End-stage Liver Disease Research Articles

Role of Serum ferritin as a marker of decompensated cirrhosis and its correlation with CTP, MELD and MELD-Na scores

Role of Serum ferritin as a marker of decompensated cirrhosis and its correlation with CTP, MELD and MELD-Na scores

Prognostic value of MELD-XI score and hemodynamic parameters in patients undergoing transcatheter tricuspid valve intervention

Abstract Background Hepatorenal dysfunction is a strong prognostic predictor in patients with tricuspid regurgitation. Patients are often hospitalized with acute heart failure due to volume overload and peripheral hypoperfusion. End-organ dysfunction is associated with the development of right ventricular failure related to hemodynamic changes such as low cardiac output and passive congestion from increased right ventricular filling pressures. Purpose This study aimed to investigate the prognostic value of hepatorenal dysfunction using the Model for End-stage Liver Disease (MELD) Score, the modified version of the score, MELD-XI, and of parameters determined during right-heart catheterization in patients undergoing transcatheter tricuspid valve intervention. Methods In this single-center prospective cohort study, data from patients undergoing edge-to-edge repair or heterotopic minimal invasive tricuspid valve repair were analyzed. Serum creatinine, INR and bilirubin were measured and the MELD score as well as the MELD XI score was calculated. All patients underwent right heart catheterization before the intervention. Receiver operator characteristics with calculation of the area under the curve (AUC) were performed to determine the predictive value of MELD (XI) score and hemodynamic parameters for the combined endpoint of rehospitalization due to decompensated heart failure and mortality within 3 months. Results Data from 36 consecutive patients were analyzed. 28 patients underwent edge-to-edge repair and 8 patients heterotopic minimal invasive tricuspid valve repair. Mean age of patients was 80.2 ± 5.9 years; 33.3% (12/36) were male. Baseline characteristics are shown in table 1. Rehospitalization due to decompensated heart failure occurred in 9/36 patients (25%). Mortality within the first 3 months was 11% (4/36). The predictive value for the composite endpoint of the modified MELD IX score was AUC 0.82 (95 % CI 0.63-0.99; p=0.009), while the conventional MELD score had an AUC of 0.77 (95 % CI 0.55-0.99; p = 0.059) (figure 1). RV pressure (AUC 0.84, 95% CI 0.66-1.00, p= 0.012) and RA pressure (AUC 0.83, 95% CI 0.67-0.98, p=0.016) showed a good predictive value for the composite endpoint (figure 2). The combination of MELD XI (at admission) and RV or PA pressure improved the AUC (MELD XI + RV: AUC 0.85; MELD XI + PA: AUC 0.84). Conclusion In this pilot-study, the modified MELD XI score, as indicator of hepatorenal dysfunction, was identified as a potential marker for short-term outcome after interventional tricuspid valve treatment.

MELD score as predictor of mortality in patients with advanced heart failure: a longitudinal evaluation

Abstract Aims Advanced heart failure (AHF) is characterized by recurrent episodes of hemodynamic instability, frequent hospitalizations leading to a progressive decline in quality of life, and high mortality rates. The objective of this study was to assess the clinical associations of the MELD score and its efficacy in predicting mortality among patients with AHF. Methods 102 patients with AHF were enrolled, all patients included in the study were on top of tolerated medical therapy according to guidelines. The MELD score was measured at baseline, and every 6 months during follow-up. All patients underwent echocardiographic assessment, six-minute walking test, and cardiopulmonary testing with evaluation of VO2 max and VE/VCO2. Results The mean age of the study group was 57.8±11.9 years. There were 26 deaths during a follow-up period of 31.9±15.4 months. The mean NYHA class was 2.8±0.6, ejection fraction was 26.5±6.3%, TAPSE was 17.5±4.1 mm, and NT-pro-BNP was 2746.0±2475.9 pg/mL. The mean VO2 max was 11.7±3.5 ml/kg/min, and the distance covered in the six-minute walk test was 270.1±151.5 meters. Data stratified by mortality showed that deceased patients had higher NYHA class (2.7±0.6 vs. 3.2±0.3; p<0.001), NT-pro-BNP levels (4767.2±2888.1 vs. 1884.0±1669.5 pg/mL; p<0.001), and MELD score (19.3±3.8 vs. 11.9±5.1; p<0.001) compared to those who were alive at follow-up. Multiple regression analysis revealed a positive correlation between MELD score and NT-pro-BNP (Beta = 0.300; p=0.010), and a negative correlation between MELD score and TAPSE (Beta = -0.236; p=0.026). Cox regression analysis identified MELD score as a predictor of mortality (HR = 1.113; 95%CI = 1.011-1.225; p=0.029), independently by the effect of age, NYHA class, NT-pro-BNP, ejection fraction, TAPSE, and VO2 max. Changes in MELD score percentage, considered as a dichotomous variable (≤100% and >100%), were found to be predictors of mortality. Receiver operating characteristic (ROC) curves showed an area under the curve (AUC) of 0.897 for MELD score and mortality. Conclusions The MELD score and its longitudinal changes are effective predictors of mortality in patients with AHF, regardless of age, NYHA class, and NT-pro-BNP.

Impaired right ventricular strain is associated with worse prognosis in patients with liver cirrhosis

Abstract Introduction Cirrhotic cardiomyopathy is a complication of liver cirrhosis accounting for significant morbidity and associated with reduced patient survival. It is characterized by reduced afterload, increased cardiac output, and diastolic dysfunction. However, there are limited data regarding the prognostic significance of right ventricular (RV) mechanics. Novel echocardiographic techniques such as speckle tracking echocardiography can detect subclinical myocardial dysfunction early in the course of non-ischemic myocardiopathies. Purpose To investigate the prognostic role of RV free wall strain (RVFWS) in patients with liver cirrhosis. Methods We prospectively enrolled 70 patients with liver cirrhosis in stable clinical condition. Patients with coronary artery disease, valvular heart disease, ongoing alcohol consumption or poor acoustic window were excluded from the study. Transthoracic echocardiography was performed and RVFWS was calculated from RV focused 4-chamber views using a dedicated software. Since RVFWS was as expected negative in all patients, absolute values were used for all calculations. Clinical and laboratory examination was also performed in all patients and the Model for End-Stage Liver Disease (MELD) score a widely used tool for assessing liver disease severity was calculated. All-cause mortality at 24 months was the primary endpoint and was available in all patients. Results Mean RVFWS in the cohort was 27.4±6.3% and using a lower normal limit of 20%, reduced RVFWS was detected in six patients. According to the Spearman coefficient analysis, RVFWS was correlated with MELD (rho=0.274, p=0.023) indicating increased values in patients with more advanced liver disease. According to the univariate Cox-regression proportion hazard models RVFWS as a continuous variable was not significantly correlated with worse two year survival (HR: 1.01 (0.95-1.08, p=0.658). Interestingly, among conventional echocardiographic parameters basal RV diameter (p=0.004) and right atrial end-systolic area (p=0.008) were associated with increased risk for the primary endpoint. The association of the primary endpoint with other parameters of RV systolic function was also not statistically significant. The Multivatiate Cox Regression survival analysis, which incorporated age, sex, MELD, hemoglobin, systolic blood pressure and cardiac output, showed that among echocardiographic parameters for the evaluation of the RV, only RVFWS showed a tendency to be associated with worse survival (p=0.062). When patients were stratified into tertiles according to RVFWS values, those in the first tertile (with lower absolute RVFWS values) had significantly increased hazard for the primary endpoint (HR: 5.82, 2.18-15.8, P<0.001) (figure 1). Conclusions RVFWS values are within normal limits in most patients with liver cirrhosis. When adjusted for the severity of the liver disease, reduced RVFWS values are associated with worse prognosis in cirrhotics.

Early detection of liver fibrosis in patients with Fontan circulation using multiparametric magnetic resonance imaging

Abstract Introduction Fontan procedure (FP), serving as the palliative intervention for complex congenital heart diseases characterized by single-ventricle physiology, precipitates a spectrum of late-stage complications. Fontan-associated liver disease (FALD) encompassing liver fibrosis (LF) which may progress to liver cirrhosis (LC) and thereby hepatocellular carcinoma (HCC) is among the most serious. Despite its importance, optimal surveillance of FALD remains undefined. Multiparametric Liver Multiscan (LMS) with corrected T1 (cT1) value emerges as a novel magnetic resonance (MRI) based non-invasive quantitative tool for liver inflammation and fibrosis evaluation. Aim of this study was to ascertain prevalence and severity of LF utilizing LMS, alongside identifying contributory risk factors for LF in adults post-FP. Material and methods Our cohort included 29 adult patients after FP who underwent LMS. Median age was 25y (20-43y) 54% were females. Liver morphology was assessed by ultrasound (USG) and MRI-based LMS protocol. Hepatic scoring systems, including the Aspartate Aminotransferase to Platelet Ratio Index (APRI), Fibrosis-4 (FIB-4) Index, and Model for End-Stage Liver Disease (MELD), were computed. Additionally, presence of fenestrations in the Fontan circulation, hemoglobin levels (Hb), and blood oxygen saturation both at rest and during exercise (SatO2%) were evaluated. Results Median cT1 was 914 (±207) ms, in 87% exceeding normal threshold . In those with elevated cT1, LF was undetected by USG in 38%. LC was identified in 27% of the cohort by USG. LC group exhibited significantly higher cT1 values (P<0.001) compared to non-LC group. cT1 value >933ms was associated with a sensitivity of 89% and a specificity of 80% for diagnosing LC (AUC 0.92). Significant correlation was found between cT1 values and Hb (P=0.01) and desaturation (SatO2 <90%/ interventional closure of fenestration, P=0.004). Conventional liver tests and hepatic scoring systems (APRI/FIB-4/MELD) did not predict cT1 nor LC. Conclusion Our study confirmed that LF is almost widely prevalentamong adult patients with single-chamber circulation. Risk factors for LF are systemic desaturation (SatO2 <90% or interventional closure of fenestration) and polyglobulia. However, reliable FALD surveillance remains challenging. Conventional liver assessments and scoring algorithms fall short in delineating the full scope of LF or LC. Consequently, the integration of non-invasive LMS into routine follow-up regimens is advocated, given its pronounced sensitivity for detecting subclinical FALD manifestations and predicting LC. The LMS-derived cT1 value >933ms is a critical predictor for LC, underscoring its importance in guiding further patient monitoring, treatment, and facilitating early HCC detection.

Comparative analysis of multi-organ failure trajectories reflected by the MELD-3.0 following heart transplantation and heartmate 3 implantation

Abstract Background Multi-organ failure (MOF) frequently complicates advanced heart failure (HF), substantially impacting patient prognosis. The Model of End-Stage Liver Disease 3.0 (MELD-3.0) scale, encompassing liver and kidney function parameters, is a valuable tool for assessing the severity of organ dysfunction. Purpose This study aims to elucidate the trajectory of MOF in individuals undergoing either heart transplantation (HTx) or left ventricular assist device (LVAD) - HeartMate 3 implantation, utilizing the MELD-3.0 scale, over a 1-year follow-up period. Methods A comprehensive analysis was conducted, examining data from 1 month preceding to 1 year subsequent to the HTx or LVAD implantation. The MELD-3.0 score was calculated using the average values of international normalized ratio, bilirubin, creatinine, sodium, and albumin levels during this timeframe. Comparative assessments of the average MELD-3.0 scores were performed between the HTx and LVAD groups at 1 month pre-procedure, as well as at 1 week, 1 month, 3 months, 6 months, and 1 year post-procedure. Results The analysis included 107 patients undergoing HTx and 31 patients undergoing HMi, with a median age of 54 years (47-62), 85% were male. There was no difference in MELD-3.0 between HTx and LVAD patients in the pre-procedure period: 12.3 (7.3-15.9) vs 13.1 (7.7-16.6), p=0.95. There was also no difference in MELD-3.0 at 1 week and 1 month post-procedure. However, in the 3rd month, the difference gained statistical significance: 7.3 (4.6-9.4) vs 13.8 (11.5-19.7), p<0.01 and continued to be significant in the next follow-ups: 12-month 5.4 (3.1-10.2) vs 11.1 (6.7—15.1), p<0.01, comparing respectively HTx vs LVAD. In both groups of patients, a significant decrease in MELD-3.0 score from 3-month follow-up when compared to 1 month preceding the procedure was observed. Within 12 months post-procedure, 30 patients (22%) died (19 in HTx group and 11 in LVAD group), 8 LVAD patients (26%) had HTx. Conclusion The utilization of the MELD-3.0 scale reveals significant differences in the trajectory of multi-organ failure between HTx and LVAD patients. Both forms of advanced HF therapy result in an improvement of liver and kidney condition, while HTx patients' benefits are larger and last longer, highlighting the distinct impacts of this intervention on organ function.MELD 3.0 score in time

MELD-albumin score is strongly associated with all-cause mortality in patients with acute myocardial infarction complicated by cardiogenic shock

Abstract Background Kidney and liver injury are frequent complications in patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) because of hypoperfusion and venous congestion. Model of End-Stage Liver Disease replacing INR with albumin (MELD-Albumin) score quantifies liver and kidney function and has been associated with mortality in acute heart failure. Higher MELD-albumin score indicates particularly more severe hepatic dysfunction. The predictive value of MELD-albumin score has yet to be assessed in AMICS. Methods This is a retrospective, multicenter observational cohort study of 1,716 patients admitted with AMICS at two tertiary facilities in Denmark between 2010 and 2017. MELD-albumin was calculated for each patient individually from 0–72-hour peak s-albumin, s-creatinine and s-bilirubin values in patients alive beyond day 2. Patients were stratified into groups according to score (Low: 1-10, Intermediate: 11-25, High: >25). Using national health registries, we performed follow-up until a maximum of 5 years (median 3.4 years). The primary outcome was all-cause mortality. Results Of 1716 patients in the cohort, 1284 (75%) were alive beyond admission day 2. Albumin, creatinine, and bilirubin measurements were available in 764 patients (60%). The median MELD-albumin score was 17. In the comparison across high vs. intermediate vs. low score groups, the high score group revealed a significantly higher prevalence of hypertension (61 vs. 49 vs. 39%, p=0.038), diabetes mellitus (33 vs. 18 vs. 13%, p=0.003), and history of acute myocardial infarction (24 vs. 13 vs. 17%, p=0.026). Fewer had suffered out-of-hospital cardiac arrest (34 vs. 52 vs. 48%, p=0.014) and revascularization attempts (82 vs. 93 vs. 92%, p=0.007) in the high score group. No significant differences were observed in the initial hemodynamic pressures, lactate levels, left ventricular ejection fraction (LVEF), number of diseased vessels and culprit lesions between the three groups. Patients in the high score group had a 30-day mortality rate of 58%, which was higher compared to 40% in the medium- and 17% in the low score group (Figure 1, p<0.001, using the log-rank test). These findings were still significant when excluding s-creatinine from the calculations. In a Cox Regression analysis, a MELD-albumin score of >25 was associated with a hazard ratio (HR) of 4.34 for 5-year mortality (p < 0.001), whereas a score of 11-25 was associated with a HR of 2.52 (p < 0.001). When adjusting for age, diabetes, hypertension, dyslipidemia, peripheral arterial disease, STEMI, left ventricular ejection fraction and baseline lactate, scores of >25 and 11-25 were still associated with similar 4- to 2.5-fold increases in 5-year mortality risks. Conclusions This study revealed a strong association between MELD-albumin score and all-cause mortality among patients with AMICS, supporting kidney and liver function inclusion in future risk stratification models.

Safety and efficacy of simultaneous liver transplantation and sleeve gastrectomy in morbid obese end-stage liver disease patients: The LT-SG study.

In obese patients, metabolic dysfunction-associated steatotic liver disease is becoming a leading aetiology of end-stage liver disease and hepatocellular carcinoma. Simultaneous liver transplantation and sleeve gastrectomy (LT-SG) has been proposed in the US, but the safety and efficacy of the procedure have not been widely explored in Europe. Between January 2016 and December 2022, morbidly obese patients listed for LT at Tor Vergata University were enrolled in the LT-SG study. Primary outcomes were: i) safety expressed as 30- and 90-days overall survival (OS) and ii) major postoperative complications (Clavien-Dindo > IIIa). The secondary outcome was efficacy expressed as a 3-year %excess BMI loss(%EBMIL). Eleven patients were enrolled in the study. The median BMI at transplantation was 42 (IQR 38-48). Indications to LT-SG were HCC (63.6%) and cirrhosis (36.4%). In 54% of cases, donors had high-risk characteristics (ET-DRI>1.6). The 30 and 90-day OS were 63.6% and 54.5%, respectively. All deaths occurred in patients with p-SOFT>15 or in patients who had at least three of the following characteristics: >60 years, BMI >45, metabolic syndrome, MELD>25 or ET-DRI >1.6. The six months, 1, 2 and 3 years %excess BMI loss was 73%, 60%, 50% and 43%, respectively. LT-SG is a complex procedure thatmay carry excess risk in an unselected population. It should be considered only in highly selected patients. Standard donors are recommended and prioritization of severely obese patients on the waiting list should be considered.

Combined evaluation of liver and kidney function improves prediction of clinical outcome in patients with chronic heart failure and reduced ejection fraction

Abstract Background/Introduction The liver and the kidneys are important organs for body homeostasis and are both affected by heart failure (HF) either by systemic venous congestion or hypoperfusion. Purpose We aimed to verify whether the Model for End-stage Liver Disease eXcluding International normalized ratio (MELD-XI), as well as a combination of cholestatic liver and kidney function tests carry prognostic value in patients with chronic HF with reduced ejection fraction (HFrEF). The liver parameters included alkaline phosphatase (ALP), gamma glutamyl-transpeptidase (GGT), and total bilirubin, while kidney parameters consisted of eGFR and the tubular damage markers urinary N-acetyl-beta-D-glucosaminidase (NAG) and kidney injury molecule (KIM)-1. Methods We categorized 250 patients with HFrEF on the basis of baseline biomarker levels. We assumed elevated NT-proBNP indicates hemodynamic congestion necessary to induce congestive liver or kidney dysfunction. Thus, in every organ damage category, NT-proBNP level above median was incorporated, next to any 2 out of 3: ALP, GGT or total bilirubin above median for liver dysfunction; any 2 out of 3 NAG or KIM-1 above median or eGFR below median for kidney dysfunction; or coexistence of liver and kidney dysfunction as defined above. Additionally, a subgroup of patients with both NT-proBNP and MELD-XI above the median was analyzed. The primary endpoint was a composite of cardiovascular death, heart transplantation, LVAD implantation, and hospitalization for acute or worsened HF, whichever occurred first. Univariable and multivariable Cox proportional hazard regression models were used. Results Median (Q1-Q3) age of the study population was 68 (58-76) years; 184 (74%) were men, 62 (25%) in NYHA class III or IV, and mean left ventricular ejection fraction (LVEF) was 31±9%. During a median (Q1-Q3) follow-up of 2.2 (1.4-2.5) years, 66 (26%) patients reached the primary endpoint. We observed that liver dysfunction, kidney dysfunction or their coexistence was associated with significantly higher risk of reaching the primary endpoint (HR 3.54, 95% CI 1.75–7.16; HR 1.85, 95% CI 1.00–3.41; HR 2.52, 95% CI 1.03–6.11 respectively) in the clinically adjusted model (Table 1). Higher MELD-XI was associated with higher risk of reaching the primary endpoint in an unadjusted model but not in a clinically adjusted model. Figure 1 presents event-free survival probability of patients falling into organ dysfunction categories. Conclusions Our results show that markers of cholestatic liver function and kidney function predict unfavorable clinical outcome and provide better prognostic value in chronic HFrEF patients than the MELD-XI alone. Thus, screening for liver and kidney damage may help identify high-risk patients in whom more careful observation and individualized therapy is warranted.Fig 1.Event-free survival probability

Clinical implications of hepatorenal function in patients undergoing percutaneous coronary intervention: insights from the SAKURA PCI2 registry

Abstract Background Hepatorenal function is a prognostic predictor for heart failure, cardiac surgery, and transcatheter intervention for structural heart disease. However, the clinical implications of hepatorenal function assessed by the Model for End-stage Liver Disease eXcluding International normalized ratio (MELD-XI) score is still unclear in patients undergoing percutaneous coronary intervention (PCI). Purpose This study aimed to clarify the association between clinical prognosis and the MELD-XI score. Methods We analyzed 993 patients who underwent PCI from June 2020 to July 2022 in the SAKURA PCI2 registry, a prospective multicenter registry. Patients were stratified into high (>10) or low (≤10) MELD-XI scores. Primary outcome was defined as 2-year major adverse cardio or cerebrovascular event (MACCE), including all-cause death, ischemic stroke, and non-fatal myocardial infarction. Secondary outcome was defined as major bleeding according to the Bleeding Academic Research Consortium 3 or 5. Results Of study participating patients, 253 patients (25.5%) were stratified into a high MELD-XI score group and had a higher prevalence of the high bleeding risk than patients with a low MELD-XI score (92.5% vs. 53.7%, p<0.01). Patients with a high MELD-XI score were associated with MACCE (13.1% vs. 2.7%, p<0.01; adjusted HR 3.78, 95%CI 1.78-8.03, p<0.01) and major bleeding (4.0% vs. 1.3%, p<0.01: unadjusted HR 3.32, 95%CI 1.35-8.18, p=0.01). Moreover, these associations remained consistent in patients with chronic and acute coronary syndrome (MACCE, p for interaction=0.89; major bleeding; p for interaction=0.64). Conclusion A high MELD-XI score was associated with an increased risk of MACCE and major bleeding within two years. Therefore, the MELD-XI score could provide information for risk stratification in patients undergoing PCI.Outcomes

Impact of Karnofsky performance status on outcomes of patients with severe alcohol-associated hepatitis: a propensity-matched analysis.

Severity scores, including the model for end-stage liver disease (MELD) and discriminant function score, guide the treatment of patients with severe alcohol-associated hepatitis (AH). We aimed to investigate the impact of functional status on outcomes of patients with AH. Medically managed patients (n = 133) with AH from 1 January 2019 to 31 December 2022 were included in this prospective study. The objectives were to compare the long-term survival, recompensation rates, corticosteroid response, incidence of infections, hepatic encephalopathy (HE) and acute kidney injury (AKI) among propensity score-matched patients with good Karnofsky performance status (KPS) (score ≥50) and poor KPS (score <50) using Kaplan-Meier analysis. Twenty-five patients with good KPS were matched with 25 patients with poor KPS and followed up for a median duration of 10 (0.5-33) months. Survival was 76% (19/25; 95% confidence interval (CI), 54.9-90.6) in patients with good KPS compared to 42.3% (11/25; 95% CI, 23.4-63.1) patients with poor KPS (P = 0.001) at 10 months. The recompensation rate was higher in the good KPS group than in the poor KPS group (68% vs 44%; P = 0.04). A higher proportion of patients in the good KPS group (78.9%) than in the poor KPS group (42.8%; P = 0.03) responded to corticosteroids. Survival was lower among non-responders in the poor KPS group (0% vs 75%; P = 0.01). The proportion of patients who developed infection (36% vs 28%; P = 0.051), HE (36% vs 12%; P = 0.01) and AKI (60% vs 16%; P < 0.001) was higher in patients with poor KPS than in good KPS. KPS is an important determinant of outcomes in patients with AH, including survival, recompensation, response to corticosteroids and complications.

5-Fluorouracil combined with CalliSphere drug-eluting beads or conventional transarterial chemoembolization for unresectable hepatocellular carcinoma: a propensity score weighting analysis

This study aimed to assess the effectiveness and safety of 5-Fluorouracil (5-Fu) combined with conventional transarterial chemoembolization (cTACE) compared to 5-Fu combined with drug-eluting bead transarterial chemoembolization (DEB-TACE) using CalliSpheres for the treatment of unresectable hepatocellular carcinoma (HCC) using propensity score weighting methods. This retrospective analysis included 131 patients with HCC treated with 5-Fu combined with cTACE (5-Fu-cTACE group, n = 65) or DEB-TACE (5-Fu-DEB-TACE group, n = 66) at the Affiliated Hospital of North Sichuan Medical College from January 2019 to December 2022. Based on the baseline data and laboratory indicators, propensity score weighting was used to reduce confounding bias. Modified response evaluation criteria in solid tumors (mRECIST) were used to evaluate clinical efficacy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the disease control rate (DCR), objective response rate (ORR) and adverse events (AEs). PFS was assessed using Kaplan‒Meier analysis and Cox proportional hazards models. The ORRs at 1 month (M1) after treatment in the 5-Fu-DEB-TACE group and 5-Fu-cTACE group were 90.9% and 76.9%, respectively (P = 0.029), while at this time, the DCRs were 93.9% in the 5-Fu-DEB-TACE group and 90.8% in the 5-Fu-cTACE group (P = 0.494). At 3 months (M3) after treatment, the 5-Fu-DEB-TACE group had a higher ORR (84.8% vs. 56.9%, P < 0.001) and DCR (84.8% vs. 72.3%, P = 0.08). The ORR at 6 months (M6) was also higher in the 5-Fu-DEB-TACE group than in the 5-Fu-cTACE group (72.7% vs. 50.8%, P = 0.01). The median PFS after treatment with 5-Fu-DEB-TACE was longer than that after treatment with 5-Fu-cTACE (11 months vs. 6 months) (P = 0.004). Cox proportional hazards regression analysis indicated that 5-Fu-DEB-TACE (HR = 0.590, P = 0.044), Model for End-Stage Liver Disease (MELD) intermediate risk (HR = 2.470, P = 0.010), BCLC stage B (HR = 2.303, P = 0.036), BCLC stage C (HR = 3.354, P = 0.002) and ascitic fluid (HR = 2.004, P = 0.046) were independent predictors of PFS. No treatment-related deaths occurred in this study. The 5-Fu-DEB-TACE group had a greater incidence of abdominal pain (72.7% vs. 47.7%, P = 0.003). However, the incidence of postoperative elevated transaminase levels was higher in the 5-Fu-cTACE group (83.1% vs. 66.6%, P = 0.031). Subgroups analysis showed patients receiving 5-Fu-DEB-TACE have better PFS compared to those receiving 5-Fu-cTACE in the BCLC stage A group (P = 0.0093), BCLC stage B group (P = 0.0096), multifocal group (P = 0.0056), Child-Pugh stage A group (P<0.001), non- extrahepatic metastasis group (P = 0.022), non-vascular invasion group (P = 0.0093), and the group with a largest tumor diameter ≥ 5 cm (P = 0.0048). At M1, M3, and M6, patients with preserved liver function and in some cases of low tumor burden had higher Objective Response Rate (ORR) and Disease Control Rate (DCR) (P < 0.05). Compared with 5-Fu-cTACE, 5-Fu-DEB-TACE has superior therapeutic efficacy, prolongs PFS, and reduces hepatotoxicity. However, it is associated with an increased incidence of postoperative abdominal pain.

Outpatient intensive nutrition therapy improves survival and frailty in males with Alcohol related ACLF - Randomised controlled trial

Background and AimsImprovement in the nutritional status of Acute on Chronic Liver Failure(ACLF) patients may lead to reduction in morbidity and mortality. This study assessed the impact of dietician supported outpatient intensive nutrition therapy(OINT) on survival and frailty in patients with alcohol related ACLF Methods70 patients with alcohol related ACLF(Asia Pacific Association for the Study of the Liver, APASL-criteria) and frailty were randomized 1:1 to receive standard medical therapy(SMT) plus OINT(intervention) versus SMT(control) alone. The primary outcome was an improvement in survival at 3 months. Secondary outcome measures included improvement in frailty, prognostic scores and hospitalization. ResultsThere was a significant improvement in overall survival in the OINT group as compared to SMT after 3 months of follow up, 91.4% (Standard error (SE): 4.7%) vs. 57.1% (SE: 8.4%), P<.00). On cox regression model, inclusion in the intervention arm, baseline Skeletal Muscle Index(SMI), and Asia Pacific Association for the Study of the Liver ACLF Research Consortium(AARC score) were independent predictors of survival (P<.05). The Liver frailty index(LFI) score also significantly improved in the OINT as compared to SMT, Δ-0.93 -(0.71-1.13) vs. Δ -0.33 -(0.44-0.72)(P<.00). The disease severity including MELD, MELD-Na, and AARC score showed a significant improvement in the OINT group as compared to the SMT group(P<.05). The patients in OINT group had lesser number of hospitalizations 6(17%) versus 16(45.7%)(P=.01) as compared to SMT group. ConclusionOutpatient intensive nutrition therapy significantly improves survival, frailty and disease severity with a reduction in number of hospitalizations and supports the key role of nutrition in treatment of alcohol related ACLF patients.

Copaiba Oleoresin Improves Weight Gain and IL-10 Concentration, with No Impact on Hepatic Histology, in Liver Cirrhosis

Copaifera sp. is a native tree in the Amazon region. Copaiba oleoresin has components such as sesquiterpenes, which have anti-inflammatory and antioxidant potential. Liver cirrhosis is the end stage of liver disease with limited therapeutic options. We aimed to evaluate the effect of copaiba oleoresin supplementation on the liver of animals with thioacetamide (TAA)-induced cirrhosis. For the induction of liver cirrhosis, 100 mg/kg of TAA was administered intraperitoneally twice a week for 8 weeks. A total of 200 mg/kg/day of copaiba oleoresin was administered via gavage for the same period. Copaiba oleoresin supplementation improved cirrhosis-associated cachexia by increasing weight gain and body fat. In addition, copaiba oleoresin attenuated systemic inflammation, as shown by the decrease in the circulating C-reactive protein. In the liver, the copaiba oleoresin decreased carbonyl proteins and increased IL-10 compared with TAA-treated rats. TAA groups demonstrated increased SOD, catalase, GST, and GSH activity in the liver. In conclusion, the supplementation of copaiba oleoresin demonstrated a beneficial systemic effect in alleviating cirrhotic cachexia and antioxidant and anti-inflammatory action in the liver. However, it failed to improve the serological and histological markers of liver damage, which could be associated with the advanced stage of the disease.

An Analysis of the Influence of a Patient’s Sex on Quality of Life in Liver and Kidney Transplantation

Background: Renal and liver transplantation influences the quality of life of the patients who undergo these procedures. Therefore, the aim of the present study was to analyze possible differences in liver and kidney transplantation in relation to the patient’s sex and to determine their impact on quality of life. Methodology: An observational study was carried out with 147 patients with liver (n = 70) and kidney (n = 77) failure on the transplantation waiting list. The possible influence of sex on clinical, sociodemographic, and psychological aspects of the patients’ quality of life before and 6 months after transplantation was analyzed. Questionnaires on health-related quality of life (SF-36), the perception of social and family support (EASP), and coping strategies (CEA), the depression and anxiety scale (HAD), and the Eysenck personality inventory (EPI) were used. A univariate analysis was performed according to sex using statistical tools including the Chi-square test, the t-test, and a univariate linear analysis of variance. Results: In patients on the waiting list for liver transplantation, we found sex differences in terms of age (p = 0.040), time of evolution of end-stage liver disease (p = 0.013), etiology (p = 0.07), and associated complications, as well as in the consumption of tobacco and other psychotropic substances (p = 0.022), while patients on the waiting list for renal transplantation showed sex-related differences in terms of etiology (p = 0.012) and alcohol consumption (p = 0.005). The results showed significant sex-related differences in sociodemographic and psychological aspects, but no significant sex-related differences were observed in global quality of life in either of the two assessments in both groups. Discussion: The findings suggest that improvement in quality of life after liver or kidney transplantation is not influenced by the patient’s sex.

Benign biliary conditions with increased risk of malignant lesions.

Numerous conditions and pathologies affect the biliary system, many of which have underlying benign courses. However, these overall benign conditions can predispose the patient to malignant pathologies, often due to malignancy arising from abnormal biliary ducts (such as with cholangiocarcinoma) or due to malignancy arising from end-stage liver disease caused by the biliary condition (such as with hepatocellular carcinoma). While these malignancies can at times be obvious, some pathologies can be very difficult to detect and distinguish from the underlying benign biliary etiology. This paper discusses various benign biliary pathologies, with discussion of epidemiology, imaging features, malignant potential, and treatment considerations, with the goal of educating radiologists and referring clinicians to the risk and appearance of hepatobiliary malignancies associated with benign biliary conditions.

Viscoelastic Hemostatic Testing as a Diagnostic Tool for Hypercoagulability in Liver Transplantation: A Narrative Review.

Liver transplantation is a complex surgical procedure in which various forms of coagulation dysfunction can occur, including perioperative hypercoagulability. The hemostasis balance in liver graft recipients with end-stage liver disease can shift to thrombosis or haemorrhage, depending on the associated risk factors and clinical conditions. Hypercoagulability can result in serious complications such as thromboembolism, which can affect the vessels of the newly transplanted liver graft. Standard coagulation tests (SCTs), such as prothrombin time and activated partial thromboplastin time (aPTT), have a poor ability to diagnose and monitor an early stage of hypercoagulability. Recent studies demonstrated that viscoelastic hemostatic elastic tests (VETs), such as rotational thromboelastometry (ROTEM) and thromboelastography (TEG), are promising alternative tools for diagnosing hypercoagulability disorders. VETs measure clotting and clot formation time, clot strength (maximum clot firmness), fibrin and platelet contribution to clot firmness, and fibrinolysis, which makes them more sensitive in identifying liver graft recipients at risk for thrombosis as compared with SCTs. However, developing evidence-based guidelines for the prophylaxis and treatment of hypercoagulability based on VET results is still needed.

Comparison of Different Prognostic Scoring Systems in Predicting the Severity and Outcome in Alcoholic Hepatitis in Indian Patients

Abstract Introduction: Alcohol abuse causes a variety of liver diseases including alcoholic steatosis, alcoholic hepatitis (AH), liver fibrosis, cirrhosis, and hepatocellular carcinoma. AH is a clinical syndrome which typically occurs after the harmful use of alcohol. There are mild forms that are likely to improve with conservative management, whereas severe cases are associated with a high mortality rate and have a high risk of death despite treatment. The identification of severe AH is important, as this can be associated with 30%–50% short-term mortality. Existing prognostic scores have been validated in the western population, and the data of application in the Indian population are scant. Materials and Methods: It is a prospective observational study conducted for 2 years at Tertiary Care Hospital Army Hospital (Research and Referral) Delhi. The sample size was kept to be 45. For each patient, clinical and laboratory values were obtained on the day of admission and used to calculate the prognostic models according to their formulas. The various scores – Maddrey’s discriminant function (mDF), Glasgow AH score (GAHS), age, bilirubin, international normalized ratio (INR), creatinine score, and model of end-stage liver disease (MELD) including its modification MELD-sodium were calculated. For patients started on steroids, early changes in bilirubin level and Lille score were calculated. Results: All the prognostic scores were found to be good predictors of mortality. When compared with each other, MELD was most indicative of mortality with maximum area under the receiver operating characteristic curve. All the scores were significantly higher in the nonsurvivors than the survivors (P &lt; 0.0001). Conclusion: AH is a clinical syndrome that occurs after the harmful use of alcohol and confers a high mortality. Effective treatment and support for patients with AH is dependent on a proper assessment of the disease severity and estimation of the risk of death as early in the course of the disease as possible.

Revisiting the Prognostic Influences of Donor-Recipient Size Mismatch in Deceased Donor Liver Transplantation.

Liver transplantation (LT) outcomes are influenced by donor-recipient size mismatch. This study re-evaluated the impact on graft size discrepancies on survival outcomes. Data from 53 389 adult LT recipients from the United Network for Organ Sharing database (2013-2022) were reviewed. The study population was divided by the body surface area index (BSAi), defined as the ratio of donor body surface area (BSA) to recipient BSA, into small-for-size (BSAi < 0.78), normal-for-size (BSAi 0.78-1.24), and large-for-size (BSAi > 1.24) grafts in deceased donor LT (SFSD, NFSD, and LFSD). Multivariate Cox regression and Kaplan-Meier survival analyses were conducted. The frequency of size mismatch in deceased donor LT increased over the past 10 y. SFSD had significantly worse 90-d graft survival (P < 0.01), and LFSD had inferior 1-y graft survival among 90-d survivors (P = 0.01). SFSD was hazardous within 90 d post-LT because of vascular complications. Beyond 1 y, graft size did not affect graft survival. LFSD risk within the first year was mitigated with lower model for end-stage liver disease (MELD) 3.0 scores (<35) or shorter cold ischemia time (<8 h). The negative impacts on donor-recipient size mismatch on survival outcomes are confined to the first year post-LT. SFSD is associated with a slight decrease in 90-d survival rates. LFSD should be utilized more frequently by minimizing cold ischemia time to <8 h, particularly in patients with MELD 3.0 scores below 35. These findings could improve donor-recipient matching and enhance LT outcomes.

Early Prediction of Acute Kidney Injury in Living Donor Liver Transplantation by Serum Cystatin C Concentration at the End of the Surgery.

Acute kidney injury (AKI) is a prevalent complication of liver transplantation, leading to prolonged hospital or intensive care unit stay and significant morbidity. Recently, biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C have been investigated for their potential role in the early detection of AKI in liver transplantation patients. Our study comprised 60 patients with end-stage liver disease undergoing living donor liver transplantation. Based on the postoperative development of AKI, the patients were categorised into two groups: the AKI group comprising 22 patients and the non-AKI group comprising 38 patients. Serum cystatin C and urine NGAL levels were measured twice: immediately after induction of anaesthesia (baseline) and at the end of the surgery. The overall incidence of AKI was 36.66%. The mean cystatin C level measured at the end of the surgery was significantly higher in the AKI group (1.12 ± 0.40 mg/L) than in the non-AKI group (0.82 ± 0.27 mg/L) [P = .001]. The receiver operating characteristic curve for the postoperative cystatin C biomarker demonstrated a significant difference between the AKI and non-AKI groups [area under the curve: 0.71, P = .007]. However, baseline cystatin C and urine NGAL levels did not significantly differ between the groups. Cystatin C levels measured at the end of the surgery showed a better predictive value and higher accuracy in identifying post-liver transplantation patients with AKI than baseline cystatin C and urine NGAL.