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BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. IMPACT AND IMPLICATIONS: 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.
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INTRODUCTION: Malnutrition and sarcopenia are common and impact the prognosis in patients with liver cirrhosis. The etiology is multifactorial and includes periods of reduced caloric intake, increased catabolism and direct molecular mechanisms that inhibit muscle synthesis. Although these conditions are widely acknowledged, and there is a growing interest in their diagnosis, robust evidence regarding the treatment and reversibility of these conditions is still lacking. AREAS COVERED: We have explored the current evidence on the pharmacological treatment of sarcopenia in patients with cirrhosis. Additionally, we have searched for drugs already in use and ongoing trials for other chronic diseases. EXPERT OPINION: The current guidelines recommend the use of a protein-adequate diet and moderate physical activity for treating sarcopenia in patients with cirrhosis. Currently, robust evidence is derived only from the supplementation of Branched-Chain Amino Acids, capable of increasing muscle mass and function. There are many drugs targeting various pathways that contribute to sarcopenia. However, evidence is sporadic and insufficient to suggest their use in clinical practice.Novel drugs specifically designed to enhance muscle mass and function should be developed. Finally, gender significantly influences the type of muscle alteration and therapeutic mechanisms; therefore, future studies should be designed taking gender differences into consideration.
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Desarrollo de Medicamentos , Cirrosis Hepática , Sarcopenia , Sarcopenia/tratamiento farmacológico , Sarcopenia/fisiopatología , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Animales , Pronóstico , Factores Sexuales , Desnutrición/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Ejercicio Físico/fisiología , Masculino , Femenino , Aminoácidos de Cadena Ramificada/administración & dosificación , Diseño de FármacosRESUMEN
Vedolizumab (VDZ) is used for treating inflammatory bowel disease (IBD) patients. A study investigating colonic epithelial barrier function ex vivo following VDZ is lacking. This work aims to evaluate ex vivo the colonic epithelial barrier function in IBD patients at baseline and during VDZ treatment, and to investigate the relationships between barrier function and clinical parameters. Colonic specimens were obtained from 23 IBD patients before, and at 24 and 52 weeks after VDZ treatment, and from 26 healthy volunteers (HV). Transepithelial electrical resistance (TEER, permeability to ions) and paracellular permeability were measured in Ussing chambers. IBD patients showed increased epithelial permeability to ions (TEER, 13.80 ± 1.04 Ω × cm2 vs. HV 20.70 ± 1.52 Ω × cm2, p < 0.001) without changes in paracellular permeability of a 4 kDa probe. VDZ increased TEER (18.09 ± 1.44 Ω × cm2, p < 0.001) after 52 weeks. A clinical response was observed in 58% and 25% of patients at week 24, and in 62% and 50% at week 52, in ulcerative colitis and Crohn's disease, respectively. Clinical and endoscopic scores were strongly associated with TEER. TEER < 14.65 Ω × cm2 predicted response to VDZ (OR 11; CI 2-59). VDZ reduces the increased permeability to ions observed in the colonic epithelium of IBD patients before treatment, in parallel to a clinical, histological (inflammatory infiltrate), and endoscopic improvement. A low TEER predicts clinical response to VDZ therapy.
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Anticuerpos Monoclonales Humanizados , Colon , Enfermedades Inflamatorias del Intestino , Mucosa Intestinal , Permeabilidad , Humanos , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Masculino , Femenino , Adulto , Persona de Mediana Edad , Permeabilidad/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/metabolismo , Enfermedades Inflamatorias del Intestino/patología , Colon/efectos de los fármacos , Colon/metabolismo , Colon/patología , Iones/metabolismo , Fármacos Gastrointestinales/farmacología , Fármacos Gastrointestinales/uso terapéutico , Impedancia Eléctrica , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/patología , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/metabolismo , Enfermedad de Crohn/patología , AncianoRESUMEN
BACKGROUND & AIMS: Little is known on nutritional parameters in patients with chronic portal vein thrombosis (PVT) and idiopathic non-cirrhotic portal hypertension (INCPH). The study aims to assess the prevalence and the clinical impact of sarcopenia in patients with non-cirrhotic portal hypertension (NCPH). A control group of cirrhotic patients was also studied. Both groups were followed up to establish the relationship between sarcopenia and clinical outcomes. METHODS: Sixty-seven patients with NCPH (51 PVT and 16 INCPH) were included in the study group and 104 patients with liver cirrhosis in the control group. The axial plane passing through the intersomatic disk between L3 and L4 was evaluated for the quantitative analysis of muscle mass and the skeletal muscle index (SMI) was calculated. The presence of sarcopenia was established according to SMI validated cut off. RESULTS: Sarcopenia was present in the 38% of patients with INCPH, 35% of patients with chronic PVT, 32% of patients with compensated cirrhosis and 54% of decompensated cirrhotics. During a mean follow-up of 51 ± 62 months, there was no difference in sarcopenic and non-sarcopenic patients with NCPH for incidence of ascites, hepatic encephalopathy, esophageal varices, variceal bleeding and death. However, the incidence of refractory variceal bleeding requiring TIPS placement was significantly higher in comparison with the non-sarcopenic ones (29% vs 7%, P = 0.01 at log-rank test). CONCLUSIONS: In patients with NCPH sarcopenia is similar to that observed in cirrhotic patients. Moreover, the rate of refractory variceal bleeding was higher in sarcopenic patients suggesting a clinical negative impact of muscle depletion.
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Hemorragia Gastrointestinal/etiología , Hipertensión Portal/complicaciones , Sarcopenia/etiología , Adulto , Anciano , Ascitis/etiología , Várices Esofágicas y Gástricas/complicaciones , Femenino , Encefalopatía Hepática/etiología , Humanos , Hipertensión Portal/fisiopatología , Cirrosis Hepática/complicaciones , Masculino , Persona de Mediana Edad , Prevalencia , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Trombosis de la Vena/etiologíaRESUMEN
Liver transplantation is currently the only curative therapy for patients with liver cirrhosis. Not all patients in the natural course of the disease will undergo transplantation, but the majority of them will experience portal hypertension and its complications. In addition to medical and endoscopic therapy, a key role in managing these complications is played by the placement of a transjugular intrahepatic portosystemic shunt (TIPS). Some indications for TIPS placement are well-established, and they are expanding and broadening over time. This review aims to describe the role of TIPS in managing patients with liver cirrhosis, in light of liver transplantation. As far as it is known, TIPS placement seems not to affect the surgical aspects of liver transplantation, in terms of intraoperative bleeding rates, postoperative complications, or length of stay in the Intensive Care Unit. However, the placement of a TIPS "towards transplant" can offer advantages in terms of ameliorating a patient's clinical condition at the time of transplantation and improving patient survival. Additionally, the TIPS procedure can help preserve the technical feasibility of the transplant itself. In this context, indications for TIPS placement at an earlier stage are drawing particular attention. However, TIPS insertion in decompensated patients can also lead to serious adverse events. For these reasons, further studies are needed to make reliable recommendations for TIPS in the pre-transplant setting.
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Background & Aims: Bacterial infections affect survival of patients with cirrhosis. Hospital-acquired bacterial infections present a growing healthcare problem because of the increasing prevalence of multidrug-resistant organisms. This study aimed to investigate the impact of an infection prevention and control programme and coronavirus disease 2019 (COVID-19) measures on the incidence of hospital-acquired infections and a set of secondary outcomes, including the prevalence of multidrug-resistant organisms, empiric antibiotic treatment failure, and development of septic states in patients with cirrhosis. Methods: The infection prevention and control programme was a complex strategy based on antimicrobial stewardship and the reduction of patient's exposure to risk factors. The COVID-19 measures presented further behavioural and hygiene restrictions imposed by the Hospital and Health Italian Sanitary System recommendations. We performed a combined retrospective and prospective study in which we compared the impact of extra measures against the hospital standard. Results: We analysed data from 941 patients. The infection prevention and control programme was associated with a reduction in the incidence of hospital-acquired infections (17 vs. 8.9%, p <0.01). No further reduction was present after the COVID-19 measures had been imposed. The impact of the infection prevention and control programme remained significant even after controlling for the effects of confounding variables (odds ratio 0.44, 95% CI 0.26-0.73, p = 0.002). Furthermore, the adoption of the programme reduced the prevalence of multidrug-resistant organisms and decreased rates of empiric antibiotic treatment failure and the development of septic states. Conclusions: The infection prevention and control programme decreased the incidence of hospital-acquired infections by nearly 50%. Furthermore, the programme also reduced the prevalence of most of the secondary outcomes. Based on the results of this study, we encourage other liver centres to adopt infection prevention and control programmes. Impact and implications: Infections are a life-threatening problem for patients with liver cirrhosis. Moreover, hospital-acquired infections are even more alarming owing to the high prevalence of multidrug-resistant bacteria. This study analysed a large cohort of hospitalised patients with cirrhosis from three different periods. Unlike in the first period, an infection prevention programme was applied in the second period, reducing the number of hospital-acquired infections and containing multidrug-resistant bacteria. In the third period, we imposed even more stringent measures to minimise the impact of the COVID-19 outbreak. However, these measures did not result in a further reduction in hospital-acquired infections.
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BACKGROUND AND AIMS: Liver cirrhosis leads to clinically significant portal hypertension. Transjugular intrahepatic portosystemic shunt (TIPS) has been shown to effectively reduce the degree of portal hypertension and treat its complications. However, poor nutritional status has been shown to be associated with hepatic encephalopathy, acute on chronic liver failure, and mortality following TIPS placement. The purpose of this systematic review is to create another perspective and evaluate the effect of TIPS placement on the nutritional status of patients with liver cirrhosis. METHODS: A comprehensive search of four major electronic databases was conducted to identify studies that assessed the nutritional status of cirrhotic patients before and after TIPS placement. The risk of bias was evaluated using ROBINS-I guidelines. RESULTS: Fifteen studies were analyzed in this review. The results indicate that among the 11 studies that evaluated changes in ascites-free weight and body mass index or body cell mass, 10 reported an improvement in one or more measures. Furthermore, all seven studies that evaluated changes in muscle mass demonstrated an increase in muscle mass. Among the four studies that evaluated subcutaneous fat tissue, three showed a significant expansion, while two out of three studies evaluating visceral fat tissue reported a significant reduction. CONCLUSIONS: The results of this systematic review suggest that TIPS placement is associated with improvement in the nutritional status of cirrhotic patients, indicated by an increase in ascites-free weight, body mass index, and muscle mass. Additionally, TIPS placement leads to a shift in the distribution of fat mass, with a preference for subcutaneous over visceral adipose tissue. Notably, sarcopenic patients seem to benefit the most from TIPS placement in terms of nutritional status.
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Encefalopatía Hepática , Hipertensión Portal , Derivación Portosistémica Intrahepática Transyugular , Humanos , Derivación Portosistémica Intrahepática Transyugular/efectos adversos , Derivación Portosistémica Intrahepática Transyugular/métodos , Estado Nutricional , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Hipertensión Portal/cirugía , Hipertensión Portal/complicaciones , Encefalopatía Hepática/etiología , AscitisRESUMEN
Since 1988, transjugular intrahepatic portosystemic shunt (TIPS) has been an effective therapy for portal hypertension in many settings. Thanks to continuous technical improvements and a wiser selection of patients, excellent results have been achieved with this therapeutic strategy. The historical indications for TIPS placement, in the context of liver cirrhosis, such as refractory ascites and variceal bleeding are now well established and known. However, in recent years, new indications are emerging. These have been investigated and approved in some studies but are not yet included in guidelines and clinical practice. This review aims to highlight what is new for the role of TIPS in portal vein thrombosis (especially in patients awaiting liver transplantation), in recurrent ascites and not only refractory ascites, as a neoadjuvant therapy before abdominal surgery and, finally, in the setting of noncirrhotic portal hypertension. All these new aspects are addressed in this review with a critical approach based on the literature revision and clinical practice. Future research is needed to explore and validate the new role of TIPS in these scenarios.
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Cardiovascular diseases are currently one of the most important causes of morbidity and mortality in liver transplant patients over the long term. Therefore, evaluating prognostic factors for cardiovascular events (CVEs) in this population is essential for taking preventive measures. The aim of this study was to identify the impact of diabetes and other metabolic disorders on CVEs in liver transplant patients. Three hundred fifty-six liver transplant recipients who survived at least 6 months after surgery were enrolled. Patients were followed for a median time of 118 months (12-250 months). All cardiovascular events were carefully recorded and detailed in the patients' charts. Demographic data, diabetes, hypertension, dyslipidemia, weight changes, and a diagnosis of metabolic syndrome both before and after transplantation were noted to assess their possible relationship with CVE. The presence of a diagnosis of metabolic-associated fatty liver disease (MAFLD) was also evaluated. Immunosuppressive therapy was included in the analysis. Diabetes mellitus (DM), especially when present before transplantation, was strongly associated with CVEs (hazard risk HR 3.10; 95% confidence interval CI: 1.60-6.03). Metabolic syndrome was found to be associated with CVEs in univariate analysis (HR 3.24; 95% CI: 1.36-7.8), while pretransplantation and de novo MAFLD were not. Immunosuppressive therapy had no influence on predisposing transplanted patients to CVEs during follow-up. Further prospective studies may be useful in investigating the risk factors for CVEs after liver transplantation and improving the long-term survival of transplant patients.
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Enfermedades Cardiovasculares , Diabetes Mellitus , Trasplante de Hígado , Enfermedades Metabólicas , Síndrome Metabólico , Enfermedad del Hígado Graso no Alcohólico , Humanos , Trasplante de Hígado/efectos adversos , Síndrome Metabólico/complicaciones , Síndrome Metabólico/epidemiología , Estudios Prospectivos , Diabetes Mellitus/epidemiología , Factores de Riesgo , Enfermedades Metabólicas/epidemiología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Enfermedad del Hígado Graso no Alcohólico/complicacionesRESUMEN
BACKGROUND: Vaccine hesitancy and lack of access remain major issues in disseminating COVID-19 vaccination to liver patients globally. Factors predicting poor response to vaccination and risk of breakthrough infection are important data to target booster vaccine programs. The primary aim of the current study was to measure humoral responses to 2 doses of COVID-19 vaccine. Secondary aims included the determination of factors predicting breakthrough infection. METHODS: COVID-19 vaccination and Biomarkers in cirrhosis And post-Liver Transplantation is a prospective, multicenter, observational case-control study. Participants were recruited at 4-10 weeks following first and second vaccine doses in cirrhosis [n = 325; 94% messenger RNA (mRNA) and 6% viral vaccine], autoimmune liver disease (AILD) (n = 120; 77% mRNA and 23% viral vaccine), post-liver transplant (LT) (n = 146; 96% mRNA and 3% viral vaccine), and healthy controls (n = 51; 72% mRNA, 24% viral and 4% heterologous combination). Serological end points were measured, and data regarding breakthrough SARS-CoV-2 infection were collected. RESULTS: After adjusting by age, sex, and time of sample collection, anti-Spike IgG levels were the lowest in post-LT patients compared to cirrhosis (p < 0.0001), AILD (p < 0.0001), and control (p = 0.002). Factors predicting reduced responses included older age, Child-Turcotte-Pugh B/C, and elevated IL-6 in cirrhosis; non-mRNA vaccine in AILD; and coronary artery disease, use of mycophenolate and dysregulated B-call activating factor, and lymphotoxin-α levels in LT. Incident infection occurred in 6.6%, 10.6%, 7.4%, and 15.6% of cirrhosis, AILD, post-LT, and control, respectively. The only independent factor predicting infection in cirrhosis was low albumin level. CONCLUSIONS: LT patients present the lowest response to the SARS-CoV-2 vaccine. In cirrhosis, the reduced response is associated with older age, stage of liver disease and systemic inflammation, and breakthrough infection with low albumin level.
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COVID-19 , Trasplante de Hígado , Vacunas Virales , Humanos , Albúminas , Infección Irruptiva , Estudios de Casos y Controles , COVID-19/prevención & control , Vacunas contra la COVID-19 , Cirrosis Hepática , Trasplante de Hígado/efectos adversos , Estudios Prospectivos , ARN Mensajero , SARS-CoV-2 , VacunaciónRESUMEN
In the last years the link between the presence of muscular alterations and hepatic encephalopathy (HE), both minimal and overt, has been deeply studied. The pathophysiological background supporting the relationship between muscle depletion, and HE is characterized by an imbalance between the capacity of muscle in ammonia metabolism and trafficking and the inability of the liver in removing ammonia through urea synthesis due to liver failure and/or the presence of porto-systemic shunts. This review will focus on the clinical burden, the physio pathological mechanisms understanding the liver muscle axis and principles of management of muscular alterations in cirrhosis.
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BACKGROUND AND AIM: Sarcopenia is considered an important risk factor for morbidity and mortality in liver cirrhosis. Beta-hydroxy-beta-methylbutyrate (HMB) has the potential to increase muscle mass and performance by stimulating protein synthesis and reducing muscle catabolism. The present study aimed at evaluating the effect of HMB supplementation on muscle mass and function in patients with liver cirrhosis. Changes in frailty during the study were also estimated, and the safety of HMB supplementation was verified. METHODS: This is a randomized, single-blind, placebo-controlled pilot trial. Twenty-four patients (14 HMB and 10 placebo) affected by liver cirrhosis were enrolled in the study. Each patient received dedicated counseling, which included nutrition and physical activity recommendations for chronic liver disease patients. Patients were randomized to receive 3 g/day of HMB or placebo (sorbitol powder) for 12 consecutive weeks. A diet interview, anthropometry, electrical bioimpedance analysis (BIA), quadriceps ultrasound, physical performance battery, Liver Frailty Index (LFI), and cognitive tests were completed at enrolment (T0), at 12 weeks (T1), and 24 weeks after enrolment (T2). RESULTS: At baseline, the two groups were similar in demography, severity of liver disease, muscle mass, muscle function, and cognitive tests. LFI at baseline was higher in patients in the HMB group vs. those in the placebo group (4.1 ± 0.4 vs. 3.4 ± 0.6, p < 0.01). After treatment, a statistically significant increase in muscle function was seen in the HMB group (chair stand test: 14.2 ± 5 s vs. 11.7 ± 2.6 s, p < 0.05; six-minute walk test: 361.8 ± 68 m vs. 409.4 ± 58 m, p < 0.05). Quadriceps muscle mass measured by ultrasound also increased (4.9 ± 1.8 vs. 5.4 ± 1.8 mm, p < 0.05) after HMB, while LFI decreased (4.1 ± 0.4 vs. 3.7 ± 0.4, p < 0.05). HMB was well tolerated by patients, and no adverse events were documented. CONCLUSIONS: Our study suggests the efficacy of 12-week beta-hydroxy-beta-methylbutyrate supplementation in promoting improvements in muscle performance in compensated cirrhotic patients. LFI was also ameliorated. Further studies with a greater number of patients are required to reinforce this hypothesis.
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Suplementos Dietéticos , Cirrosis Hepática/terapia , Fuerza Muscular/efectos de los fármacos , Sarcopenia/prevención & control , Valeratos/administración & dosificación , Antropometría , Impedancia Eléctrica , Ejercicio Físico/fisiología , Femenino , Fragilidad/etiología , Fragilidad/prevención & control , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/fisiopatología , Masculino , Persona de Mediana Edad , Músculo Esquelético/efectos de los fármacos , Proyectos Piloto , Sarcopenia/etiología , Método Simple Ciego , Resultado del TratamientoRESUMEN
BACKGROUND: Since the use of the Model for End-Stage Liver Disease (MELD) score for establishing the prognosis of cirrhotic patients has been introduced, questions have been raised whether complications of liver cirrhosis would provide additional information. Myosteatosis, sarcopenia and hepatic encephalopathy (HE) are frequent in cirrhosis and may affect prognosis. Aim of the study was analyzing if these factors are independently related to survival and may improve the accuracy of MELD. METHODS: 249 cirrhotics that underwent abdominal CT-scan were enrolled. For each patient, information about previous episodes of HE and muscle alterations were obtained. Patients were followed until transplantation or death. RESULTS: History of HE, MELD, sarcopenia and myosteatosis were independently associated with mortality. The MELD-Sarco-Myo-HE score added accuracy to the MELD score alone for 6- and 3-months mortality. By removing HE, as the only not quantifiable parameter of the model, no relevant decrease in accuracy for 6- and 3-months mortality detection was observed. CONCLUSIONS: The accuracy of MELD in predicting 3- and 6-months mortality may be improved by considering the muscle alterations. A model considering the above parameters may classify more accurately over 30% of the patients.