Programmed death ligand-1 (PD-1), as an immunotherapy target, has been increasingly used in tumour therapies. But as reactions and outcomes to PD-1 inhibitors combined with chemotherapy vary individually, it is primarily important to identify an ideal indicator for predicting the therapeutic effectiveness in individual patients. Oesophageal cancer (EC) patients often have difficulty eating due to tumour blockage of the oesophagus, leading to malnutrition and muscle loss. Sarcopenia is one of the influencing factors for poor prognosis in tumour patients, but its role in PD-1 inhibitors combined with chemotherapy of EC patients is not fully clarified. In this study, we aimed to explore the prognostic significance of Sarcopenia measured by CT in EC patients treated with PD-1 antibody combined with chemotherapy.

The third lumbar skeletal muscle mass index (L3-SMI) was obtained from 83 EC patients before and 3 months after administration of PD-1 inhibitors combined with chemotherapy using conventional CT scans.

Baseline L3-SMI and 3-month L3-SMI values were found not suitable for predicting the overall survival (OS) of EC patients (p = 0.32 & p = 0.055). Longitudinal change in L3-SMI (ΔL3-SMI) during PD-1 inhibitors combined with chemotherapy was identified as a relevant marker of OS in univariable analysis (HR: 0.98, 95% CI: 0.96-1.00, p = 0.042) and multivariable analysis (HR: 0.96, 95% CI: 0.93-0.99, p = 0.02). L3-SMI-positive patients generally had better OS (p = 0.041).

Excessive muscle loss rather than muscle loss before and after administration of PD-1 inhibitors combined with chemotherapy is an important prognostic factor for therapeutic outcomes and OS in EC patients.

Skeletal muscle atrophy (sarcopenia) is a serious complication of liver cirrhosis, and chronic muscle inflammation plays a pivotal role in its pathologenesis. However, the detailed mechanism through which injured liver tissues mediate skeletal muscle inflammatory injury remains elusive. Here, it is reported that injured hepatocytes might secrete mtDNA-enriched extracellular vesicles (EVs) to trigger skeletal muscle inflammation by activating the cGAS-STING pathway. Briefly, injured liver secreted increased amounts of EVs into circulation, which are then engulfed primarily by macrophages in skeletal muscle and subsequently induce cGAS-STING signaling and its-mediated inflammatory response in muscles. In contrast, suppression of hepatic EV secretion or STING signaling significantly alleviated cirrhosis-induced skeletal muscle inflammation and muscle atrophy in vivo. Circulating EVs from cirrhotic patients showed higher levels of mtDNA, and the levels of EV-mtDNA positively correlated with the severity of liver injury. In injured hepatocytes, mitochondrial damage promoted the release of cytosolic mtDNA and the subsequent secretion of mtDNA-enriched EVs. This study reveals that injured hepatocyte-derived EVs induce skeletal muscle inflammation via the mtDNA‒STING axis, while targeted blockade of liver EV secretion or STING signaling represents a potential therapeutic approach for preventing cirrhosis-associated skeletal muscle atrophy.

The relationship between sarcopenia and post-liver transplant (LT) mortality is still not well understood. This study aims to provide an updated and comprehensive meta-analysis evaluating the impact of sarcopenia on the survival of LT patients.

We conducted searches in PubMed, Web of Science, and EMBASE up until May 2, 2024, without language restrictions. The primary outcome measured was the overall post-LT mortality risk associated with sarcopenia. The DerSimonian-Laird random effects model was used to calculate pooled adjusted hazard ratios (HRs).

Eighteen cohort studies comprising a total 6297 LT patients were included. The overall prevalence of sarcopenia was 27% (95% CI: 26%-28%), and this rate was lower when sarcopenia was defined using the third lumbar-skeletal muscle index in men, and among patients with lower Child-Pugh class. Sarcopenia remained significantly associated with higher mortality, with a pooled adjusted HR of 1.55 (95% CI 1.28-1.89). This association held across subgroups based on sex, study location, sarcopenia definition, study quality, and living donor LT recipients. A sensitivity analysis excluding groups with a high proportion of hepatocellular carcinoma patients showed similar findings (HR 1.63, 95% CI 1.13-2.35). No significant heterogeneity was identified in any of the analyses.

This meta-analysis shows that sarcopenia is significantly associated with increased mortality after LT. Thus, the risk of sarcopenia should be factored into the initial evaluation of LT candidates.

Patients with liver cirrhosis often experience factors such as malnutrition and lack of exercise, leading to reduced quality of life. Insufficient social support is related to self-management in patients with chronic diseases. Therefore, this study explores the mediating role of social support in the relationship between self-management and quality of life, analyzing the impact of exercise frequency and malnutrition risk assessment on social support, self-management, and quality of life. Using a convenience sampling method, cross-sectional data were collected from 257 patients with liver cirrhosis at the infectious disease department of a tertiary hospital in Zunyi, China, from 2021 to 2022. The patients were evaluated using a demographic questionnaire, the Self-Management Behavior Scale for Liver Cirrhosis Patients, the Social Support Rating Scale (SSRS), the Chronic Liver Disease Questionnaire (CLDQ), and the Royal Free Hospital Nutritional Prioritizing Tool (RFH-NPT). Data were analyzed using SPSS and PROCESS software. (1) Patients in the decompensated stage of liver cirrhosis and those classified in Child-Pugh class B/C had lower scores in self-management, quality of life, and social support compared to patients in the compensated stage of liver cirrhosis and those classified in Child-Pugh Class A. (2) Quality of life was positively correlated with both social support and self-management (r = 0.668, r = 0.665, both P < 0.001). (3) Mediation analysis showed that self-management had a direct predictive effect on quality of life. Social support had a mediating effect between self-management and quality of life, with an indirect effect of 0.489 (95% CI: 0.362, 0.629), accounting for 40.58% of the total effect. (4) Exercise frequency and malnutrition risk assessment were independent influencing factors for social support, self-management, and quality of life. (5) In the regression model, after excluding confounding factors, Model I explained 14% of the variance in quality of life due to control variables, Model II explained 49.5%, and when social support was added, Model III explained 56.9% of the variance in quality of life. Under the mediating role of social support, self-management can improve quality of life. Exercise frequency and malnutrition risk assessment, as independent influencing factors, also modulate social support and self-management. These findings underscore the importance of strengthening social support and developing self-management programs targeting exercise and nutrition to enhance the quality of life in patients with liver cirrhosis.

Rapid turnover proteins (RTPs), including retinol-binding protein (RBP), prealbumin, and transferrin, are useful in evaluating dynamic nutritional status. This study aimed to investigate the relationship between serum RTP levels and mortality in patients with chronic liver disease (CLD).

We evaluated 341 patients with CLD admitted between October 2011 and December 2021. Those with RBP levels below 2.7 mg/dL for males and 1.9 mg/dL for females were included in the low RBP group. Factors associated with mortality and low RBP were evaluated using the Cox proportional hazard regression and logistic regression models.

The median age of the included patients was 67 years, and 48% were male. The median model for end-stage liver disease (MELD) score was 8 points, and the median RBP, prealbumin, and transferrin levels were 1.5 mg/dL, 11 mg/dL, and 227 mg/dL, respectively. During a median observational period, 23% of the patients died. Multivariate analysis showed that the RBP level (hazard ratio, 0.62; 95% confidence interval [CI], 0.46-0.81) was independently associated with mortality, while prealbumin and transferrin were not. Additional analysis revealed that male sex (odds ratio, 8.62; 95% CI, 2.56-29.00) and albumin level (odds ratio, 0.10; 95% CI, 0.04-0.26) were significantly associated with the low RBP levels in patients with CLD.

The serum RBP level is a dynamic biomarker associated with mortality in patients with CLD, independent of liver functional reserve, and it may be a useful indicator for nutritional intervention in these patients.

This systematic review/meta-analysis evaluated the impact of sarcopenia in patients with cirrhosis before liver transplantation (LT) on outcomes after LT.

A systematic search was conducted in six medical databases until February 2022. The primary outcome was overall mortality after LT, while several secondary outcomes including liver graft survival and rejection, the need for transfusions, the length of the intensive care unit (ICU) and hospital stay, and surgical complications were evaluated. Sub-group analyses and meta-regression analyses were also performed.

Fifty-three studies were evaluated in the systematic review, of which 30, including 5875 patients, were included in the meta-analysis. All studies included were cohort studies of good/high quality on the Newcastle-Ottawa scale (NOS), while in our analysis no publication bias was found, although there was substantial heterogeneity between the studies. Muscle mass was assessed using skeletal muscle index (SMI) in 14 studies, psoas muscle area (PMA) in seven studies, and psoas muscle index (PMI) in four studies. The prevalence of pre-LT sarcopenia ranged from 14.7% to 88.3%. Pre-LT sarcopenia was significantly associated with post-LT mortality (Relative Risk [RR] = 1.84, 95% CI:1.41,2.39), as well as with a high risk of infections post-LT, surgical complications, fresh frozen plasma (FFP) transfusions, and ICU length of stay (LOS).

Pre-LT sarcopenia in patients with cirrhosis is a strong risk factor for clinically meaningful adverse outcomes after LT. Assessment may help identify patients at the highest risk for poor outcomes who may benefit from targeted interventions.

Background/Objectives: Sarcopenia is an important clinical feature of patients with chronic liver disease (CLD). However, special devices are required to determine skeletal muscle mass. We evaluated the usefulness of body surface area (BSA) for estimating muscle mass and diagnosing sarcopenia in patients with CLD. Methods: We retrospectively studied 1889 Japanese patients with CLD who underwent bioimpedance analysis (BIA) (training cohort, n = 983; validation cohort, n = 906). The optimal cutoff values for predicting low skeletal muscle mass index (SMI) were determined using ROC analysis. We also assessed 1229 patients whose BSA and grip strength (GS) data were obtained on the same day and evaluated the diagnostic performance of the determined cutoff values of BSA for the diagnosis of sarcopenia. Results: In the training cohort, a strong correlation was observed between the SMI and BSA (r = 0.883, p < 0.0001). The cutoff values of BSA for predicting low SMI were 1.68 m2 for men and 1.48 m2 for women. Regarding the presence of low SMI, 776 (78.9%) and 730 (80.5%) patients were correctly diagnosed in the training and validation cohorts, respectively. The sensitivity and specificity of the combination of BSA and GS for sarcopenia were 82.7% and 97.1%, respectively, and 1175 patients (95.6%) were correctly diagnosed. Conclusions: BSA was highly correlated with SMI, suggesting that BSA could facilitate noninvasive estimation of low skeletal muscle mass in patients with CLD.

Dysgeusia is a distortion of the sense of taste whose prevalence and relationship with nutritional status in Metabolic dysfunction-associated Steatotic Liver Disease (MASLD)-related advanced chronic liver disease (ACLD) have never been systematically explored.

200 MASLD patients [60 ≤ F3 fibrosis, 70 compensated ACLD (cACLD), and 70 decompensated (dACLD)] were enrolled. At baseline, the Child-Pugh (CP) score was determined. Dietary habits, body composition, and frailty were evaluated. The European Working Group (EWGSOP2) criteria defined sarcopenia. Dysgeusia was assessed by the Dysgeusia-Total-Score (DTS). A visual analog scale identified appetite impairment (VASAI). During a 6-month follow-up, liver-related decompensation events (LRDEs) were recorded.

The prevalence of dysgeusia increased with the liver disease progression, appearing significantly higher in ACLD compared with ≤ F3 (65.7% vs 5%, p:0.003), as well as in dACLD compared to cACLD patients (58.5 vs 7.1% p < 0.0001). On 41 dACLD patients presenting dysgeusia, 37 (90.2%) showed a significant impairment of appetite levels. In dACLD, the CP score was positively correlated with both DTS (R:0.742) and VASAI (R:0.704), as well as DTS was directly correlated with VASAI (R:0.765) (all p < 0.0001). Compared with dACLD patients without dysgeusia, dysgeusia-affected dACLD patients presented a lower daily protein intake (g/kg/die) (1.55 ± 0.192 vs 1.34 ± 0.15, p < 0.0001). Sarcopenia (70.7 vs 41.3%) and frailty (69.29 vs 37.9%) were significantly more prevalent in dysgeusia-affected dACLD individuals (both p < 0.0001). These patients showed a higher risk of LRDEs occurrence during the follow-up [HR:2.205; C.I. 95%:1.186-4.099; p:0.01]. Logistic regression analysis revealed dysgeusia (aOR: 3.32), appetite impairment (aOR:1.32), sarcopenia (aOR: 3.75), and frailty (aOR:3.03) significantly associated with this outcome (all p < 0.0001).

Dysgeusia appears predominant in MASLD-dACLD and, via appetite impairment, in a close relationship with malnutrition, sarcopenia, and frailty, negatively influencing patients' outcomes.

One of the most pressing challenges facing society today is the rising prevalence of physical and cognitive frailty. This geriatric condition makes older adults more vulnerable to disability, illness, and a heightened risk of mortality. In this scenario, Parkinson's disease (PD) and geriatric frailty, which share several common characteristics, are becoming increasingly prevalent worldwide, underscoring the urgent need for innovative strategies. Nutraceuticals are naturally occurring bioactive compounds contained in foods, offering health benefits over and above essential nutrition. By examining the literature from the past decade, this review highlights how nutraceuticals can act as complementary therapies, addressing key processes, such as oxidative stress, inflammation, and neuroprotection. Notably, the antioxidant action of nutraceuticals appears particularly beneficial in regard to PD and geriatric frailty. For instance, antioxidant-rich nutraceuticals may mitigate the oxidative damage linked to levodopa therapy in PD, potentially reducing the side effects and enhancing treatment sustainability. Similarly, the antioxidant effects of nutraceuticals may amplify the benefits of physical activity, enhancing muscle function, cognitive health, and resilience, thereby reducing the risk of frailty. This review proposes a holistic approach integrating nutraceuticals with exercise, pharmacotherapy, and lifestyle adjustments. It promises to transform the management of ARD, prolong life, and improve the quality of life and well-being of older people.

Sarcopenia is a common complication of liver cirrhosis and can be used for predicting dismal prognostic outcomes. This study aimed to evaluate the role of sarcopenia in rebleeding and mortality of liver cirrhosis patients after endoscopic therapy.

The liver cirrhosis patients who received endoscopic treatment were enrolled. Propensity score matching (PSM) was used to overcome selection bias. Two-year rebleeding episodes and mortality after endoscopic therapy were recorded.

A total of 109 (32.4%) sarcopenia patients were reported. Before PSM, the frequency of rebleeding was significantly higher in the sarcopenia group relative to the non-sarcopenia group (41.3% vs. 15.9%, p < 0.001). Moreover, the multivariable analysis revealed that sarcopenia (p < 0.001, HR:2.596, 95% CI 1.591-4.237) was independently associated with a 2-year rebleeding episode. After PSM, the sarcopenia group exhibited an increased rebleeding rate as compared with non-sarcopenia group (44.4% vs. 15.3%, p < 0.001). According to multivariable analysis, sarcopenia (p < 0.001, HR:3.490, 95% CI 1.756-6.938) was identified as a significant predictor for 2-year rebleeding.

Sarcopenia was significantly associated with a high 2-year rebleeding rate in liver cirrhosis patients after endoscopic treatment. Therefore, the precise evaluation of a patient's nutritional status, including sarcopenia becomes mandatory before endoscopic treatment.

Hospitalized patients with end-stage liver disease are at risk of malnutrition, reduced body function, and cognitive impairment due to HE. This combination may have an impact on in-hospital falls and mortality. The purpose of this study was to identify factors associated with the risk of falls and to analyze the consequences regarding in-hospital mortality.

We performed a retrospective analysis of patients hospitalized with liver cirrhosis between 2017 and 2019 at the Department of Gastroenterology at the University Hospital Frankfurt. Clinical data, laboratory work, and follow-up data were analyzed. Factors associated with the risk of falls and in-hospital mortality were calculated using a mixed effect poisson regression model and competing risk time-to-event analyses.

Falls occurred with an incidence of 4% (80/1985), including 44 injurious falls with an incidence rate of 0.00005/100 patient-days (95% CI: 0.00001-0.00022). In the multivariate analysis malnutrition (incidence risk ratio: 1.77, 95% CI: 1.04-3.04) and implanted TIPS (incidence risk ratio: 20.09, 95% CI: 10.1-40.1) were independently associated with the risk of falling. In a total of 21/80 (26.25%) hospitalizations, patients with a documented fall died during their hospital stay versus 160/1905 (8.4%) deaths in hospitalizations without in-hospital fall. Multivariable analysis revealed as significant clinical predictors for in-hospital mortality a Nutritional Risk Screening ≥2 (HR 1.79, 95% CI: 1.32-2.4), a falling incident during hospitalization (HR 3.50, 95% CI: 2.04-6.0), high MELD, and admission for infections.

Malnutrition and TIPS are associated with falls in hospitalized patients with liver cirrhosis. The in-hospital mortality rate of patients with cirrhosis with falls is high. Specific attention and measures to ameliorate these risks are warranted.

Cirrhosis is the main cause of morbidity and mortality globally, accounting for approximately 1.2 million deaths annually. Impaired aerobic capacity, muscle wasting and reduced muscle strength are significant complications in patients with cirrhosis. Preoperative exercise intervention "prehabilitation" has been recognised as a potential approach to optimise muscle strength, aerobic capacity and body composition as well as quality of life in patients awaiting abdominal surgery. However, there is little evidence on the effects of preoperative exercise on older adults with cirrhosis and awaiting liver transplant. Thus, the primary objective of this systematic review and meta-analysis will be to assess the effects of exercise interventions in improving aerobic capacity, muscle strength and body composition of older adults with cirrhosis and awaiting liver transplant.

This systematic review and metaanalysis protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This systematic review will include all peer-reviewed randomised controlled trials (RCTs), including cluster RCTs, controlled (non-controlled), complex clinical trials (CCTs) or cluster trials, cohort, observational studies published in English from inception until July 2024. The following electronic databases will be searched: MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL (EBSCO) and Scopus (Elsevier) and supplemented by a secondary screening of the reference lists of all included articles. Searches will involve studies with both male and female participants aged ≥ 18 years with cirrhosis and awaiting liver transplant. Primary outcomes will include muscle strength, and aerobic capacity. The secondary outcomes include body composition (e.g. body mass index, and thigh circumference). The Cochrane Collaboration Risk of Bias Tool will be used to evaluate quality of the studies and Review Manager (RevMan) V.5.3 (Copenhagen, Denmark: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). Effect sizes will be expressed as a standardised mean difference, and their 95% confidence intervals will be calculated and presented as a forest plot. The standard χ2 and I2 tests will be used to test heterogeneity.

This systematic review and meta-analysis is anticipated to provide meaningful and contemporary evidence on the effects of preoperative exercise in older adults living with cirrhosis and awaiting liver transplant. In addition, the findings will help clinicians with developing safe and effective preoperative exercise regimens for these patients.

Cirrhosis is an immune dysfunction state, and as such, patients with cirrhosis are susceptible to bacterial, fungal, and viral infections. Because of infection, these patients have a propensity to develop multiorgan failure, which is associated with high mortality. Bacterial infections are the most prevalent type of infection in patients with cirrhosis, with the prevalence of bacterial infections in patients admitted for an acute decompensating event ranging from 24% to 29%. Together with invasive fungal infections, bacterial infections are the most severe. Multidrug-resistant organisms have been evolving at a rapid and alarming rate around the world, which presents enormous challenges. The development of effective measures for the prevention, early detection, and treatment of infections in patients with cirrhosis is challenging, given the rising incidence of infections in this patient population.

Chronic liver inflammation, a pervasive global health issue, results in millions of annual deaths due to its progression from fibrosis to the more severe forms of cirrhosis and hepatocellular carcinoma (HCC). This insidious condition stems from diverse factors such as obesity, genetic conditions, alcohol abuse, viral infections, autoimmune diseases, and toxic accumulation, manifesting as chronic liver diseases (CLDs) such as metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), alcoholic liver disease (ALD), viral hepatitis, drug-induced liver injury, and autoimmune hepatitis. Late detection of CLDs necessitates effective treatments to inhibit and potentially reverse disease progression. However, current therapies exhibit limitations in consistency and safety. A potential breakthrough lies in nanoparticle-based drug delivery strategies, offering targeted delivery to specific liver cell types, such as hepatocytes, Kupffer cells, and hepatic stellate cells. This review explores molecular targets for CLD treatment, ongoing clinical trials, recent advances in nanoparticle-based drug delivery, and the future outlook of this research field. Early intervention is crucial for chronic liver disease. Having a comprehensive understanding of current treatments, molecular biomarkers and novel nanoparticle-based drug delivery strategies can have enormous impact in guiding future strategies for the prevention and treatment of CLDs.

Muscle-wasting and disease-related malnutrition are highly prevalent in patients with chronic liver diseases (CLD) as well as in liver transplant (LT) candidates. Alterations of body composition (BC) such as sarcopenia, myosteatosis and sarcopenic obesity and associated clinical frailty were tied to inferior clinical outcomes including hospital admissions, length of stay, complications, mortality and healthcare costs in various patient cohorts and clinical scenarios. In contrast to other inherent detrimental individual characteristics often observed in these complex patients, such as comorbidities or genetic risk, alterations of the skeletal muscle and malnutrition are considered as potentially modifiable risk factors with a major clinical impact. Even so, there is only limited high-level evidence to show how these pathologies should be addressed in the clinical setting. This review discusses the current state-of-the-art on the role of BC assessment in clinical outcomes in the setting of CLD and LT focusing mainly on sarcopenia and myosteatosis. We focus on the disease-related pathophysiology of BC alterations. Based on these, we address potential therapeutic interventions including nutritional regimens, physical activity, hormone and targeted therapies. In addition to summarizing existing knowledge, this review highlights novel trends, and future perspectives and identifies persisting challenges in addressing BC pathologies in a holistic way, aiming to improve outcomes and quality of life of patients with CLD awaiting or undergoing LT.

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.

End-stage liver disease (ESLD) is a life-threatening clinical syndrome and when complicated with infection the mortality is markedly increased. In patients with ESLD, bacterial or fungal infection can induce or aggravate the occurrence or progression of liver decompensation. Consequently, infections are among the most common complications of disease deterioration. There is an overwhelming need for standardized protocols for early diagnosis and appropriate management for patients with ESLD complicated by infections. Asia Pacific region has the largest number of ESLD patients, due to hepatitis B and the growing population of alcohol and NAFLD. Concomitant infections not only add to organ failure and high mortality but also to financial and healthcare burdens. This consensus document assembled up-to-date knowledge and experience from colleagues across the Asia-Pacific region, providing data on the principles as well as evidence-based current working protocols and practices for the diagnosis and treatment of patients with ESLD complicated by infections.

There is neither a gold standard definition nor a universal consensus to diagnose sarcopenia in patients with chronic hepatitis C. Thus, we aimed to compare the prevalence of sarcopenia and the agreement and discrepancies between European Working Group on Sarcopenia in Older People (EWGSOP1), EWGSOP2, and Foundation for the National Institutes of Health Biomarkers Consortium Sarcopenia Project (FNIH) definitions in chronic hepatitis C.

Dual-energy x-ray absorptiometry was used to assess muscle mass by quantifying appendicular lean mass (ALM) adjusted for squared height (ALM/ht2) or for body mass index (ALMBMI). Muscle function was evaluated by handgrip strength. Subjective Global Assessment was used to assess the nutrition status.

This cross-sectional study included 103 outpatients (mean age, 50.6 ± 11.3 years; 33.0% with compensated cirrhosis). Sarcopenia prevalence was 8.7%, 9.7%, and 9.7%, according to EWGSOP1, EWGSOP2, and FNIH definitions, respectively. There was neither a sex- nor a liver disease severity-specific difference in the prevalence of sarcopenia between the criteria applied. Sixteen (15.5%) patients fulfilled at least one of these criteria, and 3 out of 16 (18.8%) simultaneously had sarcopenia by consensus of the three criteria. Sarcopenic obesity was identified in 9 out of 16 (56.3%) patients, and 6 out of 9 (66.7%) of these only met FNIH consensus.

In patients without cirrhosis or with compensated cirrhosis, and with chronic hepatitis C, the agreement between EWGSOP1 and EWGSOP2 classifications was substantial for sarcopenia diagnosis. Concerning EWGSOP and FNIH criteria, a fair agreement and limited overlap were found in these patients.

Individuals with cirrhosis experience higher morbidity and mortality rates than the general population, irrespective of the type or scope of surgery. This increased risk is attributed to adverse effects of liver disease, encompassing coagulation dysfunction, altered metabolism of anesthesia and sedatives, immunologic dysfunction, hemorrhage related to varices, malnutrition and frailty, impaired wound healing, as well as diminished portal blood flow, overall hepatic circulation, and hepatic oxygen supply during surgical procedures. Therefore, a frequent clinical dilemma is whether surgical interventions should be pursued in patients with cirrhosis. Several risk scores are widely used to aid in the decision-making process, each with specific advantages and limitations. This review aims to discuss the preoperative risk factors in patients with cirrhosis, describe and compare surgical risk assessment models used in everyday practice, provide insights into the surgical risk according to the type of surgery and present recommendations for optimizing those with cirrhosis for surgical procedures. As the primary focus is on currently available risk models, the review describes the predictive value of each model, highlighting its specific advantages and limitations. Furthermore, for models that do not account for the type of surgical procedure to be performed, the review suggests incorporating both patient-related and surgery-related risks into the decision-making process. Finally, we provide an algorithm for the preoperative assessment of patients with cirrhosis before elective surgery as well as guidance perioperative management.

Sarcopenia is common in patients with liver cirrhosis and is an independent predictor of multiple clinical outcomes. Most studies to date have used a static assessment of sarcopenia. However, there is very limited data evaluating the temporal course of muscle area in cirrhosis. To bridge this gap in clinical studies, we performed a longitudinal analysis to evaluate the impact of changes in sarcopenia for cirrhotic patients.

Adult patients with clinically diagnosed liver cirrhosis who underwent at least 2 abdominal computed tomography (CT) scans in the hospital were enrolled. The interval between the two abdominal scans was 6 ± 1 months. Patients were categorized into persistent non-sarcopenia, new-onset sarcopenia, sarcopenia to non-sarcopenia, and persistent sarcopenia based on changes in sarcopenia. Kaplan-Meier method and Log-rank tests were used to separately compare unadjusted survival curves by different statuses of sarcopenia. Cox regression analysis was performed to assess the associations between different states of sarcopenia and overall mortality. The association between persistent non-sarcopenia and new-onset sarcopenia was analyzed by multivariate logistic regression analysis.

A total of 307 patients were included for analysis. At the second assessment, 10.10% (31/307) patients were new-onset sarcopenia, 27.69% (85/307) with persistent sarcopenia status, while 13.03% (40/307) patients with sarcopenia developed non-sarcopenia and 49.19% (151/307) with persistent non-sarcopenia status. The overall survival rate was significantly lower in the persistent sarcopenia and new-onset sarcopenia than in the non-sarcopenia group and sarcopenia to non-sarcopenia group (p < 0.001). Persistent sarcopenia (HR 5.799, 95%CI 1.563-21.521, p = 0.009) and new onset sarcopenia (HR 5.205, 95%CI 1.482-18.282, p = 0.010) were identified as poor prognostic factors for cirrhotic patients. The etiology of cirrhosis and the initial skeletal muscle mass were independent risk factors for new-onset sarcopenia.

Sarcopenia is a dynamically changing process in patients with cirrhosis. Persistent and new-onset sarcopenia were independently and robustly associated with overall survival.

Frailty is linked to an increased incidence of hepatic decompensation and mortality in cirrhosis. The aim of our study was to identify a novel scanographic score that predicts frailty and its impact in cirrhosis.

This study included 51 patients with cirrhosis. We used the frailty scale risk assessment score to identify frail patients. The density and area of different muscles at L3 level were analyzed on computed tomography (CT) sections. The L3 skeletal muscle area adjusted to height and density ratio (L3-SMDHR) was defined as L3 muscle wall*height/density.

The L3-SMHDR is significantly higher in frail patients and in patients with Child B/C scores. Frailty was correlated with L3-SMHDR. Frailty and L3- SMHDR were correlated with liver-related events (LRE). We set the most appropriate cut-offs of L3-SMHDR for both sensitivity and specificity by using the ROC: 5.4 for males and 4.7 for females. The AUROC score was 0.784 for male and 0.975 for female patients. The Kappa score between frailty and L3-SMHDR was 0.752, with a percentage of agreement of 87.5%, showing a substantial agreement. This ratio with the divided categories has a sensitivity of 100%, a specificity of 76%, a positive predictive value of 79.3% and a negative predictive value of 100%. Patients with high L3-SMHDR have significantly lower survival time and a higher incidence of LRE.

The L3-SMHDR is a new index for identifying frailty in cirrhosis by using measurable and reproducible variables. It can be used as a prognostic factor for frailty in patients with cirrhosis.

Malnutrition is highly prevalent and associated with complications and mortality in patients with cirrhosis.

This was a prospective observational study. Patients with cirrhosis were screened using the Nutritional Risk Screening 2002, the Royal Free Hospital-Nutritional Prioritizing Tool and the Skeletal Muscle Index. Then, the sensitivity, specificity, positive and negative predictive values, and consistency with the Global Leadership Initiative on Malnutrition criteria results were calculated. We also analysed the association between nutritional status and short-term prognosis.

We enrolled 125 patients with cirrhosis, of whom 59.20% and 60.00% were malnourished based on the Global Leadership Initiative on Malnutrition criteria and Skeletal Muscle Index. Some 53.60% and 65.60%, respectively, were classified medium-to-high nutritional risk by Nutritional Risk Screening 2002 and the Royal Free Hospital-Nutritional Prioritizing Tool. The Royal Free Hospital-Nutritional Prioritizing Tool had the best predictive value, and it was more sensitive and had a better negative predictive value than the Nutritional Risk Screening 2002 Tool. The Skeletal Muscle Index also had good sensitivity and predictive value. The Royal Free Hospital-Nutritional Prioritizing Tool, Skeletal Muscle Index and Global Leadership Initiative on Malnutrition criteria showed high concordance. The 3- and 6-month mortality rates were significantly higher for patients with moderate-to-high nutritional risk or malnutrition, regardless of the tool.

When assessing cirrhosis with the Global Leadership Initiative on Malnutrition criteria, the Royal Free Hospital-Nutritional Prioritizing Tool is best for nutritional screening and the Skeletal Muscle Index is also a good nutritional assessment tool.

Malnutrition, sarcopenia, and frailty are prevalent in cirrhosis. We aimed to assess the correlation between assessment tools for malnutrition, sarcopenia, and frailty in patients on the liver transplant (LT) waiting list (WL), and to identify a predictive model for acute-on-chronic liver failure (ACLF) development.

This prospective single-center study enrolled consecutive patients with cirrhosis on the WL for LT (May 2019-November 2021). Assessments included subjective global assessment, CT body composition, skeletal muscle index (SMI), ultrasound thigh muscle thickness, sarcopenia HIBA score, liver frailty index (LFI), hand grip strength, and 6-minute walk test at enrollment. Correlations were analyzed using Pearson's correlation. Competing risk regression analysis was used to assess the predictive ability of the liver- and functional physiological reserve-related variables for ACLF.

A total of 132 patients, predominantly with decompensated cirrhosis (87%), were included. Our study revealed a high prevalence of malnutrition (61%), sarcopenia (61%), visceral obesity (20%), sarcopenic visceral obesity (17%), and frailty (10%) among participants. Correlations between the assessment tools for sarcopenia and frailty were poor. Sarcopenia by SMI remained prevalent when frailty assessments were not usable. After a median follow-up of 10 months, 39% of the patients developed ACLF on WL, while 28% experienced dropouts without ACLF. Multivariate analysis identified MELD-Na, SMI, and LFI as independent predictors of ACLF on the WL. The predictive model MELD-Na-sarcopenia-LFI had a C-statistic of 0.85.

The poor correlation between sarcopenia assessment tools and frailty underscores the importance of a comprehensive evaluation. The SMI, LFI, and MELD-Na independently predicted ACLF development in WL. These findings enhance our understanding of the relationship between sarcopenia, frailty, and ACLF in patients awaiting LT, emphasizing the need for early detection and intervention to improve WL outcomes.

The relationship between sarcopenia and frailty assessment tools, as well as their ability to predict acute-on-chronic liver failure (ACLF) in patients on the liver transplant (LT) waiting list (WL), remains poorly understood. Existing objective frailty screening tests have limitations when applied to critically ill patients. The correlation between sarcopenia and frailty assessment tools was weak, suggesting that they may capture different phenotypes. Sarcopenia assessed by skeletal muscle index, frailty evaluated using the liver frailty index, and the model for end-stage liver disease-Na score independently predicted the development of ACLF in patients on the WL. Our findings support the integration of liver frailty index and skeletal muscle index assessments at the time of inclusion on the WL for LT. This combined approach allows for the identification of a specific patient subgroup with an increased susceptibility to ACLF, underscoring the importance of early implementation of targeted treatment strategies to improve outcomes for patients awaiting LT.

The prevalence of metabolic-associated fatty liver disease (MAFLD) has increased substantially in recent years because of the global obesity pandemic. MAFLD, now recognized as the number one cause of chronic liver disease in the world, not only increases liver-related morbidity and mortality among sufferers but also worsens the complications associated with other comorbid conditions such as cardiovascular disease, type 2 diabetes mellitus, obstructive sleep apnoea, lipid disorders and sarcopenia. Understanding the interplay between MAFLD and these comorbidities is important to design optimal therapeutic strategies. Sarcopenia can be either part of the disease process that results in MAFLD (e.g., obesity or adiposity) or a consequence of MAFLD, especially in the advanced stages such as fibrosis and cirrhosis. Sarcopenia can also worsen MAFLD by reducing exercise capacity and by the production of various muscle-related chemical factors. Therefore, it is crucial to thoroughly understand how we deal with these diseases, especially when they coexist. We explore the pathobiological interlinks between MAFLD and sarcopenia in this comprehensive clinical update review article and propose evidence-based therapeutic strategies to enhance patient care.

The association between the presence of sarcopenia in patients with cirrhosis and the onset of hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) is yet to be established. We conducted a systematic review and meta-analysis to provide a thorough summary of the available evidence on this association.

A thorough search of the literature was performed in the PubMed, EMBASE, and Web of Science databases. The protocol was duly registered on PROSPERO (CRD42023398856). The hazard ratio (HR) and corresponding 95% confidence intervals (CIs) for the occurrence of HE after TIPS were extracted from studies comparing cirrhotic patients with and without sarcopenia. These data were then combined using a random-effect model.

A total of 1135 patients from seven cohort studies that met our eligibility criteria were included in the meta-analysis. Our findings indicate a significantly higher risk of post-TIPS HE among cirrhotic patients with sarcopenia compared to those without sarcopenia (HR, 2.35; 95% CIs 1.32-4.19; p = 0.004; I2 = 75%). The findings remained consistent across subgroups stratified by liver disease etiology, study location, and severity of hepatic dysfunction.

The study demonstrated that sarcopenia was strongly linked to an increased likelihood post-TIPS HE among cirrhotic patients.

Protein induced by vitamin K (VK) absence-II (PIVKA-II) is a sensitive marker for diagnosing hepatoma but is occasionally detected in patients without hepatoma Here, the clinical significance of serum PIVKA-II levels in patients who were not administered warfarin and did not have hepatoma or liver disease were evaluated. As VK is related to muscle and bone metabolism, PIVKA-II and clinical factors related to bone and muscle were compared. A total of 441 patients with various liver diseases were evaluated. Of these, 236 patients were female. Clinical factors and anthropometric measurements were obtained for each participant during outpatient visits. Among the clinical factors, type I procollagen N-propeptide (P1NP), a low titer of undercarboxylated osteocalcin (ucOC), and 25(OH) vitamin D (VD) were used as bone metabolic markers, and SARC-F and grip strength were used as muscle-related markers. Serum PIVKA-II levels above the upper limit were associated with Child B/C (Child-Pugh score), high titers of total P1NP, and low titers of ucOC in females, and alcohol-related liver disease and low VD in males. The titer of PIVKA-II were associated with immunoglobulin (Ig) A and prothrombin time (PT)-international normalized ratio (INR) in females, and fibrosis-4-4, IgG, total bilirubin, PT-INR, and SARC-F in males. Elevated PIVKA-II levels were associated with abnormal bone physiology in females, weak muscles in males, and severe liver disease in both sexes. Assessing PIVKA-II may assist in evaluating the clinical and bone-muscle metabolic stages in liver disease. Nutrition and supplementation with fat-soluble vitamins, including VK and VD may thus serve as a potential method to alleviate or prevent bone-muscle pathophysiology in patients with liver disease.

Malnutrition and sarcopenia are highly prevalent in patients with decompensated cirrhosis and are associated with poorer clinical outcomes. Their pathophysiology is complex and multifactorial, with protein-calorie malnutrition, systemic inflammation, reduced glycogen stores and hormonal imbalances all well reported. The direct contribution of portal hypertension to these driving factors is however not widely documented in the literature. This review details the specific mechanisms by which portal hypertension directly contributes to the development of malnutrition and sarcopenia in cirrhosis. We summarise the existing literature describing treatment strategies that specifically aim to reduce portal pressures and their impact on nutritional and muscle outcomes, which is particularly relevant to those with end-stage disease awaiting liver transplantation.

Chronic liver diseases, especially cirrhosis, are associated with significant morbidity and mortality. Besides predisposing to chronic liver disease per se, diabetes, hypertension, and dyslipidemia worsen the prognosis of patients with cirrhosis induced by other causes. There is no standard of care in the management of these factors in patients with cirrhosis. Also, in particular, it is not known whether nutritional interventions in the modification of cardiometabolic factors can improve the course of cirrhosis or not. This narrative review aimed to investigate the clinical significance of diabetes, hypertension, and dyslipidemia and appropriate nutritional interventions in cirrhotic patients. A comprehensive literature search of the published data was performed in regard to the association of cirrhosis with cardiometabolic factors and the management of cirrhosis and its complications. There is limited evidence on the association of cirrhosis with cardiometabolic risk factors. Cirrhotic cardiometabolic abnormalities are associated with an increased risk of complications, such that the coexistence of diabetes, hypertension, and dyslipidemia increases the risk of clinical decompensation in cirrhosis. Dietary management of cirrhotic patients with risk factors such as diabetes, hypertension, or dyslipidemia does not seem to be considerably different from non-cirrhotic patients.

Malnutrition is common among inpatients with cirrhosis. However, data on the prevalence of malnutrition among stable ambulatory patients with cirrhosis is lacking. We sought to investigate the prevalence of patents at risk of malnutrition (ARMN) among ambulatory patients with cirrhosis using the Royal Free Hospital-Nutrition Prioritizing Tool (RFH-NPT) and the Malnutrition Universal Screening Tool (MUST) and compare their correlation to clinical outcomes.

Patients attending an outpatient liver cirrhosis clinic at a tertiary hospital were screened for ARMN using both the RFH-NPT and MUST (defined by a score of ≥2 for either tool). Differences in clinical outcomes after 6 mo were compared.

There were 134 patients recruited. The RFH-NPT identified more ARMN patients compared with MUST (32.8% versus 8.2%; P < 0.01; Cohen κ, 0.27 [95% CI, 0.12-0.42]; P < 0.001). Fluid overload at recruitment was the only independent predictor of disagreement between the RFH-NPT and MUST (odds ratio [OR], 43.14; 95% CI, 8.70-214.00; P < 0.001). There was a trend toward an increased risk of mortality for ARMN patients by the RFH-NPT (hazard ratio, 3.58; 95% CI, 0.81-15.83; P = 0.06) but not by the MUST (P = 0.62). The incidence of hospital admissions in ARMN patients was higher by the RFH-NPT, with an incidence rate ratio of 13.27 (95% CI, 5.11-43.70; P < 0.001), but not in ARMN patients by the MUST (P = 0.85). Being ARMN by the RFH-NPT was the only independent predictor of hospital admissions (OR, 15.08; 95% CI, 2.47-91.98; P = 0.003).

The RFH-NPT identified more ARMN patients when compared with the MUST, especially among patients with fluid overload. Patients at risk of malnutrition were at an increased risk of hospital admissions and possibly death.

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.

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.

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.

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.

A glucagon-like peptide-1 receptor agonist (GLP-1RA) has recently been established as a pharmacological option for the treatment of type 2 diabetes. Recent studies have demonstrated the molecular role of GLP-1R in skeletal muscle homeostasis; however, the therapeutic efficacy of semaglutide, a GLP-1RA, on skeletal muscle atrophy in chronic liver disease (CLD) under diabetic conditions remains unclear. In the present study, semaglutide effectively inhibited psoas muscle atrophy and suppressed declines in grip strength in a diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet-fed diabetic KK-Ay mouse model. Moreover, semaglutide inhibited ubiquitin-proteosome-mediated skeletal muscle proteolysis and promoted myogenesis in palmitic acid (PA)-stimulated C2C12 murine myocytes. Mechanistically, this effect of semaglutide on skeletal muscle atrophy was mediated by multiple functional pathways. First, semaglutide protected against hepatic injury in mice accompanied by increased production of insulin-like growth factor 1 and reduced accumulation of reactive oxygen species (ROS). These effects were associated with decreased proinflammatory cytokines and ROS accumulation, leading to the suppression of ubiquitin-proteosome muscle degradation. Moreover, semaglutide inhibited the amino acid starvation-related stress signaling that was activated under chronic liver injury, resulting in the recovery of the mammalian target of rapamycin activity in the skeletal muscle of DDC-diet fed KK-Ay mice. Second, semaglutide improved skeletal muscle atrophy by directly stimulating GLP-1R in myocytes. Semaglutide induced cAMP-mediated activation of PKA and AKT, enhanced mitochondrial biogenesis, and reduced ROS accumulation, thereby resulting in inhibition of NF-κB/myostatin-mediated ubiquitin-proteosome degradation and the augmentation of heat-shock factor-1-mediated myogenesis. Collectively, semaglutide may have potential as a new therapeutic strategy for CLD-related skeletal muscle wasting.

Malnutrition, which increases the risk of liver disease-related events and mortality, is a serious complication in cirrhosis. This study aimed to investigate whether the geriatric nutritional risk index (GNRI) could predict the long-term prognosis in patients with cirrhosis.

We retrospectively evaluated 266 patients with cirrhosis and classified them into two groups based on baseline GNRI scores: risk (≤98, n = 104) and no-risk groups (>98, n = 162). The cumulative survival rates were compared between the two groups in patients with compensated and decompensated cirrhosis, respectively. Cox proportional hazards regression analysis was used to identify significant and independent factors associated with mortality.

The median observation period was 54.9 (33.6-61.7) months and 65 (24.4%) liver disease-related deaths occurred during the follow-up period. The GNRI scores significantly and inversely correlated with Child-Pugh score (r = -0.579), model for end-stage liver disease score (r = -0.286), and Mac-2 binding protein glycosylation isomer (r = -0.494). Multivariate analysis identified low GNRI as a significant and independent factor associated with mortality [overall cohort: hazard ratio (HR), 0.926; p < 0.001; compensated cirrhosis: HR, 0.947; p = 0.003; decompensated cirrhosis: HR, 0.923; p < 0.001]. The risk group demonstrated significantly lower cumulative survival rates than the no-risk group in overall cohort, and patients with compensated and decompensated cirrhosis (p < 0.001, <0.001, and = 0.013, respectively).

Low GNRI was associated with poor long-term prognosis in both patients with compensated and decompensated cirrhosis. Therefore, the GNRI is a simple and useful tool for predicting prognosis and modifying the nutritional status in patients with cirrhosis.

Pulmonary hypertension (PH) has recently been described as a complex clinical syndrome affecting multiple organ systems, including the heart, lungs, and skeletal muscle, each of which plays an important role in exercise capacity. However, the relationship between exercise capacity and skeletal muscle abnormalities in patients with PH has not been fully elucidated.

We retrospectively analysed the exercise capacity and measures of skeletal muscle of 107 patients with PH without left heart disease (mean age 63 ± 15 years, 32.7% males, n = 30/6/66/5 in the clinical classification Group 1/3/4/5).

Sarcopenia, low appendicular skeletal muscle mass index, low grip strength, and slow gait speed, determined by international criteria, were found in 15 (14.0%), 16 (15.0%), 62 (57.9%), and 41 (38.3%) patients, respectively. The mean 6-min walk distance of all patients was 436 ± 134 m and was independently associated with sarcopenia (standardised β = -0.292, p < 0.001). All patients with sarcopenia showed reduced exercise capacity defined as 6-min walk distance < 440 m. Multivariable logistic regression analysis showed that each of the components of sarcopenia was associated with reduced exercise capacity (adjusted odds ratio and 95% confidence interval of appendicular skeletal muscle mass index: 0.39 [0.24-0.63] per 1 kg/m2, p = 0.006, grip strength: 0.83 [0.74-0.94] per 1 kg, p = 0.003, and gait speed: 0.31 [0.18-0.51] per 0.1 m/s, p < 0.001).

Sarcopenia and its components are associated with reduced exercise capacity in patients with PH. A multifaceted evaluation may be important in the management of reduced exercise capacity in patients with PH.