Search Results (20)

Objectives: Personalized sepsis care requires understanding how pre-existing health status can influence outcomes. The aim of this study is to evaluate its impact on in-hospital and 12-month mortality in patients with sepsis, taking into account age, comorbidities, the Charlson Comorbidity Index, frailty, anemia, and the Sequential Organ Failure Score Assessment (SOFA) in the first 24 h. Methods: An observational and retrospective study was conducted using data from the Sepsis Code program at the Hospital Universitario de La Princesa. The relationship between risk factors and mortality, as well as Intensive Care Unit (ICU) admission, was analyzed for the period 2016–2018 using bivariate and multivariate logistic regression. Results: A total of 547 patients were included. In the multivariate analysis, the risk factors independently associated with mortality were Rockwood Clinical Frailty Scale ≥ 5 (OR 2.45, p < 0.05); SOFA ≥ 4 (OR 2.13, p < 0.05); age (OR 1.98, p < 0.05); anemia (OR 1.85, p < 0.05); and specific comorbidities such as ischemic heart disease (OR 2.34, p < 0.05), severe liver disease (OR 3.62, p < 0.05), and metastatic cancer (OR 3.14, p < 0.05). Patients who were frail, had dementia, or heart failure were less likely to be admitted to the ICU. Conclusions: Frailty, comorbidities, age, and anemia are associated with outcomes in patients with sepsis and could be incorporated into mortality prediction models to guide tailored treatment strategies. Full article

Background and Objectives: Sarcopenia and frailty adversely affect morbidity and mortality in patients with liver cirrhosis. This study aimed to investigate the prevalence of sarcopenia and frailty in cirrhotic patients and to identify the contributing factors. Materials and Methods: This study was conducted in adult patients diagnosed with cirrhosis in a single-center cohort study who were under follow-up in the gastroenterology outpatient clinic. Patients were evaluated using the SARC-F questionnaire, FRAIL index, handgrip strength measurements, and various biochemical parameters. Results: Of the 100 patients included in the study, 58.7% were male, with a median age of 66.5 years. The prevalence of sarcopenia was 32%. Patients with sarcopenia had significantly lower body mass index (BMI) and higher model for end-stage liver disease (MELD)-Na and Child–Turcotte–Pugh (CTP) scores. According to the FRAIL scale, pre-frailty was highly prevalent among patients (60%). Significant negative correlations were observed between the SARC-F score and BMI, handgrip strength, albumin, vitamin D, and sodium levels. Conversely, significant positive correlations were identified between the SARC-F score and age, CTP score, MELD-Na score, bilirubin, AST, ALT, and ferritin levels. Conclusions: This study demonstrated a high prevalence of sarcopenia and frailty among cirrhotic patients. These findings warrants further investigation in longitudinal studies for hard clinical outcome and mortality. Full article

Background/Objective: Leukocyte cell-derived chemotaxin-2 (LECT2), a hepatokine, is implicated in non-alcoholic fatty liver disease (NAFLD). Although NAFLD and sarcopenia are closely linked, the relationship between plasma LECT2 levels and sarcopenia remains unclear. Methods: We analyzed plasma LECT2 levels in 400 older adults aged 70–84 years old living in the community enrolled in the Korean Frailty and Aging Cohort Study. The appendicular skeletal muscle mass (ASM) and handgrip strength (HGS), both adjusted for the BMI, were used to evaluate the muscle mass and strength. A low muscle mass (LMM) was defined using the sex-specific lowest quintile of ASM/BMI as the cutoff value, while a low muscle strength (LMS) was determined based on the lowest quintile of the HGS/BMI. Sarcopenia was defined by the coexistence of an LMM and LMS. Results: NAFLD was identified using a fatty liver index > 30. The participants with NAFLD had significantly higher plasma LECT2 levels compared to their non-NAFLD counterparts (34.4 [29.3–41.1] vs. 29.0 [24.7–36.7] ng/mL, p < 0.001). Circulating LECT2 levels were inversely correlated with ASM/BMI (r = −0.506, p < 0.001) and HGS/BMI (r = −0.474, p < 0.001), as determined by Spearman correlation analysis. Among the study participants, 79 (19.8%) were categorized as having either an LMM or LMS, and 31 (7.8%) were identified as having sarcopenia. In multivariate logistic regression, the highest LECT2 quartile had markedly greater odds of an LMM (OR 3.31, 95% CI 1.41–7.75), LMS (OR 2.85, 95% CI 1.29–6.26), and sarcopenia (OR 5.48, 95% CI 1.57–19.05) relative to the lowest quartile. Conclusions: Our results indicate that elevated plasma LECT2, a hepatokine increased in NAFLD, contributes to an increased risk of sarcopenia in older adults. Full article

Background/aim: Frailty is increasingly recognized as a relevant prognostic factor in patients with cirrhosis, regardless of liver failure. Vitamin D deficiency is frequent in these patients and has been related to frailty and sarcopenia, but the impact of its supplementation on frailty in cirrhosis is unknown. The aim was to evaluate the effect of vitamin D supplementation on frailty in patients with decompensated cirrhosis and vitamin D deficiency or insufficiency. Methods: We included patients with cirrhosis who had vitamin D deficiency or insufficiency following their hospitalization for acute decompensation. Vitamin D was supplemented according to current recommendations, as were other micronutrients if necessary. Patients were followed for one year to evaluate changes at 6 and 12 months in frailty (Fried frailty index), health-related quality of life (SF-36, CLDQ) and mood (HADS). Body composition was assessed by DXA at baseline and at 12 months. Results: We included 39 patients, 27 of whom reached the 6-month follow-up. Serum vitamin D increased at 6 and 12 months (p < 0.001 compared to baseline). Fried frailty index improved at the 6-month visit (p = 0.004), and handgrip strength improved at 6 (p = 0.001) and 12 (p = 0.002) months, similarly in women and men. At 12 months, we observed an increase in body mass index, right arm lean mass and total fat mass. Conclusions: A multifactorial nutritional intervention, especially vitamin D supplementation after discharge in decompensated, vitamin D-deficient patients with cirrhosis, was associated with an improvement in frailty, muscular strength and lean muscle mass. However, the increase in fat mass strengthens the recommendation for diet, exercise and weight supervision. Full article

Background: The rate of morbidity after liver surgery is estimated at 30% and can be even higher when considering higher-risk subgroups of patients. Frailty is believed to better predict surgical outcomes by showcasing the patient’s ability to withstand major surgical stress and selecting frail ones. Methods: This is a single-centre, observational case–control study on patients diagnosed with liver malignancies who underwent liver resections between 2013 and 2024. The five-item modified Frailty Index (mFI-5) was used to split patients into frail and non-frail. The two groups were compared in terms of preoperative, operative and postoperative outcomes using a chi-squared and logistic regression model. Results: A total of 230 patients were included and split into two groups: non-frail, NF, n = 90, and frail patients, F, n = 140. Overall, F patients had a higher rate of morbidity (p = 0.04) but with similar mortality and length of stay. When considering only major liver resections, F patients had a higher probability of posthepatectomy liver failure (LR 6.793, p = 0.009), postoperative bleeding (LR 9.541, p = 0.002) and longer ICU stay (LR 8.666, p = 0.003), with similar rates of bile leak, surgical site infections, length of stay and mortality. Conclusions: Frailty seems to be a solid predictor of posthepatectomy liver failure in patients undergoing major liver resections and is associated with a longer ICU stay. However, mortality and surgical morbidity seem to be comparable between frail and non-frail patients. Full article

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. Full article

Background/Objectives: Sarcopenia and frailty are both multidimensional and interrelated problems for patients with cirrhosis and require prompt assessment and appropriate management because of their impact on disease outcomes. Our purpose is to identify the prevalence of sarcopenia and frailty in patients with advanced liver disease. Furtherksdnvk more, our purpose is to explore the association between sarcopenia, frailty, and various complications and the impact of these conditions on short- and long-term hospital survival rates. Methods: A prospective, observational, unicentric study was conducted in an emergency university hospital in Romania between January 2021 and December 2023 that included patients with advanced liver diseases. The patients with sarcopenia and frailty were selected using measurements of handgrip strength (HGS), Short Physical Performance Battery (SPPB), liver frailty index (LFI), and skeletal muscle index (SMI). Patients were divided into four groups based on the presence of sarcopenia and/or frailty. Results: This study included 128 patients. Younger patients associated with both sarcopenia and frailty (55.76 ± 10.46 years). Most males were without sarcopenia and frailty (63.93%) compared to those with both sarcopenia and frailty (36.07%). The Child–Pugh score C was identified in the majority of those with both sarcopenia and frailty (69.70%). Higher values for MELD-Na scores were obtained in the group with sarcopenia and frailty (25.45 ± 6.924). Biomarkers like albumin, sodium, C-reactive protein, bilirubin, and platelets were statistically significant as mortality predictors in all four groups. Patients with both sarcopenia and frailty presented more often with encephalopathy and spontaneous bacterial peritonitis. Survival rates in the short and long term were lower for the patients who associated both sarcopenia and frailty compared to those without sarcopenia and frailty. Conclusions: The presence of sarcopenia and frailty significantly impacts outcomes in patients with decompensated advanced liver disease. When both conditions coexist in the same patient, they markedly increase in-hospital mortality, as well as short- and long-term survival rates. Full article

Frailty in cirrhosis or advanced chronic liver disease (ACLD) is a relevant prognostic factor. In the present study, we aimed to analyze potential biomarkers associated with frailty and its improvement in patients with ACLD. We analyzed the serum of outpatients with ACLD who participated in a previous study (Román, Hepatol Commun 2024) in which frailty was assessed using the liver frailty index (LFI), and patients who were frail or prefrail were randomized to a multifactorial intervention (home exercise, branched-chain amino acids, and probiotics) or control for 12 months. We determined a biomarker battery of inflammation, bacterial translocation, and liver damage in blood and urine and blood metabolomics by ¹H-NMR. Thirty-seven patients were included. According to the LFI, 32 patients were frail or prefrail, and 5 were robust. At baseline, LFI correlated with LBP, sCD163, mtDNA, FGF-21, urinary NGAL, urinary claudin-3, and the metabolites mannose, ethanol, and isoleucine. During the study, patients in the intervention group showed an improvement in LFI and a decrease in CRP, LBP, sCD163, and ccK18 compared to the control group. Metabolomics showed a decrease in dimethyl sulfone and creatinine and an increase in malonate, ornithine, isoleucine, and valine in the intervention group. We conclude that frailty in patients with ACLD is associated with biomarkers of systemic inflammation, bacterial translocation, and liver damage, and alterations of amino acid and short-chain fatty acid metabolism. Full article

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. Full article

Epigenetic aging is a hot topic in the field of aging research. The present study estimated epigenetic age in long-lived individuals, who are currently actively being studied worldwide as an example of successful aging due to their longevity. We used Bekaert’s blood-based age prediction model to estimate the epigenetic age of 50 conditionally “healthy” and 45 frail long-livers over 90 years old. Frailty assessment in long-livers was conducted using the Frailty Index. The control group was composed of 32 healthy individuals aged 20–60 years. The DNA methylation status of 4 CpG sites (ASPA CpG1, PDE4C CpG1, ELOVL2 CpG6, and EDARADD CpG1) included in the epigenetic clock was assessed through pyrosequencing. According to the model calculations, the epigenetic age of long-livers was significantly lower than their chronological age (on average by 21 years) compared with data from the group of people aged 20 to 60 years. This suggests a slowing of epigenetic and potentially biological aging in long livers. At the same time, the obtained results showed no statistically significant differences in delta age (difference between the predicted and chronological age) between “healthy” long livers and long livers with frailty. We also failed to detect sex differences in epigenetic age either in the group of long livers or in the control group. It is possible that the predictive power of epigenetic clocks based on a small number of CpG sites is insufficient to detect such differences. Nevertheless, this study underscores the need for further research on the epigenetic status of centenarians to gain a deeper understanding of the factors contributing to delayed aging in this population. Full article

The association between frailty and health-related quality of life (HRQoL) among Asian patients with liver cirrhosis and sarcopenia remains largely unexplored. To address this knowledge gap, we conducted a cross-sectional study involving individuals aged 32 to 69 years, all diagnosed with liver cirrhosis. The chronic liver disease questionnaire (CLDQ) was used to assess HR-QoL, the CLDQ score was used as an outcome to measure the factors related to HR-QoL, and the liver frailty index (LFI) was used to assess the frailty status. The association between the frailty status and the CLDQ summary scales was investigated using the correlation coefficient and multiple regression analyses. A total of 138 patients in the frail (n = 62) and non-frail (n = 76) groups with (alcohol: 97; viral: 24; autoimmune: 17; and cryptogenic: 12) were included in the study. Age, CTP score, and model for end-stage liver disease (MELD) sodium were significantly higher in the frail group. In the CLDQ domains, there was a significant difference between the frail and non-frail groups (p value = 0.001). In health-related quality-of-life summary measures, there was a strong negative correlation between frailty and the scores for activities, emotional function, and fatigue (p value = 0.001). When comparing frail to non-frail patients, these characteristics demonstrated significantly increased odds as indicated by their adjusted odds ratios: OR 3.339 (p value = 0.013), OR 3.998 (p value = 0.006), and OR 4.626 (p value = 0.002), respectively. Full article

Background: Stratifying patients with liver cirrhosis for risk of rehospitalization is challenging with established scoring systems for chronic liver disease. Frailty captures the physical characteristics of patients with cirrhosis. Its value for predicting short-term rehospitalizations in hospitalized patients remains to be defined. Methods: Eighty-three non-electively hospitalized patients with liver cirrhosis were analyzed in this study. Frailty was assessed during the last 48 h of hospital stay with the liver frailty index (LFI). Patients were followed for 30-day rehospitalization. Results: In total, 26 (31%) patients were rehospitalized within 30 days. The median LFI was 4.5, and 43 (52%) patients were identified as frail. Rehospitalized patients had a significant higher LFI compared to patients without a rehospitalization within 30 days. In multivariable analysis, LFI as a metric variable (OR 2.36, p = 0.02) and lower platelet count (OR 0.98, p < 0.01) were independently associated with rehospitalization. LFI and its subtest chair stands had the best discriminative ability to predict rehospitalization, with AUROCs of 0.66 and 0.67, respectively. An LFI cut-off of >4.62 discriminated best between patients with and without elevated risk for rehospitalization within 30 days. Conclusions: Measures of frailty could be useful to identify patients at higher risk for short-term rehospitalization. Full article

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. Full article

Frailty including physical inactivity is associated with the survival of patients with hepatocellular carcinoma (HCC). We aimed to investigate the effects of in-hospital exercise on frailty in patients with HCC. This was a multi-center observational study. Patients with HCC were classified into exercise (n = 114) and non-exercise (n = 67) groups. The exercise group was treated with a mixture of aerobic and resistance exercises (20–40 min/day, median four days). Frailty was assessed using the liver frailty index (LFI). Factors for changes in LFI were examined by multivariate and decision-tree analyses. The factors were also examined after propensity score matching. During hospitalization, LFI was significantly improved in the exercise group compared to the non-exercise group (ΔLFI −0.17 vs. −0.02, p = 0.0119). In multivariate analysis, exercise (odds ratio (OR) 2.38, 95% confidence interval (CI) 1.240–4.570, p = 0.0091) and females (OR 2.09; 95%CI, 1.062–4.109; p = 0.0328) were identified as independent factors for the improvement of LFI. In the decision-tree analysis, exercise was identified as an initial classifier associated with the improvement of LFI. Similar findings were also seen in the propensity score matching analyses. We demonstrated that in-hospital exercise improved frailty in patients with HCC. Thus, in-hospital exercise may be beneficial for improving physical function in patients with HCC. Full article

Low vitamin D status is related to frailty and/or sarcopenia in elderly individuals. However, these relationships are unclear in patients with chronic liver disease (CLD). This study aimed at exploring the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and frailty or sarcopenia in 231 patients with CLD. Frailty was determined based on five factors (weight loss, low physical activity, weakness, slowness, and exhaustion). Sarcopenia was diagnosed by applying the Japan Society of Hepatology criteria. The patients were classified into three groups according to baseline 25(OH)D levels: low (L), intermediate (I), and high (H) vitamin D (VD) groups. Of the 231 patients, 70 (30.3%) and 66 (28.6%) had frailty and sarcopenia, respectively. The prevalence rate of frailty and sarcopenia significantly increased stepwise with a decline in the vitamin D status. The L-VD group showed the highest prevalence rates of frailty and sarcopenia (49.1% (28/57), p < 0.001 for both), whereas the H-VD group showed the lowest prevalence rates of frailty (15.3% (9/59)) and sarcopenia (18.6% (11/59)) (p < 0.001 for both). Multivariate analysis identified serum 25(OH)D levels as a significant independent factor related to frailty and sarcopenia. Serum 25(OH)D levels significantly correlated with handgrip strength, skeletal muscle mass index, and gait speed. In conclusion, low serum vitamin D level, especially severe vitamin D deficient status, is closely related to frailty and sarcopenia in patients with CLD. Full article