Malnutrition, defined as deficiency, excess, or imbalance of nutrients, is a common complication in patients with liver disease, especially those with cirrhosis. Malnutrition may present as an isolated micronutrient deficiency, such as zinc deficiency, and it commonly presents as frailty and/or sarcopenia in patients with advanced liver disease. Patients with cirrhosis and/or alcohol-associated hepatitis should be assessed for malnutrition because it adversely affects patient outcomes including mortality, as well as waitlist and posttransplant outcomes among liver transplant candidates. The prevalence of malnutrition varies based on the method of assessment and disease severity, being higher in those with advanced liver disease. Among stable outpatients with cirrhosis, counseling should be done to eat small frequent meals, a night-time snack between 7 PM and 10 PM, and 2 or more cups of coffee daily. In selected patients with metabolic dysfunction-associated steatohepatitis, vitamin E 800 IU/d should be provided. Among hospitalized patients with cirrhosis, nutritional supplementation preferably by enteral route should be implemented in those with poor oral intake of daily requirements of proteins and/or calories. Protein intake should not be restricted including patients with decompensated cirrhosis and hepatic encephalopathy. A vegetable source of protein seems to be better tolerated than an animal source of protein in patients with hepatic encephalopathy. Branched chain amino acids augment the efficacy of lactulose and rifaximin in the treatment of hepatic encephalopathy. Level of evidence and strength of recommendations were evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations system. This guideline was developed under the auspices of the American College of Gastroenterology Practice Parameters Committee.

The referral of patients with cirrhosis to liver transplant (LT) is a multi-stage, complex process. There is a lack of data on potential challenges to this process. We aimed to characterize challenges faced by Portuguese referring clinicians.

This was a cross-sectional survey from Curry Cabral Hospital, Lisbon, Portugal. The survey was open for 90 days, from August to November 2024. The survey included 13 questions: characterization of participants with 5 questions and characterization of the process of referral to LT with 8 questions.

Overall, 56 clinicians responded to the survey (response rate of 46.7%). Their median (IQR) age was 38.1 (33.2-42.1) years. Their level of training was specialist grade for 47 (83.9%) and fellow or intern grade for 9 (16.1%) individuals. The responders were from 21 different hospitals in Portugal; 8 (38.1%) provided tertiary care and 2 (9.5%) were LT centers. Among responders, there was heterogeneity regarding the following topics: referring criteria to LT, liver-related prognostic scores, contact channels with the LT center, tests and visits part of the LT workup. Many of them suggested the following improvements to develop national or regional referral criteria, to expedite communication with the LT team, to accelerate access to the tests or visits part of the LT workup, and to shorten the time to the first appointment with the LT team.

Portuguese clinicians identified several challenges and improvements to the referral of patients with cirrhosis to LT. These findings may inform future strategies to streamline the referral to LT.

The aim of this study was to develop a new, less cumbersome index for determining sarcopenia using axial slice images from computed tomography (CT) as a surrogate for the skeletal muscle index (SMI) measured by bioelectrical impedance analysis (BIA).

We devised the JOHAS index (Judgment of Objective Hyper-steatosis and Atrophy in Sarcopenia), calculated from the measurements of the iliopsoas and erector spinae muscles in the axial CT slices at the L4 lumbar vertebral level. The JOHAS index is defined as: JOHAS index = ∑ [(cross-sectional area of each muscle [cm2]/patient height [cm]) × (CT number + 108)], where ∑ is defined as the sum of the values in the bracket for iliopsoas and erector spinae muscles on both sides, and 108 is the adjustment factor. The accuracy of the JOHAS index for identifying sarcopenia, as determined by BIA, was examined using a receiver operating characteristic (ROC) curve analysis on a sample of 639 patients (331 men and 308 women).

The JOHAS index was able to discriminate sarcopenia with an area under the curve (AUC) of around 0.88 in men and 0.75 in women. The JOHAS index outperformed commonly used indices such as the psoas muscle index, erector spinae muscle index, intramuscular adipose tissue content, prognostic nutritional index, and neutrophil/lymphocyte ratio.

The JOHAS index is a promising, pragmatic surrogate for SMI measured by BIA. The recommendable cut-off values are 43 (sensitivity 0.7722, specificity 0.8362) for men and 32 (sensitivity 0.6377, specificity 0.7423) for women.

Liver transplantation (LT) is the standard of care for both end-stage liver failure and hepatocellular carcinoma (HCC). Side effects of the main used immunosuppressive drugs have a noteworthy impact on the long-term outcome of LT recipients. Consequently, to achieve a balance between optimal immunosuppression and minimal side effects is a cornerstone of the post-LT period. Today, there are no validated markers for overimmunosuppression and underimmunosuppression, only a few drugs have therapeutic drug monitoring, and immunosuppression regimens vary from center to center and from country to country. Currently, there are many drugs with different efficacy and safety profiles. Using different agents permits a decrease in the dosage and minimizes the toxicities. A small subset of recipients achieves immunotolerance with the chance to stop immunosuppressive therapy. This article focuses on the side effects of immunosuppressive drugs, which significantly impact long-term outcomes for LT recipients. The primary aim is to highlight the balance between achieving effective immunosuppression and minimizing adverse effects, emphasizing the role of personalized therapeutic strategies. Moreover, this review evaluates the mechanisms of action and specific complications associated with immunosuppressive agents. Finally, special attention is given to strategies for reducing immunosuppressive burdens, improving patient quality of life, and identifying immunotolerant individuals.

Frailty is one of the most common symptoms in patients with cirrhosis. Many researchers have identified it as a prognostic factor for patients with cirrhosis. However, no quantitative meta-analysis has evaluated the prognostic value of frailty in patients with cirrhosis.

This systematic review and meta-analysis aimed to assess the prognostic significance of frailty in patients with cirrhosis.

The systematic review was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) recommendations. We conducted a comprehensive search of the literature using databases such as PubMed, Cochrane Library, Embase, and Web of Science, as well as China National Knowledge Infrastructure, encompassing the period from inception to 22 December 2023. Data were extracted for frailty to predict adverse outcomes in patients with cirrhosis. RevMan (version 5.3) and R (version 4.2.2) were used to assess the extracted data.

A total of 26 studies with 9597 patients with cirrhosis were included. Compared with patients having low or no frailty, the frail group had a higher mortality rate (relative ratio, RR=2.07, 95% CI 1.82-2.34, P<.001), higher readmission rate (RR=1.50, 95% CI 1.22-1.84, P<.001), and lower quality of life (RR=5.78, 95% CI 2.25-14.82, P<.001). The summary receiver operator characteristic (SROC) curve of frailty for mortality in patients with cirrhosis showed that the false positive rate (FPR) was 0.25 (95% CI 0.17-0.34), diagnostic odds ratio (DOR) was 4.17 (95% CI 2.93-5.93), sensitivity was 0.54 (95% CI 0.39-0.69), and specificity was 0.73 (95% CI 0.64-0.81). The SROC curve of readmission showed that the FPR, DOR, sensitivity, and specificity were 0.39 (95% CI 0.17-0.66), 1.38 (95% CI 0.64-2.93), 0.46 (95% CI 0.28-0.64), and 0.60 (95% CI 0.28-0.85), respectively.

This meta-analysis demonstrated that frailty is a reliable prognostic predictor of outcomes in patients with cirrhosis. To enhance the prognosis of patients with cirrhosis, more studies on frailty screening are required.

Rodent ischemia-reperfusion injury (IRI) and liver transplantation (LT) models play crucial roles in mimicking graft injury and immune rejection, developing therapeutic approaches, and evaluating the efficacy of treatments. The application of integrated multi-omics data and advanced omics techniques like single-cell RNA sequencing in rodent models has expanded researchers' perspectives on pathophysiological processes in LT settings. This review summarizes key molecules and pathways associated with reperfusion injury and prognosis in LT models, highlighting the potential of omics data in understanding and improving transplant outcomes. In addition, we highlight the current challenges and future approaches for the application of omics data in rodent LT models. Cross-species validation with human data will improve therapeutic potential. Finally, further applications combining advanced single-cell, spatial omics technologies and machine learning algorithms will help to identify the key regulatory networks in specific cell populations underlying poor outcomes after LT.

Sarcopenia has been shown to worsen survival after liver transplantation. However, it remains unclear whether coexisting sarcopenia and obesity, so-called sarcopenic obesity (SO), may also synergistically increase their adverse effects. This meta-analysis aimed to evaluate whether pre-transplant SO independently predicts survival in this population.

We conducted this study according to the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. The PubMed, Embase, Web of Science, Wanfang, CNKI, and Cochrane databases were searched up to 15 October 2023, for studies with any study design evaluating the relationship between SO and post-transplant survival in patients undergoing liver transplantation. We used ROBINS-E to assess the study quality. The primary outcome was all-cause mortality at any length of follow-up. We calculated pooled odds risks (ORs) or hazard risks (HRs) with 95% confidence intervals (CIs). Heterogeneity was quantified with I 2 statistics. Subgroup analyses and publication bias evaluations were also conducted.

We included nine cohort studies with 2,416 patients. These studies were moderate to high quality. Pre-liver transplant patients commonly experience SO, with a mean prevalence as high as 34%. Overall, patients with SO exhibited a significantly higher overall mortality than patients without SO, as demonstrated by pooled studies using both univariate analysis [HR = 1.76, 95%C 1.33-2.33, p < 0.0001] and multivariate analysis (HR = 2.33, 95%CI 1.34-4.04, p = 0.003). Similar results were also found when comparing patients with or without SO at 1, 3, and 5 years of follow-up (OR = 1.86, 95%CI 1.22-2.83; OR = 1.83, 95%CI: 1.27-2.64; and OR = 1.54, 95% CI 1.02-2.34, respectively). In addition, subgroup analysis based on studies that reported HRs of both sarcopenia and SO indicated both had independent negative effects on post-transplant survival.

Our meta-analysis showed that SO occurs frequently in liver transplant patients. SO is associated with an increased risk of mortality in such patient populations.

https://doi.org/10.37766/inplasy2024.2.0069 [inplasy2024.2.0069].

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.

Physical frailty increases susceptibility to stressors and has been associated with increased mortality among liver transplant candidates. However, evidence about this population's frailty prevalence and mortality is inconsistent and needs to be clarified. This study aimed to quantitatively synthesize the prevalence of frailty and the role of frailty on mortality in liver transplant candidates.

All eligible studies published in Embase, PubMed, Scopus, and Web of Science from inception until March 5, 2024, were included. The pooled prevalence and hazard ratio (HR) corresponding to 95 % confidence intervals (CI) in mortality estimates were conducted. The random-effects model was used for the calculations.

A total of 17 studies containing 4509 patients with liver transplant waitlist candidates were included. The prevalence of frailty in liver transplant waitlist candidates was 32 % (95 % CI = 25-38; p < 0.01). In this population, frailty was associated with an increased hazard ratio for mortality (8 studies) (HR = 2.49; 95 % CI = 1.77-3.51; p < 0.01). Furthermore, subgroup analysis showed that frailty was associated with a higher mortality in the USA (HR = 4.03; 95 % CI = 1.77-3.51; p < 0.01) compared with the non-USA area (HR = 2.03; 95 % CI = 1.51-2.72; p < 0.01).

Our results suggest that frailty is prevalent in patients awaiting liver transplants, which strongly predicts waitlist mortality among this population. These findings highlight the importance of frailty in the decision of transplantation and in designing studies that consider frailty. Reducing the severity or impact of frailty on this population may improve prognosis.

Myostatin is a myokine involved in muscle mass regulation. The associations between circulating myostatin levels and clinical characteristics in patients with acute liver failure (ALF) and late-onset hepatic failure (LOHF) are unclear.

In this retrospective study, 51 patients with ALF or LOHF were included. Serum myostatin was measured using an enzyme-linked immunosorbent assay.

Myostatin levels were significantly lower in patients with ALF and LOHF than in controls (ALF/LOHF: 2522 pg/mL, controls: 3853 pg/mL, p = 0.003). The prevalence of low myostatin in deceased patients was significantly higher than that in spontaneous survivors and patients who underwent liver transplantation. Patients with low myostatin levels had a high incidence of complications. There was a positive correlation between the psoas muscle index and serum myostatin levels. Patients with low myostatin levels had shorter 1-year transplant-free survival and shorter 1-year overall survival than patients with high myostatin levels. Low serum myostatin levels were associated with poor prognosis independent of the Japanese scoring system for ALF ≥3, King's College criteria, or model for end-stage liver disease score >30.5. The combination of serum myostatin levels and prognostic models for ALF significantly stratified patients according to 1-year prognosis.

Low serum myostatin levels were associated with a low psoas muscle index, complication rate, and poor prognosis in patients with ALF and LOHF. Assessment of circulating myostatin levels may improve the prediction of outcomes in patients with ALF and LOHF.

Sarcopenia and frailty are common complications in patients with cirrhosis evaluated for liver transplantation (LT). Although the negative impact of sarcopenia on patient's outcome has been well studied, the prognostic role of frailty is not as clear. We assessed the prevalence of sarcopenia and frailty and the clinical impact of frailty in a prospective cohort of cirrhosis patients with and without hepatocellular carcinoma (HCC) listed for LT. Patients with cirrhosis were prospectively recruited at the time of admission into the waiting list. Clinical and lab values were collected. Physical frailty was assessed by liver frailty index (LFI) and patients were categorized into robust (< 3.2); pre-frail (between 3.2 and 4.5), and frail (> 4.5). Skeletal muscle mass was evaluated via skeletal muscle index (SMI) obtained from last CT scan before LT; sarcopenia was defined by SMI < 50 cm2/m2 in males and < 39 cm2/m2 in females. 105 patients were included, of which 42 (40%) had hepatocellular carcinoma (HCC). In patients without HCC (63.5% males, median age 61 years), 36.5% were frail, 50.8% were pre-frail and 12.7% were robust. Frail patients were older than non-frail patients (63 vs. 56; p = 0.008) and had more severe liver disease (Child C: 65% vs. 37.5%; p = 0.02). Prevalence of sarcopenia in patients without HCC was 63%, with similar value of median SMI between frail and not frail patients (p = 0.454). Patients with HCC (78.6% males, 65 years old) were 21.4% frail, 61.9% pre-frail, and 16.7% robust. Frail patients had more severe liver disease (Child C: 77% vs. 18.2%; p = 0.004), whereas age was comparable to non-frail patients; among patients without HCC, during a median follow-up of 263 days, 17% died (of which 72% were frail) and 10 patients were delisted due to clinical improvement (none of whom were frail). Among those with HCC, during a median follow-up of 289 days, 4 (9%) patients died of which 50% were frail. Frailty and sarcopenia are common complications in patients with cirrhosis awaiting LT. Frailty appears to be associated with an increased risk of mortality during wait-list time especially in those with decompensated cirrhosis. At univariate analysis Meld score, Child score and presence of frailty were found to be associated with shorter survival, however, at multivariate analysis presence of frailty and Child C vs. A/B were the only independent predictor of death. Larger cohorts are required to confirm these results.

Background: Physical frailty (PF) is a syndrome of decreased physical function and reserves, preventing patients from coping with stressful events. PF screening tools in patients with liver cirrhosis (LC) can help evaluate the risk of complications and death. The aim of this study was to assess the performance of five screening tools in detecting PF and their ability to predict 18-month mortality in LC. Methods: The Short Physical Performance Battery (SPPB), Fried frailty phenotype (FFP), Clinical Frailty Scale (CFS) and 6-Minute Walk Test (6MWT) were compared with the Liver Frailty Index (LFI) as the method of reference. Patients with an LFI ≥ 4.5, SPPB ≤ 8, FFP ≥ 3, CFS ≥ 6 points, and those walking <250 m, were considered frail. Results: A total of 109 consecutive patients with stable LC were included [63.3% male, median age 62 years, (IQR 52-70), MELD 9 (7-14.5), 46.8% with decompensated LC (DC)]. PF was present in 23.9%, 27.5%, 41.3%, 13.8%, and 28.4% as assessed by the LFI, SPPB, FFP, CFS, and 6MWT, respectively. Cohen's kappa measurement of agreement of four of the tools with LFI was 0.568, 0.334, 0.439, and 0.502, respectively (p < 0.001 for each). Kaplan-Meier survival curves at 18 months showed higher mortality in frail patients compared to non-frail patients by any method (log rank p < 0.05). In the multivariate models, PF defined by any method emerged as an independent prognostic factor of 18-month mortality after adjustment for age, gender, and MELD-score. Conclusions: Patients characterized as frail by five screening tools were not identical. However, PF defined by either method was proven to be an independent poor prognostic factor for long-term mortality after adjustment for covariates.

Frailty is a multidimensional syndrome predominantly studied in the elderly, characterized by reduced resistance to stressors due to diminished physiological reserve and resilience. Advances in surgical techniques and immunosuppressive drugs have improved long-term survival rates in solid organ transplant recipients, yet the 10-year survival is satisfying. However, liver transplant recipients have a noteworthy risk of developing frailty status. After liver transplant, frailty can be favored by socioeconomic, cultural, and health-related factors, leading to increased risks of hospitalization, morbidity, and mortality. Various tools for frailty assessment exist, but none are universally validated for post-transplant patients. The integration of socioeconomic and psychological factors into frailty evaluation could improve quality of life and long-term outcomes for transplant recipients. Multidisciplinary approaches, including psychosocial support, are essential for managing frailty and enhancing the overall care of transplanted patients. This narrative review aims to comprehensively address the principal frailty risk factors associated with liver transplantation.

Patients with cirrhosis are prone to developing acute kidney injury (AKI), a complication associated with a markedly increased in-hospital morbidity and mortality, along with a risk of progression to chronic kidney disease. Whereas patients with cirrhosis are at increased risk of developing any phenotype of AKI, hepatorenal syndrome (HRS), a specific form of AKI (HRS-AKI) in patients with advanced cirrhosis and ascites, carries an especially high mortality risk. Early recognition of HRS-AKI is crucial since administration of splanchnic vasoconstrictors may reverse the AKI and serve as a bridge to liver transplantation, the only curative option. In 2023, a joint meeting of the International Club of Ascites (ICA) and the Acute Disease Quality Initiative (ADQI) was convened to develop new diagnostic criteria for HRS-AKI, to provide graded recommendations for the work-up, management and post-discharge follow-up of patients with cirrhosis and AKI, and to highlight priorities for further research.

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.

Although the incidence of recipients and donors with overweight and obesity is increasing worldwide, few reports have focused on outcomes of preoperative weight reduction (WR) in living-donor liver transplantation (LDLT). Therefore, we examined the outcomes and the impact of WR on the postoperative course.

We analyzed 217 consecutive LDLT procedures performed from 2017 to 2022. We divided the recipients and donors into a WR group and non-WR group.

Twenty-two recipients (10.1%) achieved WR (preoperative recipient WR [RWR] group), reducing their weight by 6.8% ± 6.0% within 2.2 ± 1.4 months with a significant decrease in body mass index (BMI) (P < .0001). The RWR group showed no significant differences in short-term postoperative outcomes (operative factors, postoperative liver function tests, amount of ascites, and morbidity) or in the graft survival rate as a long-term outcome (P = .24) compared with the non-RWR group. Forty-one donors (18.9%) achieved WR (preoperative donor WR [DWR] group), reducing their weight by 9.7% ± 6.3% within 3.2 ± 5.8 months with a significant decrease in BMI (P < .0001). Compared with the non-DWR group, the DWR group showed no significant differences in short-term postoperative outcomes between themselves and recipients or in the graft survival rate (P = .49). Furthermore, WR resulted in an increase to 32 donor-eligible and 6 recipient-eligible patients.

WR in LDLT recipients and donors had no harmful effect on postoperative outcomes and should lead to increase recipients' chance of undergoing LDLT and to expand the donor pool.

BACKGROUND Physical activity is a key factor in improvement of quality of life. This study aimed to assess the extent of physical activity in solid-organ transplant recipients. MATERIAL AND METHODS The study involved 106 patients, mostly kidney (64.15%) and liver (28.30%) recipients, observed in a Warsaw transplant center. The study group was dominated by women (56.6%), mean age 49.25±14.09 years, the time since transplantation ranged from 1 month to 28 years, with a mean of 93.9±71.83 months. Recipients were educated about physical activity in the immediate post-transplant period and during follow-up visits. The study was conducted in early 2021 and used the long form of the International Physical Activity Questionnaire (IPAQ) validated for Polish patients, consisting of the of 5 parts - physical activity, professional work, travel, housework, recreation, and time spent sitting - containing a total of 27 questions in the main part of the questionnaire and 7 questions in the introductory part determining the typicality of the last 7 days. RESULTS More than half (57.5%) of the transplant recipients reported high levels of physical activity. Patients reported the highest mean physical activity in job-related physical activity (P<0.001). Patients also had high scores for walking and moderate-intensity physical activity, while the lowest mean scores were for leisure-time physical activity, total vigorous-intensity physical activity, and housework-related activity. CONCLUSIONS When undertaking physical activity, patients turn to activities that do not involve intense effort, are less physically demanding, and do not result in high energy expenditure. Employed patients had higher PA levels in all domains.

The high prevalence of obesity in the United States drives the burden of NASH, recently renamed as metabolic dysfunction-associated steatohepatitis (MASH). We assessed the most recent trends in liver transplantation in the United States.

The Scientific Registry of Transplant Recipients (SRTR 2013-2022) was used to select adult (18 years or above) candidates who underwent liver transplant.

There were 116,292 candidates who underwent liver transplant with known etiology of chronic liver disease. In candidates without HCC, the most common etiology was alcohol-associated liver disease (ALD), increasing from 23% (2013) to 48% (2022), followed by NASH/MASH, which increased from 19% to 27%; the rates of viral hepatitis decreased (chronic hepatitis C: 28%-4%; chronic hepatitis B: 1.8%-1.1%) (all trend p<0.01). The proportion of HCC decreased from 25% (2013-2016) to 17% (2021-2022). Among HCC cohort, the proportion of chronic hepatitis C decreased from 60% (2013) to 27% (2022), NASH/MASH increased from 10% to 31%, alcohol-associated liver disease increased from 9% to 24% (trend p<0.0001), and chronic hepatitis B remained stable between 5% and 7% (trend p=0.62). The rapid increase in the proportion of NASH/MASH in HCC continued during the most recent study years [20% (2018), 28% (2020), 31% (2022)]; the trend remained significant after adjustment for age, sex, ethnicity, obesity, and type 2 diabetes.

Liver transplant etiologies in the United States have changed over the last decade. Alcohol-associated liver disease and NASH/MASH remain the 2 most common indications for transplantation among those without HCC, and NASH/MASH is the most common in patients with HCC.

Intensive Care Unit (ICU)-Acquired Weakness (ICU-AW) is a generalized muscle weakness that is clinically detected in critical patients and has no plausible etiology other than critical illness. ICU-AW is uncommon in patients undergoing orthotopic liver transplantation (OLT). Our report sheds light on the highest number of ICU-AW cases observed in a single center on OLT patients with early allograft dysfunction. Out of 282 patients who underwent OLT from January 2015 to June 2023, 7 (2.5%) developed generalized muscle weakness in the ICU and underwent neurophysiological investigations. The neurologic examination showed preserved extraocular, flaccid quadriplegia with the absence of deep tendon reflexes in all patients. Neurophysiological studies, including electromyography and nerve conduction studies, showed abnormalities with fibrillation potentials and the rapid recruitment of small polyphasic motor units in the examined muscles, as well as a reduced amplitude of the compound muscle action potential and sensory nerve action potential, with an absence of demyelinating features. Pre-transplant clinical status was critical in all patients. During ICU stay, early allograft dysfunction, acute kidney injury, prolonged mechanical ventilation, sepsis, hyperglycemia, and high blood transfusions were observed in all patients. Two patients were retransplanted. Five patients were alive at 90 days; two patients died. In non-cooperative OLT patients, neurophysiological investigations are essential for the diagnosis of ICU-AW. In this setting, the high number of red blood cell transfusions is a potential risk factor for ICU-AW.

The existing literature suggests that exercise for cirrhotic patients is safe and favours significant improvement to their physical capacity. However, exercise training for this population and how to deliver activities, especially in severe stages of the disease and while waiting for a liver transplant (LT), remain undefined.

To review the existing exercise prescriptions for cirrhotic patients on the waiting list for LT, their results for frailty evolution and their effect on clinical outcomes.

A systematic review was performed following the Preferred Reporting Review and Meta-Analysis guidelines and searching the PubMed, MEDLINE, and Scopus databases. The keyword "liver transplant" was used in combination with the free terms "frailty" and "exercise" for the literature review. Clinical studies that evaluated the effect of a regular training program, independent of supervision or the duration or intensity of physical exercise, in cirrhotic patients on the waiting list for LT were reviewed. The data on safe physical activity prescriptions following Frequency, Intensity, Time, and Type recommendations were extracted and summarised.

Nine articles met the inclusion criteria for this review. Various instruments for frailty assessment were used, frequently in combination. Five studies prescribed physical activity for patients, one in-person and four to be performed remotely and unsupervised. The remaining four studies only used a self-report instrument to assess the level of physical activity. None reported adverse events related to exercise training. The exercise frequency mainly varied from daily to a minimum of twice per week. The intensity depended on frailty and included increasing levels of activity. The type of exercise was predominantly a combination of aerobic and resistance training. The duration of exercise varied from 4 to 12 wk. Three articles evaluated the effect of the exercise program on clinical outcomes, reporting a reduction in 90-d readmission rates post-transplant and improved frailty scores, as well as improved survival of cirrhotic patients waiting for LT.

Routine frailty assessment is essential for this population. Although more robust evidence is required, the prescription of exercise is safe and can improve patients' functional capacity, improving pre- and post-LT outcomes.

The efficacy of the late-evening snack (LES) has been extensively studied due to the impact of the longest intermeal duration occurring at night in patients with cirrhosis. While actual clinical guidelines on nutrition in chronic liver disease recommend an LES, no specific nutritional compositions have been reported by the European Association for the Study of the Liver (EASL) and the European Society for Clinical Nutrition and Metabolism (ESPEN). Late-evening snacks vary greatly among studies, including natural foods and/or nutritional supplements, yet oral supplements still need to fully meet the LES's nutritional composition. In addition, many hepatologists need to gain experience in nutritional approaches and have access to registered dieticians who can help them manage patients with liver disease. Therefore, this review study aims to summarise evidence regarding using LESs and the mechanisms behind long starvation in patients with cirrhosis. It also provides a practical nutritional guide with several LES options based on common natural foods tailored to special patients' nutritional requirements and geographical backgrounds. In preventing accelerated starvation and related protein malnutrition and sarcopenia in patients with cirrhosis, the nutritional composition of LESs is essential. The proper and straightforward application of the LES's rational nutrition is an advantage to cirrhotic patients and should be carried out by healthcare professionals to enhance the overall liver function and nutritional status of patients with cirrhosis.