tissues were assessed by computed tomography-derived subcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI) and total adipose tissue index (TATI), respectively. Frailty was identified by our validated self-reported Frailty Index. Multiple binary logistic models incorporating different covariates were established to assess the relationship between adipose tissue distribution and frailty. Results: The study cohort comprised 245 cirrhotic patients with 45.3% being male. The median Frailty Index, body mass index (BMI) and model for end-stage liver disease (MELD) score were 0.11, 24.3 kg/m2 and 8.9 points, respectively. In both men and women, patients who were frail exhibited lower levels of SATI in comparison with nonfrail patients. SATI inversely correlated with Frailty Index in the entire cohort (rs=-0.1361, p=0.0332). Furthermore, SATI or TATI was independently associated with frail phenotype in several multiple logistic regression models adjusting for age, BMI, presence of ascites, sodium, Child-Pugh class or MELD score in isolation. Conclusions: In the context of decompensated cirrhosis, low SATI and concomitant TATI were associated with higher risk of being frail. These findings highlight the importance to further apply tissue-specific tools of body composition in place of crude metric like BMI.

Comparison of the GLIM criteria with specific screening tool for diagnosing malnutrition in hospitalized patients with cirrhosis: A descriptive cross-sectional study.

BACKGROUND: The Global Leadership Initiative on Malnutrition (GLIM) has been built to diagnose malnutrition; however, its validity among patients with cirrhosis remains enigmatic. We aimed to investigate the prevalence of malnutrition according to GLIM criteria and compare the differences by using a specific screening tool. METHODS: We conducted a descriptive cross-sectional study analyzing hospitalized patients. The Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT) was chosen as the screening tool. Estimated prevalence was shown with and without the initial screening process. Diverse combinations of phenotypic and etiologic criteria and distinct body mass index (BMI) cutoffs were applied to detect frequency of malnourished patients with cirrhosis. RESULTS: Overall, 363 patients were recruited (median age, 64 years; 51.2% female). The prevalence of malnutrition according to GLIM criteria with and without RFH-NPT screening was 33.3% and 36.4%, respectively. Low BMI and inflammation represented the most prevalent combination resulting in a malnutrition diagnosis (42.4%), followed by low BMI and reduced food intake (39.4%). By contrast, the least prevalence was found when combining reduced muscle mass with inflammation to diagnose malnutrition. Furthermore, the frequency of malnourished and well-nourished participants was not statistically different when using divergent BMI reference values across the study population. CONCLUSIONS: GLIM criteria may serve a specific proxy to diagnose malnutrition, along with RFH-NPT screening. Relevant investigation is required to report on the applied combination of phenotypic/etiologic criteria, taking into consideration the marked impact of different models. More attempts are warranted to delineate the prognostic role of GLIM criteria in the context of cirrhosis.

Serum Ferritin Has Limited Prognostic Value on Mortality Risk in Patients with Decompensated Cirrhosis: A Propensity Score Matching Analysis.

OBJECTIVE: The prognostic value of serum ferritin remains elusive in the literature. We aimed to examine the association between serum ferritin and mortality risk in cirrhosis. METHODS: A total of 257 cirrhotic patients were recruited. The cut-off of serum ferritin was determined by X-tile. The Cox regression and Kaplan-Meier method were used. A 1:1 propensity score matching (PSM) was performed to diminish the impacts of selection bias and possible confounders. RESULTS: The difference regarding mortality was mostly significant for serum ferritin >158 ng/mL. Before PSM, serum ferritin >158 ng/mL was an independent predictor of mortality. However, the clinical relevance of high ferritin level for prognostication was blunted after PSM (survival rate: 86.8% vs 96.3%, P = .078). Cox regression indicated that model for end-stage liver disease remains only independent risk factor of 180-day mortality after PSM. CONCLUSION: Serum ferritin may not serve as an independent prognostic indicator of mortality risk in decompensated cirrhotic patients.

Associations of Multiple Serum Trace Elements with Abnormal Sleep Duration Patterns in Hospitalized Patient with Cirrhosis.

The associations of circulating trace elements with sleep health have attracted increasing attention given their potential link. However, there is scant data on the relationship between serum trace elements and abnormal sleep duration patterns in cirrhosis. We aimed to investigate these associations with the purpose of identifying modifiable risk factors. The blood samples were collected from inpatients with cirrhosis, and serum levels of several trace elements were assessed by inductively coupled plasma mass spectrometry. Self-reported sleep duration was categorized to short- (< 7 h/night), optimal (7-8 h/night), and long-sleep duration (> 8 h/night). The dose-response trends and associations of trace elements levels with sleep duration were determined by restricted cubic splines (RCS) and logistic regression, respectively. Cirrhotic patients with optimal sleep duration experienced the highest levels of serum Zinc (Zn) and the lowest values of copper to zinc ratio (CZr). RCS model corroborated non-linear associations of serum Zn and CZr against sleep duration. Multiple regression analysis showed that both CZr (short vs optimal sleep duration: OR 4.785, P < 0.001; long vs optimal sleep duration: OR 4.150, P = 0.019) and serum Zn levels (short vs optimal sleep duration: OR 0.985, P = 0.040; long vs optimal sleep duration: OR 0.956, P = 0.008) serve as independent risk factors for sleep duration abnormalities. In conclusion, our findings unraveled a close relationship of serum Zn and CZr with sleep duration in cirrhosis. Further trace element-based therapy such as Zn supplementation may be novel approach to reverse this sleep problem.

Association of myosteatosis with various body composition abnormalities and longer length of hospitalization in patients with decompensated cirrhosis.

Background: Myosteatosis is linked to dismal outcomes in the context of cirrhosis. However, the association of myosteatosis with various body composition abnormalities remains enigmatic. We aimed to clarify the determinants of myosteatosis and its relationship with other body composition profiles and length of hospitalization (LOH). Methods: We retrospectively analyzed the data of 473 consecutive patients with cirrhosis hospitalized for decompensation. Computed tomography-based segmentation of the cross-sectional area at the third lumbar vertebra was used to evaluate body composition abnormalities. The categories of myosteatosis were built according to our previously outcome-based cutoffs for each gender. Results: Totally, 83 patients (17.55%) were stratified as myosteatosis, of whom 85.54% had concomitant high visceral adiposity indicative of increased visceral adipose tissue index (VATI). The prevalence of sarcopenia showed no significant difference between the groups with and without myosteatosis. Multivariate analysis showed that advanced age [odds ratio (OR) = 1.097, p < 0.001], higher visceral to subcutaneous ratio of adipose tissue area (VSR; OR = 1.574, p = 0.032), and higher VATI (OR = 1.026, p < 0.001) are independently associated with myosteatosis. Correlation analyses revealed a positive relationship between intramuscular adipose tissue content (IMAC) and VATI (ρ = 0.48, p < 0.001), subcutaneous adipose tissue index (SATI) (ρ = 0.36, p < 0.001), and age (ρ = 0.36, p < 0.001). None of the skeletal muscle or adipose tissue indicators were significantly related to longer LOH. Conclusion: Higher VSR, higher VATI, and advanced age are associated with myosteatosis among patients with cirrhosis at the decompensation phase. It is tempting to target divergent adipose tissue depots aimed at timely intervention/prevention of myosteatosis.

Sarcopenia and frailty combined increases the risk of mortality in patients with decompensated cirrhosis.

Background: Both sarcopenia and frailty are prevalent in patients with decompensated cirrhosis and associated with negative outcomes. However, few studies investigated the impact of their coexistence on mortality. We aimed to evaluate the role of sarcopenia and frailty on survival in a cohort of hospitalized cirrhotics. Methods: This was an observational cohort study including 221 patients hospitalized for decompensated events. The cutoff for low skeletal muscle index (SMI) at the third lumbar vertebra level on computed tomography built by our previous work (male: SMI <46.96 cm2/m2; female: SMI <32.46 cm2/m2) was used for the diagnosis of sarcopenia. Individuals with a Frailty Index >0.38 were considered frail. The sample was divided into four groups: sarcopenia and frailty (SF); sarcopenia and non-frailty (SN); non-sarcopenia and frailty (NF); and non-sarcopenia and non-frailty (NN). Follow-up for survival lasted 2 years. Results: Sarcopenia and frailty were present in 21.7% and 14.5% of the patients, respectively. The frequency of frailty in the group of sarcopenic patients was significantly higher than in the patients without sarcopenia (27.1% versus 11%, p = 0.009). In the survival analysis, the SF group showed a higher hazard ratio (2.604 in model 1; 4.294 in model 2) for mortality when compared with the NN group. In addition, the concurrence of those two conditions does give rise to incremental risk for mortality when compared with the group with each disturbance separately, namely, the SN/NF group. Conclusion: In conclusion, cirrhotic patients with sarcopenia and frailty combined showed higher mortality risk.

The potential role of FNDC5/irisin in various liver diseases: awakening the sleeping beauties.

Fibronectin type III domain-containing protein 5 (FNDC5) is a transmembrane protein and the precursor of irisin, which serves as a systemic exerkine/myokine with multiple origins. Since its discovery in 2012, this hormone-like polypeptide has rapidly evolved to a component significantly involved in a gamut of metabolic dysregulations and various liver diseases. After a decade of extensive investigation on FNDC5/irisin, we are still surrounded by lots of open questions regarding its diagnostic and therapeutic values. In this review, we first concentrated on the structure-function relationship of FNDC5/irisin. Next, we comprehensively summarised the current knowledge and research findings regarding pathogenic roles/therapeutic applications of FNDC5/irisin in the context of non-alcoholic fatty liver disease, fibrosis, liver injury due to multiple detrimental insults, hepatic malignancy and intrahepatic cholestasis of pregnancy. Moreover, the prominent molecules involved in the underlying mechanisms and signalling pathways were highlighted. As a result, emerging evidence reveals FNDC5/irisin may act as a proxy for diagnosing liver disease pathology, a sensitive biomarker for assessing damage severity, a predisposing factor for surveilling illness progression and a treatment option with protective/preventive impact, all of which are highly dependent on disease grading and contextually pathological features.

Low free triiodothyronine levels are associated with frail phenotype in hospitalized inpatients with cirrhosis.

OBJECTIVE: Frailty is a prevalent complication predicting morbidity and mortality in cirrhosis. However, the association between thyroid hormone levels and frailty in cirrhotics remains elusive. Therefore, we aimed to evaluate the relationship between thyroid hormone and frail phenotype in euthyroid patients with cirrhosis. METHODS: A total of 214 adult cirrhotic inpatients were divided into two groups according to Frailty Index. Concentrations of free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) were compared. An analysis of the receiver operating characteristic (ROC) curve was implemented to determine the best cutoff for frailty. Multiple logistic regression was used to assess the association between FT3 and frailty. RESULTS: ROC analysis indicated that the optimal cutoff to stratify frailty was FT3 < 3.03 pmol/L with an area under the curve of 0.673 (95% CI: 0.582-0.764, p = 0.002), sensitivity of 81.8%, and specificity of 51.9%. Patients with FT3 < 3.03 pmol/L exhibited higher incidence of Child-Pugh class B/C, elevated model for end-stage liver disease score, higher creatinine, lower sodium as well as higher incidence of frailty (23.7 vs 6.0%, p < 0.001). A negative correlation was observed between FT3 values and Frailty Index (r = -0.220, p = 0.001). FT3 remained an independent risk factor for frailty after adjusting for age, Child-Pugh class, creatinine, sodium, and alanine aminotransferase. CONCLUSION: In our current study, FT3 < 3.03 pmol/L were significantly associated with increased risk for frailty. Measuring FT3, a readily available biomarker, may be useful for identifying frail phenotype in euthyroid patients with cirrhosis.

The prognostic value of high-density lipoprotein cholesterol in patients with decompensated cirrhosis: a propensity score matching analysis.

BACKGROUND: Emerging evidence has implicated that high-density lipoprotein cholesterol (HDL-C) as a prognostic surrogate in the context of cirrhosis. However, an exact cutoff has not been fully elucidated. OBJECTIVE: We aimed to clarify optimal cutoff of HDL-C for short-term mortality based on time-to-event analysis and validated this association by performing propensity score matching (PSM) analysis. METHOD: A total of 238 patients with decompensated cirrhosis were enrolled. The optimal cutoff of HDL-C was initially determined by X-tile program. Independent risk factors for 180-day mortality were identified by multiple Cox regression. The Kaplan-Meier method was implemented to generate survival curves. A 1:2 ratio PSM was performed to diminish selection bias and potential confounders. RESULTS: The X-tile implied that the difference in survival was most significant for HDL <0.4mmol/L (<16mg/dL). Circulating HDL <0.4mmol/L exhibited an independent risk factor both in the entire cohort and PSM subset (HR 2.696, 95% CI 1.082-6.791, P = 0.033; HR 2.735, 95% CI 1.027-7.734, P = 0.048). Furthermore, HDL-C combined with conventional scoring systems had higher AUCs associated with poor prognosis than Child-Pugh classification or model for end-stage liver disease (MELD) in isolation (0.78 vs 0.66; 0.74 vs 0.54, P < 0.05 for both). CONCLUSION: HDL-C <0.4 mmol/L may serve as a readily available and robust cutoff for stratifying cirrhotic patients at high 180-day mortality risk. The incorporation of HDL-C to Child-Pugh classification or MELD has the potentials to provide substantially clinical relevance without extra economic cost.

Health-Related Quality of Life and Its Contributors According to a Preference-Based Generic Instrument in Cirrhosis.

It is essential to determine contributors around impairment in health-related quality of life (HRQoL) in patients with cirrhosis aiming at improving health care and therapeutic strategy. Studies simultaneously incorporating disease severity based on biochemical parameters and other physical/psychological effects (i.e., sleep disturbance and frailty) are heterogeneous and the subject of the present study. We analyzed and compared HRQoL, using the EuroQol Group 5 Dimension (EQ-5D) questionnaire and the utility index retrieved, in patients with cirrhosis and across groups stratified by sleep disturbance or frailty phenotype. Sleep disturbance and frailty were determined by the Pittsburgh Sleep Quality Index (PSQI) and Frailty Index, respectively. Multiple linear regression was implemented to clarify contributors of poor HRQoL. In this cohort of 227 patients with mean age of 61.7 years and 47.2% male, more than half of the study population represented impairment in HRQoL in at least one domain, according to EQ-5D. Furthermore, sleep disturbance and frailty have proved to be independently associated with poor HRQoL in two separate regression models, whereas conventional scoring systems such as Child-Pugh classification and Model for End-Stage Liver Disease are not closely relevant. Intriguingly, not all health domains within EQ-5D correlated well with PSQI and Frailty Index, with the exception of usual activities. Pain and anxiety/depression were the most frequently affected HRQoL domains even in patients without sleep disturbance or frailty. Conclusion: Impaired HRQoL is prevalent in patients with decompensated cirrhosis. Sleep disturbance and frailty are independently associated with poor HRQoL. It is imperative to timely intervene with these symptoms and deliver tailored health care.