Child-Turcotte-Pugh Score Research Articles

Pharmacokinetics/pharmacodynamics of L-ornithine phenylacetate in overt hepatic encephalopathy and the effect of plasma ammonia concentration reduction on clinical outcomes.

Hepatic encephalopathy (HE) is a serious neurocognitive complication of liver dysfunction, often associated with elevated plasma ammonia. Ornithine phenylacetate (OP), a potent ammonia scavenger, is being evaluated for the treatment of acute/overt HE. The pharmacokinetics and pharmacodynamics of OP in patients with HE were characterized in this phase IIb study (NCT01966419). Adult patients hospitalized with an overt HE episode, cirrhosis, and plasma ammonia above the upper limit of normal (ULN) who failed to improve after 48 hours’ standard care were randomly assigned to continuous intravenous OP (10, 15, or 20 g/day, based on Child–Turcotte–Pugh score) or matching placebo for 5 days. Plasma levels of ornithine and phenylacetic acid (PAA) and plasma/urinary levels of phenylacetylglutamine (PAGN) (primary metabolite of PAA) were regularly assessed; plasma ammonia level was the primary pharmacodynamic variable. PAA demonstrated dose‐dependent pharmacokinetics; ornithine and PAGN levels increased with dose. PAGN urinary excretion represented ~50%–60% of administered PAA across all doses. Mean reduction in plasma ammonia with OP at 3 hours postinfusion was significantly greater versus placebo (p = 0.014); and time to achieve plasma ammonia less than or equal to the ULN was significantly reduced (p = 0.028). Achievement of clinical response based on HE stage was associated with a greater reduction in mean plasma ammonia level (p = 0.009). OP effects on plasma ammonia were consistent with its proposed mechanism of action as a primary ammonia scavenger, with a significant association between reduced plasma ammonia and improvement in HE stage. OP should be further evaluated as a promising treatment for hyperammonemia in patients with overt HE.

Effectiveness of cell- and colony stimulating factor-based therapy for liver cirrhosis: a network meta-analysis of randomized controlled trials

Background aimsCirrhosis is the 11th leading cause of death worldwide. Because of the limitations of liver transplantation, cell- and granulocyte colony-stimulating factor (G-CSF)-based therapies are considered potential treatment methods. This work analyzes the effectiveness of cell- and G-CSF-based therapies by network meta-analysis. MethodsA literature search was performed in four databases from inception to September 10, 2021. Registered randomized controlled trials (RCTs) evaluating cell-based therapies and/or G-CSF-based therapies for cirrhosis patients were included. Traditional and network meta-analyses were analyzed in terms of survival, model for end-stage liver disease (MELD) score, Child–Turcotte–Pugh (CTP) score, alanine aminotransferase levels and aspartate aminotransferase levels. ResultsTwenty-four studies were included in this analysis. The results showed that G-CSF-based therapies (odds ratio [OR], 2.38, 95% confidence interval [CI], 1.49–3.79, P < 0.01) and cell-based therapies (OR, 1.54, 95% CI, 1.00–2.40, P = 0.048) improved the transplantation-free survival rate compared with standard medical treatment. Network analysis results showed that G-CSF combined with erythropoietin (EPO) and growth hormone (GH) had a therapeutic advantage, and cell-based therapy with mononuclear cell (MNC) hepatic artery injection and intravenous mesenchymal stem cells (MSCs) combined with G-CSF also had a relative advantage in terms of survival outcome. For the MELD score, G-CSF plus GH and MSC portal vein injection had relative advantages. G-CSF plus GH and G-CSF plus EPO had advantages in terms of CTP scores. The included strategies demonstrated no obvious improvement in liver injury indicators. ConclusionsCell-based therapy has potential therapeutic effects for liver cirrhosis. Among cell-based therapies, intravenous MSCs and hepatic artery injection of MNCs have advantageous therapeutic effects. The use of G-CSF was also noted in regimens that improved survival outcomes. However, more well-designed, large-scale RCTs are needed to confirm this conclusion.

Predicting in-hospital mortality of cirrhotic patients hospitalized with hepatic encephalopathy

BackgroundHepatic encephalopathy (HE) is a serious condition associated with high rates of mortality. Many scoring systems are used to predict the outcome of HE in patients admitted to the intensive care unit (ICU). The most used scores are Child-Turcotte-Pugh (CTP), Model for End-stage Liver Disease (MELD), Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II). These scores were thoroughly investigated in HE associated with acute liver failure (type A). In the present study, we aimed to evaluate the prognostic value of these scores in patients with HE on a background of liver cirrhosis (type C). Two hundred cirrhotic patients hospitalized with HE were included in the study. Diagnosis and classification of HE were based on the West Haven criteria. APACHE II, CLIF-SOFA, MELD, MELD-Na, and CTP scores were calculated for all patients within the first 24 h after admission. According to survival outcomes, patients were categorized into either improved or deceased. Demographic, clinical, and laboratory data as well as prognostic scores were compared in both deceased and improved groups. The receiver operating characteristic (ROC) curve was plotted, and the area under the ROC curve (AUROC) was calculated for each score. Backward logistic regression analysis was used to identify the predictors of mortality.Results60.5% of patients were males. The mean age was 61.09 ± 8.94 years. The main precipitating factors of HE was infections predominantly spontaneous bacterial peritonitis (n = 108, 54.0%) followed by variceal bleeding (n = 39, 19.5%). All scores were significantly higher in the deceased patients. AUROC were 0.734 (CI95% 0.666–0.803), 0.717 (CI95% 0.647–0.787), 0.663 (CI95% 0.589–0.738), 0.626 (CI95% 0.549–0.704), and 0.609 (CI95% 0.531–0.686) for CLIF-SOFA, MELD-Na, MELD, APACHE II, and CTP scores, respectively. MELD, MELD-Na, and CLIF-SOFA scores were the independent predictors of mortality. Among these scores, CLIF-SOFA was the strongest independent predictor of mortality (OR = 1.142, CI95% = 0.888–1.467, p = 0.001).ConclusionsCLIF-SOFA score was superior to other prognostic scores in predicting mortality in hospitalized patients with HE type C.

ASSESSMENT OF BASIC HEMATOLOGICAL CHANGES AND CLINICAL SEVERITY IN CHRONIC LIVER DISEASE WITH PERIPHERAL BLOOD NEUTROPHIL LYMPHOCYTE RATIO.

Introduction: A wide variety of hematological manifestations occur in chronic liver disease. Mild to moderate anemia and thrombocytopenia are the most common hematological abnormalities. Neutrophil-Lymphocyte Ratio, a novel inammatory biomarker can be used to predict mortality independent of Child-Turcotte-Pugh score in liver cirrhosis. Material And Methods: A cross sectional prospective study was conducted in 100 patients to assess hematological abnormalities and to correlate Neutrophil - Lymphocyte Ratio (NLR) with Child-Turcotte-Pugh (CTP) score for prediction of clinical outcome. NLR and CTP score were correlated using Chi square test and Spearman correlation test. Results: Mild anemia was common in females (61%) whereas moderate anemia was common in males (45%). Anemia was seen in 86% and thrombocytopenia in 72% of cases. Hypochromic microcytic anemia was the most common morphological type of anemia seen in chronic liver disease. NLR had a signicant positive correlation with CTP score in this study (r=0.288 and p=0.003). Conclusions: Mild anemia and moderate thrombocytopenia were the most common hematological abnormalities in chronic liver disease. Early diagnosis and correction of these abnormalities will reduce mortality. Neutrophil-Lymphocyte ratio can be used as an independent prognostic tool to predict clinical severity in chronic liver disease.

Predictors of Outcome of Cirrhotic Patients Requiring Invasive Mechanical Ventilation: Experience From a Non-Transplant Tertiary Care Hospital in Pakistan.

BackgroundPatients with known liver cirrhosis, irrespective of the etiology, have poor outcomes when put on invasive mechanical ventilation in an intensive care unit (ICU) setting. The clinical situation becomes even more complicated when such patients are managed in a non-transplant center. Various factors are associated with poor outcomes, and hence, various scoring systems are available to help determine the prognosis in patients with liver cirrhosis. These scoring systems are broadly classified into two categories, namely, ICU-specific scoring systems and liver disease-specific scoring systems. There is a dearth of data from Pakistan regarding which score better determines the prognosis of patients with liver cirrhosis admitted to the ICU. In this study, we aimed to determine the outcome of cirrhotic patients requiring invasive mechanical ventilation in a non-transplant tertiary care hospital in Pakistan using ICU-specific and liver disease-specific scoring systems.MethodologyA retrospective study design was applied to a record of 88 cirrhotic patients admitted to the medical ICU of a tertiary care teaching hospital in Karachi, Pakistan, from January 2016 to November 2016. Patients with acute hepatitis were excluded. Data on patients’ characteristics, the reason for intubation, hepatic encephalopathy, the need for vasopressor support, and the duration of ICU and hospital stay were collected. Moreover, the first-day Acute Physiology and Chronic Health Evaluation (APACHE) II, Sequential Organ Failure Assessment (SOFA), Child-Turcotte-Pugh (CTP), and Model for End-Stage Liver Disease (MELD) scores were calculated, with mortality being the primary outcome measure.ResultsThe most common etiology was hepatitis C (52.3%, 46/88). The most common reason for intubation was airway protection (57.9%, 51/88). Overall mortality was 71.6% (63/88). On univariate analysis, CTP score >10, MELD score >18, hepatic encephalopathy, bilirubin, prothrombin time, presence of tense ascites, and APACHE II were significantly associated with mortality. On multivariate analysis, CTP score >10 (odd ratio = 21; 95% confidence interval (CI): 4-104; p < 0.001) was an independent predictor of mortality. Area under curve was 0.89 (95% CI = 0.82-0.96) for CTP, 0.86 (95% CI = 0.77-0.95) for MELD, 0.81 (95% CI = 0.69-0.92) for APACHE II, and 0.81 (95% CI = 0.71-0.91) for SOFA in predicting mortality.ConclusionsCTP and MELD scores are better predictors of short-term mortality in patients with liver cirrhosis requiring invasive mechanical ventilation compared to APACHE II and SOFA scores. CTP score >10 was an independent predictor of mortality.

Assessment of frailty in cirrhosis using bedside measures and its correlation with Child-Turcotte-Pugh, MELD & MELD-Na Scores.

Objectives:To assess frailty in cirrhotic by calculating Liver Frailty Index (LFI) using bedside clinical tests and correlate it with Child-Turcotte-Pugh (CTP), MELD, MELD Na, Fib- 4 and Transient Elastography (TE) scoresMethods:This cross-sectional observational comparative study was carried out in Dr Ruth KM Pfau Civil Hospital, Karachi from August 2020 to September 2021. Patients were subjected to three performance-based testing including dominant hand grip strength (HGS), Chair to Stand (CTS) Time & Three Position Balance (TPB). LFI was calculated using the online LFI calculator, available at http://liverfrailtyindex.ucsf.edu and classified as ‘Robust’ if LFI <3.2, ‘Prefrail’ LFI between 3.2 and 4.4, and ‘Frail’ as LFI ≥4.5. Correlation of frailty with MELD, MELD-Na and CTP Scores was done. Means of MELD & MELD-Na Scores and CTP scores were calculated in all 3 classes of frailty using one way ANOVA. A p-value of ≤.05 was taken as significant.Results:Out of 118 patients, 62 (52.5%) were males. Mean MELD score was 11.4 ±3.3, MELD-Na was 15.97 ±8.54, CTP 8.25 ±2.21, Fib-4 was 2.79 ±1.034 and TE score was 18.20 ±9.17. Mean LFI was 3.87 ±1.07; mean HGS was 18.12 ±4.68; mean of CTS was 9.62 ±3.55. LFI Class distribution in our cohort showed Robust were 36 (30.5%), Prefrail 34 (28.8%) and Frail were 48 (40.8%). Correlation of all these variables with LFI showed significant correlation with LFI, but highest correlation coefficient was seen with MELD-Na.Conclusion:Significant correlation between frailty score in cirrhotic with cirrhosis severity scores highlights the need for frequently assessing LFI in all cirrhotic at regular follow up visits.

The predictive value of MELDNa (model for end-stage liver disease-sodium) and mean platelet volume/platelet count for patients' 30-day mortality after liver transplantation.

Aim of the studyTo investigate the disease-specific score and improve the existing scores to better determine the prognosis of patients after liver transplantation (LT). For this purpose, we evaluated the relationship of prognostic scores with 30-day mortality after LT. In addition, we planned to investigate whether the mean platelet volume/platelet count (MPR) would contribute to score improvement.Material and methodsA total of 178 adult patients admitted to the intensive care unit after LT in our hospital between 2011 and 2019 were retrospectively analyzed. Model for end-stage liver disease-sodium (MELDNa), Child-Turcotte-Pugh (CTP) score, and MPR values were compared in patients with and without 30-day mortality who underwent LT. Logistic regression analysis was performed to determine the predictive factors for mortality. A model was created with multivariate analysis.ResultsOur study included 135 (75.8%) male and 43 (24.2%) female patients. There was a significant difference in the postLT-MELDNa score in the evaluation between those with and without mortality (p < 0.001). Age, postLT-MELDNa and CTP score were found to be significant in terms of the prediction of 30-day mortality in the univariate analysis (p < 0.05). mean platelet volume (MPV) and MPR were not significant in univariate analysis. Multivariate analysis revealed a model in which age and postLT-MELDNa were significant.ConclusionsIn our study, postLT-MELDNa predicted 30-day mortality and was much more effective in predicting mortality when evaluated with age. The MELDNa score, which is currently used in the prognosis of candidates awaiting LT, may be useful for the prognosis of patients after LT in intensive care units.

Significance of altered anticoagulant proteins and D-dimer in cirrhotic portal vein thrombosis: relation to the degree of liver dysfunction.

Portal vein thrombosis (PVT) is a well-known consequence of cirrhosis. Its pathophysiology is complex, with possible downstream hepatic decompensation. This study was conducted to describe the changes of protein C (PC), protein S (PS) and D-dimer blood levels associated with PVT formation in cirrhosis and the relation to the degree of liver dysfunction. This was a case-control study that included 50 cirrhotic patients who presented with acute de novo non-malignant PVT and 50 cirrhotic patients without PVT as a control group. The severity of liver disease was classified as per the Child-Turcotte-Pugh (CTP) score. Doppler ultrasonography identified acute portal vein occlusion, and dynamic contrast-enhanced computed tomography confirmed the extent and nature of PVT. Blood PC, PS and D-dimer levels were measured using enzyme-linked immunosorbent assay. PC and PS levels were significantly lower, and the D-dimer level was significantly higher, in cirrhotic patients with PVT compared to the control group. PC and PS levels were significantly decreased in patients with higher CTP score of both groups. The D-dimer level did not vary significantly with the degree of liver dysfunction in patients of either group. PC, PS and D-dimer at the cut-off points of ≤ 77 IU/dl, ≤ 63 IU/dl, and > 300 ng/ml, respectively, significantly suggested PVT occurrence. Alteration of the anticoagulant proteins and D-dimer contributed to PVT formation in cirrhotic patients and could help stratify the degree of liver dysfunction. Blood level of these hemostatic proteins could be incorporated into a probability score for early diagnosis and treatment of PVT in cirrhosis.

Lipid Profiles as Markers for the Severity of Liver Diseases in Cirrhotic Patients

Background Liver cirrhosis is a diffuse process in which the anatomical structure and function of the liver are disturbed. Lipid metabolism occurs mainly in the hepatocytes. In liver cirrhosis, it is expected to detect abnormal lipid profile and abnormal neutrophil to lymphocyte ratio due to necro-inflammation and hepatocyte dysfunction. This study aimed to estimate the lipid profile in patients with liver cirrhosis and to assess its relation to the severity of the liver disease based on Child-Pugh Turcotte score and Neutrophil to Lymphocyte Ratio (NLR). Methods: This study included 500 cirrhotic patients. All patients are subjected to history taking, clinical examination, liver and renal function tests, lipid profile, and also abdomino-pelvic ultrasound. Child -Pugh score, fibrosis-4 score (FIB4), and neutrophil and platelet lymphocyte ratio were calculated. Results: A total of 500 patients were enrolled in this study; 12 patients were excluded (two patients were on the immunosuppressive drug, three patients had body mass index (BMI) &gt;30, and seven patients took lipid-lowering drugs). Cholesterol level was significantly higher in patients with Child- Score A than B and C. Cholesterol, Low-Density Lipoprotein (LDL), and very-low-density lipoprotein (VLDL) cholesterol were significantly higher in Child B than C. A significant negative correlation was found between cholesterol level and each of FIB4 and NLR ratios. Conclusion: There was a significant negative correlation between the severity of liver cirrhosis and lipid profiles (except triglyceride), FIB4 and NLR ratio.

A Prospective Multicenter Study of the Chinese Scoring System for Hepatitis B Liver Failure.

Objective: To evaluate the clinical utility of a Chinese scoring system for hepatitis B liver failure in a prospective and multicenter study.Methods: Clinical data for 1,143 patients with hepatitis B liver failure who had been followed up for a minimum of 6 months were collected from seven liver disease centers across China. The disease severity and prognosis for the patients were predicted using the Chinese scoring system and compared to those predicted with the model for end-stage liver disease (MELD) score, MELD-Na score, and Child-Turcotte-Pugh (CTP) score.Results: The Chinese scoring system was more effective at predicting the outcomes of survival and mortality than the MELD score. In the peak disease stage, the area under the receiver operating characteristic curve for the Chinese scoring system was 0.954, significantly higher than that (0.896) for the MELD scoring system (P < 0.001). The positive prediction at 30, 90, and 180 days with the Chinese scoring system was 0.764 (95% CI: 0.714–0.808), 0.731 (95% CI: 0.694–0.769), and 0.724 (95% CI: 0.679–0.765), also significantly higher than that with the MELD, MELD-Na, and CTP scores (P < 0.001). In addition, the Chinese scoring system was superior to the MELD, MELD-Na, and CTP scores (P < 0.001) at predicting the prognosis of patients with hepatitis B liver failure at both 30 and 180 days.Conclusion: The Chinese scoring system demonstrated superior performance to the three established scoring systems in assessing the severity and outcomes of hepatitis B liver failure in this cohort.

Serum zonulin levels in patients with liver cirrhosis: Prognostic implications.

BACKGROUNDIncreased gut permeability and bacterial translocation play an important role in liver cirrhosis. Zonulin is a recently recognized protein involved in the disintegration of the intestinal barrier.AIMTo investigate possible differences in serum zonulin levels among patients with different cirrhosis stages and their potential prognostic implications.METHODSConsecutive cirrhotic patients who attended our liver clinic were included in the study. Serum zonulin levels, clinical, radiological and biochemical data were collected at baseline. Patients who accepted participation in a regular surveillance program were followed-up for at least 12 mo.RESULTSWe enrolled 116 cirrhotics [mean Child-Turcotte-Pugh (CTP) score: 6.2 ± 1.6; model for end-stage liver disease score: 11 ± 3.9]. The causes of cirrhosis were viral hepatitis (39%), alcohol (30%), non-alcoholic fatty liver disease (17%), and other (14%). At baseline, 53% had decompensated cirrhosis, 48% had ascites, and 32% had history of hepatic encephalopathy. Mean zonulin levels were significantly higher in patients with CTP-B class than CTP-A class (4.2 ± 2.4 ng/dL vs 3.5 ± 0.9 ng/dL, P = 0.038), with than without ascites (P = 0.006), and with than without history of encephalopathy (P = 0.011). Baseline serum zonulin levels were independently associated with the probability of decompensation at 1 year (P = 0.039), with an area under the receiving operating characteristic of 0.723 for predicting hepatic decompensation. Higher CTP score (P = 0.021) and portal vein diameter (P = 0.022) were independent predictors of mortality.CONCLUSIONSerum zonulin levels are higher in patients with more advanced chronic liver disease and have significant prognostic value in identifying patients who will develop decompensation.

From Child-Pugh to MELD score and beyond: Taking a walk down memory lane

The Child-Turcotte-Pugh (CTP) and the MELD (Model for End-Stage Liver Disease) scores were designed to predict the outcome of decompressive therapy for portal hypertension. They were prospectively validated to predict mortality risk in patients with a wide spectrum of liver disease etiology and severity. Unlike the CTP score, the MELD score was derived from prospectively gathered data. Its calculation was based on serum bilirubin, serum creatinine, international normalized ratio (INR) and etiology of liver disease. Instituting a continuous disease severity score that de-emphasizes waiting time resulted in better categorization of waiting patients and enhanced transparency. The US instituted the MELD system in 2002 and soon thereafter, MELD-based liver allocation was adopted throughout the world including Latin America. The most significant impact of MELD-based policies has been the reduction of waiting-list mortality. In the years after implementation of the MELD system, several options have been proposed to improve the MELD score's accuracy. Adding serum sodium (MELD-Na) increased the accuracy of the score in predicting waiting list mortality, thus completing the original MELD score as a prognostic model in liver allocation. On the 20th anniversary of the creation of MELD score we present a brief account of its development, its use to stratify patients on the waiting list for liver transplantation as well as its adoption as liver allocation system .

P-13 COMPARISON OFF DIFFERENT PROGNOSTIC SCORES FOR PATIENTS WITH CIRRHOSIS HOSPITALIZED WITH SARS – COV 2 INFECTION

Introduction and ObjectivesViral infections have been described to increase the risk of decompensation in patients with cirrhosis. We aimed to determine the impact of SARS-CoV-2 infection on clinical outcome of hospitalized patients with cirrhosis and to compare the performance of different prognostic models for predicting mortality.PatientsWe performed a prospective cohort study including 2211 hospitalized patients with confirmed SARS-CoV-2 infection from April 15, 2020 through October 1, 2020 in 38 Hospitals from 11 Latin American countries. We registered clinical and laboratory parameters of patients with and without cirrhosis. All patients were followed until discharge or death. We evaluated the prognostic performance of different scoring systems to predict mortality in patients with cirrhosis using ROC curves.ResultsOverall, 4.6%(CI 3.7-5.6) subjects had cirrhosis (n=96). Baseline Child-Turcotte-Pugh (CTP) class was assessed: CTP-A (23%), CTP-B (45%) and CTP-C (32%); median MELD-Na score was 19 (IQR 14-25). Mortality was 47% in patients with cirrhosis compared to 16% in those without cirrhosis (P<.0001). Cirrhosis was independently associated to death [OR 3.1(CI 1.9-4.8);P<.0001], adjusted by age, gender, and body mass index >30. The areas under the ROC curves for performance evaluation in predicting 28-days mortality for Chronic Liver Failure Consortium (CLIF-C), North American Consortium for the Study of End-Stage Liver Disease (NACSELD), CTP score and MELD-Na were 0.85, 0.75, 0.69, 0.67; respectively (P<.0001).ConclusionsSARS-CoV-2 infection is associated with elevated mortality in patients with cirrhosis. CLIF-C had better performance in predicting mortality than NACSELD, CTP and MELD-Na in patients with cirrhosis and SARS-CoV-2 infection.Clinicaltrials.gov: NCT04358380.

Patients with HIV and cirrhosis: the risk for hepatocellular carcinoma after direct-acting antivirals for hepatitis C virus.

Hepatocellular carcinoma (HCC) has become a major issue in coinfected HIV/HCV patients with liver cirrhosis. We aimed to determine the rate of HCC occurrence after a direct-acting antiviral (DAA) treatment and to evaluate the factors associated with the risk of HCC in this population. We conducted a retrospective multicenter observational study including cirrhotic HIV/HCV-coinfected patients treated with DAAs, between October 2014 and January 2017. We collected demographics characteristics, data regarding HIV and HCV infections and treatment with DAAs. We investigated the rate and the time of occurrence of HCC. Statistical analysis explored the factors associated to development of liver cancer. During a median follow-up of 55 months, 24 out of 232 patients developed HCC, after a median of 22.5 months from starting DAAs. Factors associated with HCC were a higher Child--Pugh Turcotte (CPT) score (P = 0.002), HCV genotype 3 (P = 0.04), previous HCC (P < 0.001) and CD4+ cell count nadir greater than 350 cells/μl (P = 0.001), whereas antiretroviral therapy (ART) was associated to a lower rate of cancer (P = 0.02). At multivariable analysis CPT score and a history of HCC remained independently associated with HCC after DAAs (P = 0.003 and P < 0.001, respectively), and ART administration maintained its protective role (P = 0.047), regardless of HIV RNA at baseline. Our study highlights the importance of a long-lasting follow-up for HCC after HCV eradication, mostly in those patients with advanced cirrhosis and history of HCC. Furthermore, our data showed a potential role of ART itself (and not of undetectable HIV RNA) in reducing the risk for HCC development.

Elevated serum tyrosine concentration is associated with a poor prognosis among patients with liver cirrhosis.

Chronic liver insufficiency is often associated with changes in amino acid metabolism. We evaluated whether change in serum amino acid concentrations had prognostic value among patients with liver cirrhosis. This retrospective study evaluated 158 patients who had been hospitalized with cirrhosis. Baseline serum concentrations of branched-chain amino acids (BCAAs) and tyrosine, as well as the BCAA-to-tyrosine ratio, were evaluated. Cox proportional hazards analysis was used to calculate the hazard ratios for factors that were associated with mortality or liver transplantation. Among the 158 patients, baseline measurements showed decreased serum BCAA concentrations for 59 patients (37.3%), elevated serum tyrosine concentrations for 80 patients (50.6%), and a decreased BCAA-to-tyrosine ratio for 114 patients (72.2%). During a median follow-up period of 3.0years, death or liver transplantation occurred at a rate of 0.136 cases/1 person-year. Multivariable analysis showed that transplant-free survival was independently predicted by older age, male sex, comorbid hepatocellular carcinoma, Child-Turcotte-Pugh score, and serum tyrosine concentration. Receiver operating characteristic curve analysis showed that a serum tyrosine concentration of >110µmol/L was the optimal cut-off value for predicting transplant-free survival (adjusted hazard ratio 1.89, 95% confidence interval 1.15-3.11, p=0.012). Kaplan-Meier analysis showed a significant difference in the 5-year transplant-free survival probability between patients with high and low serum tyrosine concentrations (42.1% vs. 60.7%, p<0.001). Elevated serum tyrosine concentration, but not changes in serum BCAA concentration or the BCAA-to-tyrosine ratio, may indicate a high risk of death or liver transplantation for patients with liver cirrhosis.

Evaluation of Non-invasive Fibrosis Markers in Predicting Esophageal Variceal Bleeding.

Background/AimsEsophageal variceal bleeding (EVB) is an important cause of mortality and morbidity in liver cirrhosis. In this study, we aimed to predict the possibility of EVB in patients with cirrhosis using a non-invasive score. MethodsA total of 359 patients with cirrhosis were divided into two groups based on the presence or absence of EVB. ChildTurcotte-Pugh (CTP) score, a model for end-stage liver disease, aspartate aminotransferase to alanine aminotransferase ratio, aspartate aminotransferase to platelet ratio index (APRI), fibrosis-4-index (FIB-4), aspartate aminotransferase to alanine aminotransferase ratio/platelet ratio index (AARPRI), and S-index were measured for all participants. Receiver operating characteristic curves were obtained for all parameters, and the optimal cut-off value was determined in predicting EVB. ResultsIn patients with EVB, the number of platelets (PLT) were low (p<0.001) and APRI, AARPRI, FIB-4, and S-index were significantly higher than those in patients without EBV. APRI, AARPRI, FIB-4, PLT, and S-index were statistically significant predictors of EVB (p<0.05). ConclusionsFIB-4 and AARPRI, which are non-invasive markers of fibrosis, can be used to predict EVB. In addition, the 66.5 109/L cut-off value for PLT is important for EVB.

Comparison of different prognostic scores for patients with cirrhosis hospitalized with SARS-CoV-2 infection

Introduction and ObjectivesViral infections have been described to increase the risk of decompensation in patients with cirrhosis. We aimed to determine the effect of SARS-CoV-2 infection on outcome of hospitalized patients with cirrhosis and to compare the performance of different prognostic models for predicting mortality. PatientsWe performed a prospective cohort study including 2211 hospitalized patients with confirmed SARS-CoV-2 infection from April 15, 2020 through October 1, 2020 in 38 Hospitals from 11 Latin American countries. We registered clinical and laboratory parameters of patients with and without cirrhosis. All patients were followed until discharge or death. We evaluated the prognostic performance of different scoring systems to predict mortality in patients with cirrhosis using ROC curves. ResultsOverall, 4.6% (CI 3.7–5.6) subjects had cirrhosis (n = 96). Baseline Child-Turcotte-Pugh (CTP) class was assessed: CTP-A (23%), CTP-B (45%) and CTP-C (32%); median MELD-Na score was 19 (IQR 14−25). Mortality was 47% in patients with cirrhosis and 16% in patients without cirrhosis (P < .0001). Cirrhosis was independently associated with death [OR 3.1 (CI 1.9−4.8); P < .0001], adjusted by age, gender, and body mass index >30. The areas under the ROC curves for performance evaluation in predicting 28-days mortality for Chronic Liver Failure Consortium (CLIF-C), North American Consortium for the Study of End-Stage Liver Disease (NACSELD), CTP score and MELD-Na were 0.85, 0.75, 0.69, 0.67; respectively (P < .0001). ConclusionsSARS-CoV-2 infection is associated with elevated mortality in patients with cirrhosis. CLIF-C had better performance in predicting mortality than NACSELD, CTP and MELD-Na in patients with cirrhosis and SARS-CoV-2 infection. Clinicaltrials.gov:NCT04358380.

Evaluating the Correlation of Hemostatic and Endocrine Parameters with Child-Turcotte-Pugh Scoring in Patients with Non-Alcoholic Liver Cirrhosis

Background: Liver cirrhosis is one of the most significant causes of death in many regions worldwide. This study aimed to assess the correlation of hemostatic and endocrine parameters with Child-Turcotte-Pugh (CTP) scoring in patients with non-alcoholic liver cirrhosis. Materials and Methods: This study included 59 patients monitored for non-alcoholic liver cirrhosis in a gastroenterology clinic from January 2018 to February 2019. The subjects were grouped according to the CTP scores, and their adrenocorticotropic hormone (ACTH), cortisol, dehydroepiandrosterone sulfate (DHEA-SO4), progesterone, growth hormone (GH), insulin-like growth factor-1 (IGF-1), GH/ IGF-1 ratio, fibrinogen, D-dimer, and D-dimer/fibrinogen ratio were measured. Results: According to CTP scoring, 20.3% of patients were CTP-A (n=12), 35.6% were CTP-B (n=21), and 44.1% were CTP-C (n=26). There were statistically significant differences for IGF-1, DHEA-SO4, and GH/IGF-1 ratios between CTP-A and CTP-B groups (P=0.002, P=0.043, P=0.038, respectively). Additionally, there were statistically significant differences between the CTP-B and CTP-C groups for D-dimer and GH values (P=0.024, P=0.006, respectively). There were statistically significant differences for D-dimer, GH, IGF-1, and D-dimer/fibrinogen ratio between the CTP-A and CTP-C groups (P&lt;0.001, P=0.016, P=0.002, P=0.031, respectively). Conclusion: Severe hemostatic and endocrine complications develop in patients with liver cirrhosis due to non-alcoholic causes. Additionally, it seems that using D-dimer and D-dimer/fibrinogen ratio, along with fibrinogen level, can be beneficial in showing liver damage in these patients.

English

BACKGROUND Chronic liver disease causes an imbalance in the coagulation system, but available data on liver disease and risk of venous thrombosis are conflicting. Clinical studies are therefore needed to understand the prevalence and risk factors associated with mortality to decide appropriate care of these patients. We studied the incidence of venous thrombosis in three CTP (Child-Turcotte-Pugh) class of cirrhotic patients and associated risk factors predicting 90-day mortality. METHODS A cross sectional observational study of one-year duration was conducted at a tertiary-care teaching hospital among patients admitted with chronic liver disease. 150 hospitalised patients with cirrhosis were enrolled and followed up for 3 months. Incidence of thrombosis was recorded in different CTP subclass. Threemonth mortality rates in different subgroups were compared by using normal test of proportions. The association between types of thrombosis and CTP class of liver cirrhosis was studied using Mann-Whitney U test, a non-parametric test. Mortality association with various parameters was evaluated using non-parametric test. Pvalue of ≤ 0.05 was considered significant. RESULTS Incidence of venous thrombosis in cirrhotic patients was 4 % in this study. Association of thrombosis with various clinical parameters and different CTP subclass was statistically non-significant. During the 3-months follow-up 24 patients died. Deceased had higher CTP score (mean CTP score - 9.58) as compared to survivors (mean CTP - 8.48) (P-value 0.049). Presence of ascites (Pvalue 0.037), higher serum urea (P-value 0.001), creatinine (P = 0.004), and total leucocyte count (P = 0.008) were significantly associated with mortality. CONCLUSIONS Thrombosis in chronic liver disease (CLD) especially portal vein is common and presents a therapeutic challenge as these patients are also at increased risk of bleeding. Higher CTP score, serum creatinine, leucocyte count and presence of ascites in CLD patients at admission are poor prognostic markers. KEYWORDS Deep Venous Thrombosis, Chronic Liver Disease, Cirrhosis, Thrombosis, Portal Vein Thrombosis

The Predictive Scoring Systems for Outcomes of Heart Transplantation in Patients with Pre-Existing Liver Cirrhosis

<h3>Purpose</h3> There are few data assessing factors and clinical outcomes in patients with liver cirrhosis for heart transplantation. The aim of this study was to compare the Model for End-Stage Liver Disease (MELD) score, the MELD-XI score and Child-Turcotte-Pugh (CTP) score risk prediction in cirrhotic patients undergoing heart transplantation. <h3>Methods</h3> Between 1994 and 2019, forty-nine consecutive patients (19 men and 30 women, median age 46 years, range 12-68 years) had liver cirrhosis, among 170 patients underwent heart transplantations in our institution. Potential preoperative predictors of outcomes, as well as preoperative MELD score, MELD-XI score and CTP classification were calculated. <h3>Results</h3> Causes of heart failure were dilated cardiomyopathy in 26, ischemic disease in 7, congenital heart disease in 6 and valvular heart disease 7 patients. Cause of liver cirrhosis was majority of cardiac origin, except hepatitis in two and alcoholism in one patient. The median follow-up duration was 45.2 months. The MELD score (p=0.010) and MELD-XI score (p=<0.001) were significantly differed between survivors and non-survivors. Cox regression analysis showed high MELD score (HR 1.211; 95% CI, 1.059-1.386; p=0.005), MELD-XI score (HR, 1.184; 95% CI, 1.042-1.345; p=0.010) and CTP score (HR, 1.694; 95% CI, 1.040-2.760; p=0.034) were associated with the risk of all-cause mortality. Receiver operating characteristic (ROC) curve analysis revealed the optimal cut-off value of MELD, MELD-XI and CTP score was 12.2, 12.0 and 7.5, respectively (sensitivity: 69.2 vs. 61.5 vs. 69.2%, specificity 68.6 vs. 60.0 vs. 62.9%) for all-cause mortality (AUC: 0.745 vs. 0.690, 0.729). <h3>Conclusion</h3> The patients with advanced heart failure and liver cirrhosis were high mortality and morbidity of heart transplantation. However, these scoring systems can be a tool to risk-stratification for liver cirrhotic patients undergoing heart transplantation.