End-stage Liver Disease Research Articles

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.

Liver Status Assessment After Coronary Artery Bypass Grafting.

Background Coronary artery bypass grafting (CABG) is a common surgical intervention used to treat severe coronary artery disease. The Model for End-Stage Liver Disease (MELD) score has become a widely used prognostic index for assessing the severity of liver disease and prioritizing liver transplantation. However, its utility in predicting outcomes in cardiac surgery procedures has not been extensively evaluated. Methods This retrospective study gathered data on patients who underwent CABG or CABG combined with other concomitant surgical interventions, such as carotid common or external carotid artery endarterectomy, thoracic aortic aneurysm repair, and aortic or mitral valve replacement or decalcification procedures, at a single tertiary care facility from January 2011 to December 2020. Researchers collected demographic, clinical, and laboratory information, including MELD score and European System for Cardiac Operative Risk Evaluation (EuroSCORE) data. The patients were divided into two groups: the first group included only those who underwent CABG, while the second group comprised patients who underwent CABG along with other concomitant cardiac interventions. Results The MELD score at discharge was significantly higher in the CABG and other interventions group compared to the CABG-only group (median = 14.09, IQR = 7.41-18.7 vs. median = 6.41, IQR = 4.61-9.44, p < 0.001). However, the difference in MELD score at admission between the two groups was not statistically significant (p = 0.328). A p-value < 0.05 was considered statistically relevant, indicating that liver function worsened postoperatively in the patients with additional interventions. The EuroSCORE was also significantly higher in the CABG and other interventions group, suggesting a higher surgical risk as expected (median = 5.74, IQR = 3.54-11.47 vs. median = 3.34, IQR = 1.97-5.66, p < 0.001). Additionally, differences in laboratory parameters, especially coagulation and hemostasis indicators throughout the postoperative period, including the ICU stay (divided into four equal periods based on each patient's total ICU length of stay) and at discharge, indicate a more complex biological state in patients with additional interventions. These findings may have implications for perioperative management and long-term outcomes. Conclusions The elevated MELD score in patients undergoing CABG with additional interventions emphasizes the need for close monitoring of liver function and coagulation status. Evaluating hepatic status preoperatively would be beneficial, and incorporating liver-protective strategies could help mitigate postoperative repercussions. It may also be useful to include liver function parameters in existing cardiovascular risk scores to improve risk assessment.

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.

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. 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. 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. 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.

Clinical characteristics of ABCB4 gene variant-associated cholestatic liver disease in adults

Objective: To investigate the clinical manifestations, pathological, and gene mutation characteristics of ABCB4 gene variant-associated cholestatic liver disease in adults. Methods: Eight adult cases of ABCB4 gene variant-associated cholestatic liver disease who were hospitalized in the Department of Hepatology, Fifth Medical Center of the People's Liberation Army General Hospital from May 2010 to December 2022 were enrolled in this study. The clinical manifestations, pathological features, gene variant features, and prognostic conditions were analyzed. Patient gene testing and biological information analysis were performed using whole-exome next-generation sequencing. SPSS 19.0 software was used to conduct descriptive analysis. Results: Among the eight adult cases of the ABCB4 gene variant, there were three males and five females, with a median age of onset of 24 (20, 37) years. There were three cases with a compound heterozygous variant in ABCB4, and the clinical phenotypes included two cases of progressive familial intrahepatic cholestasis type 3 and one case of intrahepatic cholestasis of pregnancy overlapping with low-phospholipid-associated cholelithiasis syndrome. There were five cases with a single heterozygous variant in ABCB4, and the clinical phenotypes included two cases of intrahepatic cholestasis of pregnancy overlapping with drug-induced liver injury and three cases of low-phospholipid-associated cholelithiasis syndrome. Imaging of all eight cases showed liver fibrosis, and six cases already had cirrhosis. All patients underwent liver histopathological examination, which mainly showed cholestasis and portal fibrosis in eight cases, small bile duct hyperplasia in seven cases, copper deposition in three cases, and cirrhosis in five cases. ABCB4 screening revealed 11 different mutations, including eight new mutations. The pathogenicity assessment showed that c.2394+82C>T (intron) was a benign mutation, and the rest were deleterious mutations. Ursodeoxycholic acid was the treatment for all patients, with a follow-up time of 7.5 (0.5, 12.7) years. One case died of end-stage liver disease, two cases developed cholestatic cirrhosis, and five cases were in stable condition. Conclusion: The adult ABCB4 gene variant-associated cholestatic liver disease are mostly single heterozygous mutations, the clinical phenotypes are diverse and overlapping, the disease is more severe in those who carried non-functional mutations.

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.

Clinical characteristics and outcomes in middle-aged Fontan patients

BackgroundMiddle-aged Fontan patients are underrepresented in contemporary studies. The purpose of this study was to describe the clinical characteristics and outcomes in middle-aged patients with Fontan palliation. MethodsAll adults with Fontan palliation were divided into ‘middle-aged’ group (>40 years of age at baseline encounter), and ‘young adult’ group. Clinical characteristics were assessed across multiple domains (atrial arrhythmias, heart failure, and hepatorenal function). Clinical outcomes were assessed as composite outcome of death/heart transplant. ResultsOf 455 adults (median age 26 years), 63 (14 %) were middle-aged adults while 392 (86 %) were young adults. Compared to the young adult group, the middle-aged group had a higher prevalence of atrial arrhythmias, greater neurohormonal activation, and worse hepatorenal function. Of 63 patients in the middle-aged group, 26 (41 %) patients died, and 4 (6 %) patients underwent heart transplant. The middle-aged group had a higher 5-year cumulative incidence of death/transplant (45 % versus 21 %, p < 0.001), and 10-year cumulative incidence of death/transplant (64 % versus 29 %, p < 0.001) compared to the young adult group. Higher pulmonary artery wedge pressure (hazard ratio 1.18 [1.09–1.27]), and higher model for end-stage liver disease excluding international normalized ratio score (hazard ratio 1.07, [1.03–1.14]), were associated with death/transplant. ConclusionsAbout 14 % of adults with Fontan palliation were middle-aged, and these patients had higher prevalence of cardiovascular comorbidities, hepatorenal dysfunction, and mortality. These data underscore the need for better risk stratification strategies to identify patients at risk for adverse outcomes and allow for early referral for transplant evaluation in this emerging subpopulation. Clinical summaryThe purpose of this study was to describe the clinical characteristics (comorbidities and end-organ dysfunction) and outcomes (death/transplant) in middle-aged patients with Fontan palliation. Of 455 patients (median age 26 years), 63 (14 %) were middle-aged adults while 392 (86 %) were young adults. Compared to the young adult group, the middle-aged group had a higher prevalence of atrial arrhythmias, greater neurohormonal activation, worse hepatorenal function, and higher risk of death/transplant. The correlates of death/transplant were higher pulmonary artery wedge pressure and hepatorenal dysfunction. These data underscore the need for better risk stratification in this emerging population.

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.

Perioperative and Long-Term Outcomes After Combined Liver and Kidney Transplantation: A Single-Center Experience.

Combined liver-kidney transplantation (CLKT) has evolved as a therapeutic option for patients with concurrent end-stage liver and renal diseases. This study evaluates the perioperative and long-term outcomes of CLKT at a single center in Slovenia, highlighting the challenges and successes of simultaneous organ transplantation. We retrospectively analyzed all patients undergoing simultaneous CLKT at the University Medical Centre Ljubljana from April 2014 to June 2023. Data on demographics, cause of liver and kidney disease, operative details, postoperative complications, patient and graft survival, and follow-up were collected and analyzed. Five patients aged 27 to 60 years underwent CLKT within the study period. All transplants involved deceased donors with whole-liver grafts. Indications for CLKT were polycystic liver disease (n = 3), Caroli's disease (n = 1), and alcoholic cirrhosis (n = 1). The mean follow-up duration was 45.2 months, with a 100% survival rate. The incidence of surgical and postoperative complications was low. This pioneering series of simultaneous CLKTs in Slovenia demonstrates the feasibility and effectiveness of the procedure in smaller transplant centers. Despite challenges, including T cell-mediated kidney rejection and surgical complications, the study emphasizes the importance of comprehensive postoperative care and management in optimizing outcomes for CLKT recipients.

Key genes and immune pathways in T-cell mediated rejection post-liver transplantation identified via integrated RNA-seq and machine learning

Liver transplantation is the definitive treatment for end-stage liver disease, yet T-cell mediated rejection (TCMR) remains a major challenge. This study aims to identify key genes associated with TCMR and their potential biological processes and mechanisms. The GSE145780 dataset was subjected to differential expression analysis, weighted gene co-expression network analysis (WGCNA), and machine learning algorithms to pinpoint key genes associated with TCMR. Gene Set Enrichment Analysis (GSEA), immune infiltration analysis, and regulatory networks were constructed to ascertain the biological relevance of these genes. Expression validation was performed using single-cell RNA-seq (scRNA-seq) data and liver biopsy tissues from patients. We identified 5 key genes (ITGB2, FCER1G, IL-18, GBP1, and CD53) that are associated with immunological functions, such as chemotactic activity, antigen processing, and T cell differentiation. GSEA highlighted enrichment in chemokine signaling and antigen presentation pathways. A lncRNA-miRNA-mRNA network was delineated, and drug target prediction yielded 26 potential drugs. Evaluation of expression levels in non-rejection (NR) and TCMR groups exhibited significant disparities in T cells and myeloid cells. Tissue analyses from patients corroborated the upregulation of GBP1, IL-18, CD53, and FCER1G in TCMR cases. Through comprehensive analysis, this research has identified 4 genes intimately connected with TCMR following liver transplantation, shedding light on the underlying immune activation pathways and suggesting putative targets for therapeutic intervention.

Spot Urine Sodium to Potassium Ratio as a Tool to Assess Severity and Mortality among Patients with Decompensated Cirrhosis having Ascites

Background: Decompensated cirrhosis of liver is considered as a systemic disease affecting the functions of several other organs. Renal function is an independent prognostic factor for patients with decompensated cirrhosis, but assessing renal function through glomerular filtration rate are not convenient, especially for routine use. Previous study found that spot urinary sodium to potassium ratio (UNa/K) was associated with renal dysfunction which influences the severity and outcome in decompensated cirrhosis of liver patients having ascites. Aims and objectives: The present study was aimed to determine the relation of the ratio of sodium to potassium in randomly collected urine samples with severity of disease and mortality in decompensated cirrhosis having ascites. Materials and Methods: This longitudinal study was conducted at the Department of Gastrointestinal, Hepatobiliary and Pancreatic Disorders, BIRDEM General Hospital, Shahbagh, Dhaka, Bangladesh, from July, 2019 to August, 202l. A total of 150 patients with a confirmed diagnosis of decompensated cirrhosis with ascites were enrolled in this study. A detailed history and thorough clinical examination were carried out in each patient, along with relevant investigations. Data collection was done through a structured questionnaire. Data were analyzed using the statistical software SPSS 23. Results: Age of the patients was 59.0±12.91 (mean±SD) years, male predominance was observed (52%). The UNa/K ratio was 4.24±3.25 (mean±SD) with a range of 0.42 to 18.46. Diagnostic accuracy of UNa/K ratio in the detection of severity and mortality was estimated by the receiver operating characteristic (ROC) curve. The AUC of UNa/K ratio was 0.608 and 0.640 for severity and mortality respectively. Sensitivity, specificity, PPV and NPV at cut-off 2.55 were 50.0, 66.0, 42.4 and 72.5; at 2.65 were 54.0, 66.0, 44.3, and 74.2; at 2.87 were 58.0, 62.0, 43.3, and 74.7; at 3.21 were 58.0, 58.0, 40.8, and 73.4 respectively for severity score (MELD). Patients with UNa+/K+ less than 2.87 or equal, had a significantly higher MELD score category (p= 0.02). At 3 months follow-up, 24.7% mortality was observed. Sensitivity, specificity, PPV and NPV at cut-off 1.62 were 51.4, 85.8, 54.3 and 84.3; at 1.79 were 54.1, 79.7, 46.5 and 84.1; at 1.83 were 59.5, 77.0, 45.8 and 85.3; at 2.87 were 58.0, 62.0, 43.3, and 74.7 respectively for mortality. The UNa/K ratio was statistically low among the patients who didn’t survive (p&lt;.05). Conclusion: This study revealed that decreased ratio of spot urinary sodium to potassium was associated with the severity and mortality among decompensated cirrhosis of liver patients with ascites. Bangladesh Crit Care J September 2024; 12 (2): 118-124

Hepatitis B Virus Increases SphK1-S1P Synthesis by Promoting the Availability of the Transcription Factor USF1.

Hepatitis B virus (HBV) is the most common chronic viral infection globally, affecting ∼360 million people and causing about 1 million deaths annually due to end-stage liver disease or hepatocellular carcinoma. Current antiviral treatments rarely achieve a functional cure for chronic hepatitis B, highlighting the need for improved monitoring and intervention strategies. This study explores the role of the sphingosine kinase 1 (SphK1)-sphingosine-1-phosphate (S1P) axis in HBV-related liver injury. We investigated the association between serum S1P concentration and HBV DNA levels in chronic hepatitis B patients, finding a significant positive correlation. Additionally, SphK1 was elevated in liver tissues of HBV-positive hepatocellular carcinoma patients, particularly in HBsAg-positive regions. HBV infection models in HepG2-sodium taurocholate cotransporting polypeptide cells confirmed that HBV enhances SphK1 expression and S1P production. Inhibition of HBV replication through antiviral agents and the CRISPR-Cas9 system reduced SphK1 and S1P levels. Further, we identified the transcription factor USF1 as a key regulator of SphK1 expression during HBV infection. USF1 binds to the SphK1 promoter, increasing its transcriptional activity, and is upregulated in response to HBV infection. In vivo studies in mice demonstrated that HBV exposure promotes the expression of USF1 and SphK1-S1P. These findings suggest that the SphK1-S1P axis, regulated by HBV-induced USF1, could serve as a potential biomarker and therapeutic target for HBV-related liver injury.

Liver transplantation for critically ill patients with acute on chronic liver failure: a prospective national programme of waitlist prioritisation

Acute on Chronic Liver Failure (ACLF) complicates chronic liver disease (CLD) combining rapidly progressive hepatic with extra-hepatic multiple organ failure and high short-term mortality. Effective therapeutic options are very limited, and liver transplantation (LT) seldom utilised through concerns of high recipient mortality and resource use. Retrospective reports suggest recent outcomes may have improved, but use of LT for ACLF has not been prospectively assessed. A prospective programme of prioritised liver graft allocation for selected recipients with ACLF through registration on a new national tier, initiated in May 2021 in all 7 United Kingdom LT centres. Candidates were selected by centre multidisciplinary teams, with inclusion criteria mandating cirrhotic CLD with ACLF requiring critical care (CC) organ support and expected 1-month mortality >50%. Exclusion criteria included age ≥60 years, previous LT, comorbidity or substance misuse profile precluding elective LT. A pilot 50 registrations were planned, with pre-specified futility criteria of a 1-year post-LT survival of 60%. Fifty-two patients were registered on the ACLF tier, median (IQR) age 46 (39-52) years, ACLF grade 3 (3-3) and Model for End-stage Liver Disease (MELD) 39 (35-40). At registration 32 (62%) required mechanical ventilation, 44 (85%) vasopressors and 46 (89%) renal replacement. Forty-two (81%) underwent LT 2 (2-5) days after registration: 10 (19%) did not. All non-transplanted died at median 7 (4-13) days after registration (p<0.0001 vs. LT). Post-LT follow-up was 212 (119-530) days and patient survival 81% (95% CI 66-91): 28-, 90-day and 1-year survival after registration 93%, 86% and 77%. Median length of CC and hospital stay in LT recipients was 16 (8-28) and 35 (23-54) days respectively. We report the first prospective national series of prioritised liver transplantation for critically ill patients with ACLF. For selected recipients LT is a practical and highly effective treatment option where no other similarly effective interventions exist. There was no funding for the study.

Robust Predictive Performance of the SALT-M Score for Clinical Outcomes in Asian Patients With Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is a syndrome of patients with chronic liver disease presenting with multiple organ failures. Recently, Sundaram-ACLF-LT Mortality (SALT-M) score has been developed to predict 1-year post-liver transplantation mortality. We validated the SALT-M score in a large-volume, Asian single-centre cohort. We validated the SALT-M score in a large-volume, Asian single-centre cohort. We analysed 224 patients of ACLF grade 2-3. Area under the receiver operating characteristic curve (AUROC) and concordance index (c-index) were used to assess and compare the predictability of posttransplant mortality of SALT-M and other scores. Moreover, we compared the survivals of patients with high and low SALT-M, in conjunction with MELD score and ACLF grade. The AUROC for prediction of 1-year post-LT survival was higher in SALT-M (0.691) than in MELD, MELD-Na, MELD 3.0 and delta-MELD. Similarly, the c-index of the SALT-M (0.650) was higher than aforementioned MELD systems. When categorised by the cut-off of SALT-M ≥ 20 and MELD ≥ 30, patients with high SALT-M exhibited lower post-LT survival than those with low SALT-M scores regardless of high or low MELD (40.0% for high SALT-M/high MELD vs. 42.9% for high SALT-M/low MELD vs. 73.8% for low SALT-M/high MELD vs. 63.7% for low SALT-M/low MELD, p < 0.001). In patients with ACLF grade 3, SALT-M effectively stratified the posttransplant mortality (39.4% for high SALT-M vs. 63.1% for low SALT-M, p = 0.018). SALT-M outperformed previous MELD systems for predicting posttransplant mortality in Asian LT cohort with severe ACLF. Transplantability for patients with severe ACLF could be determined based on SALT-M.