Natural history of NASH cirrhosis in liver transplant waitlist registrants.

BACKGROUND AND AIMS: Non-alcoholic steatohepatitis (NASH) cirrhosis is rapidly growing as an indication for liver transplant(ation) (LT). However, the natural history of NASH cirrhosis among LT waitlist registrants has not been established. The present study aimed to define the natural history of NASH cirrhosis using the Scientific Registry of Transplant Recipients database. METHODS: The study cohort comprised patients registered on the LT waitlist between 1/1/2016 to 12/31/2021. The primary outcomes included probability of LT and waitlist mortality, comparing NASH (n = 8,120) vs. non-NASH (n = 21,409) cirrhosis. RESULTS: Patients with NASH cirrhosis were listed with lower model for end-stage liver disease (MELD) scores despite bearing a greater burden of portal hypertension, especially at lower MELD scores. The overall transplant probability in LT waitlist registrants with NASH [vs. non-NASH] cirrhosis was significantly lower at 90 days (HR 0.873, p <0.001) and 1 year (HR 0.867, p <0.001); this was even more pronounced in patients with MELD scores >30 (HR 0.705 at 90 days and HR 0.672 at 1 year, p <0.001 for both). Serum creatinine was the key contributor to MELD score increases leading to LT among LT waitlist registrants with NASH cirrhosis, while bilirubin was in patients with non-NASH cirrhosis. Finally, waitlist mortality at 90 days (HR 1.15, p <0.001) and 1 year (1.25, p <0.001) was significantly higher in patients with NASH cirrhosis compared to those with non-NASH cirrhosis. These differences were more pronounced in patients with lower MELD scores at the time of LT waitlist registration. CONCLUSIONS: LT waitlist registrants with NASH cirrhosis are less likely to receive a transplant compared to patients with non-NASH cirrhosis. Serum creatinine was the major contributor to MELD score increases leading to LT in patients with NASH cirrhosis. IMPACT AND IMPLICATIONS: This study provides important insights into the distinct natural history of non-alcoholic steatohepatitis (NASH) cirrhosis among liver transplant (LT) waitlist registrants, revealing that patients with NASH cirrhosis face lower odds of transplantation and higher waitlist mortality than those with non-NASH cirrhosis. Our study underscores the significance of serum creatinine as a crucial contributor to model for end-stage liver disease (MELD) score in patients with NASH cirrhosis. These findings have substantial implications, emphasizing the need for ongoing evaluation and refinement of the MELD score to more accurately capture mortality risk in patients with NASH cirrhosis on the LT waitlist. Moreover, the study highlights the importance of further research investigating the impact of the implementation of MELD 3.0 across the US on the natural history of NASH cirrhosis.

Soluble CD137 is a novel serum marker of liver cirrhosis in patients with hepatitis C and alcohol-associated disease etiology.

Defective T-cell functions play a role in the persistence of HCV infection. Activated T cells express CD137, which costimulates antivirus T-cell responses, and this activity is antagonized by soluble CD137 (sCD137). Here, we show that in sera of 81 patients with chronic HCV, sCD137 levels did not correlate with measures of viral infection, and did not decline after virus eradication using direct-acting antivirals. Thus, serum sCD137 was similar in patients infected with HCV and in uninfected controls. Of note, in HCV patients with liver cirrhosis and patients with mostly alcohol-associated liver cirrhosis, sCD137 was increased. A negative association of sCD137 and albumin existed in both cohorts. sCD137 concentrations were similar in hepatic and portal vein blood excluding the liver as the origin of higher levels. Recombinant sCD137 reduced Th1 and Th2 but not Th17 cell polarization in vitro, and accordingly lowered IFN-γ, TNF, and IL-13 in cell media. Serum sCD137 is associated with inflammatory states, and positively correlated with serum TNF in cirrhotic HCV patients following virus eradication. Our study argues against a role of sCD137 in HCV infection and suggests a function of sCD137 in liver cirrhosis, which yet has to be defined.

High plasma levels of betaine, a trimethylamine N-Oxide-related metabolite, are associated with the severity of cirrhosis.

BACKGROUND AND AIMS: The gut microbiome-related metabolites betaine and trimethylamine N-oxide (TMAO) affect major health issues. In cirrhosis, betaine metabolism may be diminished because of impaired hepatic betaine homocysteine methyltransferase activity, whereas TMAO generation from trimethylamine may be altered because of impaired hepatic flavin monooxygenase expression. Here, we determined plasma betaine and TMAO levels in patients with end-stage liver disease and assessed their relationships with liver disease severity. METHODS: Plasma betaine and TMAO concentrations were measured by nuclear magnetic resonance spectroscopy in 129 cirrhotic patients (TransplantLines cohort study; NCT03272841) and compared with levels from 4837 participants of the PREVEND cohort study. Disease severity was assessed by Child-Pugh-Turcotte (CPT) classification and Model for End-stage Liver Disease (MELD) score. RESULTS: Plasma betaine was on average 60% higher (p < .001), whereas TMAO was not significantly lower in cirrhotic patients vs. PREVEND population (p = .44). After liver transplantation (n = 13), betaine decreased (p = .017; p = .36 vs. PREVEND population), whereas TMAO levels tended to increase (p = .085) to higher levels than in the PREVEND population (p = .003). Betaine levels were positively associated with the CPT stage and MELD score (both p < .001). The association with the MELD score remained in the fully adjusted analysis (p < .001). The association of TMAO with the MELD score did not reach significance (p = .11). Neither betaine nor TMAO levels were associated with mortality on the waiting list for liver transplantation (adjusted p = .78 and p = .44, respectively). CONCLUSION: Plasma betaine levels are elevated in cirrhotic patients in parallel with disease severity and decrease after liver transplantation.

Gender-Specific Differences in Serum Sphingomyelin Species in Patients with Hepatitis C Virus Infection-Sphingomyelin Species Are Related to the Model of End-Stage Liver Disease (MELD) Score in Male Patients.

Hepatitis C virus (HCV) replication depends on cellular sphingomyelin (SM), but serum SM composition in chronic HCV infection has been hardly analyzed. In this work, 18 SM species could be quantified in the serum of 178 patients with chronic HCV infection before therapy with direct-acting antivirals (DAAs) and 12 weeks later, when therapy was completed. Six SM species were higher in the serum of females than males before therapy and nine at the end of therapy; thus, sex-specific analysis was performed. Type 2 diabetes was associated with lower serum levels of SM 36:2;O2 and 38:2;O2 in men. Serum SM species did not correlate with the viral load in both sexes. Of note, three SM species were lower in males infected with HCV genotype 3 in comparison to genotype 1 infection. These SM species normalized after viral cure. SM 38:1;O2, 40:1;O2, 41:1;O2, and 42:1;O2 (and, thus, total SM levels) were higher in the serum of both sexes at the end of therapy. In males, SM 39:1;O2 was induced in addition, and higher levels of all of these SM species were already detected at 4 weeks after therapy has been started. Serum lipids are related to liver disease severity, and in females 15 serum SM species were low in patients with liver cirrhosis before initiation of and after treatment with DAAs. The serum SM species did not correlate with the model of end-stage liver disease (MELD) score in the cirrhosis and the non-cirrhosis subgroups in females. In HCV-infected male patients, nine SM species were lower in the serum of patients with cirrhosis before DAA treatment and eleven at the end of the study. Most of the SM species showed strong negative correlations with the MELD score in the male cirrhosis patients before DAA treatment and at the end of therapy. Associations of SM species with the MELD score were not detected in the non-cirrhosis male subgroup. In summary, the current analysis identified sex-specific differences in the serum levels of SM species in HCV infection, in liver cirrhosis, and during DAA therapy. Correlations of SM species with the MELD score in male but not in female patients indicate a much closer association between SM metabolism and liver function in male patients.

Effect of liver cirrhosis on theophylline trough concentrations: A comparative analysis of organ impairment using Child-Pugh and MELD scores.

AIMS: Theophylline clearance is known to be reduced in patients with chronic liver diseases (CLDs) such as chronic hepatitis (CH) and liver cirrhosis (LC). The Child-Pugh (CP) score is generally used for pharmacokinetic evaluation, whilst a model for end-stage liver disease (MELD) has not yet been fully evaluated. This study aimed to predict theophylline clearance in patients with LC classified based on CP and MELD scores by population pharmacokinetic (PPK) analysis. METHODS: PPK analysis included 433 steady-state trough concentrations from 192 Japanese bronchial asthma patients with and without CLDs and was performed using NONMEM. The severity of LC was assessed by CP and MELD scores. RESULTS: The final CP and MELD models which described apparent theophylline clearance (CL/F) were obtained. The CP model showed that the mean CL/F in patients without CLDs, CH patients and LC patients with CP class A, B and C was 0.0473, 0.0413, 0.0330, 0.0280 and 0.0209 L/h kg-1 , respectively. The MELD model predicted that CL/F in patients without CLDs, CH patients and LC patients with MELD scores of <10, 10-14, 15-19, 20-24 and ≥25 was 0.0472, 0.0413, 0.0324, 0.0268, 0.0230, 0.0197 and 0.0155 L/h kg-1 , respectively. CONCLUSIONS: CL/F in various stages of LC was evaluated, and a change in CL/F was highly dependent on the severity of CLDs in both models. The MELD model provided a more accurate and precise description of theophylline clearance in LC than the CP model, which may be due to the wider dynamic range of the MELD score.

Is it safe to expand the indications for split liver transplantation in adults? A single-center analysis of 155 in-situ splits.

INTRODUCTION: Split liver transplantation (SLT) enables two recipients to be transplanted using a single donor liver; typically, an adult and a child. Despite equivalent long-term outcomes to whole grafts in selected adults, the use of these grafts in high-risk adult recipients with high model for end-stage liver disease (MELD) scores (≥30), a poor pre-transplant clinical status (ICU or hospital-bound), acute liver failure or retransplantation remains controversial. METHODS: We retrospectively analyzed all deceased donor adult liver transplants performed between July 2002 and November 2019 at a single high-volume center and performed a propensity score-matched analysis. A subgroup analysis was performed to assess utility of these grafts for high-risk recipients. RESULTS: A total of 1090 adult liver transplants were performed, including 155 SLT (14%). Graft survival at 1-, 3- and 5-years were comparable between recipients of split and whole liver grafts (82%, 79% and 74% vs. 86%, 81% and 77%, respectively, log rank P = .537), as was patient survival at 1-, 3- and 5-years. Recipients of split grafts were more likely to have biliary complications and hepatic artery thrombosis, but equivalent long-term survival. Recipients with high MELD scores or a poor pre-transplant clinical status had similar patient and graft survival and complication profiles irrespective of whether they received split or whole grafts. CONCLUSIONS: SLT is an important method for addressing donor shortages and provides comparable long-term outcomes in adult recipients despite an increase in short-term complications. SLT use in high-risk recipients should be considered to allow for sickest-first allocation policies.

Postreperfusion syndrome in liver transplantation: Outcomes, predictors, and application for recipient selection.

BACKGROUND: This study aimed to identify risk factors for postreperfusion syndrome (PRS) and its impact on LT outcomes. METHODS: Data analysis was performed in 1021 adult patients undergoing donation after brain death (DBD) LT to identify PRS incidence, the risk factors for PRS development, and its impact on LT outcomes. RESULTS: The overall incidence of PRS was 16.1%. Independent risk factors for PRS included donor age (odds ratio (OR) 1.01, P = .02), donor body mass index (BMI) (OR 1.04, P = .003), moderate macrosteatosis (OR 2.48, P = .02), and cold ischemia time (CIT) (OR 1.06, P = .02). On multivariable analysis for 30-day graft failure, PRS (hazard ratio (HR) 3.49; P < .001) and Model for End-stage Liver Disease (MELD) score (HR 1.01; P = .05) were independent risk factors. Patients were categorized into four distinct groups based on PRS risk groups and MELD groups, which showed different 1-year graft survival (P < .001). There were comparable outcomes between low PRS risk - high MELD and high PRS risk - low MELD group (P = .33). CONCLUSIONS: Donor age, donor BMI, moderate macrosteatosis, and CIT were identified as risk factors for the development of PRS in LT using DBD grafts. PRS risk evaluation may improve donor-to-recipient matching based on their MELD scores.

A machine learning approach to model for end-stage liver disease score in cardiac surgery.

OBJECTIVE: Model for end-stage liver disease (MELD) likely has nonlinear effects on operative outcomes. We use machine learning to evaluate the nonlinear (dependent variable may not correlate one to one with an increased risk in the outcome) relationship between MELD and outcomes of cardiac surgery. METHODS: Society of Thoracic Surgery indexed elective cardiac operations between 2011 and 2018 were included. MELD was retrospectively calculated. Logistic regression models and an imbalanced random forest classifier were created on operative mortality. Cox regression models and random forest survival models evaluated survival. Variable importance analysis (VIMP) ranked variables by predictive power. Linear and machine-learned models were compared with receiver operator characteristic (ROC) and Brier score. RESULTS: We included 3872 patients. Operative mortality was 1.7% and 5-year survival was 82.1%. MELD was the fourth largest positive predictor on VIMP analysis for operative long-term survival and the strongest negative predictor for operative mortality. MELD was not a significant predictor for operative mortality or long-term survival in the logistic or Cox regressions. The logistic model ROC area was 0.762, compared to the random forest classifier ROC of 0.674. The Brier score of the random forest survival model was larger than the Cox regression starting at 2 years and continuing throughout the study period. Bootstrap estimation on linear regression demonstrated machine-learned models were superior. CONCLUSIONS: MELD and mortality are nonlinear. MELD was insignificant in the Cox multivariable regression but was strongly important in the random forest survival model and when using bootstrapping, the superior utility was demonstrated of the machine-learned models.

Notes from an Organ Recipient: Once is Enough.

In this paper, the author describes her personal experiences with liver disease and the challenges both before and after receiving an organ transplant. She describes how organs are currently allocated and offers her perspective on what fairness entails in situations where organs fail and patients need multiple organs.

Albumin-Bilirubin Grade as a Novel Predictor of the Development and Short-Term Survival of Post-Banding Ulcer Bleeding Following Endoscopic Variceal Ligation in Cirrhotic Patients.

Background and Objectives: Endoscopic variceal ligation (EVL) is the primary and secondary treatment for acute esophageal variceal bleeding. Post-banding ulcer bleeding (PBUB) may lead to bleeding episodes following EVL, increasing mortality. The aim of this study was to evaluate the risk factors for PBUB and predict the 6-week mortality risk after PBUB. Materials and Methods: We retrospectively analyzed the data collected from cirrhotic patients with EVL from 2015 to 2017. The incidence of PBUB and the 6-week mortality rate were evaluated. Risk factors for PBUB and predictive factors for mortality after PBUB were analyzed. Results: A total of 713 patients were enrolled in this study. Among the studied subjects, the incidence of PBUB was 5.8% (N = 41). The 6-week mortality rate was 63.4% (26/41). In multivariate analysis, MELD score ≥20 (OR: 3.77, 95% CI: 1.94−7.33, p < 0.001), ALBI score of 3 (OR: 2.67, 95% CI: 1.34−5.3, p = 0.005) and the presence of gastric varices (OR: 2.1, 95% CI: 1.06−4.16, p = 0.03) were associated with the development of PBUB. Patients with ALBI grade 3 (OR: 4.8, 95% CI: 1.18−19.6, p = 0.029) and Child-Pugh scores B and C (OR: 16.67, 95% CI: 1.75−158.1, p = 0.014) were associated with 6-week mortality after PBUB. Conclusions: PBUB is a complication with low incidence but increased mortality following EVL. The ALBI grade is a useful score to predict not only the development of PBUB but also the 6-week mortality after PBUB.

Clinical outcomes following DAA therapy in patients with HCV-related cirrhosis depend on disease severity.

BACKGROUND & AIMS: HCV-infected patients with cirrhosis achieve high sustained virological response (SVR) rates with direct-acting antivirals (DAAs) even after hepatic decompensation. We aimed to assess the clinical outcome following DAAs among patients with compensated and decompensated cirrhosis in relation to SVR and changes in model for end-stage liver disease (MELD) score. METHODS: Consecutive DAA-treated chronic HCV-infected patients with cirrhosis from 4 hepatology clinics were included. The primary endpoint in survival analyses was clinical disease progression, defined as liver failure, hepatocellular carcinoma, liver transplantation or death. RESULTS: In total, 868 patients were included with a median age of 59 (IQR 54-65) years; 719 (83%) with Child-Pugh A cirrhosis and 149 (17%) with Child-Pugh B/C cirrhosis. SVR was attained by 647 (90%) Child-Pugh A patients and 120 (81%) Child-Pugh B/C patients. During a median follow-up of 28 (IQR 20-36) months, 102 (14%) Child-Pugh A patients and 96 (64%) Child-Pugh B/C patients experienced clinical disease progression. SVR was independently associated with an improved event-free survival in patients with Child-Pugh A cirrhosis (adjusted hazard ratio [HR] 0.47; 95% CI 0.27-0.82, p = 0.007), but not in patients with Child-Pugh B/C cirrhosis (adjusted HR 1.23; 95% CI 0.67-2.26; p = 0.51). Twelve weeks post-DAAs, 28 (19%) patients with Child-Pugh B/C cirrhosis had ≥2-point MELD decline, but their 2-year event-free survival did not differ from those with a stable MELD (47.9%; 95% CI 28.7-67.1 vs. 48.9%; 95% CI 38.1-59.7, respectively, p = 0.99). CONCLUSIONS: Among patients with chronic HCV infection, DAA-induced SVR was associated with a reduced risk of clinical disease progression in patients with Child-Pugh A cirrhosis but not in patients with Child-Pugh B/C cirrhosis. In Child-Pugh B/C cirrhosis, a ≥2-point MELD decline did not translate into improved clinical outcome. LAY SUMMARY: Chronic HCV infection can be cured with antiviral therapy. In this study, we evaluated the long-term effects of antiviral therapy on liver-related complications in patients with cirrhosis. Our results suggest that patients with compensated cirrhosis who were cured of their HCV infection have a lower rate of complications. In contrast, the rate of complications was not related to virological cure among those with decompensated cirrhosis. While these patients seem to remain in need of liver transplantation, antiviral therapy may lower their priority on the liver transplantation waiting list.

'Equity' and 'Justice' for patients with acute-on chronic liver failure: A call to action.

Acute-on-chronic liver failure (ACLF) occurs in hospitalised patients with cirrhosis and is characterised by multiorgan failures and high rates of short-term mortality. Without liver transplantation (LT), the 28-day mortality rate of patients with ACLF ranges from 18-25% in those with ACLF grade 1 to 68-89% in those with ACLF grade 3. It has become clear that patients with ACLF do not have equitable access to LT because of current allocation policies, which are based on prognostic scores that underestimate their risk of death and a lack of appreciation of the clear evidence of transplant benefit in carefully selected patients (who can have excellent post-LT outcomes). In this expert opinion, we provide evidence supporting the argument that patients with ACLF should be given priority for LT based on prognostic models that define the risk of death for these patients. We also pinpoint risk factors for poor post-LT outcomes, identify unanswered questions and describe the design of a global study, the CHANCE study, which will provide answers to the outstanding issues. We also propose the worldwide adoption of new organ allocation policies for patients with ACLF, as have been initiated in the UK and recommended in Spain.

Refining prediction of survival after TIPS with the novel Freiburg index of post-TIPS survival.

BACKGROUND & AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) implantation is an effective and safe treatment for complications of portal hypertension. Survival prediction is important in these patients as they constitute a high-risk population. Therefore, the aim of our study was to develop an alternative prognostic model for accurate survival prediction after planned TIPS implantation. METHODS: A total of 1,871 patients with de novo TIPS implantation for ascites or secondary prophylaxis of variceal bleeding were recruited retrospectively. The study cohort was divided into a training set (80% of study patients; n = 1,496) and a validation set (20% of study patients; n = 375). Further, patients with early (preemptive) TIPS implantation due to variceal bleeding were included as another validation cohort (n = 290). Medical data and overall survival (OS) were assessed. A Cox regression model was used to create an alternative prediction model, which includes significant prognostic factors. RESULTS: Age, bilirubin, albumin and creatinine were the most important prognostic factors. These parameters were included in a new score named the Freiburg index of post-TIPS survival (FIPS). The FIPS score was able to identify high-risk patients with a significantly reduced median survival of 5.0 (3.1-6.9) months after TIPS implantation in the training set. These results were confirmed in the validation set (median survival of 3.1 [0.9-5.3] months). The FIPS score showed better prognostic discrimination compared to the Child-Pugh, MELD, MELD-Na score and the bilirubin-platelet model. However, the FIPS score showed insufficient prognostic discrimination in patients with early TIPS implantation. CONCLUSIONS: The FIPS score is superior to established scoring systems for the identification of high-risk patients with a worse prognosis following elective TIPS implantation. LAY SUMMARY: Implantation of a transjugular intrahepatic portosystemic shunt (TIPS) is a safe and effective treatment for patients with cirrhosis and clinically significant portal hypertension. However, risk stratification is a major challenge in these patients as currently available scoring systems have major drawbacks. Age, bilirubin, albumin and creatinine were included in a new risk score which was named the Freiburg index of post-TIPS survival (FIPS). The FIPS score can identify patients at high risk and may guide clinical decision making.

Outcomes of Pregnant Women With Cirrhosis and Their Infants in a Population-Based Study.

BACKGROUND & AIMS: The incidence of cirrhosis is increasing among women of childbearing age. Contemporary outcomes of pregnant women with cirrhosis and their infants, as well as liver-related complications, have not been described in North America, to our knowledge. We investigated the association between cirrhosis and perinatal outcomes and evaluated perinatal liver-related events. METHODS: We performed a retrospective cohort study using population-based administrative health care data from Ontario, Canada (2000-2017). We identified pregnant women with compensated cirrhosis (n = 2022) using validated case definitions and routine mother-infant linkage; the women were matched to 10,110 pregnant women in the general population (1:5) based on birth year and socioeconomic status. Maternal and infant outcomes up to 6 weeks postpartum and liver-related complications up to 1 year postpartum were evaluated by using multivariate log-binomial regression. RESULTS: After we adjusted for demographic and metabolic risk factors, cirrhosis was independently associated with intrahepatic cholestasis of pregnancy (relative risk [RR], 10.64; 95% confidence interval [CI], 7.49-15.12), induction of labor (RR, 1.15; 95% CI, 1.03-1.28), puerperal infections (RR, 1.32; 95% CI, 1.02-1.70), preterm birth (RR, 1.60; 95% CI, 1.35-1.89), infants who were large for gestational age (RR, 1.24; 95% CI, 1.05-1.46), and neonatal respiratory distress (RR, 1.20; 95% CI, 1.02-1.42). Fewer than 2% of pregnant women with cirrhosis had liver-related complications, but these occurred in a significantly higher proportion of women with a history of hepatic decompensation (13%) than women with compensated cirrhosis (1.2%) (P < .001). CONCLUSIONS: In a population-based study, we found that cirrhosis is an independent risk factor for adverse perinatal outcomes. However, liver-related complications are rare. Multidisciplinary teams are needed to coordinate care for pregnant women with cirrhosis during pregnancy and postpartum to optimize outcomes.

Relation between the severity of liver cirrhosis and neurological symptoms, nerve conduction study results, and motor unit number estimation.

Liver cirrhosis is a global health problem that can be associated with several neurological manifestations. We aimed to assessment of the relation between the severity of the liver cirrhosis and the neurological symptoms, nerve conduction studies (NCS), as well as detecting subclinical neuropathic affection using motor unit number estimation (MUNE) technique. This cross-sectional study was conducted on 56 cirrhotic patients and 61 age- and sex-matched healthy controls. Neurological manifestations, Child-Pugh classification, Model for End-Stage Liver Disease score, NCS and MUNE using a modified spike-triggered averaging technique were studied. Forty-five (80.3%) of the cirrhotic patients had neurological manifestations. Muscle cramps were the most frequently reported manifestation, followed by fatigue and then numbness. NCS abnormality was significantly related to the presence of neurological symptoms (p < 0.001) and not only to peripheral numbness. Only fatigue was significantly related to the lower MUNE values (p < 0.017). Child-Pugh classification progression was significantly related to the presence of fatigue and abnormal NCS results (p < 0.001); no similar relation was detected between the Child-Pugh classification and the MUNE value (p = 0.103). Higher MELD scores were significantly related to NCS abnormalities (p = 0.014) and negatively correlated, although not significantly, with the MUNE values (r = -0.246 and p = 0.067). The progression of liver cirrhosis was related to the presence of neurological manifestations and nerve conduction abnormalities. Nerve conduction abnormalities may be present even in the absence of clinical numbness. A decline in motor unit number could explain the pathophysiology of fatigue in cirrhotic patients.

Magnesium deficiency in liver cirrhosis: a retrospective study.

BACKGROUND: Magnesium, known as "the forgotten electrolyte", is an essential element of life. Magnesium deficiency is implicated in many diseases, including liver cirrhosis. This study aimed to explore the prevalence of magnesium deficiency in liver cirrhosis and investigate the relationship between magnesium levels and complication of liver cirrhosis and clinical outcomes. PATIENTS AND METHODS: Cirrhotic patients with serum magnesium levels measured were retrospectively identified from 2016 to 2017. Demographics, laboratory parameters, complications were collected. The Child-Pugh class, MELD score, and ALBI score were calculated. RESULTS: The mean serum magnesium level of all 152 patients was lower than the normal, including 92 patients diagnosed with magnesium deficiency. Compared to Child-Pugh class A, magnesium levels were significantly lower in the patients with Child-Pugh class B or C (F = 10.26, p < .05). Magnesium levels were also considerably lower in the group with MELD score ≥21, compared to the other two groups with MELD score < 15 or 15-20 (F = 6.59, p < .05). Similarly, magnesium levels were significantly lower in the group with ALBI score > -1.39 (grade 3), compared to the other two groups with ALBI with score ≤ -2.6 (grade 1) or > -2.6, ≤ -1.39 (grade 2) (F = 8.44, p<.001). Furthermore, magnesium levels were lower in cirrhotic patients with infection. Magnesium-deficient patients had lower transplant-free survival rates than non-deficient patients. CONCLUSION: Magnesium deficiency is highly prevalent in cirrhotic patients. Magnesium deficiency is related to worse transplant-free survival, infection and the severity of liver cirrhosis.

Prognosis of liver transplantation: Does postoperative ileus matter?

BACKGROUND: Nowadays, liver transplantation has become a main therapy for end-stage liver disease. However, studies show that there are high mortality and severe complications after liver transplantation. Although gastrointestinal dysfunction is a common and major complication after liver transplantation, there was rarely relative research. This study aims to elucidate the factors about ileus after liver transplantation and patients' survival. METHODS: We collected and analyzed the data (n = 318, 2016-2019) from the First Affiliated Hospital of Xi'an Jiaotong University. After excluding cases, a total of 293 patients were included for this study. The subjects were divided into a non-ileus group and an ileus group. We reviewed 38 variables (including preoperative, operative and postoperative relative factors). Additionally, other complications after liver transplantation and survival data were compared between two groups. RESULTS: Of the 293 patients, 23.2% (n = 68) experienced postoperative ileus. Ileus patients were not different with non-ileus patients in preoperative, operative and postoperative factors. HBV-positive patients with ileus had a lower MELD score (P = 0.025), and lower postoperative total bilirubin was correlated with ileus (P = 0.049). Besides, Child-Pugh score of HCC patients with ileus was low (P = 0.029). The complications after liver transplantation were not different between two groups. Compared with the patients without ileus, the patients with ileus had a higher mortality rate. CONCLUSION: According to our research, ileus-patients had a lower 1-year survival rates. The preoperative MELD score and postoperative total bilirubin of HBV-positive patients with ileus were lower, and Child-Pugh score of HCC patients with ileus was also lower.

Social Support Does Not Modify the Risk of Readmission for Patients with Decompensated Cirrhosis.

BACKGROUND: Patients with decompensated cirrhosis are at high risk of frequent hospitalizations. Whether the level of perceived social support impacts this risk is unknown. We sought to determine the relationship between social support and burden of hospitalization in patients with decompensated cirrhosis. METHODS: A total of 73 patients, all with decompensated cirrhosis and an index cirrhosis-related admission between 7/1/2017 and 7/1/2019, completed the modified medical outcomes study social support (mMOS-SS) survey. We retrospectively assessed the relationship between mMOS-SS scores and probability of readmission 90-days after the index admission. Additionally, we prospectively analyzed the association between mMOS-SS scores at enrollment and risk of 90-day hospitalization. RESULTS: At enrollment, 50.7% were female, median age 61 years, and median mMOS-SS score was 87.5. Median model for end-stage liver disease sodium (MELD-Na) at the time of the index admission was 15 and was 13 at the time of enrollment. The mMOS-SS score did not modify the rate of readmission 90 days after the index admission date (adjusted HR 1.01, 95%CI 0.98-1.03) nor was it associated with the rate of admission 90 days after enrollment prospectively (adjusted HR 0.99, 95%CI 0.96-1.02). The MELD-Na score at enrollment was the only significant predictor of hospitalization during prospective follow-up (adjusted HR 1.18, 95%CI 1.09-1.27). CONCLUSIONS: Social support, as measured by the mMOS-SS survey, in patients with decompensated cirrhosis was high. However, this did not modify the risk of cirrhosis-related hospitalizations. Future investigation to define the specific components of social support that could modify readmission risk is needed.

CLIF-C AD Score Predicts Development of Acute Decompensations and Survival in Hospitalized Cirrhotic Patients.

BACKGROUND AND AIMS: Patients with decompensated cirrhosis are at increased risk of mortality, even in absence of ACLF. The CLIF-C AD score (CLIF-C ADs) was proposed as a prognostic score but lacks sufficient validation. Our aim was to describe clinical characteristics and hospital evolution according to score groups and evaluate prognostic capability of CLIF-C ADs alone or in combination with other scores. METHODS: Two hundred and sixty-six patients (55 ± 14 years, ascites in 63%, MELD 14 ± 5) were included, and classified as high, intermediate and low CLIF-C ADs in 13, 60 and 27% of cases. Development of new complications of cirrhosis during hospitalization and survival at 3 months were evaluated. RESULTS: Patients with high CLIF-C ADs had more severe systemic inflammation parameters and higher frequency of organ dysfunction. CLIF-C ADs ≥ 60, when compared to intermediate and low groups, was associated with higher incidence of complications of cirrhosis (90% vs 70% and 49%, p < 0.001) and lower survival (93%, 80% and 50%, p < 0.0001). In multivariate analysis, CLIF-C ADs, ascites and MELD were predictors of survival [(AUROC 0.76 (95% CI 0.69-0.83)]. Absence of ascites or MELD < 14 identified patients with intermediate CLIF-C ADs and good survival (89 and 84%, respectively). CONCLUSION: CLIF-C ADs predicts survival in cirrhotic patients with AD. High CLIF-C ADs is associated with higher frequency of organ dysfunction, increased risk of new complications of cirrhosis and high short-term mortality. On the contrary, individuals with low CLIF-C ADs, as well as those with intermediate score without ascites or with low MELD have excellent prognoses.

Frailty as a predictive factor for survival after liver transplantation, especially for patients with MELD≤15-a prospective study.

INTRODUCTION: Frailty has been discussed as a predictor of morbidity and mortality for liver cirrhosis. The aim of our study is to evaluate the role of frailty in liver transplantation, particularly for patients with MELD scores < 15. METHODS: All patients listed for liver transplantation between September 2015 and November 2018 were prospectively included in the study. Frailty was assessed by Fried's frailty classification. Pre-, intra-, and postoperative data were prospectively recorded. Univariate and multivariate regression analyses were performed. The ethical approval of the institutional board review was obtained for the study. RESULTS: There were 114 patients included in the study, and their median MELD score was 16. Of these, 86 patients were defined as frail (75.4%). A total of 62 patients (54.4%) underwent liver transplantation, 11 (17.7%) died postoperatively, and 24 patients (21.0%) died while on the waitlist. All postoperative mortality cases were frail, and only 3 patients (12.5%) were non-frail in the waitlist mortality group. There were 14 patients who had MELD scores of <15 (58.3%). The overall survival of non-frail patients was significantly better than that of frail patients. The multivariate regression analyses identified frailty criteria, including unintended weight loss and low hand grip strength, and platelet count and being married or living in a solid partnership were prognostic factors for survival in all patients. CONCLUSION: The addition of frailty assessment can be beneficial for predicting mortality after liver transplantation, especially in patients with low MELD score. Frail patients on the waitlist have significant risk for mortality even with low MELD score.