Model For End-stage Liver Disease Score Research Articles

Longitudinal analysis of liver transplant candidates for hepatocellular carcinoma in a single center.

Wailitst lost is an critical issue and we investigated the long-term effect of insufficient liver functional reserve at liver transplantation evaluation on waitlist outcomes in patients with hepatocellular carcinoma (HCC). Clinical data of patients with HCC waitlisted for liver transplantation were retrospectively collected from a single hospital cohort during the period from 2014 to 2021. Parameters of liver reserve, including cirrhosis, Child-Pugh grade, and Model for End-Stage Liver Disease (MELD) scores, were analyzed for patient survival, after adjustment for tumor factors. Of 292 eligible patients, 94.2% had cirrhosis, 55.8% had Child-Pugh grade B or C, and the median MELD score was 13.2. The median follow-up time was 2.2years, with a dropout rate of 62.7%. Eighty-nine candidates (30.5%) eventually received liver transplant, including 67 from live donors. The estimated 1-year mortality rate reached 40.6% in 203 patients who remained on the waitlist without receiving a transplant, of whom 143 died. Most deaths were attributed to liver failure (37.1%) and cancer death (35.7%). After we adjusted for tumor confounders, including alpha fetoprotein, primary HCC stage, tumor number at evaluation, and sequential cancer treatment before and while waiting, hazard ratios (HRs) for patient survival were 1.69 (95% confidence interval, 1.18-2.41) for cirrhotic stage B or C, 1.07 (1.04-1.10) for MELD scores, and 1.14 (1.04-1.25) for tumor size at transplant evaluation. Transplantation was a protective disease modifier with adjusted HR 0.22 (0.14-0.33). Insufficient liver functional reserve poses more risk than expected to liver transplant waitlist outcomes with HCC.

Is salvage Plug-Assisted Retrograde Transvenous Obliteration (PARTO) safe and effective for bleeding gastric varices ?- A preliminary single-center experience.

Vascular plug-assisted retrograde transvenous obliteration (PARTO) obliterates the gastric varices and portosystemic shunt, thus resulting in a lower rebleeding rate than endoscopic glue/sclerotherapy. To evaluate the safety and efficacy of PARTO as salvage therapy in liver cirrhosis with gastric variceal bleed (GVB) after failed endotherapy. We assessed the clinical success rate and changes in liver function at 6- months. Patients who underwent salvage PARTO after failed endotherapy for GVB (between December 2021 and November 2022) were searched and analyzed from the hospital database. Clinical success rate and rebleed rate were obtained at six months. Child-Pugh score (CTP) and Model for end-stage liver disease (MELD) score were calculated and compared between baseline and 6-month follow-up. Fourteen patients (n = 14, Child-Pugh class A/B) underwent salvage PARTO. Nine had GOV-2, and five had IGV-1 varices. The mean shunt diameter was 11.6 ± 1.6mm. The clinical success rate of PARTO was 100% (no recurrent gastric variceal hemorrhage within six months). No significant deterioration in CTP (6.79 ± 0.98 vs. 6.21 ± 1.52; p = 0.12) and MELD scores (11.5 ± 4.05 vs. 10.21 ± 3.19; p = 0.36) was noted at 6months. All patients were alive at 6months. One patient (n = 1, 7.1%) bled from esophageal varices after three days of PARTO and was managed with variceal banding. 21.4% (3/14) patients had progression of esophageal varices at 6months requiring prophylactic band ligation. Three patients (21.4%) had new onset or worsening ascites and responded to low-dose diuretics therapy. PARTO is a safe and effective procedure for bleeding gastric varices without any deterioration in liver function even after six months. Patient selection is critical to prevent complications. Further prospective studies with larger sample size are required to validate our findings.

Expansion of effector regulatory T cells in steroid-responders of severe alcohol-associated hepatitis

While steroid therapy is the preferred treatment for severe alcohol-associated hepatitis, the role of effector regulatory T (eTreg) cells and their association with steroid response and clinical outcomes in these patients remains to be elucidated. We prospectively enrolled 47consecutive patients with alcohol-associated hepatitis, consisting of severe alcohol-associated hepatitis treated with steroid (n=18; steroid-treated group) and mild alcohol-associated hepatitis (n=29; non-treated group). After isolating peripheral blood mononuclear cells (PBMCs) from the patients at enrollment and again 7 days later, eTreg cells frequency was examined using flow cytometry. Single-cell RNA sequencing analysis was conducted using paired PBMCs. In vitro experiments were also performed to assess phenotype changes and the suppressive function of Treg cells following steroid treatment. The steroid-treated group exhibited significantly higher Model for End-Stage Liver Disease (MELD) scores than the non-treated group ( P <0.01). Within the steroid-treated group, the proportion of eTreg cells significantly expanded in the steroid responders (n=13; P=0.01). Furthermore, a significant positive correlation was observed between the decrease in MELD score and the increase in eTreg cells ( P <0.05). Single-cell RNA sequencing using paired peripheral blood mononuclear cells (pre- and post-steroid therapy) from a steroid responder revealed gene expression changes in T cells and monocytes, suggesting enhancement of Treg cell function. In vitro results showed an elevation in eTreg cells proportion after steroid therapy. In conclusion, our findings suggest that the efficacy of steroid therapy in patients with severe alcohol-associated hepatitis is mediated by an increase in the number of eTreg cells.

From Patients to Providers: Assessing Impact of Normothermic Machine Perfusion on Liver Transplant Practices in the US.

Normothermic machine perfusion (NMP) of livers allows for the expansion of the donor pool and minimization of posttransplant complications. Results to date have focused on both donor and recipient outcomes, but there remains potential for NMP to also impact transplant providers. Using United Network for Organ Sharing Standard Transplant Analysis file data, adult deceased donors who underwent transplantation between January 1, 2016, and December 31, 2022, were identified. Transplanted livers were divided by preservation methods (static cold storage [SCS] and NMP) and case time (day-reperfusion 8 am to 6 pm ). Patient factors, transplant characteristics, and short-term outcomes were analyzed between Mahalanobis-metric-matched groups. NMP livers represented 742 (1.4%) of 52,132 transplants. NMP donors were more marginal with higher Donor Risk Index scores (1.78 ± 0.50 NMP vs 1.49 ± 0.38 SCS, p < 0.001) and donation after cardiac death frequency (36.9% vs 8.4%, p < 0.001). NMP recipients more often had model for end-stage liver disease (MELD) exception status (29.9% vs 23.4%, p < 0.001), lower laboratory MELD scores (20.7 ± 9.7 vs 24.3 ± 10.9, p < 0.001), and had been waitlisted longer (111.5 [21.0 to 307.0] vs 60.0 [9.0 to 245.0] days, p < 0.001). One-year graft survival (90.2% vs 91.6%, p = 0.505) was similar between groups, whereas length of stay was lower for NMP recipients (8.0 [6.0 to 14.0] vs 10.0 [6.0 to 16.0], p = 0.017) after adjusting for confounders. Notably, peak case volume occurred at 11 am with NMP livers (vs 9 pm with SCS). Overall, a higher proportion of transplants was performed during daytime hours with NMP (51.5% vs 43.0%, p < 0.001). NMP results in increased use of marginal allografts, which facilitated transplantation in lower laboratory MELD recipients who have been waitlisted longer and often have exception points. Importantly, NMP also appeared to shift peak caseloads from nighttime to daytime, which may have significant effects on the quality of life for the entire liver transplant team.

Appraisal of a newly developed ALBI-sarcopenia score as a prognostic marker in patients with hepatocellular carcinoma

Objective This study aimed to evaluate the impact of the combined Albumin–bilirubin (ALBI)/sarcopenia score as a newly developed prognostic model for hepatocellular carcinoma (HCC), with a focus on its utility in predicting mortality. Methods This prospective study was conducted on HCC patients who were followed for 1 year or until death. Sarcopenia was assessed radiologically by computed tomography at the level of L3. The study consisted of two sets: a development set in which the new ALBI-sarcopenia score was created, comprising 262 HCC patients, followed by an internal validation set with 100 patients. Results The development cohort primarily included males (69.5%), aged 59.6 ± 8.09 years. In patients with sarcopenia, the ALBI score was −2.03 ± 0.42 (P &lt; 0.006), the model for end-stage liver disease (MELD) score was 11.29 ± 2.43 (P &lt; 0.001*), and the MELD-sarcopenia score was 21.29 ± 2.43 (P &lt; 0.001*). The distribution of barcelona clinic liver cancer (BCLC) staging was as follows: BCLC A 18 (15.9%), BCLC B 63 (55.8%) and BCLC C 32 (28.3%) (P &lt; 0.001*), with a notable association with higher mortality (P &lt; 0.001). Multivariate analysis identified sarcopenia and ALBI scores as independent predictors of mortality in HCC (P &lt; 0.001*). In the development set, the ALBI-sarcopenia score successfully predicted mortality at a cutoff &gt;−11 with an area under a curve of 0.837 (95% CI, 0.784–0.889), while in the validation set, it predicted mortality at a cutoff &gt;−11.55 with an area under a curve of 0.842 (95% CI, 0.753–0.930). Conclusion The newly introduced ALBI-sarcopenia score has demonstrated superior effectiveness in comparison to MELD-sarcopenia score, overcoming the shortcomings associated MELD score in forecasting outcomes for patients with HCC.

Longitudinal changes in bone mineral density may be associated with long-term survival in patients with cirrhosis: A proof of concept of study.

The impact of longitudinal changes in different body components measured via body composition analysis (BCA) on liver-related outcomes in patients with cirrhosis is poorly understood. We evaluated the prognostic relevance of longitudinal changes in body composition over one year in patients with cirrhosis. This was a follow-up study of a randomized controlled trial evaluating changes in bone density measured via dual energy X-ray absorptiometry (DEXA) upon vitamin D supplementation. Patients with available anthropometric indices, fat mass (FM), fat-free mass (FFM), bone-density at lumbar spine (LD) and left femur-neck (FD) (assessed by T score) at two time points one year apart were assessed for outcomes. The prognostic relevance of change in parameters such as ΔFM, ΔFFM, ΔLD and ΔFD over one year was assessed and compared with baseline model for end-stage liver disease (MELD) score. Patients with cirrhosis (n=112) (mean age 41.8±12 years, 58.5% males) were followed up for median duration of 5.7 years interquartile range [IQR 3.5-5.7], with five-year survival rate of 77%. On serial BCA, ΔLD (p=0.029) and ΔFD (p=0.003) emerged as significant predictors of survival, whereas ΔFM (p=0.479), ΔFFM (p=0.245) and ΔBMI (p=0.949) were not. The area under curve of ΔLD and MELD score for predicting survival was 0.636 (0.5-0.773) and 0.664 (0.555-0.773), respectively. ΔFD<0.1 over one year had sensitivity and specificity of 70.4% and 56.5% to predict poor survival. The combination of ΔFD, MELD and ascites predicted five-year survival with an optimism-corrected c-statistic of 0.785. Among body composition parameters, changes in bone mineral density correlate best with survival and have prognostic relevance similar to that of ascites and MELD score.

Improvement in Thrombocytopenia after Direct Acting Anti-Viral (DAA)Therapy in Patients with Hepatitis C Virus-Related Chronic Liver Disease in Pakistani Population-A Single Centered Study

Background: Hepatitis C Virus (HCV) infection remains a significant global health challenge, often leading to chronic liver diseases such as cirrhosis and associated complications like thrombocytopenia. Directly acting antivirals (DAAs) have revolutionized HCV treatment due to their high efficacy and favorable safety profiles but the impact on thrombocytopenia, particularly in the Pakistani population, has been less studied. Objective: This study aimed to evaluate the effects of DAA therapy on platelet count and other laboratory parameters in chronic HCV patients with thrombocytopenia in Pakistan and to establish correlations between treatment outcomes and baseline laboratory values. Methods: A retrospective observational study was conducted at the Sindh Institute of Urology and Transplantation from January 2018 to December 2022. Patients with chronic HCV genotype 3a infection, compensated cirrhosis, and a baseline platelet count of less than 150 × 10^9/L were included. Exclusion criteria encompassed decompensated liver disease, liver cancer, and other specific conditions. The treatment regimens were Sofosbuvir plus Daclatasvir or Velpatasvir plus Ribavirin over three months. Parameters such as complete blood counts, serum creatinine, liver enzymes, and Child-Turcotte-Pugh (CTP) and Model for End-Stage Liver Disease (MELD) scores were recorded at baseline and post-treatment. Statistical analysis was performed using SPSS version 25, employing paired t-tests and Pearson correlation coefficients. Results: A total of 195 patients were studied, with a mean baseline platelet count of 100.7 × 10^9/L, which significantly increased to 122.2 × 10^9/L post-treatment (p &lt; 0.001). Improvements were also noted in mean serum creatinine (0.96 mg/dL to 0.87 mg/dL; p = 0.009), total bilirubin (1.6 mg/dL to 1.2 mg/dL; p &lt; 0.001), liver enzymes (ALT from 63.9 IU to 45.9 IU; p &lt; 0.001 and AST from 86.8 IU to 59.5 IU; p &lt; 0.001), and MELD scores (11.5 to 9.3; p &lt; 0.001). Hemoglobin levels and total leukocyte counts also showed significant improvements. Conclusion: DAA therapy significantly improves platelet counts and other laboratory parameters in chronic HCV patients with thrombocytopenia, suggesting a positive impact on liver function and patient management. This study highlights the importance of DAAs in the therapeutic regimen for HCV in the Pakistani population, contributing to better clinical outcomes and healthcare practices.

Bayesian network-based survival prediction model for patients having undergone post-transjugular intrahepatic portosystemic shunt for portal hypertension.

Portal hypertension (PHT), primarily induced by cirrhosis, manifests severe symptoms impacting patient survival. Although transjugular intrahepatic portosystemic shunt (TIPS) is a critical intervention for managing PHT, it carries risks like hepatic encephalopathy, thus affecting patient survival prognosis. To our knowledge, existing prognostic models for post-TIPS survival in patients with PHT fail to account for the interplay among and collective impact of various prognostic factors on outcomes. Consequently, the development of an innovative modeling approach is essential to address this limitation. To develop and validate a Bayesian network (BN)-based survival prediction model for patients with cirrhosis-induced PHT having undergone TIPS. The clinical data of 393 patients with cirrhosis-induced PHT who underwent TIPS surgery at the Second Affiliated Hospital of Chongqing Medical University between January 2015 and May 2022 were retrospectively analyzed. Variables were selected using Cox and least absolute shrinkage and selection operator regression methods, and a BN-based model was established and evaluated to predict survival in patients having undergone TIPS surgery for PHT. Variable selection revealed the following as key factors impacting survival: age, ascites, hypertension, indications for TIPS, postoperative portal vein pressure (post-PVP), aspartate aminotransferase, alkaline phosphatase, total bilirubin, prealbumin, the Child-Pugh grade, and the model for end-stage liver disease (MELD) score. Based on the above-mentioned variables, a BN-based 2-year survival prognostic prediction model was constructed, which identified the following factors to be directly linked to the survival time: age, ascites, indications for TIPS, concurrent hypertension, post-PVP, the Child-Pugh grade, and the MELD score. The Bayesian information criterion was 3589.04, and 10-fold cross-validation indicated an average log-likelihood loss of 5.55 with a standard deviation of 0.16. The model's accuracy, precision, recall, and F1 score were 0.90, 0.92, 0.97, and 0.95 respectively, with the area under the receiver operating characteristic curve being 0.72. This study successfully developed a BN-based survival prediction model with good predictive capabilities. It offers valuable insights for treatment strategies and prognostic evaluations in patients having undergone TIPS surgery for PHT.

Direct-Acting Antiviral Therapy for Patients with Chronic Hepatitis C Infection and Decompensated Cirrhosis.

Patients with chronic hepatitis C virus (HCV) infection and decompensated cirrhosis are an important population for antiviral therapy yet under-represented in clinical trials. HCV direct-acting antiviral (DAA) therapies, unlike interferon-containing regimens, can be safely utilized in decompensated patients. Per guidelines from the American Association for the Study of Liver Diseases (AASLD), therapy of choice in HCV and decompensated cirrhosis is sofosbuvir, an HCV polymerase inhibitor, combined with a replication complex inhibitor (NS5A inhibitor) with or without ribavirin. Combination therapy with a HCV protease inhibitor and an NS5A inhibitor is effective in this population but is specifically not recommended in AASLD guidelines due to safety concerns. Important risk factors for further decompensation during DAA therapy are serum albumin < 3.5g/dL, MELD (Model for End-Stage Liver Disease) score > 14, or HCV genotype 3 infection. Although sustained virologic response (SVR) is achieved less often in patients with decompensated vs compensated cirrhosis, in clinical studies response rates are > 80%. Both Child-Turcotte-Pugh Class at baseline and viral genotype can affect these response rates. Achieving SVR lowers risk of mortality, but to a lesser extent than in individuals with compensated cirrhosis. Likewise, treating patients for HCV infection along with successful treatment for hepatocellular carcinoma improves risks of both liver-related and overall mortality. In fewer than one third of cases, treating transplant-eligible, HCV-infected patients pre-transplant enables their delisting from transplant wait lists.

[The predictive value of dynamic changes of neutrophil/lymphocyte ratio (NLR) combined with the model of end-stage liver disease (MELD) score in patients with acute-on-chronic hepatitis B liver failure].

Objective: To determine the predictive value of dynamic changes of neutrophil/lymphocyte ratio (NLR) combined with the model of end-stage liver disease (MELD) score in patients with acute-on-chronic hepatitis B liver failure. Methods: Patients with acute-on-chronic hepatitis B liver failure who were hospitalized in the Department of Hepatology of Qilu Hospital of Shandong University from January 2010 to July 2023 were retrospectively enrolled. According to the clinical outcomes of patients within 30 days of admission, they were divided into the survival group and the death group. The dynamic changes in NLR and initial values on day 3, 5, 8, and 12 in two groups were analyzed for the diagnostic value of 30-day prognosis in patients with acute-on-chronic hepatitis B liver failure. Logistic regression analysis and machine learning XGBoost algorithm were used to evaluate the risk factors influencing the prognosis of patients at 30 days. Receiver operating characteristic(ROC) curve was used to evaluate the diagnostic value of NLR and initial value change combined with MELD score on day 12 of admission in patients with chronic acute hepatitis B liver failure. Results: A total of 243 patients were enrolled in the study, including 145 patients in the survival group [115 males, 30 females, aged 25-74 (47±11)] and 98 patients in the death group [80 males, 18 females, aged 22-80 (49±13) ]. The median initial NLR of survival group and death group were 3.5 (2.1, 5.3) and 4.9 (2.9, 8.3), respectively, and the difference was statistically significant (P=0.003). The variation of NLR from the initial value on day 3, 5, 8, and 12 in the survival group [1.6 (0, 4.3), 1.9 (-0.2, 4.1), 2.0 (-0.1, 4.3) and 2.9 (0.3, 7.0), respectively] were lower than that in the death group [3.2 (0.9, 7.5), 5.1 (1.8, 7.6), 5.8 (2.0, 10.6) and 9.6 (3.5, 16.4), respectively] (all P<0.001). Logistic regression multivariate analysis showed that the changes in NLR on the 12th day and initial value (OR=1.07,95%CI:1.01-1.14, P=0.014), the changes in NLR on the 3rd day and initial value (OR=2.71, 95%CI: 1.32-5.55, P=0.007), the initial value of NLR (OR=1.18,95%CI:1.01-1.37,P=0.035) and fibrinogen (OR=0.21,95%CI:0.05-0.96,P=0.044) were related factors for death within 30 days. Machine learning XGBoost algorithm showed that the weight of the change between the NLR on the 12th day and the initial value was the highest. The area under the ROC curve of the combined MELD score was 0.812 (95%CI: 0.728-0.895), the specificity was 67.78%, and the sensitivity was 82.35%. Conclusion: Dynamic change of NLR combined with MELD score has high predictive value for the short-term prognosis of patients with acute-on-chronic hepatitis B liver failure.

Cirrhosis and Portal Hypertension Worsen Bowel Preparation for Screening Colonoscopy.

Colonoscopy is a diagnostic and therapeutic procedure that reduces colorectal cancer incidence and mortality but requires adequate bowel cleansing for high-quality examination. Past studies have suggested cirrhosis as a risk factor for worse bowel preparation. We carried out a match-controlled retrospective study evaluating patients with and without cirrhosis who underwent outpatient screening colonoscopies to assess the effect of cirrhosis and portal hypertension complications on preparation quality and endoscopic measures. We also did a subgroup analysis excluding patients with obesity. We examined 1464 patients with cirrhosis and matched controls. Cirrhotic patients had lower mean Boston Bowel Preparation Scale (BBPS) scores and slower cecal intubation times. We found a single point increase in the Model for End-stage Liver Disease (MELD) score, as well as ascites, hepatic encephalopathy, and variceal hemorrhage were all associated with a longer cecal intubation time. Subgroup analysis excluding patients with obesity again found a significantly lower BBPS score and longer cecal intubation time while also finding a 24% drop in polyp detection. Patients with cirrhosis have worse BBPS scores and longer cecal intubation times. Nonobese cirrhotic patients additionally have a lower polyp detection rate. Portal hypertension complications were associated with worsened preparation quality and longer cecal intubation times. Each incremental increase in MELD score lengthened cecal intubation time. These findings support a more aggressive bowel preparation strategy for patients with cirrhosis, especially patients with severe disease or portal hypertension complications.

Comparison of Lymphocyte/Monocyte ratio (LMR) with Child-Pugh Score and MELD Score in the Determination of Hepatic Dysfunction Severity and Outcome in Cirrhotic Patient

Background: Lymphocyte/monocyte ratio (LMR) is a simple and effective marker that has the potential to predict the severity of hepatic dysfunction in a cirrhotic patient, like the Model for End-Stage Liver Disease (MELD) score and the Child- Pugh (CP) score. However, the usefulness of this newer tool has not yet been tested. Objectives: Comparison of Lymphocyte/Monocyte ratio with Child-Pugh Score and MELD Score in the determination of hepatic dysfunction severity in patients with cirrhosis was the objective of the study. Materials and Methods: This cross-sectional analytical study was conducted on cases of cirrhotic patients in the Department of Gastroenterology, Bangabandhu Sheikh Mujib Medical University, dated from September 2018 to August 2019. A total of 40 compensated cases and 82 decompensated cases were included in the process of obtaining informed written consent. Information about clinical profile, laboratory parameters (complete blood count including ESR, serum total bilirubin, serum albumin, ALT, AST, serum creatinine, prothrombin time, INR, etc.) were collected. LMR, MELD score, and CP score were calculated both in compensated and decompensated cirrhotic patients to assess the relationship with the severity of hepatic dysfunction. The correlation between LMR and the CP/MELD score was established by the Pearson correlation test. The receiver operating characteristic (ROC) curve and cut-off values of LMR were obtained, and areas under the ROC (AUROC) curve were calculated to identify the best LMR and/or the MELD score or CPS for predicting hepatic decompensation. The Bland-Altman plot and the Heliey- MacNeil test were used for comparison of measurement techniques. The data were analyzed with the help of SPSS version 20. Observation and Results: The mean age of the decompensated group was higher than that of the compensated group (p&lt;0.05). The mean values for LMR and MELD and CP scores were 7.93±3.08, 5.25±0.43 &amp; 7.10 ±1.19, respectively. Average LMR was significantly higher in compensated cirrhosis patients while CP and MELD Score was lower in that group (p&lt;0.001). MELD and CP were positively correlated with each other (p&lt;0.001). LMR was negatively correlated to both MELD and CP scores (p&lt;0.001). Of all patients, only 4 died (3.3%) and rest 118 (96.7%) survived. The cut off value of LMR, CP and MELD were LMR ≤ 2.18 (sensitivity: 75%, specificity: 87.3%), CPS ≥13.5 (sensitivity: 75%, specificity: 98.3%) &amp; MELD ≥30.5 (sensitivity: 75%, specificity: 94.9%) respectively. Pairwise comparison showed that the difference between the AUCs of MELD and LMR was not statistically significant (0.953 vs 0.887; p=0.081). Patients in the low LMR group showed decreased survival than those in the high LMR group (p=0.000). The no survived group had lower LMR and higher MELD and CP scores than those of the survived group (p&lt;0.001). Conclusion: In comparison with Child-Pugh Score and MELD Score in the determination of hepatic dysfunction severity in cirrhotic patients, Lymphocyte/ Monocyte ratio is a useful tool.

Controversies in terlipressin and transplantation in the United States: How do we MELD the two?

Hepatorenal syndrome-acute kidney injury (HRS-AKI) is a severe complication of cirrhosis that carries a poor prognosis. The recent Food and Drug Administration approval of terlipressin has substantial implications for managing HRS-AKI and liver allocation in the United States (US). Terlipressin has been available in Europe for over a decade, and several countries have adapted policy changes such as Model for End-Stage Liver Disease (MELD) score "lock" for HRS-AKI. In this article, we outline the European experience with terlipressin use and explore the question of whether terlipressin treatment for HRS-AKI should qualify for MELD score "lock" in the US in those who respond to therapy. Arguments for the MELD lock include protecting waitlist priority for terlipressin responders or partial responders who may miss offers due to MELD reduction in the terlipressin treatment window. Arguments against MELD lock include the fact that terlipressin may produce a durable response and improve overall survival, and that equitable access to terlipressin is not guaranteed due to cost and availability. We subsequently discuss proposed next steps for studying terlipressin implementation in the US. A successful approach will require the involvement of all major stakeholders and the mobilization of our transplant community to spearhead research in this area.

Hepatic arterial hemodynamics and model for end-stage liver disease (MELD) scores in chronic liver disease: insights from Doppler ultrasonography

BackgroundDoppler ultrasonography is essential to provide insights into hemodynamic alterations and liver function changes in pre-cirrhotic and cirrhotic patients. Utilizing Doppler examinations, this study aims to explore the correlation between hepatic arterial hemodynamics and Model for end-stage liver disease (MELD) scores in chronic liver disease patients.MethodsA study of 50 chronic liver disease patients included sonographic assessments, measuring liver, portal vein size, and flow. Hepatic artery velocity, resistive index (RI), pulsatility index (PI), and acceleration time (AT) were evaluated. Biochemical parameters (serum bilirubin, creatinine, INR) were used to calculate MELD scores, compared with different Doppler sonographic parameters.ResultsThe study found a mean peak systolic velocity (PSV) of 107.42 ± 48.10, with end-diastolic velocity (EDV) of 26.40 ± 14.68, RI of 0.74 ± 0.06, and PI of 1.47 ± 0.24. The mean MELD score was 19.28 ± 6.09. Correlations between MELD scores and PSV, EDV, RI, PI, and AT did not yield statistically significant correlations. 80% of subjects displayed high RI (> 0.7) values in the hepatic artery, and a significant correlation was found between portal vein thrombosis and hepatic artery PSV and RI (p < 0.05).ConclusionsHepatic artery RI and PSV show a significant correlation with portal vein thrombosis. Doppler ultrasonography, while not directly tied to MELD scores, is valuable for non-invasive liver disease monitoring when invasive methods are impractical. Further research is needed to unravel the relationships between hemodynamic changes, MELD scores, and clinical outcomes in a broader patient population.

Predictive Value of Serial Model of End-Stage Liver Disease Score Determination in Patients with Postcardiotomy Extracorporeal Membrane Oxygenation.

(1) Background: The use of extracorporeal membrane oxygenation (ECMO) in low cardiac output states after cardiac surgery may aid in patient recovery. However, in some patients, the clinical state may worsen, resulting in multiple organ failure and high mortality rates. In these circumstances, calculating a model of end-stage liver disease (MELD) score was shown to determine organ dysfunction and predicting mortality. (2) Methods: We evaluated whether serial MELD score determination increases mortality prediction in patients with postcardiotomy ECMO support. (3) Results: Statistically, a cutoff of a 2.5 MELD score increase within 48 h of ECMO initiation revealed an AUC of 0.722. Further, we found a significant association between hospital mortality and 48 h MELD increase (HR: 2.5, 95% CI: 1.33-4.75, p = 0.005) after adjustment for possible confounders. (4) Conclusions: Therefore, serial MELD score determinations on alternate days may be superior to single measurements in this special patient cohort.

A Novel Nomogram for Predicting Early Rebleeding After Endoscopic Treatment of Esophagogastric Variceal Hemorrhage.

Early rebleeding is a significant complication of endoscopic treatment for esophagogastric variceal hemorrhage (EGVH). However, a reliable predictive model is currently lacking. To identify risk factors for rebleeding within 6weeks and establish a nomogram for predicting early rebleeding after endoscopic treatment of EVGH. Demographic information, comorbidities, preoperative evaluation, endoscopic features, and laboratory tests were collected from 119 patients who were first endoscopic treatment for EGVH. Independent risk factors for early rebleeding were determined through least absolute shrinkage and selection operator logistic regression. The discrimination, calibration, and clinical utility of the nomogram were assessed and compared with the model for end-stage liver disease (MELD), Child-Pugh, and albumin-bilirubin (ALBI) scores using receiver-operating characteristic (ROC) curves, calibration plots, and decision curve analyses (DCA). Early rebleeding occurred in 39 patients (32.8%) within 6weeks after endoscopic treatment. Independent early rebleeding factors included gastric variceal hemorrhage (GVH), concomitant hepatocellular carcinoma (HCC), international normalized ratio (INR), and creatinine. The nomogram demonstrated exceptional calibration and discrimination capability. The area under the curve for the nomogram was 0.758 (95% CI 0.668-0.848), and it was validated at 0.71 through cross-validation and bootstrapping validation. The DCA and ROC curves demonstrated that the nomogram outperformed the MELD, Child-Pugh, and ALBI scores. Compared with existing prediction scores, the nomogram demonstrated superior discrimination, calibration, and clinical applicability for predicting rebleeding in patients with EGVH after endoscopic treatment. Therefore, it may assist clinicians in the early implementation of aggressive treatment and follow-up.

Neurofilament light chain but not glial fibrillary acidic protein is a potential biomarker of overt hepatic encephalopathy in patients with cirrhosis

Introduction and ObjectivesHepatic encephalopathy (HE) is a frequent complication of cirrhosis and may cause cerebral damage. Neurodegenerative diseases can induce the release of neuroproteins like neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in body fluids, including blood plasma. We investigated whether NfL and GFAP could serve as potential diagnostic plasma biomarkers for overt HE (oHE). Materials and MethodsWe included 85 patients from three prospective cohorts with different stages of liver disease and HE severity. The following patients were included: 1) 34 patients with primary sclerosing cholangitis (PSC) with compensated disease; 2) 17 patients with advanced liver disease without oHE before elective transjugular intrahepatic portosystemic shunt (TIPS) placement; 3) 17 intensive care unit (ICU) patients with oHE and 17 ICU patients without cirrhosis or oHE. Plasma NfL and GFAP were measured using single molecule assays. ResultsICU oHE patients had higher NfL concentrations compared to pre-TIPS patients or ICU controls (p < 0.05, each). Median GFAP concentrations were equal in the ICU oHE and pre-TIPS patients or ICU controls. Plasma NfL and GFAP concentrations correlated with Model for End-Stage Liver Disease (MELD) scores (R = 0.58 and R = 0.40, p < 0.001, each). ConclusionsPlasma NfL deserves further evaluation as potential diagnostic biomarker for oHE and correlates with the MELD score.

Adult-to-adult right lobe graft living donor liver transplantation for acute-on-chronic liver failure: a single-centre retrospective study in Vietnam.

Acute-on-chronic liver failure (ACLF) has a high mortality rate, and liver transplantation is considered a definite treatment for patients with this condition. This study aims to evaluate the outcomes of living donor liver transplantation (LDLT) in ACLF patients in a single centre in a lower middle-income country, Vietnam. This was a retrospective study at the 108 Military Central Hospital (Hanoi, Vietnam), enroling 51 patients diagnosed with ACLF based on Asian Pacific Association for the Study of the Liver (APASL) criteria who underwent LDLT with a right lobe graft from December 2019 to December 2022. The authors utilize the model for end-stage liver disease (MELD) and APASL ACLF Research Consortium (AARC) scores to evaluate and stratify the severity of ACLF. The average age of all patients was 47.27±13.61, with 88.24% being male. The average BMI was 22.78±2.61. The most common underlying liver disease was chronic viral hepatitis B (88.2%). The average MELD score of the patients was 34.90±5.61, with 33.3% having MELD score greater than or equal to 40. In terms of ACLF severity, five patients (9.8%) had grade I ACLF, 35 patients (68.6%) had grade II ACLF, and 11 patients (21.6%) had grade III ACLF. The average AARC score was 9.43±1.68. The duration of treatment in the ICU was 8.59±7.27 days, and the length of hospital stay was 28.02±13.45 days. The most common post-transplant complication was biliary complication (19.61%). Death occurred in 7 patients (13.7%). The survival rates at 6 months, 1 year, and 3 years were 84%, 81.7%, and 81.7%, respectively. Living donor liver transplantation for ACLF patients is safe and has a high post-transplant survival rate. Multidisciplinary care before, during, and after surgery, and the decision to do a liver transplant early, is essential in saving the lives of ACLF patients.

Analytical Performance Specifications for Input Variables: Investigation of the Model of End-Stage Liver Disease.

Artificial intelligence models constitute specific uses of analysis results and, therefore, necessitate evaluation of analytical performance specifications (APS) for this context specifically. The Model of End-stage Liver Disease (MELD) is a clinical prediction model based on measurements of bilirubin, creatinine, and the international normalized ratio (INR). This study evaluates the propagation of error through the MELD, to inform choice of APS for the MELD input variables. A total of 6093 consecutive MELD scores and underlying analysis results were retrospectively collected. "Desirable analytical variation" based on biological variation as well as current local analytical variation was simulated onto the data set as well as onto a constructed data set, representing a worst-case scenario. Resulting changes in MELD score and risk classification were calculated. Biological variation-based APS in the worst-case scenario resulted in 3.26% of scores changing by ≥1 MELD point. In the patient-derived data set, the same variation resulted in 0.92% of samples changing by ≥1 MELD point, and 5.5% of samples changing risk category. Local analytical performance resulted in lower reclassification rates. Error propagation through MELD is complex and includes population-dependent mechanisms. Biological variation-derived APS were acceptable for all uses of the MELD score. Other combinations of APS can yield equally acceptable results. This analysis exemplifies how error propagation through artificial intelligence models can become highly complex. This complexity will necessitate that both model suppliers and clinical laboratories address analytical performance specifications for the specific use case, as these may differ from performance specifications for traditional use of the analyses.

Revising model for end-stage liver disease from calendar-time cross-sections with correction for selection bias

BackgroundEurotransplant liver transplant candidates are prioritized by Model for End-stage Liver Disease (MELD), a 90-day waitlist survival risk score based on the INR, creatinine and bilirubin. Several studies revised the original MELD score, UNOS-MELD, with transplant candidate data by modelling 90-day waitlist mortality from waitlist registration, censoring patients at delisting or transplantation. This approach ignores biomarkers reported after registration, and ignores informative censoring by transplantation and delisting.MethodsWe study how MELD revision is affected by revision from calendar-time cross-sections and correction for informative censoring with inverse probability censoring weighting (IPCW). For this, we revised UNOS-MELD on patients with chronic liver cirrhosis on the Eurotransplant waitlist between 2007 and 2019 (n = 13,274) with Cox models with as endpoints 90-day survival (a) from registration and (b) from weekly drawn calendar-time cross-sections. We refer to the revised score from cross-section with IPCW as DynReMELD, and compare DynReMELD to UNOS-MELD and ReMELD, a prior revision of UNOS-MELD for Eurotransplant, in geographical validation.ResultsRevising MELD from calendar-time cross-sections leads to significantly different MELD coefficients. IPCW increases estimates of absolute 90-day waitlist mortality risks by approximately 10 percentage points. DynReMELD has improved discrimination over UNOS-MELD (delta c-index: 0.0040, p < 0.001) and ReMELD (delta c-index: 0.0015, p < 0.01), with differences comparable in magnitude to the addition of an extra biomarker to MELD (delta c-index: ± 0.0030).ConclusionCorrecting for selection bias by transplantation/delisting does not improve discrimination of revised MELD scores, but substantially increases estimated absolute 90-day mortality risks. Revision from cross-section uses waitlist data more efficiently, and improves discrimination compared to revision of MELD exclusively based on information available at listing.