Model For End-stage Liver Disease Sodium Research Articles

#1663 Utilizing the MELD-Na score to predict renal replacement therapy and mortality among adult patients with leptospirosis-associated acute kidney injury

Abstract Background and Aims Leptospirosis is a zoonotic disease with manifestations ranging from mild to severe. Acute kidney injury (AKI) in leptospirosis is usually a marker of poor prognosis and there remains a paucity of scoring systems utilized to predict renal replacement therapy (RRT) and mortality. The Model for End-Stage Liver Disease-Sodium (MELD-Na) was originally developed to predict survival in patients with liver cirrhosis. The components of the MELD-Na score evaluate renal and hepatic dysfunction, which are frequent complications in leptospirosis. This study aims to evaluate the prognostic significance of the admission MELD-Na score in predicting renal replacement therapy and mortality among patients with leptospirosis-associated AKI. Method A retrospective, single-center, cross-sectional study was conducted at a tertiary hospital in Manila, Philippines. The study enrolled patients from January 2018 to September 2023 and collected demographic and clinical data, along with laboratory values taken on admission. The MELD-Na score was developed using these values and its distribution was visualized by histogram. Receiver operating characteristic curve analysis was used to determine the score's predictive ability and the optimum cut-off was determined by the cut-point with the highest Youden index. Results The study included a total of 298 patients. The median age of the participants was 39, with 88.59% being males, and 77.52% having no known comorbidities. Of the study population, 74.16% underwent RRT, while the in-hospital mortality rate was 12.08%. Univariate analysis revealed that oliguria, serum creatinine, arterial pH, serum bicarbonate, and administration of methylprednisolone pulse therapy were among the predictive factors for RRT, in line with clinical practice guidelines. Other parameters found to be predictive of RRT were serum sodium and bilirubin. An admitting MELD-Na score of >26 predicted RRT with 91.0% sensitivity [86.4, 94.4] and 87.7% specificity [76.3, 94.9], yielding an area under the curve (AUC) of 0.953 (95% CI). Conversely, an admitting MELD-Na score >31 was found to be 77.8% sensitive [60.8, 89.9] and 64.9% specific [58.8, 70.7] for predicting mortality, with an AUC of 0.748 (95% CI). Conclusion The MELD-Na is a good predictor of renal replacement therapy and in-hospital mortality among patients with leptospirosis-associated AKI. This scoring system holds the potential to serve as a tool for risk stratification and prognostication in moderate to severe cases of the disease. A validation cohort study is recommended for formulating a prediction scoring system based on the individual components of the MELD-Na score, such as bilirubin and sodium.

Low serum manganese as a noninvasive marker predicting the presence of myosteatosis among hospitalized patients with cirrhosis

Emerging evidence expands on a close connection between trace elements and muscular abnormalities, mostly focusing on sarcopenia. We hypothesized an association between concentrations of serum trace elements and myosteatosis, given that myosteatosis has a more pronounced clinical implication relative to sarcopenia, but there is a paucity of data in patients with cirrhosis. Consecutive patients were hospitalized for cirrhosis-associated complications. Serum trace elements (zinc, copper, manganese [Mn], magnesium, calcium, and iron) were measured by inductively coupled plasma mass spectrometry. The presence of myosteatosis was defined according to computed tomography–demarcated intramuscular adipose tissue content. In total, the 295 patients with cirrhosis analyzed had a median age of 63 years and 53.6% were male. Among them, 42 patients presented with myosteatosis (14.2%) and concomitant higher Model for End-stage Liver Disease-Sodium and triglyceride concentrations and lower neutrophil counts and serum Mn concentrations (all P < .05). No differences were found regarding other 5 trace elements in patients with versus without myosteatosis. The median serum Mn concentrations were 1.16 µg/L, and this population was categorized into high-Mn and low-Mn groups. The proportion of myosteatosis was significantly lower in high-Mn group than that in low-Mn group (8.1% vs 20.4%, P < .001). Univariable binary logistic regression indicated that low Mn was associated with myosteatosis (odds ratio, 2.906; 95% confidence interval, 1.424–5.932; P = .003) in the context of cirrhosis. This result was validated according to multivariable analysis by adjusting for confounding factors. In conclusion, low serum Mn can be predictive of myosteatosis, a novel muscular abnormality representing more clinical relevance and close relation to inferior outcomes among cirrhosis.

Continuous home terlipressin infusion increases handgrip strength and reduces ascites-A prospective randomized crossover study.

Observational studies suggest a beneficial effect of continuous terlipressin infusion (CTI) on ascites and sarcopenia in decompensated cirrhosis with portal hypertension. This single-center, prospective, cross-over study randomized 30 patients with cirrhosis, ascites, and sarcopenia to commence on 12 weeks of home CTI or 12 weeks of observation prior to cross-over. The co-primary outcomes were change in handgrip strength and paracentesis volume. Secondary outcomes included quality of life, sarcopenia measures, renal function, safety, and hospitalization. The median age of participants was 62 years (IQR: 57-64), the median Model for End-Stage Liver Disease-Sodium was 16 (12.3-20.8), and 22 (73%) were male. Handgrip strength increased by a mean adjusted difference (MAD) of 3.09 kg (95% CI: 1.11-5.08 kg) between CTI and observation ( p =0.006); an 11.8% increase from baseline. The total volume of ascites drained decreased by a MAD of 11.39L (2.99-19.85, p =0.01), with 1.75 fewer episodes of paracentesis (0.925-2.59, p <0.001) on CTI. Serum creatinine decreased, urinary sodium excretion increased, and quality of life was significantly higher on CTI (all p <0.001), with an increase in Chronic Liver Disease Questionnaire score of 0.41 points (0.23-0.59). There were 7 minor line-related complications but no cardiac events or pulmonary edema. This novel study demonstrates a significant increase in handgrip strength, reduction in paracentesis volume, and improved quality of life in patients with decompensated cirrhosis treated with continuous terlipressin infusion. These findings provide a strong rationale for the use of ambulatory CTI in appropriately selected patients with cirrhosis.

Improved Waitlist Outcomes in Liver Transplant Patients With Mid-MELD-Na Scores Listed in Centers Receptive to Use of Organs Donated After Circulatory Death.

Liver transplant (LT) using organs donated after circulatory death (DCD) has been increasing in the United States. We investigated whether transplant centers' receptiveness to use of DCD organs impacted patient outcomes. Transplant centers were classified as very receptive (group 1), receptive (2), or less receptive (3) based on the DCD acceptance rate and DCD transplant percentage. Using organ procurement and transplantation network/UNOS registry data for 20 435 patients listed for LT from January 2020 to June 2022, we compared rates of 1-y transplant probability and waitlist mortality between groups, broken down by model for end-stage liver disease-sodium (MELD-Na) categories. In adjusted analyses, patients in group 1 centers with MELD-Na scores 6 to 29 were significantly more likely to undergo transplant than those in group 3 (aHR range 1.51-2.11, P < 0.001). Results were similar in comparisons between groups 1 and 2 (aHR range 1.41-1.81, P < 0.001) and between groups 2 and 3 with MELD-Na 15-24 (aHR 1.19-1.20, P < 0.007). Likewise, patients with MELD-Na score 20 to 29 in group 1 centers had lower waitlist mortality than those in group 3 (scores, 20-24: aHR, 0.71, P = 0.03; score, 25-29: aHR, 0.51, P < 0.001); those in group 1 also had lower waitlist mortality compared with group 2 (scores 20-24: aHR0.69, P = 0.02; scores 25-29: aHR 0.63, P = 0.03). One-year posttransplant survival of DCD LT patients did not vary significantly compared with donation after brain dead. We conclude that transplant centers' use of DCD livers can improve waitlist outcomes, particularly among mid-MELD-Na patients.

Patient Portal Use and Risk of Readmissions in Decompensated Cirrhosis: Retrospective Study.

Patient portals are a common electronic medical record tool that allow for the asynchronous exchange of health information between patients and their health care teams. Patients can leverage patient portals to perform tasks such as viewing test results, reviewing clinical notes, and messaging their health care team. The impact of patient portal use on clinical outcomes in cirrhosis is unknown. In this study, we evaluated the relationship between patient portal use patterns and readmissions in cirrhosis. We identified 131 patients with decompensated cirrhosis with an index cirrhosis-related admission between May 1, 2018, and May 1, 2019. We then examined patient portal enrollment and use data during the 6-month period preceding the study period. Portal functions evaluated included sending a message, reading a message, and reading a test result. Use was categorized as active (sending a message) and passive (reading a message or test result) and was further stratified as no, moderate, or frequent use based on the frequency of portal function use compared to the mean. The primary outcomes were 90-day and overall readmissions, adjusted for age, model for end-stage liver disease-sodium, alcohol-related cirrhosis etiology, ascites, and hepatic encephalopathy. Portal functions assessed included sending a message, reading a message, and reading a result; the total number of times a portal function was performed was divided by the number of months the patient was enrolled in the patient portal during the 6-month period. The study population was 50.4% (66/131) female, with a mean age of 58 years. Enrollment in the patient portal was 63.4% (83/131), and there was no significant difference in enrollment based on clinical or demographic characteristics. For the entire cohort, 14.5% (19/131) and 22.1% (29/131) of patients were moderate and frequent active users, respectively. Of those enrolled in the patient portal, 97.6% (81/83) of patients were moderate or frequent passive users for both reading a message and reading a test result. Moderate active users had less 90-day readmissions (odds ratio 0.77, 95% CI 0.60-1.00) and overall readmissions (subdistribution hazard ratio 0.42, 95% CI 0.21-0.84), compared to nonactive users. There was no relationship between readmissions and passive use. Passive use of the patient portal is very high but is not associated with the risk of readmissions in people with decompensated cirrhosis. However, moderately active use of the patient portal is associated with a reduced risk of readmissions. Further work is needed to identify possible confounders and refine key use behaviors that may be protective with regard to the risk of readmission in this population.

Reduced left ventricular elastance as a novel marker of cardiac dysfunction in patients with severe liver disease

Abstract Introduction Left ventricular (LV) elastance reflects the contractility of the myocardium and is an index of cardiac performance. Liver cirrhosis is characterized by reduced systemic vascular resistance, leading to reduced afterload on the LV. This, combined with increased blood volume, results in increased preload, increased stroke volume and remodeling of the LV. The latter may result to alterations in end-systolic LV elastance (Ees) a parameter that has not been extensively studied in cirrhotics. Purpose To investigate the relationship between Ees and the severity of liver cirrhosis. Methods We conducted a cross-sectional study in which transthoracic echocardiography was performed in 75 patients with liver cirrhosis (mean age 58.9±8.5 years, 74.7% males). A verified noninvasive single-beat formula was used to calculate Ees. Specifically, Ees was calculated employing systolic and diastolic blood pressures, echo-derived stroke volume (SV), ejection fraction (LVEF) and the estimated normalized ventricular elastance at arterial end-diastole (ENd). The ENd was estimated from a group-averaged value adjusted for individual contractile/loading effects. The Model for End-Stage Liver Disease-Sodium (MELDNa) score, a widely used tool for assessing liver disease severity was also calculated. We compared Ees between patients with MELDNa scores above and below 15, which is the cutoff commonly used to indicate severe liver disease. Results Mean Ees in the cohort of the 75 patients was 2.34±0.81mmHg/ml. Ees was correlated with end-systolic LV volume (rho=-0.448, p&amp;lt;0.001), SV (rho=-0.568, p&amp;lt;0.001) and systolic blood pressure (rho=0.283, p=0.014), but not with LVEF. Mean MELDNa score was 15.5±7.3 and 32 (42.7%) of patients had MELDNa score ≥ 15. Mean Ees in patients with MELDNa score above 15 was significantly lower than in patients with MELDNa score below 15 (2.08±0.61mmHg/ml vs 2.54±0.89mmHg/ml, p=0.015). The association remained significant in a multivariate model after adjusting for age, sex, and body surface area (B=-0.426, p=0.015). Conclusion Our study demonstrates that patients with severe liver disease have lower Ees, indicating impaired LV function. Ees could be a useful marker for identifying patients with liver cirrhosis who are at increased risk of cardiovascular complications. Further research is needed to better understand the mechanisms underlying this association and to propose therapeutic interventions aimed at improving LV function in this special population.

A specialized HE testing clinic improves rational decision-making for therapy in cirrhosis.

Cognitive complaints in cirrhosis are often attributed to HE with reflexive therapy if specialized tests are not performed. The aim was to determine the utility of a specialized HE clinic for management decisions. Cirrhosis patients with cognitive complaints were referred through a dedicated consult pathway to a specialized clinic and followed for 6 months. This clinic included detailed history, medication review, standardized tests [Mini-Mental Status Exam (MMSE), Psychometric HE Score, and others], and obstructive sleep apnea screening. Results were communicated with patients and referring providers. A subset was offered repeat testing. A total of 286 patients were tested between 2012 and 2022. Of the 286 patients, 4 patients who showed a Mini-Mental State Exam <25 were referred to neurology. Thirty-nine percent had normal Psychometric HE Score (higher in younger patients, without prior HE, depression, and lower Model for End-Stage Liver Disease-Sodium), while 172 (61%) patients had cognitive impairment. Of the 172 patients, 51 did not want management change, 84 were started on HE therapy, and 37 were considered impaired due to other causes. In 51 without management change, 32 refused lactulose, while the remaining were counseled regarding lactulose titration. Of the 84 patients with HE-therapy initiation, lactulose was initiated in 56 and rifaximin in 28; most therapies continued over 6 months. The ones who were retested improved their Psychometric HE Score. The 37 with other causes (obstructive sleep apnea, mood disorders, substance use, and mild cognitive impairment) led to specialized referrals. No overt HE was found over 6 months in those without HE-related impairment. The clinic was billed for. A specialized HE clinic for patients with cirrhosis and cognitive complaints established through a dedicated consult pathway showed that 39% of referred patients had normal cognitive performance, while the results guided management changes, including for HE and other causes in the remaining patients.

Living donor liver transplantation can address disparities in transplant access for patients with primary sclerosing cholangitis.

Liver transplantation (LT) is frequently lifesaving for people living with primary sclerosing cholangitis (PSC). However, patients are waitlisted for LT according to the model for end-stage liver disease-sodium (MELD-Na) score, which may not accurately reflect the burden of living with PSC. We sought to describe and analyze the clinical trajectory for patients with PSC referred for LT, in a mixed deceased donor/living donor transplant program. This was a retrospective cohort study from November 2012 to December 2019, including all patients with PSC referred for assessment at the University Health Network Liver Transplant Clinic. Patients who required multiorgan transplant or retransplantation were excluded. Liver symptoms, hepatobiliary malignancy, MELD-Na progression, and death were abstracted from chart review. Competing risk analysis was used for timing of LT, transplant type, and death. Of 172 PSC patients assessed, 84% (n = 144) were listed of whom 74% were transplanted. Mean age was 47.6 years, and 66% were male. Overall mortality was 18.2% at 2 years. During the follow-up, 16% (n = 23) were removed from the waitlist for infection, clinical deterioration, liver-related mortality or new cancer; 3 had clinical improvement. At listing, 82% (n = 118) had a potential living donor (pLD). Patients with pLD had significantly lower waitlist and liver-related waitlist mortality (HR 0.20, p<0.001 and HR 0.17, p<0.001, respectively), and higher rates of transplantation (HR 1.83, p = 0.05). Exception points were granted to 13/172 (7.5%) patients. In a high-volume North American LT center, most patients with PSC assessed for transplant were listed and subsequently transplanted. However, this was a consequence of patients engaging in living donor transplantation. Our findings support the concern from patients with PSC that MELD-Na allocation does not adequately address their needs.

Outpatient albumin infusions reduce hospitalizations and improve outcomes in decompensated cirrhosis: A real-world cohort study.

Long-term human albumin (HA) infusions improve survival in cirrhotic patients with diuretic resistant ascites. We aimed to determine whether there is a significant benefit in a more unwell real-world cohort. This is a single-center retrospective cohort study. Patients received outpatient HA between April 2017 and June 2021. Inclusion criteria were age ≥18 years, cirrhosis with ascites, and received at least 1 month of HA. Patients with significant comorbidities and ongoing alcohol use were not excluded. Outcomes assessed were transjugular intrahepatic portosystemic shunt (TIPS)/transplant-free survival (TTFS), and biochemical and prognostic outcomes. Twenty-four patients were included. Median age was 59.5 years. Seven were female (29.2%). Etiology included were alcohol (50%), non-alcoholic steatohepatitis (16.7%), and viral/alcohol (12.5%). Median model for end-stage liver disease-sodium (MELD-Na) was 18.5, with Child-Pugh scores (CPS) A (4.2%), B (50%), and C (45.8%). Improvements in serum sodium (P = 0.014), albumin (P = 0.003), and CPS (P = 0.017) were observed. Reduction in hospitalizations (P = 0.001), particularly portal hypertensive related admissions was observed (relative risk 0.39; 95% confidence interval [CI] 0.21-0.69, P = 0.003), needed to treat 2.09 (95% CI 1.25-3.67). There was a reduction in total paracentesis requirements (P = 0.005). On multivariate analysis, type 2 diabetes mellitus significantly increased risk of TIPS/transplant/death (hazard ratio 6.16; 95% CI 1.23-30.84, P = 0.027). Median TTFS improved in patients with a change in MELD-Na ≤1 at 1 month: 29.4 months versus 7.7 months (P = 0.011). Outpatient HA infusions decrease portal hypertensive related hospital admissions, improve serum sodium, albumin levels, and CPS. Type 2 diabetes mellitus and change in MELD-Na score help discriminate those likely to benefit most.

Oxidative stress-related markers as prognostic factors for patients with primary sclerosing cholangitis in Japan.

Primary sclerosing cholangitis (PSC) is a rare chronic liver disease. The mechanisms and prediction of PSC progression are unclear. Recent investigations have shown that general conditions, such as oxidative stress, affect the course of chronic diseases. We investigated the clinical course and oxidative stress-related condition of PSC to determine prognostic factors. We recruited 58 patients with PSC (mean age; 37.4years, mean observation period; 1382days) who visited our department from 2003 to 2021. Clinical characteristics were investigated to define prognostic factors. Oxidative stress status was evaluated using two types of markers: an oxidative stress marker (serum reactive oxygen metabolite; dROM) and an antioxidant marker (serum OXY adsorbent test; OXY). The revised Mayo risk, Child-Pugh, model for end-stage liver disease-sodium (MELD-Na) scores or fibrosis-related FIB-4 index significantly predicted poor overall survival. High intestinal immunoglobulin A (IgA) levels predicted poor survival. Among patients with high and intermediate revised Mayo risk scores, those with physiologically high dROM levels showed better survival than those with lower dROM levels. In this population, dROM was negatively correlated with AST and IgA, which are both correlated with survival. High and intermediate revised Mayo risk score group predicted a poor clinical course in PSC. Additionally, the Child-Pugh score, MELD-Na score, FIB-4 index, and serum IgA were significantly correlated with survival. In patients with high and intermediate revised Mayo risk scores, physiologically high oxidative stress status correlated with low IgA levels and a good prognosis.

Clinical Significance of Ascitic Fluid Polymorphonuclear Leukocyte Percentage in Patients With Cirrhosis Without Spontaneous Bacterial Peritonitis.

Absolute polymorphonuclear leukocyte (PMN) count (PMN-C) ≥250 cells/mm 3 in ascites is the diagnostic hallmark of spontaneous bacterial peritonitis (SBP) and is associated with high morbidity and mortality. However, the clinical significance of ascitic PMN percentage (PMN-%) and PMN-C in the absence of SBP as additional biomarkers for mortality and future incidence of SBP has not been determined. This retrospective cohort included adults with cirrhosis undergoing first-recorded paracentesis with initial PMN-C < 250 cells/mm 3 at 2 tertiary medical centers between 2015 and 2020. Patients with prior SBP were excluded. Outcomes were death and SBP development. Cox regression estimated hazard ratios (HRs) for risk of death and SBP development and Akaike information criterion to compare model fit. Three hundred eighty-four adults (73% male, median age 58 years, 67% with alcohol-associated cirrhosis, median PMN-C 14 cells/mm 3 [interquartile range 5-34], and median PMN-% 10% [interquartile range 4-20]) were included in this study. Univariate risk of death increased 10% per 25-unit increase in PMN-C (95% confidence interval 1.01-1.21, P = 0.03) and 19% per 10-unit increase in PMN-% (95% confidence interval 1.06-1.33, P = 0.003) with PMN-% demonstrating better model fit in assessing mortality risk (Akaike information criterion: 1,044 vs 1,048, respectively). In models adjusted for age, chronic hepatitis C virus infection, and Model for End-Stage Liver Disease-Sodium, PMN-% was associated with risk of death (PMN-% 10%-29%, HR 1.17, P = 0.50; PMN-% ≥ 30% group, HR 1.94, P = 0.03; vs PMN-% < 10%) and SBP development (PMN-% 10%-29%, HR 1.68, P = 0.07; PMN-% ≥ 30%, HR 3.48, P < 0.001; vs PMN-% < 10%). Our results suggest PMN-% at first paracentesis represents a better biomarker compared with PMN-C for assessing risk of death and future SBP development in patients with PMN-C < 250 cells/mm 3 .

Factors Associated With Liver Transplant Referral Among Patients With Cirrhosis at Multiple Safety-Net Hospitals

A high proportion of underserved patients with cirrhosis receive care at safety-net hospitals (SNHs). While liver transplant (LT) can be a life-saving treatment for cirrhosis, data on referral patterns from SNHs to LT centers are lacking. To identify factors associated with LT referral within the SNH context. This retrospective cohort study included 521 adult patients with cirrhosis and model for end-stage liver disease-sodium (MELD-Na) scores of 15 or greater. Participants received outpatient hepatology care at 3 SNHs between January 1, 2016, and December 31, 2017, with end of follow-up on May 1, 2022. Patient demographic characteristics, socioeconomic status, and liver disease factors. Primary outcome was referral for LT. Descriptive statistics were used to describe patient characteristics. Multivariable logistic regression was performed to evaluate factors associated with LT referral. Multiple chained imputation was used to address missing values. Of 521 patients, 365 (70.1%) were men, the median age was 60 (IQR, 52-66) years, most (311 [59.7%]) were Hispanic or Latinx, 338 (64.9%) had Medicaid insurance, and 427 (82.0%) had a history of alcohol use (127 [24.4%] current vs 300 [57.6%] prior). The most common liver disease etiology was alcohol associated liver disease (280 [53.7%]), followed by hepatitis C virus infection (141 [27.1%]). Median MELD-Na score was 19 (IQR, 16-22). One hundred forty-five patients (27.8%) were referred for LT. Of these, 51 (35.2%) were wait-listed, and 28 (19.3%) underwent LT. In a multivariable model, male sex (adjusted odds ratio [AOR], 0.50 [95% CI, 0.31-0.81]), Black race vs Hispanic or Latinx ethnicity (AOR, 0.19 [95% CI, 0.04-0.89]), uninsured status (AOR, 0.40 [95% CI, 0.18-0.89]), and hospital site (AOR, 0.40 [95% CI, 0.18-0.87]) were associated with lower odds of being referred. Reasons for not being referred (n = 376) included active alcohol use and/or limited sobriety (123 [32.7%]), insurance issues (80 [21.3%]), lack of social support (15 [4.0%]), undocumented status (7 [1.9%]), and unstable housing (6 [1.6%]). In this cohort study of SNHs, less than one-third of patients with cirrhosis and MELD-Na scores of 15 or greater were referred for LT. The identified sociodemographic factors negatively associated with LT referral highlight potential intervention targets and opportunities to standardize LT referral practices to increase access to life-saving transplant among underserved patients.

Using machine learning methods to predict 28-day mortality in patients with hepatic encephalopathy

BackgroundHepatic encephalopathy (HE) is associated with marked increases in morbidity and mortality for cirrhosis patients. This study aimed to develop and validate machine learning (ML) models to predict 28-day mortality for patients with HE.MethodsA retrospective cohort study was conducted in the Medical Information Mart for Intensive Care (MIMIC)-IV database. Patients from MIMIC-IV were randomized into training and validation cohorts in a ratio of 7:3. Training cohort was used for establishing the model while validation cohort was used for validation. The outcome was defined as 28-day mortality. Predictors were identified by recursive feature elimination (RFE) within 24 h of intensive care unit (ICU) admission. The area under the curve (AUC) and calibration curve were used to determine the predictive performance of different ML models.ResultsIn the MIMIC-IV database, 601 patients were eventually diagnosed with HE. Of these, 112 (18.64%) experienced death within 28 days. Acute physiology score III (APSIII), sepsis related organ failure assessment (SOFA), international normalized ratio (INR), total bilirubin (TBIL), albumin, blood urea nitrogen (BUN), acute kidney injury (AKI) and mechanical ventilation were identified as independent risk factors. Validation set indicated that the artificial neural network (NNET) model had the highest AUC of 0.837 (95% CI:0.774–0.901). Furthermore, in the calibration curve, the NNET model was also well-calibrated (P = 0.323), which means that it can better predict the 28-day mortality in HE patients. Additionally, the performance of the NNET is superior to existing scores, including Model for End-Stage Liver Disease (MELD) and Model for End-Stage Liver Disease-Sodium (MELD-Na).ConclusionsIn this study, the NNET model demonstrated better discrimination in predicting 28-day mortality as compared to other models. This developed model could potentially improve the early detection of HE with high mortality, subsequently improving clinical outcomes in these patients with HE, but further external prospective validation is still required.

Serum and plasma protein biomarkers associated with frailty in patients with cirrhosis.

Frailty, a clinical phenotype of decreased physiologic reserve, is a strong determinant of adverse health outcomes in patients with cirrhosis. The only cirrhosis-specific frailty metric is the Liver Frailty Index (LFI) which must be administered in person and may not be feasible for every clinical scenario. We sought to discover candidate serum/plasma protein biomarkers that could differentiate frail from robust patients with cirrhosis. Included were 140 adults with cirrhosis awaiting liver transplantation in the ambulatory setting with LFI assessments and available serum/plasma samples. We selected 70 pairs of patients on opposite ends of the frailty spectrum (LFI> 4.4 for frail and LFI<3.2 for robust) who were matched by age, sex, etiology, HCC, and MELDNa. Twenty-five biomarkers with biologically plausible associations with frailty were analyzed by ELISA by a single laboratory. Conditional logistic regression was used to examine their association with frailty. Of the 25 biomarkers analyzed, we identified 7 proteins that were differentially expressed between frail and robust. We observed differences in 6 of the 7 proteins in the expected direction: a) higher median values in frail versus robust with growth-differentiation factor-15 (3682 vs. 2249pg/mL), interleukin-6 (17.4 vs. 6.4pg/mL), tumor necrosis factor-alpha receptor 1 (2062 vs. 1627pg/mL), leucine-rich alpha-2 glycoprotein (44.0 vs. 38.6ug/mL), and myostatin (4066 vs. 6006ng/mL), and b) lower median values in frail versus robust with alpha-2-Heremans-Schmid glycoprotein (0.11 vs. 0.13mg/mL) and free total testosterone (1.2 vs. 2.4ng/mL). These biomarkers represent inflammatory, musculoskeletal, and endocrine/metabolic systems, reflecting the multiple physiologic derangements observed in frailty. These data lay the foundation for confirmatory work and development of a laboratory frailty index for patients with cirrhosis to improve diagnosis and prognostication.

MELD 3.0 adequately predicts mortality and renal replacement therapy requirements in patients with alcohol-associated hepatitis

Model for End-Stage Liver Disease (MELD) score better predicts mortality in alcohol-associated hepatitis (AH) but could underestimate severity in women and malnourished patients. Using a global cohort, we assessed the ability of the MELD 3.0 score to predict short-term mortality in AH. This was a retrospective cohort study of patients admitted to hospital with AH from 2009 to 2019. The main outcome was all-cause 30-day mortality. We compared the AUC using DeLong's method and also performed a time-dependent AUC with competing risks analysis. A total of 2,124 patients were included from 28 centres from 10 countries on three continents (median age 47.2 ± 11.2 years, 29.9% women, 71.3% with underlying cirrhosis). The median MELD 3.0 score at admission was 25 (20-33), with an estimated survival of 73.7% at 30 days. The MELD 3.0 score had a better performance in predicting 30-day mortality (AUC:0.761, 95%CI:0.732-0.791) compared with MELD sodium (MELD-Na; AUC: 0.744, 95% CI: 0.713-0.775; p= 0.042) and Maddrey's discriminant function (mDF) (AUC: 0.724, 95% CI: 0.691-0.757; p= 0.013). However, MELD 3.0 did not perform better than traditional MELD (AUC: 0.753, 95% CI: 0.723-0.783; p= 0.300) and Age-Bilirubin-International Normalised Ratio-Creatinine (ABIC) (AUC:0.757, 95% CI: 0.727-0.788; p= 0.765). These results were consistent in competing-risk analysis, where MELD 3.0 (AUC: 0.757, 95% CI: 0.724-0.790) predicted better 30-day mortality compared with MELD-Na (AUC: 0.739, 95% CI: 0.708-0.770; p= 0.028) and mDF (AUC:0.717, 95% CI: 0.687-0.748; p= 0.042). The MELD 3.0 score was significantly better in predicting renal replacement therapy requirements during admission compared with the other scores (AUC: 0.844, 95% CI: 0.805-0.883). MELD 3.0 demonstrated better performance compared with MELD-Na and mDF in predicting 30-day and 90-day mortality, and was the best predictor of renal replacement therapy requirements during admission for AH. However, further prospective studies are needed to validate its extensive use in AH. Severe AH has high short-term mortality. The establishment of treatments and liver transplantation depends on mortality prediction. We evaluated the performance of the new MELD 3.0 score to predict short-term mortality in AH in a large global cohort. MELD 3.0 performed better in predicting 30- and 90-day mortality compared with MELD-Na and mDF, but was similar to MELD and ABIC scores. MELD 3.0 was the best predictor of renal replacement therapy requirements. Thus, further prospective studies are needed to support the wide use of MELD 3.0 in AH.

The Predictors of Hepatorenal Syndrome Development in HCV Cirrhotic Ascitic Egyptian Patients with Spontaneous Bacterial Peritonitis.

Spontaneous bacterial peritonitis is considered a precipitating factor for renal impairment in patients with liver cirrhosis. No specific study addressing this problem has been reported. This study aimed to detect the incidence and predictive factors of hepatorenal syndrome in these patients. This study enrolled 121 hepatic cirrhotic patients with spontaneous bacterial peritonitis. History taking, clinical examination, and laboratory investigations including ascitic fluid analysis were carried out. Kidney function tests were repeated 3 days after the initiation of treatment. Patients were divided into 2 groups after one week of treatment during the follow-up period: Group I: patients without hepatorenal syndrome, and Group II: patients with hepatorenal syndrome. Multivariate analysis was performed to determine independent predictors of hepatorenal syndrome development. A total of 30 patients (24.8%) developed hepatorenal syndrome. Patients with hepatorenal syndrome had significantly lower sodium and albumin levels as well as higher creatinine, bilirubin, Child-Turcotte-Pugh score, portal vein diameter, Model for End-Stage Liver Disease score. Higher percentage of them had a history of recurrent spontaneous bacterial peritonitis and multiple therapeutic paracentesis of ascites. Multivariate analysis detected that serum bilirubin, Model for End-Stage Liver Disease-Sodium, and portal vein diameter were significant predictors of hepatorenal syndrome. Cutoff values were determined as 3.3 mg/dl for bilirubin, 15.9 mm for portal vein diameter, and 26 for Model for End-Stage Liver Disease-Sodium. Hepatorenal syndrome is a common complication of spontaneous bacterial peritonitis. In our study, high serum bilirubin, Model for End-Stage Liver Disease-Sodium, and portal vein diameter are predictors of the development of hepatorenal syndrome in patients with spontaneous bacterial peritonitis.

Urine neutrophil gelatinase-associated lipocalin as a biomarker of acute kidney injury and prognosis in decompensated chronic liver disease: A prospective study.

Acute kidney injury (AKI) heralds deterioration in patients with decompensated chronic liver disease (DCLD). Serum creatinine (sCr), a component of the model for end-stage liver disease-sodium (MELD-Na) prognostic score, has limitations in patients with DCLD. We evaluated the prognostic role of urine neutrophil gelatinase-associated lipocalin (NGAL) in DCLD and its ability to sub-type AKI. Total 147consecutive patients hospitalized between June 2018 andJune 2020 for complications of DCLD were evaluated. Urine NGAL was estimated and demographic, clinical and biochemical parameters recorded at baseline. Participants were followed up till theend of study period or mortality, whichever came earlier. Primary outcomes included all-cause mortality and time to death after index hospitalization. Secondary outcomes included thepresence and type of AKI, need for intensive care unit (ICU) stay, length of ICU/hospital stay, in-hospital mortality, development of new-onset/recurrent AKI and recurrent hospitalization after index admission. Urine NGAL was highest in acute tubular necrosis (ATN), lowest in pre-renal azotemia (PRA) and intermediate in hepatorenal syndrome (HRS-AKI). Urine NGAL (p = 0.0208) was superior to sCr (p = 0.0388) and inferior to fractionated excretion of sodium (FENa) (p = 0.0013) in stratifying AKI. A cut-off of 203.9ng/mL discriminated between HRS and PRA with sensitivity 77.8% and specificity 68.7%. Urine NGAL correlated with MELD-Na score, need for ICU stay, in-hospital mortality and mortality at three and sixmonths. Two-year survival was significantly lower in patients with urine NGAL > 205ng/mL. Addition of log-urine-NGAL score did not improve predictive performance of MELD-Na. Urine NGAL could identify AKI sub-types and correlated with short-term clinical outcomes, including mortality.

Etiological Spectrum, Epidemiological Characteristics in Compensated and Decompensated Cirrhosis at First Presentation

ABSTRACT Context and Aim: Decompensation as a presenting feature is uncommon among cirrhosis-seeking consultations and may indicate the poor outcomes. This study will be assessing the etiology and epidemiological characteristics among compensated and decompensated cirrhosis at first presentation. Settings and Design: A cross-sectional study in a tertiary care hospital in south Kerala, India. Subjects and Methods: Two hundred and nine patients with liver cirrhosis were evaluated for: age at presentation to the hospital, biochemical, virologic, Child–Pugh and Model for end-stage liver disease (MELD), and MELD Sodium (MELD Na) scores. Using cutoff for MELD Na and Child scores A versus B and C, the degree of association in those with or without decompensation was evaluated. Results: The mean (standard deviation) age of participants was 58.24 (±9.9) years. Seventy-seven percent were males. 11.5% were with decompensated cirrhosis (DC). 61.2% had alcoholic liver disease (ALD); 8.1% had hepatitis B; 2.4% hepatitis C virus; 0.5% autoimmune hepatitis; and 27.8% had nonalcoholic steatohepatitis (NASH). In compensated cirrhosis (CC), 60.5% had ALD and 28.1% (n = 52) had NASH, whereas, in those with decompensation, 66.7% had ALD and 25% had NASH. In CC, 54.1% were Child A and the rest B and C compared to DC, wherein 58.3% were with Child B and C and 41.7% in Child A. MELD Score of 9+ was more in DC compared to CC (P = 0.05). Alcoholic hepatitis was observed in 32% of DC. Conclusions: Decompensation was the presenting feature in 11.5%, and alcohol abuse was the major risk factor. Those with DC have higher MELD scores.

Negative impact of the pandemic on hospital admissions, morbidity and early mortality for acute cirrhosis decompensation

IntroductionThe global pandemic has diverted resources away from management of chronic diseases, including cirrhosis. While there is increasing knowledge on COVID-19 infection in liver cirrhosis, little is described on the...

Correlation of Serum Testosterone Section Levels in Men with Severity of Liver Dysfunction in Chronic Liver DiseaseAn Observational Study at a Tertiary Care Centre in Uttarakhand, India

Introduction: Chronic Liver Disease (CLD) and/or cirrhosis of liver represent different liver disorders of varying severity in which liver injury, inflammation, and fibrosis continue for more than 6 months. Various aetiologies including drugs toxins, alcohol abuse, infections, autoimmune disorders, genetic and metabolic diseases are implicated for CLD. Regardless, the aetiology of the CLD, the serum testosterone falls as the disease advances. Aim: To study the serum testosterone level in male patients with CLD and its correlation with the severity of the disease. Materials and Methods: A prospective observational study was conducted on patients reporting to Himalayan Hospital in OPD and IPD between June 2021 to May 2022. A total of 58 male patients of CLD were recruited. All patients were examined with clinical history, physical examination, laboratory blood and biochemical and radiological investigations, including total serum testosterone estimation. Testosterone value of &lt;3 ng/mL was considered as low level. Child-Turcotte-Pugh (CTP) scores and Model for End-Stage Liver Disease-sodium (MELD-Na) scores were calculated to assess the severity of CLD. Results: The mean age of the patients was 47.87±10.3 years. The majority of patients, 52/58(89.65%), had low serum testosterone levels. As the severity of CLD increases, the testosterone falls progressively, and the finding was statistically significant (p-value=0.001). The mean testosterone levels (0.9±0.38) in patients with MELD-Na score of ≥20 was significantly (p-value=0.02) lower than the patients with MELDNa score of &lt;20. There was a strong negative correlation between low testosterone and CLD severity. Conclusion: Overall, 89.65% of the patients had a low testosterone level. Serum testosterone level can be an independent marker for the severity of CLD in male patients.