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Muscle alterations (myosteatosis and sarcopenia) are frequent in cirrhosis and related to some complications including overt hepatic encephalopathy (HE). The aim of our study was to investigate the relationship between muscle alterations and minimal HE (MHE) and their role in the risk of overt HE. Sixty-four patients with cirrhosis were administered the Psychometric Hepatic Encephalopathy Score and animal naming test to detect MHE. Computed tomography was used to analyze the skeletal muscle index and attenuation. The incidence of the first episode of HE, taking into account the competing risk nature of the data, was estimated. Myosteatosis was observed in 24 patients (37.5%), sarcopenia in 37 (58%), and MHE in 32 (50%). Both myosteatosis (62.5% versus 12.5%, P < 0.001) and sarcopenia (84% versus 31%, P < 0.001) were more frequent in patients with MHE. The variables independently associated with the presence of MHE were sarcopenia, previous overt HE, and myosteatosis. Thirty-one (48%) patients developed overt HE over 16.1 ± 13 months; myosteatosis was detected in 68% and sarcopenia in 84% of them. Sarcopenia and myosteatosis were also independently associated with the development of overt HE. Venous ammonia was significantly higher in patients with sarcopenia (62.6 ± 17.7 versus 41.4 ± 16.1 μg/dL, P < 0.001) and in patients with myosteatosis (65.2 ± 19.2 versus 46.7 ± 17.1 μg/dL, P < 0.001) and inversely correlated to both parameters. Survival was significantly lower in malnourished patients compared to patients without myosteatosis or sarcopenia (P < 0.001). Conclusion: Myosteatosis and sarcopenia, probably by reducing the handling of ammonia in the muscle, are independently associated with MHE and the risk of overt HE in patients with cirrhosis; in malnourished patients, the amelioration of nutritional status may be a goal to decrease both the prevalence of MHE and the incidence of overt HE.

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 &lt, 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 &lt, 0.05, six-minute walk test: 361.8 ± 68 m vs. 409.4 ± 58 m, p &lt, 0.05). Quadriceps muscle mass measured by ultrasound also increased (4.9 ± 1.8 vs. 5.4 ± 1.8 mm, p &lt, 0.05) after HMB, while LFI decreased (4.1 ± 0.4 vs. 3.7 ± 0.4, p &lt, 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.

BACKGROUND & AIMS Severe infections and muscle wasting are both associated to poor outcome in cirrhosis. A possible synergic effect of these two entities in cirrhotic patients has not been previously investigated. We aimed at analysing if a low muscle mass may deteriorate the outcome of cirrhotic patients with sepsis. METHODS Consecutive cirrhotic patients hospitalized for sepsis were enrolled in the study. Patients were classified for the severity of liver impairment (Child-Pugh class) and for the presence of "low muscle mass" (mid-arm muscle circumference

BACKGROUND: Biliary complications (BC) are frequently observed following liver transplantation. The aim of the present retrospective study, conducted at an outpatients' tertiary care hospital, was to determine the incidence of biliary complications and risk factors associated with their development in liver transplantation (lT) patients.MATERIALS AND METHODS: The medical records were reviewed for all patients who underwent liver transplantation at the Rigshospitalet, Copenhagen, Denmark, from 2000 to 2011 and were referred to the Aarhus University Hospital for follow-up. Patients who died within 3 months of surgery or had incomplete clinical information were excluded. All data for demographic characteristics and possible risk factors for development of biliary stricture were collected. Fifty-one patients were included.RESULTS: The median age at transplantation was 40 (range=7-64) years, and 53% of patients were males. Biliary complications occurred in 18 patients (35%), the majority of whom developed strictures (12 patients, 24%). Univariate and multivariate analyses revealed that cytomegalovirus infection (p=0.008), hepatic artery obstruction (p=0.03) and hepatic artery graft abnormalities (p=0.03) were independent risk factors for the development of biliary strictures.CONCLUSION: One-third of patients presented biliary complications after liver transplantation, among which biliary strictures were the most common. Cytomegalovirus infection, hepatic artery stenosis and anatomical abnormality of the graft's hepatic artery are independent risk factors for the development of biliary stricture.

Background Recent innovations in the field of liver transplantation have led to a wealth of new treatment regimes, with potential impact on the onset of de novo malignancies (DNM). The aim of this multicenter cohort study was to provide contemporary figures for the cumulative incidences of solid and hematological DNM after liver transplantation. Methods We designed a retrospective cohort study including patients undergoing LT between 2000 and 2015 in three Italian transplant centers. Cumulative incidence was calculated by Kaplan–Meyer analysis. Results The study included 789 LT patients with a median follow-up of 81 months (IQR: 38–124). The cumulative incidence of non-cutaneous DNM was 6.2% at 5-years, 11.6% at 10-years and 16.3% at 15-years. Post-Transplant Lymphoproliferative Disorders (PTLD) were demonstrated to have a cumulative incidence of 1.0% at 5-years, 1.6% at 10-years and 2.2% at 15-years. Solid Organ Tumors (SOT) demonstrated higher cumulative incidences – 5.3% at 5-years, 10.3% at 10-years and 14.4% at 15-years. The most frequently observed classifications of SOT were lung (rate 1.0% at 5-years, 2.5% at 10-years) and head & neck tumors (rate 1.3% at 5-years, 1.9% at 10-years). Conclusions Lung tumors and head & neck tumors are the most frequently observed SOT after LT.

Sarcopenia and frailty are frequent in liver cirrhosis and are associated with a worse prognosis. For this reason, and being potentially modifiable disorders, to find a strategy to prevent or improve these conditions is of great importance in cirrhotic patients.

Sarcopenia is a frequent complication in liver transplant (LT) recipients. &beta, hydroxy-&beta, methyl-butyrate (HMB) has the potential to increase muscle-performance and tropism. Our study aims at evaluating the effect on muscle mass and functioning, and the safety of 12 weeks of HMB supplementation in patients after LT. This is a pilot, randomized study. Male patients undergoing LT were randomly assigned to the HMB or control group. A diet interview, anthropometry and body composition by dual energy X-ray absorptiometry (DEXA) were performed at enrollment (T0), after 12 weeks (T1) and after 12 months (T12). Twenty-two liver transplant male patients were enrolled in the study: 12 in the HMB group and 10 as the control group. At enrollment, demographic, clinical and nutritional data were similar. According to the appendicular skeletal muscle index, sarcopenia was present in 50% of patients. The appendix skeletal muscle mass index (ASMI) showed a significant increase at T1 and T12 in HMB patients, but not in controls. The mid-arm muscle-circumference and hand grip strength also increased at T1 and T12 versus T0 only in the HMB group. No side effects were reported in either group. The study showed a positive effect of HMB in the recovery of muscle mass and strength after LT. HMB supplement in patients after LT was safe and well tolerated.

Background & Aims: We performed a randomized trial to determine whether albumin should be administered to patients with infections unrelated to spontaneous bacterial peritonitis (SBP). Methods: We performed a multicenter, open-label trial in which 118 patients with cirrhosis, non-SBP infections, and additional risk factors for poor outcome were randomly assigned to receive antibiotics plus albumin (study group; n = 61) or antibiotics alone (control group; n = 57). The primary outcome was in-hospital mortality; secondary outcomes were effect of albumin on disease course. Results: There were no significant differences at baseline between groups in results from standard laboratory tests, serum markers of inflammation, circulatory dysfunction, or liver severity scores. However, the combined prevalence of acute on chronic liver failure (ACLF) and kidney dysfunction was significantly higher in the study group (44.3% vs 24.6% in the control group; P = .02), indicating greater baseline overall severity. There was no significant difference in the primary outcome between groups (13.1% in the study group vs 10.5% in the control group; P = .66). Circulatory and renal functions improved in only the study group. A significantly higher proportion of patients in the study group had resolution of ACLF (82.3% vs 33.3% in the control group; P = .03). A significantly lower proportion of patients in the study group developed nosocomial infections (6.6% vs 24.6% in the control group; P = .007). Conclusions: In a randomized trial of patients with advanced cirrhosis and non-SBP infections, in-hospital mortality was similar between those who received albumin plus antibiotics vs those who received only antibiotics (controls). However, patients given albumin were sicker at baseline and, during the follow-up period, a higher proportion had ACLF resolution and a lower proportion had nosocomial infections. ClinicalTrials.gov no: NCT02034279., SCOPUS: ar.j, info:eu-repo/semantics/published

INTRODUCTION: Muscle mass has been shown to be a prognostic marker in patients with liver cirrhosis. Transversal psoas muscle thickness normalized by height (TPMT/height) obtained by routine computed tomography is a simple surrogate parameter for sarcopenia. TPMT/height, however, is not sex specific, which might play a role in risk stratification. Its association with acute-on-chronic liver failure (ACLF) has not been established yet. ACLF is associated with systemic inflammatory dysregulation. This study aimed at evaluating the role of sarcopenia in ACLF development of patients with decompensated cirrhosis receiving transjugular intrahepatic portosystemic shunt (TIPS) using sex-specific TPMT/height. METHODS: One hundred eighty-six patients from the prospective Non-invasive Evaluation Program for TIPS and Follow Up Network cohort (observational, real-world TIPS cohort with structured follow-up) were analyzed. TPMT/height was measured from routine computed tomography. The sex-specific cutoff was determined to classify patients as sarcopenic and nonsarcopenic for 1-year mortality after TIPS. Clinical outcome was compared. Primary end points were ACLF and 1-year mortality after TIPS. Secondary end points were development of decompensations (hepatic encephalopathy and ascites) after TIPS. RESULTS: The sex-specific cutoff increases the diagnostic accuracy with regard to primary and secondary end points compared with the unisex cutoff. Sex-specific sarcopenia classification is an independent predictor of 1-year mortality and ACLF development in patients with cirrhosis receiving TIPS. Patients in the sarcopenia group showed significantly higher rates of mortality, ascites, overt hepatic encephalopathy, and ACLF after TIPS compared with the nonsarcopenia group. The Chronic Liver Failure Consortium Acute Decompensation score as a marker of systemic inflammation was significantly higher in sarcopenic patients. CONCLUSIONS: This study demonstrates for the first time that sarcopenia is related to ACLF development and systemic inflammation. The prognostic value of TPMT/height can be improved by using sex-specific cutoffs. ClinicalTrials.gov identifier: NCT03584204.

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steato hepatitis have an increasing prevalence among liver diseases. Overweight and obesity are frequently associated conditions in patients with fatty liver. Skeletal muscle mass depletion may also coexist with chronic liver disease even in obese patients. This review will focus on the relationship between sarcopenic obesity and fatty liver.Obesity and sarcopenia are frequently encountered in patients with NAFLD. Adipose tissue is able to release molecules (adipokines) that regulate lipid metabolism, interact with insulin sensitivity and may contribute to induce fibrogenesis in the liver. Skeletal muscle tissue is able to secrete myokines regulating muscle metabolism and insulin sensitivity. Myokines perturbation has been reported to influence adipose tissue mass and fat deposition in the liver. Sarcopenia has been reported as independent risk factor for the development of NAFLD, and for a more severe liver fibrosis in patients with NAFLD.The interaction between skeletal muscle, adipose tissue and the liver may play a role in the development of NAFLD. Sarcopenia and sarcopenic obesity are risk factors for the development of fatty liver and associated with more severe liver fibrosis. Management is not standardized, but dietary counseling and physical training have been proposed as promising strategies. Bariatric surgery may be considered in patients with severe 'resistant' obesity.

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.

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.

Background & Aims: Bacterial infections are common and life-threatening in patients with cirrhosis. Little is known about the epidemiology of bacterial infections in different regions. We performed a multicenter prospective intercontinental study to assess the prevalence and outcomes of bacterial and fungal infections in patients with cirrhosis. Methods: We collected data from 1302 hospitalized patients with cirrhosis and bacterial or fungal infections at 46 centers (15 in Asia, 15 in Europe, 11 in South America, and 5 in North America) from October 2015 through September 2016. We obtained demographic, clinical, microbiology, and treatment data at time of diagnosis of infection and during hospitalization. Patients were followed until death, liver transplantation, or discharge. Results: The global prevalence of multidrug-resistant (MDR) bacteria was 34% (95% confidence interval 31%–37%). The prevalence of MDR bacteria differed significantly among geographic areas, with the greatest prevalence in Asia. Independent risk factors for infection with MDR bacteria were infection in Asia (particularly in India), use of antibiotics in the 3 months before hospitalization, prior health care exposure, and site of infection. Infections caused by MDR bacteria were associated with a lower rate of resolution of infection, a higher incidence of shock and new organ failures, and higher in-hospital mortality than those caused by non-MDR bacteria. Administration of adequate empirical antibiotic treatment was independently associated with improved in-hospital and 28-day survival. Conclusions: In a worldwide study of hospitalized patients, we found a high prevalence of infection with MDR bacteria in patients with cirrhosis. Differences in the prevalence of MDR bacterial infections in different global regions indicate the need for different empirical antibiotic strategies in different continents and countries. While we await new antibiotics, effort should be made to decrease the spread of MDR bacteria in patients with cirrhosis.

Background. No data are available on liver transplantation (LT) outcome and donor liver steatosis, classified as large droplet macrovesicular (Ld-MaS), small-droplet macrovesicular (Sd-MaS), and true microvesicular (MiS), taking into account the recipient Hepatitis C virus (HCV) status. Aim. We investigate the impact of allograft steatosis reclassified according to the Brunt classification on early graft function and survival after LT. Methods. We retrospectively reviewed 204 consecutive preischemia biopsies of grafts transplanted in our center during the period 2001-2011 according to recipient HCV status. Results. The median follow-up after LT was 7.5 years (range: 0.0-16.7). In negative recipients (n=122), graft loss was independently associated with graft Sd-MaS, in multivariable Cox regression models comprehending only pre-/intraoperative variables (HR=1.03, 95%CI=1.01-1.05; P=0.003) and when including indexes of early postoperative graft function (HR=1.04, 95%CI=1.02-1.06; P=0.001). Graft Sd-MaS>15% showed a risk for graft loss > 2.5-folds in both the models. Graft Sd-MaS>15% was associated with reduced graft ATP content and, only in HCV- recipients, with higher early post-LT serum AST peaks. Conclusions. In HCV-negative recipients, allografts with >15% Sd-MaS have significantly reduced graft survival and show low ATP and higher AST peaks in the immediate posttransplant period. Donors with >15% Sd-MaS have significantly higher BMI, longer ICU stays, and lower PaO2.

Sarcopenia is an important burden in liver cirrhosis representing a negative prognostic factor for mortality. Moreover, sarcopenia is an independent predictor of complications in patients with liver cirrhosis, including Hepatic Encephalopathy (HE). An association between sarcopenia and HE in liver cirrhosis has been reported in recent studies, indeed both these complications often affect patients with advanced liver cirrhosis and may exert a synergic effect in deteriorating patients’ outcome. Episodes of HE occur more often in patients with muscle depletion. The rationale for these finding is based on the role played by muscle in ammonia detoxification due to the inability of urea synthesis in the cirrhotic liver. Consequently, muscle depletion may have relevant implications in favoring hyperammonemia and HE. At the same time hyperammonemia has been found to impair muscle protein synthesis through myostatin down-regulation. From this point of view, modulation of diet and amelioration of nutritional status and muscle mass can be considered a potential goal to prevent this vicious circle and improve the cognitive impairment in cirrhotic patients.

Background Hepatic encephalopathy (HE) is the major complication of transjugular intrahepatic portosystemic shunt (TIPS). In cirrhotic patients, a correlation between sarcopenia and HE has been suggested. Aim To evaluate the evolution of the skeletal muscle quantity and quality at CT scan and of the patients' cognitive impairment (both overt and minimal HE) before and after TIPS. Patients and methods Twenty-seven cirrhotic patients submitted to TIPS were studied. The modification of Skeletal Muscle Index (SMI), muscle attenuation, HE and plasma ammonia were evaluated before and after a mean follow-up of 9.8 ± 4 months after TIPS. Results During the follow-up, the mean SMI and muscle attenuation increased significantly, although not uniformly in all patients. Psychometric Hepatic Encephalopathy Score (PHES) and ammonia improved significantly in the patients with amelioration in SMI >10% (n = 16) and not in those without (n = 11) (PHES: -1.6 ± 2 vs -4.8 ± 2.1; P = 0.0005; ammonia: 48.5 ± 28.7 vs 96 ± 31.5 μg/dL; P = 0.0004). Moreover, the prevalence of minimal HE (12.5% vs 73%, P = 0.001) as well as the number of episodes of overt HE during the follow-up were significantly reduced in the patients with improved SMI. Model for end-stage liver disease remained stable or worsened after TIPS and was not significantly different between the groups with or without SMI improvement. Conclusion The amelioration of muscle wasting and HE independent of liver function observed after TIPS supports the causal relationship between muscle wasting and HE.

Early diagnosis and appropriate treatment of infections in cirrhosis are crucial because of their high morbidity and mortality. Multidrug-resistant (MDR) infections are on the increase in health care settings. Health-care–associated (HCA) infections are still frequently treated as community-acquired with a detrimental effect on survival. We aimed to prospectively evaluate in a randomized trial the effectiveness of a broad spectrum antibiotic treatment in patients with cirrhosis with HCA infections. Consecutive patients with cirrhosis hospitalized with HCA infections were enrolled. After culture sampling, patients were promptly randomized to receive a standard or a broad spectrum antibiotic treatment (NCT01820026). The primary endpoint was in-hospital mortality. Efficacy, side effects, and the length of hospitalization were considered. Treatment failure was followed by a change in antibiotic therapy. Ninety-six patients were randomized and 94 were included. The two groups were similar for demographic, clinical, and microbiological characteristics. The prevalence of MDR pathogens was 40% in the standard versus 46% in the broad spectrum group. In-hospital mortality showed a substantial reduction in the broad spectrum versus standard group (6% vs. 25%; P = 0.01). In a post-hoc analysis, reduction of mortality was more evident in patients with sepsis. The broad spectrum showed a lower rate of treatment failure than the standard therapy (18% vs. 51%; P = 0.001). Length of hospitalization was shorter in the broad spectrum (12.3 ± 7 days) versus standard group (18 ± 15 days; P = 0.03). Five patients in each group developed a second infection during hospitalization with a similar prevalence of MDR (50% broad spectrum vs. 60% standard). Conclusions: A broad spectrum antibiotic therapy as empirical treatment in HCA infections improves survival in cirrhosis. This treatment was significantly effective, safe, and cost saving. (Hepatology 2016;63:1632-1639)

Sarcopenia evaluated by computed tomography (CT) scan at the lumbar site has been identified as a risk factor for morbidity and mortality in cirrhosis.The aim of this study was to compare the measurement of muscle mass through CT scan, considered the gold standard, with other reliable techniques to evaluate the rate of agreement between different available methods for the assessment of muscle mass in cirrhosis. The correlation between measurements of muscle mass and of muscle strength was also investigated.Adult patients eligible for liver transplantation were studied. Lumbar skeletal muscle cross-sectional area was measured by CT and muscle depletion was defined using previously published cut-offs. Mid-arm muscle circumference was calculated following anthropometric measures. The Fat-Free Mass Index and the Appendicular Skeletal Muscle Index were calculated using dual-energy X-ray absorptiometry. Muscle strength was evaluated using the Hand Grip test.Fifty-nine patients with cirrhosis were included. Sarcopenia was diagnosed in 76% of the patients according to CT evaluation. A significant reduction in Fat-Free Mass Index and Appendicular Skeletal Muscle Index was observed in 42-52% of the patients, whereas 52% showed a mid-arm muscle circumference less than 10th percentile. Skeletal muscle mass evaluation through CT was only weakly correlated with dual-energy X-ray absorptiometry and anthropometry evaluation. No correlation was observed between CT measurement of muscle mass and Hand Grip test.CT scan can identify the highest percentage of sarcopenia in cirrhosis and no other techniques are actually available as a replacement. Future efforts should focus on approaches for assessing both skeletal muscle mass and function to provide a better evaluation of sarcopenia in cirrhotic patients.

The purpose of this review is to summarize recent knowledge on malnutrition and sarcopenia in liver cirrhosis with special focus on hospitalized cirrhotic patients. Assessment tools and treatment options are briefly discussed. During hospitalization, cirrhotic patients frequently deteriorate their nutritional status due to multiple factors. Evaluation of nutritional risk followed by nutritional assessment has been suggested in cirrhotic patients and may alert the need of special nutritional care in those hospitalized. Few recent studies, although in small series, proposed to ameliorate sarcopenia in cirrhotic patients by protein/calorie supplementation and also encouraging physical activity. Malnutrition and sarcopenia are negative predictors of morbidity and mortality in hospitalized cirrhotic patients. When malnutrition is diagnosed, care should be taken to provide adequate nutritional support. Physical movement, whenever possible, has been suggested for prevention of muscle loss.

Background Microbial translocation from the gut lumen has been involved in the pathogenesis of liver damage in hepatitis C virus (HCV) infection. Aim To investigate the impact of direct-acting antiviral treatment on microbial translocation and T-cell activation, in patients with hepatitis C-related liver disease. Methods We enrolled two groups of HCV-infected patients undergoing direct-acting antiviral treatment: patients with fibrosis ≥F3 according to Metavir (Group ≥F3); patients with hepatitis C recurrence after liver transplantation and Metavir ≥F2 (Group Liver Transplantation + ≥F2). All patients were treated with direct-acting antivirals based on ongoing guidelines. Surrogate biomarkers of microbial translocation (plasma concentrations of soluble-CD14, lipopolysaccharide-binding protein and intestinal fatty acid-binding protein) were evaluated at baseline, at first month, at the end of treatment and 3 months later. T-cell activation was measured by expression of CD38+ HLA-DR at the same time points, only in Group ≥F3. Results There were 32 patients in Group ≥F3 and 13 in Group LT + ≥F2. At baseline, levels of soluble-CD14 and lipopolysaccharide-binding protein were significantly higher in both groups vs healthy controls. Baseline soluble-CD14 correlated with glutamic-oxalacetic transaminase (r = 0.384, P = 0.009) and glutamic-pyruvic transaminase (r = 0.293, P = 0.05). A significant decrease in plasma levels of surrogate microbial translocation biomarkers was observed during and after treatment in the two groups although values were not normalised. In Group ≥F3, CD38+ HLADR+ T-cell expression was significantly decreased by direct-acting antiviral treatment. Relapsers (9%) showed higher soluble-CD14 levels at baseline. Conclusion Surrogate microbial translocation markers and T cell activation are increased in HCV-infected patients with liver fibrosis and decrease during direct-acting antiviral treatment.

AIM To perform a systematic review and meta-analysis on donor-to-recipient gender mismatch as a risk factor for post-transplant graft loss. METHODS A systematic literature search was performed using PubMed, Cochrane Library database and EMBASE. The primary outcome was graft loss after liver transplantation. Odds ratios and 95% confidence intervals were calculated to compare the pooled data between groups with different donor-to-recipient gender matches. Three analyses were done considering (1) gender mismatches (F-M and M-F) vs matches (M-M and F-F); (2) Female-to-Male mismatch vs other matches; and (3) Male-to-Female mismatch vs other matches. RESULTS A total of 7 articles were analysed. Gender mismatch (M-F and F-M) was associated with a significant increase of graft loss respect to match (M-M and F-F) (OR: 1.30; 95%CI: 1.13-1.50; P < 0.001). When F-M mismatch was specifically investigated, it confirmed its detrimental role in terms of graft survival (OR: 1.83; 95%CI: 1.20-2.80; P = 0.005). M-F mismatch failed to present a significant role (OR: 1.09; 95%CI: 0.73-1.62; P = 0.68). CONCLUSION Gender mismatch is a risk factor for poor graft survival after liver transplantation. Female-to-male mismatch represents the worst combination. More studies are needed with the intent to better clarify the reasons for these results.

Background and aim Alcoholic liver disease (ALD) represents a frequent indication for liver transplantation (LT). Since 2004, we have adopted a program of multidisciplinary support(MS) to assist patients undergoing LT for ALD. We aimed at analyzing the relapse rate and the risk factors for relapse. The relapse rate was also compared with that of a historical group of patients who underwent transplantation. Their survival rate was also analyzed. Patients and methods Consecutive patients with ALD transplanted from 2004 were included. The most important demographic, psychosocial, and clinical characteristics known to be associated with alcohol relapse were recorded. Results Sixty-nine patients underwent MS: 8.7% presented alcohol relapse. At multivariate analysis female gender (sHR 9.02, 95% CI 1.71-47.56, P = .009), alcohol withdrawal syndrome (sHR 5.89, 95% CI 1.42-24.46, P = .015) and a shorter time of MS program before LT (sHR 0.928 per month, 95% CI 0.870-0.988, P = .021) were identified as independent risk factors for relapse. The rate of alcohol relapse was significantly lower than that of the historical group who did not undergo MS (sHR 0.21, 95% CI: 0.06-0.68; P = .009). Conclusion This study shows that a MS program may contribute to alcohol relapse prevention after LT in ALD patients. However, the relevance of this support needs to be confirmed by clinical trials.

The development of nutritional and metabolic abnormalities represents an important burden in patients after liver transplantation (LT). Our study aimed at evaluating the incidence, time of onset, and risk factors for nutritional and metabolic abnormalities in patients after LT. The study was a single-center retrospective study. Consecutive patients undergoing elective LT from 2000 to 2016 were enrolled. The presence of at least two among arterial hypertension (AH), diabetes mellitus (DM), dyslipidemia, and obesity (BMI &ge, 30 Kg/m2) was utilized to define patients with the metabolic disorder (MD). Three hundred and fifteen patients were enrolled, the median age was 56 years (68% males). Non-alcoholic steatohepatitis (NASH) was the origin of liver disease in 10% of patients. During follow-up, 39% of patients developed AH, 18% DM, and 17% dyslipidemia. Metabolic disorders were observed in 32% of patients. The NASH etiology (OR: 6.2, CI 95% 0.5&ndash, 3, p = 0.003) and a longer follow-up (OR: 1.2, CI 95% 0.004&ndash, 0.02, p = 0.002) were associated with de novo MD. In conclusion, nutritional and metabolic disorders are a frequent complication after LT, being present in up to one-third of patients. The NASH etiology and a longer distance from LT are associated with de novo MD after LT.

Background & Aims A causal relationship between infection, systemic inflammation, and hepatic encephalopathy (HE) has been suggested in cirrhosis. No study, however, has specifically examined, in cirrhotic patients with infection, the complete pattern of clinical and subclinical cognitive alterations and its reversibility after resolution. Our investigation was aimed at describing the characteristics of cognitive impairment in hospitalized cirrhotic patients, in comparison with patients without liver disease, with and without infection. Methods One hundred and fifty cirrhotic patients were prospectively enrolled. Eighty-one patients without liver disease constituted the control group. Bacterial infections and sepsis were actively searched in all patients independently of their clinical evidence at entry. Neurological and psychometric assessment was performed at admission and in case of nosocomial infection. The patients were re-evaluated after the resolution of the infection and 3months later. Results Cognitive impairment (overt or subclinical) was recorded in 42% of cirrhotics without infection, in 79% with infection without SIRS and in 90% with sepsis. The impairment was only subclinical in controls and occurred only in patients with sepsis (42%). Multivariate analysis selected infection as the only independent predictor of cognitive impairment (OR 9.5; 95% CI 3.5–26.2; p =0.00001) in cirrhosis. The subclinical alterations detected by psychometric tests were also strongly related to the infectious episode and reversible after its resolution. Conclusions Infections are associated with a worse cognitive impairment in cirrhotics compared to patients without liver disease. The search and treatment of infections are crucial to ameliorate both clinical and subclinical cognitive impairment of cirrhotic patients.

Psychopathological symptoms and reduced health related quality of life (HRQoL) are frequent in cirrhotics, but no data on their association with cirrhosis prognosis assessed by the MELDNa score are available. Prospective data on the long-term effect of deceased donor liver transplantation (LT) on psychopathological symptoms are needed. Before entering the LT waiting list, 44 consecutive LT cirrhotic candidates without a major psychiatric disorder underwent a psychopathological assessment, including Symptom Checklist-90-revised (SCL-90-R) and Defense Style Questionnaire (DSQ). HRQoL was measured by Short Form 36 Health Survey (SF-36). Abnormal performance at each questionnaire was defined by using 44 age, gender, BMI and education-matched healthy subjects. Separate binary logistic regression models were used to test the association of the Child-Pugh, MELD and MELDNa scores with abnormal performance at each questionnaire. Fourteen patients repeated the battery tests 3 years after LT. Before LT, increasing MELDNa was the only prognostic score independently associated with an abnormal SCL-90-R global psychopathological score index (OR: 1.207; 95% CI: 1.026–1.420; P = 0.02) and the best independent predictor of reduced HRQoL. After LT, compared to status prior to LT, performance at SF-36 general health perception scale ameliorated (P = 0.02), performance at SCL-90-R somatization scale (P = 0.001) and global psychopathological score index (P

Hepatic encephalopathy (HE) is an important complication in patients with cirrhosis who received transjugular intrahepatic portosystemic shunts (TIPS). We investigated whether a decrease in muscle mass was associated independently with the occurrence of HE after TIPS.We performed a prospective study of 46 consecutive patients with cirrhosis (mean age, 58.6 ± 9.1 y; mean model for end-stage liver disease score, 11.3 ± 3.3; mean Child-Pugh score, 7.6 ± 1.5) who received TIPS from January 2013 through December 2014 at a tertiary center in Rome, Italy. All patients underwent computed tomography analysis at the level of the third lumbar vertebrae to determine the skeletal muscle index; sarcopenia was defined by sex-specific cut-off values. We estimated the incidence of the first episode of HE after TIPS, taking into account the competing risk nature of the data (death or liver transplantation).Twenty-six patients (57%) were found to have sarcopenia. Twenty-one patients (46%) developed overt HE in the 7 ± 9 months after TIPS placement; all of these patients were sarcopenic, according to the skeletal muscle index. Of the 25 patients without HE after TIPS, only 5 had sarcopenia. In multivariate analysis, model for end-stage liver disease score (subdistribution hazard ratio, 1.16; 95% confidence interval, 1.01-1.34; P = .043) and sarcopenia (subdistribution hazard ratio, 31.3; 95% confidence interval, 4.5-218.07; P.001) were associated independently with the development of HE after TIPS placement.In a prospective study of 46 patients with cirrhosis, we found muscle wasting, probably owing to reduced processing of ammonia, to be associated with the development of HE after TIPS placement. Sarcopenia should be considered in selecting patients for TIPS therapy. Nutritional status should be evaluated in patients with sarcopenia before TIPS placement, which might reduce the incidence of HE.

Despite its documented prognostic relevance, hepatic encephalopathy (HE) is not considered in liver transplantation (LT) due to its possible poor objectivity. To override this problem, we aimed to analyze if an objective diagnosis of HE may confer additional mortality risk beyond MELD. Study and validation cohorts of patients with cirrhosis were considered in Italy and Canada, respectively. Patients were considered to be HE+ if an episode of overt HE was documented in a hospitalization. Of the 486 patients enrolled in Italy, 184 (38%) were HE+. During the 6-month follow-up, 77 patients died and 50 underwent transplantation. The 6-month mortality of HE+ versus HE- patients was significantly higher (P

Muscle depletion is frequently encountered in cirrhotic patients. As muscle may represents an alternative site of ammonia detoxification in liver diseases, our study was aimed at investigating whether a decrease in muscle mass or function may independently influence the prevalence of neurocognitive alterations in cirrhosis. Three-hundred consecutive hospitalized cirrhotic patients were prospectively enrolled. Liver function, a complete neurocognitive assessment for the diagnosis of clinical or subclinical hepatic encephalopathy (HE) and parameters of nutritional status and muscle function were evaluated in each patient at admission. Clinically overt HE, at admission or in the last 12 months, or a diagnosis of minimal HE were significantly higher in cirrhotic patients with muscle depletion or decreased muscle strength. The fasting venous blood ammonia concentrations were also higher in this group. Muscle depletion was an independent risk factor at multivariate analysis both for overt and minimal HE. In conclusion cirrhotic patients with muscle depletion are at higher risk of HE and the amelioration of nutritional status is a possible goal to decrease the prevalence of neurocognitive alterations in these patients.