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.

Sarcopenia is a syndrome of severe muscle wasting, associated with adverse outcomes related to liver transplantation (LT). There are several approaches used to identify sarcopenia. We aimed to investigate the prevalence of sarcopenia using 3 different criteria and determine how these performed in relation to clinical outcomes.

The cohort study included 237 adults with cirrhosis referred for LT. Sarcopenia was identified using (1) CT-defined; and the (2) original and (3) updated European Working Group on Sarcopenia in Older People criteria (EWGSOP1 and 2). Logistic regression was used to estimate OR and 95% CI for the relationships between sarcopenia and receiving an LT, unplanned admissions pre-LT, surgical complications, and length of stay for the LT admission. Fine-Gray competing risk analysis explored the impact of sarcopenia on receiving an LT and unplanned admissions. The AUC determined the predictive utility of the criteria.

The prevalence of CT-defined sarcopenia (52%) was more than twice and 4-fold that of EWGSOP1-defined (22%) and EWGSOP2-defined (11%) sarcopenia, respectively. No criteria demonstrated a significant association with time to LT nor the time to unplanned admissions pre-LT. Similarly, none of the 3 criteria had superior predictive utility for the clinical outcomes for unplanned hospital admissions pre-LT of receiving an LT, with all 3 criteria having identical moderate AUCs for unplanned admissions (0.70) and similar weak AUCs (≤0.55) for the likelihood of receiving an LT.

Sarcopenia in patients undergoing LT evaluation is prevalent. EWGSOP criteria appear to offer no advantage over CT-only criteria in identifying patients at increased risk of adverse LT outcomes. Bedside measures of muscle function may be of benefit in tracking the effectiveness of interventions targeting sarcopenia.

Hepatic encephalopathy (HE) is a frequent decompensation in patients with cirrhosis, which significantly affects morbidity and mortality. Ammonia is a major neurotoxin implicated in the pathogenesis, progression, and severity of HE, and various organs including the gut, muscle, kidney, and brain are involved in its metabolism. Therefore, therapeutic management involves reducing ammonia production and increasing its elimination from the blood and the brain. Prevention of HE in patients at high risk of first and recurrent episodes is important for prolonging survival. Various anti-ammonia therapies with synergistic and complementary actions have been attempted for overt HE and for prophylaxis of the first and recurrent episodes of HE. In the current review, we summarize the currently used and under-development pharmacotherapies/procedure(s) for HE in cirrhosis and their mechanism of action. Primary and secondary prophylaxis with monotherapies and combination therapies are also discussed.

This scoping review aimed to delineate the detailed components of exercise therapy and the evaluation methods used for patients with liver cirrhosis.

The methodology involved searching the original PubMed, Web of Science, and Scopus for studies published between January 1975 and March 2025. The search was completed on 13 March 2025. Studies describing exercise therapy for liver cirrhosis patients were selected. Relevant information matching the study objectives, such as intervention duration, content, intensity setting, evaluation criteria, and outcomes, was extracted and documented.

Of the 2314 articles identified, 18 fit the inclusion and exclusion criteria, with a total of 950 participants. The most prevalent form of exercise therapy was a combined aerobic exercise and strength training program (55.6%). Commonly used assessment criteria included the 6-minute walking distance for endurance evaluation (44.4%) and the Chronic Liver Disease Questionnaire for quality of life assessment (33.3%). Intervention durations ranged from 30 to 60 min per day, 2 to 7 days per week, and 8 to 12 weeks. Concerning intensity setting, subjective fatigue levels and heart rate were frequently used (38.9%), though detailed descriptions were limited.

For the establishment of effective exercise therapy for patients with liver cirrhosis, future research should concentrate on tailoring intensity settings according to individual patient needs. Additionally, standardized reporting of intervention details and assessment methods is crucial for improving the quality and comparability of studies in this field.

Two main stages are differentiated in patients with advanced chronic liver disease (ACLD), one compensated (cACLD) with an excellent prognosis, and the other decompensated (dACLD), defined by the appearance of complications (ascites, variceal bleeding and hepatic encephalopathy) and associated with high mortality. Preventing the progression to dACLD might dramatically improve prognosis and reduce the burden of care associated with ACLD. Portal hypertension is a major driver of the transition from cACLD to dACLD, and a portal pressure of ≥10 mmHg defines clinically significant portal hypertension (CSPH) as the threshold from which decompensating events may occur. In recent years, innovative studies have provided evidence supporting new strategies to prevent decompensation in cACLD. These studies have yielded major advances, including the development of noninvasive tests (NITs) to identify patients with CSPH with reasonable confidence, the demonstration that aetiological therapies can prevent disease progression and even achieve regression of cirrhosis, and the finding that non-selective β-blockers can effectively prevent decompensation in patients with cACLD and CSPH, mainly by reducing the risk of ascites, the most frequent decompensating event. Here, we review the evidence supporting new strategies to manage cACLD to prevent decompensation and the caveats for their implementation, from patient selection using NITs to ancillary therapies.

Malnutrition is common in liver cirrhosis and is associated with increased rates of complications, hospitalization, and mortality. There are no consensus guidelines for malnutrition assessment in liver cirrhosis and a large number of clinicians do not routinely assess for malnutrition in patients with liver cirrhosis. This review explores the tools available for assessment of malnutrition in patients with liver cirrhosis, including nutritional screening protocols, anthropometric tools, biochemical tools, techniques analyzing body composition and functional assessments. We evaluate these tools and offer recommendations regarding their suitability for outpatient settings. In this review, we recommend the Royal Free Hospital-Nutritional Prioritising Tool for identifying patients at risk of malnutrition. Additionally, we recommend the use of the anthropometric tools Triceps Skinfold Thickness for females and Mid-Arm Muscle Circumference for males, due to differing patterns of muscle and fat malnutrition. Complementing this Bioelectrical Impedance Analysis can be utilized to assess body composition for the diagnosis of malnutrition. Biochemical markers have thus far failed to show a correlation with malnutrition. While hand grip strength is useful for detecting sarcopenia, a common complication of malnutrition, further evidence is required to validate its correlation with malnutrition.

Over the past six decades, liver transplantation (LT) has evolved from an experimental procedure into a standardized and life-saving intervention, reshaping the landscape of organ transplantation. Driven by pioneering breakthroughs, technological advancements, and a deepened understanding of immunology, LT has seen remarkable progress. Some of the most notable breakthroughs in the field include advances in immunosuppression, a revised model for end-stage liver disease, and artificial intelligence (AI)-integrated imaging modalities serving diagnostic and therapeutic roles in LT, paired with ever-evolving technological advances. Additionally, the refinement of transplantation procedures, resulting in the introduction of alternative transplantation methods, such as living donor LT, split LT, and the use of marginal grafts, has addressed the challenge of organ shortage. Moreover, precision medicine, guiding personalized immunosuppressive strategies, has significantly improved patient and graft survival rates while addressing emergent issues, such as short-term complications and early allograft dysfunction, leading to a more refined strategy and enhanced post-operative recovery. Looking ahead, ongoing research explores regenerative medicine, diagnostic tools, and AI to optimize organ allocation and post-transplantation car. In summary, the past six decades have marked a transformative journey in LT with a commitment to advancing science, medicine, and patient-centered care, offering hope and extending life to individuals worldwide.

Background: Liver cirrhosis is associated with significant nutritional challenges, including malnutrition, sarcopenia, and frailty, which impact clinical outcomes. The severity of these issues may vary between inpatient and outpatient settings, but there is a limited understanding of how these conditions manifest in these populations. This study aims to compare the nutritional status, dietary intake, and frailty in outpatients and inpatients with liver cirrhosis and to explore potential sex-specific differences. Methods: This prospective observational study enrolled 195 patients with liver cirrhosis from the Gastroenterology ward and Outpatient Clinic of Policlinico Umberto I, Sapienza University of Rome, between May 2023 and July 2024. Nutritional status was assessed using anthropometric measurements, dietary recall, and food frequency questionnaires. Sarcopenia was evaluated using the SARC-F questionnaire and handgrip strength. Frailty was assessed using the Liver Frailty Index (LFI). Data on clinical characteristics, comorbidities, and disease severity were also recorded. Results: The inpatient group (n = 69) had significantly lower BMI, mid-upper arm circumference, and triceps skinfold compared to outpatients (n = 126). Inpatients exhibited higher frailty, with 73.9% classified as frail according to the LFI, compared to 39.6% in outpatients (p < 0.001). Dietary intake revealed that 91% of inpatients had an energy intake deficit compared to 76% of outpatients (p = 0.009). Protein intake was inadequate in 84% of inpatients versus 61% of outpatients (p < 0.001). Sex-specific analysis showed that females had a higher prevalence of sarcopenia than males (64.4% vs. 38.2%, p < 0.001) and experienced more significant protein deficits (74.3% vs. 57.6%, p = 0.021). Females also had higher LFI score (4.77 ± 0.88 vs. 4.45 ± 0.91, p = 0.034). Multivariate analysis showed that CTP, LFI, and protein deficit are independently associated with hospitalization. Conclusions: Inpatients with liver cirrhosis are at higher risk for malnutrition, frailty, and inadequate nutrient intake compared to outpatients, emphasizing the need for targeted nutritional interventions in hospital settings. Additionally, females with cirrhosis are more prone to sarcopenia and frailty, requiring gender-specific approaches to nutrition.

Sarcopenia and hepatic encephalopathy (HE) are complications of chronic liver disease (CLD), which negatively impact clinical outcomes. Hyperammonemia is considered to be the central component in the pathogenesis of HE, however ammonia's toxic effects have also been shown to impinge on extracerebral organs including the muscle. Our aim was to investigate the effect of attenuating hyperammonemia with ornithine phenylacetate (OP) on muscle mass loss and associated molecular mechanisms in rats with CLD. Six-week bile duct-ligated (BDL) rats and Sham-operated controls were treated with OP (1 g/kg, oral) for 5 weeks. Body composition, assessed by EchoMRI, and muscle protein fractional synthesis rate were evaluated. Signalling mechanisms regulating protein homeostasis, ATP content and metabolic intermediates in the tricarboxylic acid cycle (TCA) in skeletal muscle were quantified. OP treatment attenuated hyperammonemia, prevented brain edema and improved locomotor activity in BDL rats. Increased muscle ammonia, reduction in lean body mass, decreased muscle protein synthesis rate and ATP content were restored in OP-treated versus saline-treated BDL rats. TCA cycle intermediary metabolite, α-ketoglutarate, alterations of molecular markers regulating protein homeostasis including mTOR signalling and autophagy, were also preserved in muscle of OP-treated BDL rats. OP attenuated hyperammonemia, preserved muscle protein synthesis and prevented muscle mass loss in a preclinical model of CLD through restoration of perturbed signalling responses and altered TCA intermediary metabolites. Ammonia-lowering strategies have the potential for rapid clinical translation for simultaneous neuroprotection and sarcopenia prevention in patients with CLD.

Malnutrition is prevalent, detrimental, and associated with worse outcomes, including higher rates of hospitalization, morbidity, and mortality. In this review article, we aimed to define malnutrition in patients with chronic liver disease (CLD), elucidate the pathogenesis of malnutrition, discuss the advantages and disadvantages of current screening methods, and highlight the latest evidence-based dietary recommendations. Emerging evidence suggests that CLD-specific tools such as the Liver Disease Undernutrition Screening Tool and the Royal Free Hospital-Nutritional Prioritizing Tool can accurately identify patients at high risk for malnutrition and should be used in conjunction with more standard tools such as subjective global assessments. The pathogenesis of malnutrition in CLD is multifactorial but seems to arise in large from altered metabolism, namely a reduction in protein synthesis and an increase in resting energy expenditure. However, decreased nutrient intake, impaired nutrient absorption and increased nutrient losses have also been shown to contribute. Key findings in this review argue against protein-restricted diets in patients with CLD and support the use of plant-based proteins over dairy and meat proteins for those with liver cirrhosis complicated by hepatic encephalopathy. Frequent small meals are recommended in patients with liver cirrhosis in addition to the avoidance of prolonged fasts >12 hours due to their hypercatabolic state. CLD covers a wide spectrum of diseases, and this review calls for an individualized approach to addressing the specific nutritional needs, depending on the etiology of CLD, its severity, associated complications, and comorbid conditions. This can be best achieved by close, longitudinal follow-up with a multidisciplinary team including a registered dietitian who can obtain a comprehensive, accurate nutritional assessment.

It has been shown that in patients with liver cirrhosis, sarcopenia is a predictor of acute decompensation (AD), acute-on-chronic liver failure (ACLF) and death. However, computer tomography (CT), as a suggested standard method for diagnosing sarcopenia, is resource intensive and involves radiation exposure. Therefore, in this study, we evaluate the muscle thickness of quadriceps femoris measured by ultrasound (US) as a prognostic parameter for AD and all-cause mortality in chronic liver disease.

Sixty-three patients with chronic liver disease and signs of portal hypertension were analysed in this prospective monocentric study for the occurrence of acute decompensation such as hepatic encephalopathy, ascites, haemorrhage and liver-related death within 1 year. We assessed muscle thickness at three different heights in terms of suitability as a predictor.

Among all 63 patients, 15 patients experienced acute decompensation, and 9 patients died due to liver-related death. We found the upper third of the muscle, measured without applying pressure with the transducer, to be the most significant for predicting AD/ACLF [AUC 0.739 (confidence interval (CI) 0.604-0.874, p = 0.006]. A cut-off value of US-defined muscle thickness standardized per height for identifying sarcopenia was determined (1.83 cm/m). Patients with US-defined sarcopenia showed significantly higher rates of AD (38.9% vs. 3.7%, p = 0.001) and all-over 1-year mortality (27.8% vs. 3.7%, p = 0.013). The mean AD free survival time is 8.3 months (95% CI 6.6-9.9) for sarcopenic patients and 11.8 months (95% CI 11.0-12.6) for the non-sarcopenic cohorts. Corresponding CT analysis displayed similar results for AD free survival for both groups (40% AD rate in the sarcopenic group vs. 7% AD rate in the non-sarcopenic group, p = 0.001). The risk for AD was significantly higher in the sarcopenic cohort compared with those without sarcopenia in both US and CT (US: HR 16.6; p = 0.009; 95% CI 2.0-136.0; CT: HR 8.7; p = 0.017; 95% CI 1.5-51.0). CT and US displayed a moderate agreement (p = 0.006; κ = 0.379).

Sarcopenia classification based on US measurements is shown to be an independent predictor of AD occurrence within 1 year. This pilot study is the first to suggest that screening for sarcopenia by ultrasonography may be useful for risk assessment in patients with chronic liver disease and signs of portal hypertension.

Cardiovascular disease and physical decline are prevalent and associated with morbidity/mortality in liver transplant (LT) patients. Cardiopulmonary exercise testing (CPX) provides comprehensive cardiopulmonary and exercise response assessments. We investigated cardiorespiratory fitness (CRF) and cardiac stress generated during CPX in LT candidates.

LT candidates at 2 centers underwent CPX. Standard-of-care cardiac stress testing (dobutamine stress echocardiography, DSE) results were recorded. Physical function was assessed with liver frailty index and 6-min walk test. CPX/DSE double products were calculated to quantify cardiac stress. To better study the association of CPX-derived metrics with physical function, the cohort was divided into 2 groups based on 6-min walk test median (372 m).

Fifty-four participants (62 ± 8 y; 65% men, Model for End-Stage Liver Disease-Na 14 [10-18]) underwent CPX. Peak oxygen consumption was 14.1 mL/kg/min for an anerobic threshold of 10.2 mL/kg/min, with further CRF decline in the lower 6MWT cohort despite lack of liver frailty index-frailty in 90%. DSE was nondiagnostic in 18% versus 4% of CPX (P = 0.058). All CPX were negative for ischemia. A double product of ≥25 000 was observed in 32% of CPX and 11% of DSE (P = 0.020). Respiratory function testing was normal. No patient presented major cardiovascular events at 30 d post-LT.

CPX provided efficient and effective combined cardiopulmonary risk and frailty assessments of LT candidates in a 1-stop test. The CRF was found to be very low despite preserved physical function or lack of frailty.

Pharmacological treatment of unresectable hepatocellular carcinoma (uHCC) includes sorafenib and lenvatinib, a tyrosine kinase inhibitor, which are linked to low serum levels of carnitine and reduced skeletal muscle volume. Nowadays, atezolizumab plus bevacizumab (Atezo/Bev) combination therapy is recommended as the first-line treatment for patients with uHCC. However, the association with decreased muscle mass or cardiac function is unknown. Therefore, this study aimed to evaluate the effects of Atezo/Bev on skeletal muscle volume and cardiac function in patients with uHCC.

This retrospective study included 55 adult Japanese patients with chronic liver diseases and uHCC treated with Atezo/Bev. Patients were divided into three groups according to age: middle, preold, and old. Serum levels of carnitine and cardiac function were measured before and after 3 weeks of treatment. The psoas muscle index (PMI) was measured before and after 6 weeks of treatment.

After treatment, the global longitudinal strain was significantly lower in the old group, whereas the PMI and ejection fraction were significantly lower in the preold and old groups. However, no significant difference in serum levels of total carnitine and those fractions with treatment in each group was found. Cardiac function decreased in the preold and old groups.

When treating patients with uHCC by Atezo/Bev, caution should be taken in preold and old patients because they are vulnerable to decreased skeletal muscle mass and deterioration of cardiac function. Strength training and regular monitoring of cardiac function are encouraged in these groups.

The aim of this study was to comprehensively compare the predictive effect of 10 body fat indexes on MAFLD in different sex, age and BMI subgroups.

A total of 5403 physical examination data were included and divided into the MAFLD group (N=2632) and non-MAFLD group (N=2771). The differences and correlation of 10 promising indicators between the two groups were compared, including fatty liver index (FLI), hepatic steatosis index (HSI), lipid accumulation product (LAP), visceral fat index (VAI), cardiometabolic index (CMI), body adiposity index (BAI), and triglyceride-glucose index (TyG), waist circumference index (WC), body mass index (BMI), waist to height ratio (WHtR). Logistic regression was used to analyze the risk of MAFLD under different adjustment conditions. The operating characteristic curve of different genders, BMI levels and age subgroups was plotted.

Male gender, smoking, alcohol drinking, and higher age are risk factors for MAFLD. In addition to BAI, the other 9 indicators had a high correlation with MAFLD, the area under the curve (AUC) value was >0.7, and the prediction effect was better in females, BMI<24 kg/m2, age <35 years subgroup, among which FLI (AUC: 0.912, 95% CI: 0.905-0.920), LAP (AUC: 0.894, 95% CI: 0.8866-0.903), and HSI (AUC: 0.881, 95% CI: 0.872-0.890) have better prediction effects.

Our study confirmed the accuracy of body fat-related indexes in predicting MAFLD in people of different sexes, ages, and BMI levels. Among them, FLI, LAP and HSI have high predictive value and can be utilized as simple and cost-effective tools for screening MAFLD in clinical settings.

Sarcopenia, characterized by the loss of skeletal muscle mass and function, is a significant complication in patients with cirrhosis. This condition not only exacerbates the overall morbidity and mortality associated with liver disease but also complicates patient management, increasing the risk of hospitalization, infections, and hepatic encephalopathy. Despite its clinical significance, sarcopenia in cirrhotic patients remains underdiagnosed and undertreated. This review aims to summarize current knowledge on the pathophysiology of sarcopenia in cirrhosis, including mechanisms such as altered metabolism, hormonal imbalances, and inflammation. Additionally, we explore diagnostic challenges and discuss emerging therapeutic strategies, including nutritional support, exercise, and pharmacological interventions. By highlighting the gaps in existing research and proposing directions for future studies, this review seeks to improve the management and outcomes of cirrhotic patients affected by sarcopenia.

Advances in surgical procedures and immunosuppressive therapies have considerably improved the outcomes of patients who have undergone liver transplantation in the past few decades. In 2020, the Italian Liver Transplant Working Group published practice-oriented algorithms for immunosuppressive therapy (IT) in adult liver transplant (LT) recipients. Due to the rapidly evolving LT field, regular updates to the recommendations are required. This review presents a consensus- and evidence-based update of the 2020 recommendations.

The Italian Liver Transplant Working Group set out to address new IT issues, which were discussed based on supporting literature and the specialists' personal experiences. The panel deliberated on and graded each statement before consensus was reached.

A series of consensus statements were formulated and finalized on: (i) oncologic indications for LT; (ii) management of chronic LT rejection; (iii) combined liver-kidney transplantation; (iv) immunosuppression for transplantation with an organ donated after circulatory death; (v) transplantation in the presence of frailty and sarcopenia; and (vi) ABO blood group incompatibility between donor and recipient. Algorithms were updated in the following LT groups: standard patients, critical patients, oncology patients, patients with specific etiology, and patients at high immunologic risk. A steroid-free approach was generally recommended, except for patients with autoimmune liver disease and those at high immunologic risk.

The updated consensus- and evidence-based 2024 recommendations for immunosuppression regimens in adult patients with ABO-compatible LT address a range of clinical variables that should be considered to optimize the choice of the immunosuppression treatment in clinical practice in Italy.

Sarcopenia and myosteatosis are common in patients with cirrhosis. This study aimed to determine the prevalence of these muscle changes, their interrelations and their prognostic impact over a 12-month period.

We conducted a prospective multicentre study involving 433 patients. Sarcopenia and myosteatosis were evaluated using computed tomography scans. The 1-year cumulative incidence of relevant events was assessed by competing risk analysis. We used a Fine-Gray model adjusted for known prognostic factors to evaluate the impact of sarcopenia and myosteatosis on mortality, hospitalization, and liver decompensation.

At enrolment, 166 patients presented with isolated myosteatosis, 36 with isolated sarcopenia, 135 with combined sarcopenia and myosteatosis and 96 patients showed no muscle changes. The 1-year cumulative incidence of death in patients with either sarcopenia and myosteatosis (13.8%) or isolated myosteatosis (13.4%) was over twice that of patients without muscle changes (5.2%) or with isolated sarcopenia (5.6%). The adjusted sub-hazard ratio for death in patients with muscle changes was 1.36 (95% CI 0.99-1.86, p = 0.058). The cumulative incidence of hospitalization was significantly higher in patients with combined sarcopenia and myosteatosis than in patients without muscle changes (adjusted sub-hazard ratio 1.18, 95% CI 1.04-1.35). The cumulative incidence of liver decompensation was greater in patients with combined sarcopenia and myosteatosis (p = 0.018) and those with isolated sarcopenia (p = 0.046) than in patients without muscle changes. Lastly, we found a strong correlation of function tests and frailty scores with the presence of muscle changes.

Myosteatosis, whether alone or combined with sarcopenia, is highly prevalent in patients with cirrhosis and is associated with significantly worse outcomes. The prognostic role of sarcopenia should always be evaluated in relation to the presence of myosteatosis.

This study investigates the prognostic role of muscle changes in patients with cirrhosis. The novelty of this study is its multicentre, prospective nature and the fact that it distinguishes between the impact of individual muscle changes and their combination on prognosis in cirrhosis. This study highlights the prognostic role of myosteatosis, especially when combined with sarcopenia. On the other hand, the relevance of sarcopenia could be mitigated when considered together with myosteatosis. The implication from these findings is that sarcopenia should never be evaluated individually and that myosteatosis may play a dominant role in the prognosis of patients with cirrhosis.

Frailty and sarcopenia are well-recognized factors related to worse outcomes in patients with cirrhosis, including liver transplant (LT) candidates. Implications of pre-LT functional and muscle deterioration also affect post-LT outcomes. Patients with cirrhosis and acute-on-chronic liver failure (ACLF) have a lower survival rate, both before and after LT. There is a need to better identify those patients with ACLF who would benefit from LT. This review aims to present the available data about frailty and sarcopenia in patients with ACLF in the LT setting. An exhaustive review of the published literature was conducted. Data regarding frailty and sarcopenia in LT candidates with ACLF are scarce and heterogeneous. Studies evaluating frailty and sarcopenia in critically ill patients outside the liver literature are also presented in this review to enrich the knowledge of this field in expansion. Frailty and sarcopenia seem to contribute to worse outcomes in LT candidates with ACLF, both before and after LT. Sarcopenia evaluation may be the most prudent approach for those very sick patients. Skeletal muscle index assessed by computed tomography is recommended to evaluate sarcopenia. The role of muscle ultrasound and bioelectrical impedance analysis is to be determined. Frailty and sarcopenia are crucial factors to consider on a case-by-case basis in LT candidates with ACLF to improve patient outcomes.

Sarcopenia's impact on hepatocellular carcinoma (HCC) outcomes is well-documented, but the effects of pre-sarcopenia remain unclear. This study investigates the impact of pre-sarcopenia on tumor response and survival in patients with unresectable HCC undergoing transarterial chemoembolization (TACE). We retrospectively evaluated muscle volume using the SliceOmatic software in patients with unresectable HCC treated with TACE. Pre-sarcopenia was defined by Japan Society of Hepatology standards (men: 42 cm2/m2; women: 38 cm2/m2). Pre-sarcopenia and non-pre-sarcopenia groups were compared, and Cox proportional hazards model was used to identify survival-influencing variables. Subgroup analysis was conducted stratified by the tumor burden, using serum alpha-fetoprotein (AFP) levels at a diagnostic cutoff value of 200 ng/mL. Of the 100 patients, 39 had pre-sarcopenia. The presence of pre-sarcopenia was not associated with tumor complete response achievement. The median overall survival (OS) was significantly lower in the pre-sarcopenia group (18 months) than in the non-pre-sarcopenia group (30 months; log-rank P = 0.039). Subgroup analysis among 77 patients with AFP < 200 ng/mL revealed that OS was particularly poor in the pre-sarcopenia group (16 vs. 34 months; log-rank P < 0.001). Multivariate analysis identified increased AFP (adjusted hazard ratio [HR] per 10-unit increase 1.142; P < 0.001), higher Model for End-Stage Liver Disease score (adjusted HR per 1-unit increase 1.176; P < 0.001), and pre-sarcopenia (adjusted HR 2.965; P < 0.001) as predictors of shorter OS. Pre-sarcopenia is a significant predictor of increased mortality in patients with unresectable HCC undergoing TACE, especially in those with AFP < 200 ng/mL, suggesting its potential as a target for early intervention.

Evidence-based guidelines (EBGs) in the nutrition management of advanced liver disease and enhanced recovery after surgery recommendations state that normal diet should recommence 12-24 h following liver transplantation. This study aimed to compare postoperative nutrition practices to guideline recommendations, explore clinician perceptions regarding feeding after transplant surgery, and implement and evaluate strategies to improve postoperative nutrition practices.

A pre-post multimethod implementation study was undertaken, guided by the knowledge-to-action framework. A retrospective chart audit of postoperative dietary practice and semistructured interviews with clinicians were undertaken. Implementation strategies were informed by the Consolidated Framework for Implementation Research-Expert Recommendations for Implementing Change matching tool and then evaluated.

An evidence-practice gap was identified, with the median day to initiation of nutrition (free-fluid or full diet) on postoperative day (POD) 2 and only 25% of patients aligning with the EBGs. Clinician interviews identified belief in the importance of nutrition, with variation in surgical practice in relation to early nutrition, competing clinical priorities, and vulnerabilities in communication contributing to delays in returning to feeding. An endorsed postoperative nutrition protocol was implemented along with a suite of theory- and stakeholder-informed intervention strategies. Following implementation, the median time to initiate nutrition reduced to POD1 and alignment with EBGs improved to 60%.

This study used implementation frameworks and strategies to understand, implement, and improve early feeding practices in line with EBGs after liver transplant. Ongoing sustainability of practice change as well as the impact on clinical outcomes have yet to be determined.

Sarcopenia has a detrimental impact on the prognosis of individuals with liver cirrhosis, however, the clinical significance of alterations in muscle mass remains uncertain. This study aims to investigate the influence of loss of skeletal muscle mass (LSMM) on the prognostic outcomes among patients diagnosed with cirrhosis.

In this retrospective analysis, a total of 158 individuals with cirrhosis who visited our hospital during the period from January 2018 to August 2023 were included. Computed tomography was utilized to measure the cross-sectional area of the skeletal muscles at the level of the third lumbar vertebra. This measurement enabled the determination of the skeletal muscle index for the purpose of diagnosing sarcopenia. The annual relative change in skeletal muscle area (ΔSMA/y) was calculated for each patient, and LSMM was defined as ΔSMA/y < 0. To assess the risk factors associated with liver-related mortality, a competing risk model was applied.

Of the 158 cirrhotic patients, 95 (60.1 %) patients were identified as LSMM. The median of ΔSMA/y% was -0.9 (interquartile range [IQR], -3.8, 1.6) in all patients. Chronic kidney disease (CKD) was confirmed as a risk factor of LSMM. During a median follow-up period of 68.1 (IQR, 43.5, 105.0) months, 57 patients (36.1 %) died due to the liver-related diseases. The competing risk model found that LSMM was significantly associated with liver-related mortality in cirrhotic patients (hazard ratio [HR], 1.86; 95 % CI, 1.01-3.44, p = 0.047). Cumulative survival was significantly higher in patients without LSMM than in those with LSMM (p = 0.004). Survival rates at 1-, 3-, and 5-years were 96.8 %, 81.0 %, and 65.1 %, respectively, in patients without LSMM, and 97.9 %, 80.0 %, and 56.8 %, respectively, in patients with LSMM.

The utilization of LSMM can be valuable in the prediction of liver-related mortality among individuals diagnosed with liver cirrhosis. Paying attention to the management of skeletal muscle might play a role in enhancing the prognosis of patients with cirrhosis.

This study provides an additional indicator-LSMM for clinicians to help predict the liver-related mortality in patients diagnosed with cirrhosis.

Sarcopenia is associated with increased morbidity and mortality in patients with cirrhosis, but its definition in current literature is very heterogeneous. We performed a systematic review and meta-analysis to assess the association between mortality and sarcopenia evaluated by computed tomography (CT) in patients with cirrhosis, both overall and stratified for the criteria used to define sarcopenia.

Medline, Embase, Scopus, and Cochrane Library were searched up to January 2023. We included studies assessing sarcopenia presence with CT scans and providing data on the risk of mortality. Adjusted hazard ratios (HRs) and 95% CIs were pooled using a random-effects model.

Thirty-nine studies comprising 12,827 patients were included in the meta-analysis. The summary prevalence of sarcopenia was 44% (95% CI 38-50%). The presence of sarcopenia (any definition) was an independent predictor of mortality with an adjusted HR of 2.07 (95% CI 1.81-2.36), and the result was consistent in all subgroup analyses. The prognostic role of the EASL/AASLD criteria was confirmed for the first time with an HR of 1.86 (95% CI 1.53-2.26) (n = 14 studies). The cut-offs used to define sarcopenia based on psoas muscle parameters varied among studies, thus, a subgroup analysis was not feasible. There was no substantial heterogeneity for the main estimates and no significant risk of publication bias.

Sarcopenia on CT is associated with a 2-fold higher risk of mortality in patients with cirrhosis. The cut-offs proposed by EASL/AASLD are prognostically relevant and should be the recommended criteria used to define sarcopenia in clinical practice.

Sarcopenia assessed by the reference standard (computed tomography scan) is an independent predictor of mortality in patients with cirrhosis, with a 2-fold increase in the risk of death in all sensitivity analyses. This finding is particularly valid in patients from Europe and North America, and in transplant candidates. Stratifying for the parameters and cut-offs used, we confirmed for the first time the prognostic impact of the definition proposed by EASL/AASLD, supporting their use in clinical practice. Psoas muscle assessment is promising, but data are still limited and too heterogeneous to recommend its routine use at present.

Sarcopenia is associated with many adverse outcomes in patients with cirrhosis. The tools currently in use for assessing sarcopenia have numerous flaws. We evaluated the utility of portable ultrasonography and a dynamometer for the bedside assessment of sarcopenia and its implications in hospitalized cirrhosis patients.

A dynamometer was used to test the hand-grip strength (HGS) and ultrasound was used to measure the thickness of the forearm and quadriceps muscles. HGS value < 27 kg for men and < 16 kg for women was taken as significant according to the European Working Group on Sarcopenia in Older People (EWGSOP2) criteria. The lower normal limit of muscle mass (5th percentile) was determined on 100 matched healthy controls.

According to the EWGSOP2 criteria and HGS values, the prevalence of sarcopenia and probable sarcopenia among 300 cirrhosis patients were 56% and 62.3%, respectively. HGS alone identified sarcopenia in 88.9% of patients, while overestimated it in 6.3% of cases. The prevalence rate of sarcopenic obesity was 11%. Compared to patients without sarcopenia, sarcopenic patients had more complications of cirrhosis such as ascites, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, sepsis, hepatorenal syndrome and refractory ascites. In-hospital (p = 0.037), three-month (p < 0.001), and six-month (p < 0.001) mortality rates were all higher among sarcopenic patients. On cox regression survival analysis, overall six-month mortality was significantly higher in sarcopenic patients compared to patients without sarcopenia (hazard ratio, 6.37; 95% confidence interval, 3.15-12.8, p < 0.001).

Bedside assessment of sarcopenia using a portable ultrasound machine and a dynamometer detects liver cirrhosis patients with high risk of complications and mortality.

Cirrhosis is a chronic liver disease with severe consequences for a patient's health and survival. Exercise is an essential therapeutic strategy for both cirrhosis prevention and treatment. On the other hand, information regarding the present status of exercise-related research in cirrhosis is limited. Therefore, this study seeks to close the information gap in the scientific literature by using bibliometric techniques to analyze the trends, focal points, and cutting-edge research areas on exercise and cirrhosis. On September 22, 2023, research articles and reviews on exercise intervention for cirrhosis were obtained and downloaded from the Web of Science Core Collection (WoSCC). Subsequently, we employed CiteSpace (version 6.1.R6) to conduct bibliometric and knowledge graph analyses. 588 papers in 301 scholarly journals were written by 673 authors from 460 institutions spread over 63 countries and regions. The most productive nation among them is the United States. Not only is Zobair M. Younossi 1 of the most prolific writers, but he also receives the most co-citations. Most articles were published by the University of Michigan in the US, with the University of Alberta in Canada coming in second. Meanwhile, the WORLD JOURNAL OF GASTROENTEROLOGY has the most published articles, whereas HEPATOLOGY has the greatest number of co-citations. Apart from the theme words, the most frequently utilized keywords were "quality of life," "insulin resistance," and "mortality." Future research may concentrate on "obesity," "sarcopenia," and "Mediterranean diet," according to the analysis of keyword emergence. CiteSpace is used in this work to visually represent the topic of exercise intervention in cirrhosis, offering valuable information to researchers regarding the field's current status and possible future direction.

Sarcopenia, characterized by progressive skeletal muscle loss, poses significant health risks, including physical impairment and mortality. The relationship between sarcopenia and insulin resistance suggests insulin therapy's potential in preserving muscle mass, particularly in Type 2 diabetes mellitus (T2DM) patients. This study aims to evaluate the Psoas Muscle Index (PMI) via computed tomography (CT) in middle-aged T2DM patients on insulin therapy versus oral antidiabetic drugs (OAD) and controls.

This retrospective study included 107 middle-aged T2DM patients undergoing non-contrast CT scans and 58 age-matched controls. CT images were analyzed to calculate PMI. Statistical analysis included Chi-square tests, independent samples t-tests, Mann-Whitney U tests, and correlation analyses.

Insulin-treated patients exhibited higher PMI than OAD users (p < 0.001), while OAD users had lower PMI than controls (p < 0.001). No significant difference was found between insulin-treated patients and controls (p = 0.616). Negative correlations were observed between T2DM duration/age and PMI across all groups, with a positive correlation between T2DM duration and BMI observed in the OAD group.

Insulin therapy in T2DM patients, regardless of age or disease duration, positively impacts muscle mass, highlighting its potential in preserving muscular health and advocating for tailored treatment strategies in T2DM management.

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.

Frailty and sarcopenia are associated with an increased risk of hospitalization and mortality in patients with end-stage liver disease. The ability to identify frail patients at risk of adverse outcomes could help optimize liver transplant (LT) evaluations and pre-transplant care. This study compared sarcopenia, via L3-psoas muscle index (L3-PMI), to frailty, via liver frailty index (LFI) and analyzed associated outcomes after liver transplantation (LT).

A retrospective review of consecutive LT-recipients with cross-sectional abdominal/pelvic imaging were reviewed over 5 years at a single transplant center.

Four hundred and twenty-six patients underwent transplant during this study interval; 31% of patients were sarcopenic. Two hundred eight patients underwent LFI evaluation: 25% were frail, 59% were prefrail, and 16% were robust. Sarcopenic patients had higher LFI scores indicating greater frailty (p = 0.02). Both sarcopenia and LFI-frailty were associated with significantly higher MELD-Na scores. Length of post-LT hospital stay was increased in sarcopenic (mean 14 vs. nonsarcopenic 11 days, p = 0.02) and LFI-frail patients (mean 13 vs. 10 prefrail, 8 robust, p = 0.04). As a categorical variable, neither LFI-frailty nor sarcopenia were significantly associated with reduced survival at 1-year (robust 100%, prefrail 93.5%, frail 91.1%, p = 0.31) (nonsarcopenic 94.4%, sarcopenic 91.4%, p = 0.30). However, LFI score was significantly associated with mortality at 1-year (OR 2.133, p = 0.047).

Radiographic sarcopenia is a suitable proxy for in-person frailty assessment as both L3-PMI and LFI capture frail patients' pre-LT. However, physical assessment with frailty better predicts 1-year mortality post-LT than the measurement of muscle mass.

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 prevalent in patients with inflammatory bowel disease (IBD) and impacts surgical and therapeutic outcomes; thus, effective diagnostic tools are needed to assess muscle mass and function in this population.

153 consecutive patients were included, 100 in the training cohort and 53 in the study cohort. Three superficial muscles (rectus femoris = RF, rectus abdominis = RA, and biceps brachii = BB) were selected for the detection of sarcopenia using muscle ultrasound (US). The training cohort consisted of consecutive patients with or without IBD and was used to evaluate the feasibility and inter- and intra-observer variability of the US measurement. The study cohort consisted of only IBD patients and served to test US diagnostic accuracy. In the latter, muscle US, bioelectrical impedance analysis (BIA), and magnetic resonance imaging (MRI) were used to measure muscle parameters.

Sarcopenia prevalence in IBD patients was 50%. Muscle US showed excellent inter-rater and intra-rater reliability (ICC >0.95) and a good diagnostic accuracy in detecting sarcopenia compared to BIA with area under the receiver operating characteristic curve (AUROC) values of 80% and 85% for RA and BB thickness, respectively. Moreover, an Ultrasound Muscle Index (USMI) was defined as the sum of the RA, BB, and RF thickness divided by the square of the patient's height, resulting in an AUROC of 81%. Muscle thresholds for sarcopenia were detected, with RA and USMI values correlated with the highest positive (84.3%) and negative (99%) predictive values, respectively. Additionally, the agreement between the US and MRI measurements of RA was excellent (ICC 0.96).

The findings of this study emphasize the potential of muscle US as a reliable diagnostic tool for assessing sarcopenia in IBD patients. This research has significant implications for disease management in IBD patients and underscores the need for further investigations to validate these findings in larger cohorts.

Liver transplantation (LT) is the second most common solid organ transplantation worldwide. LT is considered the best and most definitive therapeutic option for patients with decompensated chronic liver disease (CLD), hepatocellular carcinoma (HCC), acute liver failure (ALF), and acute-on-chronic liver failure (ACLF). The etiology of CLD shows wide geographical variation, with viral hepatitis being the major etiology in the east and alcohol-related liver disease (ALD) in the west. Non-alcoholic fatty liver disease (NAFLD) is on an increasing trend and is expected to be the most common etiology on a global scale. Since the first successful LT, there have been radical changes in the indications for LT. In many circumstances, not just the liver disease itself but factors such as extra-hepatic organ dysfunction or failures necessitate LT. ACLF is a dynamic syndrome that has extremely high short-term mortality. Currently, there is no single approved therapy for ACLF, and LT seems to be the only feasible therapeutic option for selected patients at high risk of mortality. Early identification of ACLF, stratification of patients according to disease severity, aggressive organ support, and etiology-specific treatment approaches have a significant impact on post-transplant outcomes. This review briefly describes the indications, timing, and referral practices for LT in patients with CLD and ACLF.

Rapid nutrition screening (NS) is vital for apt management in patients with alcoholic liver cirrhosis (ALC).

To identify a quick method of NS having high reliability and prognostic significance.

NS of patients with ALC was assessed using mid-upper arm circumference (MUAC), handgrip strength (HGS), fat-free mass index (FFMI), and the Royal Free Hospital-Global Assessment (RFH-GA). Baseline clinical and biochemical information were recorded along with 90-day survival data. The classification and regression tree method was used to classify HGS, MUAC, and FFMI values as well nourished (WN), moderately malnourished (MM), and severely malnourished (SM), and their concordance with RFH-GA categories was assessed using Kendall tau-b coefficient. The prognostic proficiency of each method was tested by Cox regression analysis.

According to the RFH-GA, of 140 male patients with ALC, 13 of 140 (9.3%) were WN, 93 of 140 (66.4%) were MM, and 34 of 140 (26.8%) were SM. HGS has the strongest association with the RFH-GA (Kendall tau-b = 0.772; diagnostic accuracy -81.4%). HGS was found to be the independent predictor of 90-day mortality (26 of 140 [18.6%]; hazard ratio, 0.93; 95% CI, 0.88-0.98; P = 0.002) after adjusting for age, body mass index, and disease severity. The hazard of mortality was 8.5-times higher in patients with ALC with HGS < 22 kg as compared with those with HGS > 29.

HGS is a reliable tool for rapid NS. HGS < 22 kg suggests a high risk for severe malnutrition and is strongly associated with short-term mortality in male patients with ALC.

Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.

There is a need to adopt valid techniques to assess skeletal muscle (SM) in clinical practice. SM can be precisely quantified from computed tomography (CT) images. This study describes how registered dietitians (RDs), trained to quantify SM from CT images, implemented this technique in clinical practice.

This was an explanatory sequential mixed-methods design with a quantitative and a qualitative phase. RDs collected data describing how they implemented CT SM assessments in clinical practice, followed by a focus group exploring barriers and enablers to using CT SM assessments.

RDs (N = 4) completed 96 CT SM assessments, with most (94%, N = 90/96) taking <15 min to complete. RDs identified reduced muscle mass in 63% (N = 45/72) of men and 71% (N = 17/24) of women. RDs used results of CT SM assessments to increase protein composition of the diet/nutrition support, advocate for initiation or longer duration of nutrition support, coordinate nutrition care, and provide nutrition education to patients and other health service providers. The main barriers to implementing CT SM assessments in clinical practice related to cumbersome health system processes (ie, CT image acquisition) and challenges integrating CT image analysis software into the health system computing environment.

Preliminary results suggest RDs found CT SM assessments positively contributed to their nutrition care practice, particularly in completing nutrition assessments and in planning, advocating for, and implementing nutrition interventions. Use of CT SM assessments in clinical practice requires innovative IT solutions and strategies to support skill development and use in clinical nutrition care.

The relationship between sarcopenia and prognosis in solid organ transplantation recipients (SOTr) remains unverified. We aimed to quantify the prevalence of pretransplant sarcopenia and its effect on patient and graft survival in SOTr. We used PubMed, EMBASE, Cochrane Library and Web of Science to search relevant studies published in English (from inception to December 31, 2021). Prospective and retrospective cohort studies that reported the prevalence of sarcopenia before transplant or the association between sarcopenia and clinical outcomes in SOTr were included. Primary outcomes were the prevalence of sarcopenia and its impact on patient and graft survival. Secondary outcomes included perioperative complications, acute rejection, length of hospital stay, length of intensive care unit stay (ICU LOS) and early readmission. Thirty-nine studies involving 5792 patients were included. Pooled prevalence of sarcopenia amongst SOTr candidates was 40 % (95 % confidence interval [CI]: 34%-47 % and I2 = 97 %). Sarcopenia was associated with increased risk of death (hazard ratio [HR] = 1.87, 95 % CI: 1.46-2.41 and I2 = 60 %), poor graft survival (HR = 1.71, 95 % CI: 1.16-2.54 and I2 = 57 %) and increased liver graft loss (HR = 1.43, 95 % CI: 1.03-1.99 and I2 = 38 %). Patients with sarcopenia demonstrated increased incidence of perioperative complications (risk ratio [RR] = 1.34, 95 % CI: 1.17-1.53 and I2 = 40 %), long ICU LOS (mean difference = 2.31 days, 95 % CI: 0.58-4.04 and I2 = 97 %) and decreased risk of acute rejection (RR = 0.61, 95 % CI: 0.42-0.89 and I2 = 0 %). In Conclusion, sarcopenia is prevalent in SOTr candidates and associated with death and graft loss. Identifying sarcopenia before transplantation and intervening may improve long-term outcomes.