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Background/objectives: Malnutrition coexisting with abdominal adipose tissue accumulation bring a double burden on prognosis. More recently, the Global Leadership Initiative on Malnutrition (GLIM) has reached a novel consensus concerning the diagnostic criteria, that is, a two-step modality combining nutritional risk screening and subsequent phenotypic/etiologic parameters for comprehensive evaluation in hopes of harmonizing the malnutrition diagnosis. We aimed to elucidate their synergistic impact among inpatients with decompensated cirrhosis concerning long-term mortality., Subjects/methods: Malnutrition, visceral obesity, and visceral adiposity were defined by the Global Leadership Initiative on Malnutrition (GLIM), visceral fat area (VFA), and visceral to subcutaneous adipose tissue area ratio (VSR) on computed tomography, respectively. Accordingly, the patients were categorized into different groups given their nutritional status and visceral obesity/adiposity. Multivariate Cox regression was performed to identify independent risk factors associated with 1-year all-cause mortality. Kaplan-Meier curves with log-rank tests were compared among distinct groups., Results: Totally, 295 patients were recruited. GLIM, VFA, and VSR identified 131 (44.4%), 158 (53.6%), and 59 (20%) patients with malnutrition, visceral obesity and visceral adiposity, respectively. Malnutrition coexisted with visceral obesity in 55 (MO group) relative to visceral adiposity in 40 patients (MA group). Multivariate Cox analysis showed that MA (hazard ratio: 2.48; 95% confidence interval: 1.06, 5.79; P = 0.036) was independently associated with dire outcome rather than MO. Moreover, patients with cirrhosis in the MA group had the worst survival status when compared with other groups (log-rank test: P < 0.001)., Conclusions: The current study indicated that coexisting GLIM-defined malnutrition and VSR-defined visceral adiposity were in relation to worse long-term mortality among inpatients. It is imperative to delicately manage nutritional status and provide personalized treatment in this vulnerable subgroup for achieving better prognosis., (© 2024. The Author(s).)

We sought to develop and validate a machine learning (ML) model for predicting multidimensional frailty based on clinical and laboratory data. Moreover, an explainable ML model utilizing SHapley Additive exPlanations (SHAP) was constructed. This study enrolled 622 patients hospitalized due to decompensating episodes at a tertiary hospital. The cohort data were randomly divided into training and test sets. External validation was carried out using 131 patients from other tertiary hospitals. The frail phenotype was defined according to a self-reported questionnaire (Frailty Index). The area under the receiver operating characteristics curve was adopted to compare the performance of five ML models. The importance of the features and interpretation of the ML models were determined using the SHAP method. The proportions of cirrhotic patients with nonfrail and frail phenotypes in combined training and test sets were 87.8% and 12.2%, respectively, while they were 88.5% and 11.5% in the external validation dataset. Five ML algorithms were used, and the random forest (RF) model exhibited substantially predictive performance. Regarding the external validation, the RF algorithm outperformed other ML models. Moreover, the SHAP method demonstrated that neutrophil-to-lymphocyte ratio, age, lymphocyte-to-monocyte ratio, ascites, and albumin served as the most important predictors for frailty. At the patient level, the SHAP force plot and decision plot exhibited a clinically meaningful explanation of the RF algorithm. We constructed an ML model (RF) providing accurate prediction of frail phenotype in decompensated cirrhosis. The explainability and generalizability may foster clinicians to understand contributors to this physiologically vulnerable situation and tailor interventions., (© The Author(s) 2024. Published by Oxford University Press.)

Background: There is a paucity of data regarding sex-oriented analyses of connection between muscle quantity and quality and health-related quality of life (HRQoL), taking into account the pathophysiological differences of sarcopenia/myosteatosis in males versus females. We sought to investigate the associations between skeletal muscle index (SMI)-defined sarcopenia and intramuscular adipose tissue content (IMAC)-defined myosteatosis and EuroQol-5D (EQ-5D)-defined HRQoL in patients with decompensated cirrhosis concerning sex disparities., Methods: Totally, 382 patients were enrolled. The relationship between SMI/IMAC and HRQoL was evaluated with restricted cubic spline and Pearson correlation analyses. Furthermore, association between SMI or sarcopenia and EQ-5D utility index was determined by multiple linear regression, adjusted for age, BMI and concurrent disease severity., Results: The study population comprised evenly distributed male and female patients (190: 192), mean age 61.9 years. The prevalence of sarcopenia (40.5 versus 9.9%, P < 0.001) and SMI (48.8 versus 42.2 cm 2 /m 2 , P < 0.001) were significantly higher in males relative to females, with comparable myosteatosis prevalence (15.3 versus 16.7%, P = 0.708). Self-care, usual activities and pain within EQ-5D scale were more prevalent in the sarcopenia compared with non-sarcopenia groups across entire population and stratified by sex. The SMI values exhibited a significantly linear correlation with EQ-5D utility index in male but not female patients (P for non-linearity = 0.281). In multiple analysis, SMI or the presence of sarcopenia was both significantly associated with EQ-5D utility index. Subgroup analyses unveiled no discernible interactions between sarcopenia and EQ-5D utility index., Conclusions: Muscle quantity measured by SMI was associated with declined HRQoL in males rather than females, whereas no associations were found regarding muscle quality measured by IMAC in both sexes. It is tempting to manage sarcopenia by increasing SMI levels as high as possible in hopes of achieving better health consequence. Our findings represent the importance of connecting CT-demarcated body composition abnormalities to meaningful patient-centered outcomes. Future targeted studies with sizable multi-center populations are warranted to clarify this causality, and in consequence develop optimized intervention against sarcopenia/myosteatosis or key determinants concerning impaired HRQoL., (© 2024. The Author(s).)

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., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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. [ABSTRACT FROM AUTHOR]

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: β 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Rifaximin, derived from rifamycin, is a broad-spectrum antibiotic by inhibiting bacterial RNA synthesis. Rifaximin has a very low intestinal absorption and exerts its antimicrobial activity primarily in the intestinal tract. It regulates the gut microbiota with limited side effects systemically. Rifaximin has been recommended for the treatment of hepatic encephalopathy but some studies shed light on its medicinal effects in many other diseases. For instance, rifaximin may suppress the progression of liver fibrosis and its related complications, and ameliorate metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease, etc. Rifaximin can also mediate anti-inflammation, antiproliferation, and proapoptotic events by activating pregnane X receptor, which is efficious in cancers such as colon cancer. In addition, some investigations have shown rifaximin may play a therapeutic role in various autoimmune and neurological disorders. However, these findings still need more real-world practices and in-depth investigations to obtain more precise indications and fully elucidate the multifaceted potentials of rifaximin. [Display omitted] • Rifaximin affects the gut-liver axis, brain-gut axis, and gut-lung axis by regulating the gut microbiota. • Rifaximin is confined to the intestinal tract to exert multiple medicinal effects. • Rigorously designed animal experiments and clinical trials should be conducted to foster rifaximin-based precision medicine. [ABSTRACT FROM AUTHOR]