Mean Model For End-stage Liver Disease Research Articles

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 < 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 < 0.001), liver enzymes (ALT from 63.9 IU to 45.9 IU; p < 0.001 and AST from 86.8 IU to 59.5 IU; p < 0.001), and MELD scores (11.5 to 9.3; p < 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.

Clinical criteria accurately diagnose severe but not moderate alcohol-associated hepatitis: A systematic review and meta-analysis.

The precision of clinical criteria and the utility of liver biopsy for diagnosis or prognosis remain unclear in patients with alcohol-associated hepatitis (AH). We systematically reviewed the literature to answer these questions. Four databases were searched for studies describing the precision of clinical criteria (National Institute on Alcohol Abuse and Alcoholism, European Association for Study of Liver, or classical) and the role of histology in AH. The precision(positive predictive value) of criteria was pooled through random-effects meta-analysis, and its variation was investigated through subgroups and meta-regression of study-level factors with their percent contribution to variation (R2). The risk of bias among studies was evaluated through the QUADAS2 tool (PROSPERO-ID-CRD4203457250). Of 4320 studies, 18 in the systematic review and 15 (10/5: low/high risk of bias, N=1639) were included in the meta-analysis. The pooled precision of clinical criteria was 80.2% (95% CI: 69.7-89.7, I2:93%, p < 0.01), higher in studies with severe AH (mean-Model for End-Stage Liver Disease > 20) versus moderate AH (mean-Model for End-Stage Liver Disease < 20): 92% versus 67.1%, p < 0.01, and in studies with serum bilirubin cutoff 5 versus 3 mg/dL (88.5% vs.78.8%, p = 0.01). The factors contributing to variation in precision were Model for End-Stage Liver Disease (R2:72.7%), upper gastrointestinal bleed (R2:56.3%), aspartate aminotransferase:aspartate aminotransferase ratio (R2:100%), clinical criteria (R2:40.9%), bilirubin (R2:22.5%), and Mallory body on histology (R2:19.1%).The net inter-pathologist agreement for histologic findings of AH was variable (0.33-0.97), best among 2 studies describing AH through simple and uniform criteria, including steatosis, ballooning, and neutrophilic inflammation. Few studies reported the utility of histology in estimating steroid responsiveness (N = 1) and patient prognosis (N = 4); however, very broad septa, pericellular fibrosis, and cholestasis were associated with mortality. Bilirubinostasis was associated with infection in 1 study. Clinical criteria are reasonably precise for diagnosing severe AH, while there is an unmet need for better criteria for diagnosing moderate AH. Histologic diagnosis of AH should be simple and uniform.

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.

Predictors and Outcomes of Post-transjugular Intrahepatic Portosystemic Shunt Liver Failure in Patients with Cirrhosis.

Post-transjugular intrahepatic portosystemic shunt (TIPS) liver failure (PTLF) is a serious complication of TIPS procedure with poor patient prognosis. This study tried to investigate the incidence of PTLF following elective TIPS procedure and evaluated possible predictive factors for the same. A retrospective analysis of patients who underwent elective TIPS placement between 2012 and 2022 and was conducted to determine development of PTLF (≥ 3-fold bilirubin and/or ≥ 2-fold INR elevation from the baseline) within 30days following TIPS procedure. Medical record review was done and factors predicting development of PTLF and the 90-day transplant-free survival was determined. Thirty of 352 (8.5%) patients developed PTLF within 30days of TIPS (mean age 54.2 ± 9.8years, 83% male). The etiology of cirrhosis was related to non-alcoholic steatohepatitis (NASH) in 50%, alcohol in 33.3%, and hepatitis B/C virus infection in 16.7% of the patients. The mean Child-Turcotte-Pugh (CTP) score was 9.5 ± 1.2 and mean model for end stage liver disease (MELD) score was 14.6 ± 4.5 at the time of admission in patients who developed PTLF. The indication for TIPS was recurrent variceal bleed in 50% (15 of 30) and refractory ascites in 46.7% (14 of 30) patients with PTLF. Multivariate analysis identified prior HE (OR 6.1; CI 2.57-14.5, p < 0.0001) and higher baseline CTP score (OR 1.47; CI 1.07-2.04; p = 0.018) as predictors of PTLF. PTLF was associated with significantly lower 90-day transplant-free survival, as compared to patients without PTLF (40% versus 96%, p < 0.001). Almost 10% of patients with cirrhosis develop post-TIPS liver failure and is associated with significant early mortality and morbidity. Higher baseline CTP score and prior HE were identified as predictors for PTLF.

Spatial inequalities and non-linear association of continuous variables with mortality risk of liver transplantation in Iran: a retrospective cohort study

Liver transplantation is the second most common solid organ transplant and the best option for liver failure. Of course, patient survival after transplantation depends on many risk factors. The aim of this study was to investigate the spatial and non-linear effects of continuous risk factors on patient survival after liver transplantation. This retrospective cohort study (n = 3148) used data on liver transplantation in Iran (2004–2019). A generalized additive model with spatial effects and non-linear effects of age and Model for End-Stage Liver Disease (MELD) score variables by penalized spline was used. The majority of patients were male (63.3%), with a mean (SD) age of 42.65 (13.31) and a mean (SD) MELD score of 24.43 (6.72). The 1, 5, and 10-year survival rates were 88.2%, 84.6%, and 82.5% respectively. The non-linear effect showed a steeper slope of the age effect on the hazard of death after the age of 50 (p < 0.05), and the MELD score had a direct but non-linear relationship with the hazard of death (p < 0.05). In the spatial pattern, the provinces with a greater distance from the transplant center had significantly fewer old patients than other provinces. Also, more distant provinces with an older transplant age had higher post-transplant mortality rates. Our study showed that it is better to take age and MELD score into account in postoperative care. The spatial pattern of mortality risk reflects inequalities in access to transplantation and public health services after transplantation.

Osteoporosis and Fragility Fractures in Patients with Liver Cirrhosis: Usefulness of FRAX® as a Screening Tool.

The purpose of this study is to assess the prevalence of osteoporosis and fragility fractures in patients with liver cirrhosis (LC) and determine the associated risk factors, evaluating the usefulness of FRAX® as a screening method to identify patients at a higher risk of fracture. This was a cross-sectional study. Demographic, clinical, and analytical data were collected in a randomized sample of LC patients attending the Hepatology Department of a university hospital. We assessed the absolute risk of fracture at 10 years (FRAX®) and based on the bone mineral density (BMD), the presence of morphometric vertebral fracture with a vertebral fracture assessment (VFA), or a thoracic and lumbar X-ray and bone microarchitecture with a trabecular bone score (TBS). Ninety-two patients were included (71% male); the mean age was 63 ± 11.3 years. The main etiology of LC was alcoholism (52.2%), and most patients were Child-Pugh A (80.4%), with a mean model for end-stage liver disease (MELD) score of 10.1 ± 3.6. Sixteen patients (17.4%) had osteoporosis, and fifty-four (58.7%) had osteopenia. Eight patients (8.7%) had suffered at least one fragility fracture. The absolute risk of a major fracture according to FRAX without the BMD was 5.7 ± 4.5%. Risk factors associated with osteoporosis were age and the female sex. BMI > 30 was a protective factor. A FRAX cut-off point for a major fracture > 6.6% had a sensitivity of 69% and a specificity of 85% for a diagnosis of osteoporosis. The prevalence of osteoporosis and fractures in patients with LC is high, particularly in older women. FRAX® may be a useful method to identify candidates for bone densitometry. A FRAX value below 6.6% without the BMD can avoid unnecessary testing.

MELD-Na score may underestimate disease severity and risk of death in patients with metabolic dysfunction-associated steatotic liver disease (MASLD)

Portal hypertension often precedes the development of advanced fibrosis in patients with Metabolic dysfunction-associated steatotic liver disease (MASLD) and may accelerate disease progression to cirrhosis. We aimed to evaluate whether prioritization tools accurately predict survival in patients with MASLD and clinically significant portal hypertension (CSPH). We retrospectively identified patients diagnosed with esophageal or gastric varices (EGV). Laboratory results, endoscopy reports and outcomes of patients with MASLD were compared to patients with advanced stage chronic liver disease (CLD) of other etiologies. During the study period 326 patients were diagnosed with EGV. 88 (26.9%) had MASLD, 113 (34.6%) viral hepatitis (VH), 63 (19.3%) alcoholic liver disease (ALD) and 62 (19%) both VH and ALD (VHALD). EGV bleeding events were significantly more frequent in patients with MASLD (36.3%), compared to VH (28.3%), ALD (30.1%) and VHALD (25.8%), respectively (p < 0.01). Mean Model for End-Stage Liver Disease (MELD)-Na score surrounding 1 year of first event of EGV bleeding was significantly lower in MASLD patients compared to all other etiologies (p = 0.02). At a MELD-Na score of 11–20, cumulative survival rate was significantly lower in MASLD patients compared to all other etiologies (log rank p < 0.01). MASLD patients present with EGV bleeding at lower MELD-Na scores compared to other etiologies of CLD. MELD-Na score may therefore underestimate disease severity and risk of death in patients with MASLD and CSPH.

Outcomes of direct-acting antivirals in patients with HCV decompensated cirrhosis: a systematic review and meta-analysis

BackgroundDirect-acting antivirals (DAA) are effective for chronic hepatitis C virus (HCV) treatment. However, their impact on overall survival (OS), hepatocellular carcinoma (HCC) occurrence, HCC-free survival, and liver function in patients with HCV decompensated cirrhosis remains uncertain. This study aimed to evaluate the effects of DAA treatment on this population.MethodsStudies were identified by searching the MEDLINE, SCOPUS, and CENTRAL databases. OS and HCC-free survival probabilities and time data were extracted from Kaplan-Meier curves. A one-stage meta-analysis using parametric Weibull regression was conducted to estimate the relative treatment effects of DAA vs. no DAA. The primary outcome was the OS rate. The secondary outcomes were HCC-free survival, HCC occurrence rate, and improvement in the Model for End-stage Liver Disease (MELD) score.ResultsEight cohorts comprising 3,430 participants (2,603 in the DAA group and 1,999 in the no-DAA group) were included. The OS probabilities at 12 and 24 months were 95 and 90% for the DAA group, respectively, compared with 89 and 80% in the no-DAA group, respectively. Hazard ratio (HR) was 0.48 (95% confidence interval (CI): 0.39, 0.60; p &amp;lt; 0.001). The HCC-free survival probabilities at 12 and 24 months were 96 and 90%, respectively, in the former, and 94 and 85%, respectively, in the latter. The HR of HCC occurrence was 0.72 (95% CI: 0.52, 1.00; p = 0.05), which suggests that DAA treatment in decompensated cirrhosis may lead to a 28% lower risk of HCC occurrence. The mean MELD score difference was −7.75 (95% CI: −14.52, −0.98; p = 0.02).ConclusionImprovement in OS and MELD score is a long-term benefit of DAA treatment in patients with HCV decompensated cirrhosis, with a marginal effect of the treatment on HCC development.

Corrected QT interval in cirrhosis: A systematic review and meta-analysis.

Corrected QT (QTc) interval is prolonged in patients with liver cirrhosis and has been proposed to correlate with the severity of the disease. However, the effects of sex, age, severity, and etiology of cirrhosis on QTc have not been elucidated. At the same time, the role of treatment, acute illness, and liver transplantation (Tx) remains largely unknown. To determine the mean QTc in patients with cirrhosis, assess whether QTc is prolonged in patients with cirrhosis, and investigate whether QTc is affected by factors such as sex, age, severity, etiology, treatment, acute illness, and liver Tx. In the present systematic review and meta-analysis, the searching protocol "{[QTc] OR [QT interval] OR [QT-interval] OR [Q-T syndrome]} AND {[cirrhosis] OR [Child-Pugh] OR [MELD]}" was applied in PubMed, EMBASE, and Google Scholar databases to identify studies that reported QTc in patients with cirrhosis and published after 1998. Seventy-three studies were considered eligible. Data concerning first author, year of publication, type of study, method used, sample size, mean age, female ratio, alcoholic etiology of cirrhosis ratio, Child-Pugh A/B/C ratio, mean model for end-stage liver disease (MELD) score, treatment with β-blockers, episode of acute gastrointestinal bleeding, formula for QT correction, mean pulse rate, QTc in patients with cirrhosis and controls, and QTc according to etiology of cirrhosis, sex, Child-Pugh stage, MELD score, and liver Tx status (pre-Tx/post-Tx) were retrieved. The Newcastle-Ottawa quality assessment scale appraised the quality of the eligible studies. Effect estimates, expressed as proportions or standardized mean differences, were combined using the random-effects, generic inverse variance method of DerSimonian and Laird. Subgroup, sensitivity analysis, and meta-regressions were applied to assess heterogeneity. The study has been registered in the PROSPERO database (CRD42023416595). QTc combined mean in patients with cirrhosis was 444.8 ms [95% confidence interval (CI): 440.4-449.2; P < 0.001 when compared with the upper normal limit of 440 ms], presenting high heterogeneity (I2 = 97.5%; 95%CI: 97.2%-97.8%); both Egger's and Begg's tests showed non-significance. QTc was elongated in patients with cirrhosis compared with controls (P < 0.001). QTc was longer in patients with Child-Pugh C cirrhosis when compared with Child-Pugh B and A (P < 0.001); Child-Pugh B patients presented longer QTc when compared with Child-Pugh A patients (P = 0.003). The MELD score was higher in patients with cirrhosis with QTc > 440 ms when compared with QTc ≤ 440 ms (P < 0.001). No correlation of QTc with age (P = 0.693), sex (P = 0.753), or etiology (P = 0.418) was detected. β-blockers shortened QTc (P< 0.001). QTc was prolonged during acute gastrointestinal bleeding (P = 0.020). Tx tended to improve QTc (P < 0.001). No other sources of QTc heterogeneity were revealed. QTc is prolonged in cirrhosis independently of sex, age, and etiology but is correlated with severity and affected by β-blockers and acute gastrointestinal bleeding. QTc is improved after liver Tx.

Prediction of In-Hospital Mortality in Spontaneous Bacterial Peritonitis Patients with Advanced Liver Disease

Introduction: Bacterial infections are known reason for morbidity and mortality in hospitalized patients with cirrhosis among which Spontaneous bacterial peritonitis (SBP) is most common, accounts for around 20% to 30% mortality rate. Objective: To evaluate the frequency of in-hospital mortality in SBP patients. Study Design: Descriptive case series. Setting: Asian Institute of Medical Sciences Hospital Hyderabad. Duration: From 1st January 2019 to 30th June 2019. Material and Methods: Adult patients diagnosed to have spontaneous bacterial peritonitis and followed for outcome. Results: 223 patients of spontaneous bacterial peritonitis I,e 165 (74%) male and 58 (26%) female fulfilling the inclusion criteria were enrolled in study. Mean age obtained was 47.56 ± 13.069 years and Hepatitis C with most common etiology for CLD was 128 (57.4%) followed by Hepatitis B 26 (11.7%), Hepatitis B + D 30 (13.5 %) and Alcohol 8 (3.6 %). Hepatocellular carcinoma in 70 (31.4 %) only. CTP (Child-Turcot-Pugh) score and MELD (Model for End-stage Liver Disease) score used to access stage of cirrhosis. 38 (17 %) patients with CTP class B and 185 (83 %) with CTP class C. The mean MELD score of all patients found to be 23.09 ± 15.686. Among 223 patients, in-hospital mortality was observed in 61 (27.4%), 115 (51.6%) were discharged with improvement and rest 47 (21.1%) discharged with no improvement. Practical Implication: This study's findings underscore the need for early detection and aggressive management of Spontaneous Bacterial Peritonitis in patients with advanced liver disease, especially those with CTP Class C and high MELD scores, to reduce the high in-hospital mortality rate. Conclusion: Significantly high in-hospital mortality was found to be associated with SBP, with CTP Class C, High MELD Score, increased creatinine, bilirubin, PT, INR and decreased albumin especially in females. Keywords: Cirrhosis; In-hospital mortality; Spontaneous bacterial peritonitis

Machine Learning-Based Radiomic Features on Pre-Ablation MRI as Predictors of Pathologic Response in Patients with Hepatocellular Carcinoma Who Underwent Hepatic Transplant

The aim was to investigate the role of pre-ablation tumor radiomics in predicting pathologic treatment response in patients with early-stage hepatocellular carcinoma (HCC) who underwent liver transplant. Using data collected from 2005-2015, we included adult patients who (1) had a contrast-enhanced MRI within 3 months prior to ablation therapy and (2) underwent liver transplantation. Demographics were obtained for each patient. The treated hepatic tumor volume was manually segmented on the arterial phase T1 MRI images. A vector with 112 radiomic features (shape, first-order, and texture) was extracted from each tumor. Feature selection was employed through minimum redundancy and maximum relevance using a training set. A random forest model was developed based on top radiomic and demographic features. Model performance was evaluated by ROC analysis. SHAP plots were constructed in order to visualize feature importance in model predictions. Ninety-seven patients (117 tumors, 31 (32%) microwave ablation, 66 (68%) radiofrequency ablation) were included. The mean model for end-stage liver disease (MELD) score was 10.5 ± 3. The mean follow-up time was 336.2 ± 179 days. Complete response on pathology review was achieved in 62% of patients at the time of transplant. Incomplete pathologic response was associated with four features: two first-order and two GLRM features using univariate logistic regression analysis (p < 0.05). The random forest model included two radiomic features (diagnostics maximum and first-order maximum) and four clinical features (pre-procedure creatinine, pre-procedure albumin, age, and gender) achieving an AUC of 0.83, a sensitivity of 82%, a specificity of 67%, a PPV of 69%, and an NPV of 80%. Pre-ablation MRI radiomics could act as a valuable imaging biomarker for the prediction of tumor pathologic response in patients with HCC.

Development and Validation of a Novel Tool to Predict Model for End-Stage Liver Disease (MELD) Scores in Cirrhosis, Using Administrative Datasets.

The Model for End-Stage Liver Disease (MELD) score predicts disease severity and mortality in cirrhosis. To improve cirrhosis phenotyping in administrative databases lacking laboratory data, we aimed to develop and externally validate claims-based MELD prediction models, using claims data linked to electronic health records (EHR). We included adults with established cirrhosis in two Medicare-linked EHR networks (training and internal validation; 2007-2017), and a Medicaid-linked EHR network (external validation; 2000-2014). Using least absolute shrinkage and selection operator (LASSO) with 5-fold cross-validation, we selected among 146 investigator-specified variables to develop models for predicting continuous MELD and relevant MELD categories (MELD<10, MELD≥15 and MELD≥20), with observed MELD calculated from laboratory data. Regression coefficients for each model were applied to the validation sets to predict patient-level MELD and assess model performance. We identified 4501 patients in the Medicare training set (mean age 75.1 years, 18.5% female, mean MELD=13.0), and 2435 patients in the Medicare validation set (mean age: 74.3 years, 31.7% female, mean MELD=12.3). Our final model for predicting continuous MELD included 112 variables, explaining 58% of observed MELD variability; in the Medicare validation set, the area-under-the-receiver operating characteristic curves (AUC) for MELD<10 and MELD≥15 were 0.84 and 0.90, respectively; the AUC for the model predicting MELD≥20 (using 27 variables) was 0.93. Overall, these models correctly classified 77% of patients with MELD<10 (95% CI=0.75-0.78), 85% of patients with MELD≥15 (95% CI=0.84-0.87), and 87% of patients with MELD≥20 (95% CI=0.86-0.88). Results were consistent in the external validation set (n=2240). Our MELD prediction tools can be used to improve cirrhosis phenotyping in administrative datasets lacking laboratory data.

Aspartate aminotransferase-to-platelet ratio index can predict the outcome in patients with stable decompensated cirrhosis.

Platelet (PLT)-based biomarkers have been studied for the evaluation of liver fibrosis and cirrhosis. There are no data regarding their prognostic significance in decompensated cirrhosis. We studied 525 stable decompensated patients from the 2 Greek transplant centers. We measured PLT values, mean PLT volume (MPV), red cell distribution width, γ-globulins, and calculated PLT-based scores: aspartate aminotransferase-to-PLT ratio index (APRI), γ-globulin-to-PLT model, and γ-glutamyl transpeptidase-to-PLT ratio (GPR). We followed our cohort for 12 (range: 1-84) months. Baseline mean model for end-stage liver disease (MELD) and Child-Turcotte-Pugh (CTP) scores were 15±6 and 8±2, respectively. On univariate analysis, MPV/PLT (hazard ratio [HR] 3.75, 95% confidence interval [CI] 1-14.5; P=0.05), APRI (HR 1.03, 95%CI 1.006-1.06; P=0.016), GPR (HR 1.096, 95%CI 1.016-1.182; P=0.017) were significantly associated with our patients' outcome (survival vs. death or liver transplantation). In a multivariate model without MELD and CTP scores, APRI was the only significant factor associated with the outcome (HR 1.054, 95%CI 1.009-1.101; P=0.018). APRI had good discriminative ability for the outcome (area under the curve 0.723 vs. 0.675 and 0.656 for MELD and CTP scores, respectively). The optimal cutoff point was 1.3 (sensitivity 71%, specificity 65%). There were 200 patients (38%) with APRI scores <1.3 who had better survival than patients with APRI >1.3 (log rank 22.4, P<0.001). This study found a prognostic role for APRI in stable decompensated cirrhosis, regardless of the underlying etiology of chronic liver disease. This suggests new perspectives for PLT-based noninvasive scores to discriminate patients' outcomes.

1852. Recurrent Bacteremia after Endoscopic Injection of N-butyl-2-cyanoacrylate for Gastric Variceal Bleeding

Abstract Background Gastric variceal bleeding is associated with a high mortality rate, and sclerotherapy using N-butyl-2-cyanoacrylate is the treatment of choice. The risk of recurrent bacteremia after N-butyl-2-cyanoacrylate injection has rarely been reported. We aimed to evaluate the frequency of this complication in a real-world setting. Methods We analyzed retrospective data from a single-center cohort of patients with liver cirrhosis who underwent N-butyl-2-cyanoacrylate injection for the treatment of bleeding gastric varices from January 2010 to March 2021. Recurrent bacteremia was defined as repeated bacteremia caused by the same microorganism after the resolution of the first event occurring at least two weeks from the date of the final positive blood culture of the first event. Results A total of 232 patients receiving 338 sessions of N-butyl-2-cyanoacrylate injection were enrolled. All patients received antibiotics prophylaxis; third-generation cephalosporins were used. The average age of patients was 59.5 ± 12.2 years and the mean Model for End-Stage Liver Disease (MELD) score was 14.8 ± 7.3. Of the patients following cyanoacrylate injection, 62 patients developed primary bacteremia at a median of 294 (range, 3−3710) days from N-butyl-2-cyanoacrylate injection. Nine out of 62 patients developed recurrent bacteremia following sclerotherapy with N-butyl-2-cyanoacrylate. The identified organisms were: Extended-Spectrum ß-Lactamase (ESBL)-producing Escherichia coli (3), ESBL-producing Klebsiella pneumoniae (2), non-ESBL-producing Klebsiella pneumoniae (2), Pseudomonas aeruginosa (1), and Methicillin-resistant Staphylococcus aureus (1). The median number of episodes of recurrent bacteremia per patient was 3 (range, 2−8) during the median 972 (range, 78−1997) days of follow-up. Four of these nine recurrent bacteremia patients died. Conclusion Recurrent bacteremia occurred in 3.9% of cirrhotic patients following cyanoacrylate injection for the treatment of gastric variceal bleeding. Foreign-body-type infection of the polymerized N-butyl-2-cyanoacrylate should be suspected in patients who had received previous endoscopic treatment with N-2-butyl-cyanoacrylate and fails to disclose another source of infection. Disclosures All Authors: No reported disclosures.

Dysnatremia in patients with chronic liver disease: a cross-sectional observational study

Background: The clinical significance of serum sodium levels and its association with a higher rate of complications in cirrhosis is debatable. This study was done to study the serum sodium levels in chronic liver disease (CLD) patients and establish its association with the severity of disease in such patients.Methods: In this cross-sectional study, we included adult patients diagnosed with CLD and assessed their serum electrolytes. The severity of liver disease was assessed using Child Pugh score (CPS) and model for end stage liver disease (MELD). Those with serum sodium levels less than 130 mEq/l were classified as group A, 131 to 135 mEq/l as normal group B and greater or equal to 136 mEq/l as Group C.Results: In the present study, hepatic encephalopathy (p&lt;0.01), hepatorenal syndrome (p&lt;0.01) and coagulopathy (p&lt;0.01) were found to occur significantly more common among patients from Group A, as compared to those in patients from group B or C. Mean MELD, CPS score and mortality was significantly higher among group A patients.Conclusions: Patients with lower serum salt levels had a substantially higher MELD score and CPS. Low blood sodium levels were linked to more severe liver disease, greater complications, and increased death. As a result, we urge that serum salt levels be checked on a frequent basis in patients with chronic liver disease.

Physical Effects, Safety and Feasibility of Prehabilitation in Patients Awaiting Orthotopic Liver Transplantation, a Systematic Review.

Prehabilitation improves surgical outcomes in patients undergoing surgery. However, patients preparing for orthotopic liver transplantation (OLT) are physically "frail" and suffer from comorbidities that generally hamper physical activity. This systematic review aims to evaluate the physical effects, safety and feasibility of prehabilitation in OLT candidates. Relevant articles were searched, in Embase, Web of Science, Cochrane, Medline and Google Scholar, to December 2021. Studies reporting on specified preoperative exercise programs, including adult OLT candidates with end-stage liver disease, with a model for end-stage liver disease (MELD) score ≥12 or Child-Pugh classification B/C, were included. This resulted in 563 potentially eligible studies, out of which eight were selected for inclusion, consisting of 1,094 patients (male sex 68%; mean age 51-61years; mean MELD score 12-21). Six of the included studies were classified as low-quality by the GRADE system, and three studies had high risk for ineffectiveness of the training program according to the i-CONTENT tool. Significant improvement was observed in VO2 peak, 6-minute walking distance, hand grip strength, liver frailty index and quality of life. Feasibility ranged from an adherence of 38%-90% in unsupervised-to >94% in supervised programs. No serious adverse events were reported. In conclusion, prehabilitation in patients awaiting OLT appears to improve aerobic capacity, and seems feasible and safe. However, larger clinical trials are required to accurately examine the preoperative and postoperative effects of prehabilitation in this specific patient population.

The impact of rifaximin on the hospital burden and infections in patients with hepatic encephalopathy: a retrospective observational study.

Advanced liver disease frequently culminates in hepatic encephalopathy (HE), which can be classified as covert or overt HE, with subtle or clinically obvious changes respectively. 30-40% of patients with cirrhosis develop overt HE, which negatively affects the patients' quality of life. Next to lactulose, rifaximin-α has been prescribed as a second line therapy to treat and reduce the risk of recurrence of overt HE. In this study, we aimed to evaluate the effect of rifaximin-α therapy, both on the number of occurring infections and on the evolution in hospital admissions of patients with overt HE. A total of 66 cirrhotic patients, treated for at least 6 months with rifaximin-α at AZ Maria Middelares, between October 1st 2014 and January 1st 2020, were included in the study analysis. Medical records of all patients were evaluated over a period of 6 months prior and after initiation of rifaximin-α therapy. Data analysis revealed that the included cirrhotic patients were severely ill, with a mean model for end-stage liver disease (MELD) score of 21, and a median Child Pugh score of 11. Among these patients, rifaximin-α treatment significantly downgraded the total number of infections, with a main effect on respiratory infections. Furthermore, rifaximin-α therapy led to a significant decrease in HE-related, as well as in other liver-related hospital admissions. This study confirms the potential value of rifaximin-aα in reducing the number of developing infections and hospital admissions in a severely ill cirrhotic patient population.

346.2: Preoperative Neutrophil and Platelet-To-Lymphocyte Ratio As Predictors of Mortality and Surgical Related Complications After Liver Transplantation

Introduction: Liver transplantation (LT) is considered the only definitive treatment in patients with end-stage liver disease (ESLD). Nowadays, the 5-year overall survival (OS) after LT is 75%–85%. In addition, short-term mortality has decreased due to better perioperative care, advancements in operative techniques, as well as changes in patient selection. Despite these improvements, a subset of patients still dies within the first year after LT. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been recently reported as simple and useful markers of various inflammatory changes and are calculated based on complete blood count data. It has been suggested that both parameters in the acute phase of LT are prognostic factors for early post-transplant survival. Method: We conducted a retrospective and analytic study. Among 410 LT recipients between January 2013 and February 2022 who were operated at the HPB surgery and liver transplant department of the Hospital de Alta Complejidad “El Cruce”, we selected 120 patients after simple random sampling. Patients’ demographic data, cirrhosis etiology, model for end-stage liver disease (MELD) scores, and hematological parameters were analyzed. Latest hematological parameters prior to surgery were recorded. NLR and PLR values were calculated based on the measured hematological parameters. Time and incidence of postoperative complications were analyzed. Fisher exact test, Mann–Whitney U test and Students T-test were used when appropriate. Two-sided p value equal or less than 0.05 was considered to indicate statistical significance with a confidence interval of 95%. All analyses were conducted using MedCalc version 20.027 (https://www.medcalc.org/). Results: The mean age of the 120 patients included in the study was 58.73 ± 7.04 years; 66.67% were male. All patients received decesead donor liver transplantation. The most common indication for LT was liver cirrhosis due to hepatitis C virus (HCV) (30%) followed by alcoholic liver cirrhosis (26.67%) (table 1). The mean MELD score was found to be 24.85 ± 4.67. 23 out of 120 patients died after LT (19.16%). 5 patients (4.16%) presented surgical-related complications. Mortality was higher in patients with higher MELD scores (p = 0.011). The mean preoperative NLR was 3.54 ± 4.08 and PLR was 80.73 ± 50.59. When NLR and PLR results with cut-off values of >3,77 and ≤34,18 respectively were compared with the incidence of major complications (Dindo-Clavien ≥3) a significant result was found (p = 0.01). No statistical significance was found between NLR, PLR and age and mortality (p=0.91, 0.93 and 0.47 respectively). Conclusion: Preoperative NLR and PLR were not found useful to predict mortality after OLT in our series. However, they may be of value to anticipate poor prognosis or major incidence of complications in patients undergoing OLT. With this simple indices, high-risk patients can be identified and preventive measures can be taken.

Impact of COVID-19 on Liver Transplant Activity in the USA: Variation by Etiology and Cirrhosis Complications.

The COVID-19 pandemic has impacted the care of patients with liver disease. We examined impact of COVID-19 on liver transplant (LT) activity in the USA. LT listings in the United Network for Organ Sharing (UNOS) database (April 2018-May 2021) were analyzed to examine the impact of COVID-19 pandemic on the LT activity based on etiology: hepatitis C virus (HCV), alcohol-associated liver disease (ALD), alcoholic hepatitis (AH), and nonalcoholic steatohepatitis (NASH) complications: hepatocellular carcinoma (HCC) and acute-on-chronic liver failure (ACLF) grade 2 or 3) and Model for End-Stage Liver Disease (MELD) score. Joinpoint regression models assessed time trend changes on a log scale. Of 23,871 recipients (8,995 in the COVID era, April 2018-February 2020), mean age 52 years, 62% men, 61% Caucasian, 32% ALD, 15% HCC, 30% ACLF grades 2-3, and mean MELD score 20.5), monthly LT changes were a decrease of 3.4% for overall LTs and 22% for HCC after September 2020, and increase of 4.5% for ALD since 11/2020 and 17% since 03/2021 for ACLF grade 2-3. Monthly MELD scores increased by 0.7 and 0.36 after June 2020 for HCV and HCC respectively. The COVID-19 pandemic has impacted LT activity, with a decrease of LTs especially for HCC, and an increase of LTs for ALD and severe ACLF. Strategies are needed to reorganize cirrhosis patients to overcome the aftereffects of COVID-19 pandemic.

Liver resection for single large hepatocellular carcinoma: a prognostic factors study

Introduction and objectivesLiver resection is the only curative therapeutic option for large hepatocellular carcinoma (> 5 cm), but survival is worse than in smaller tumours, mostly due to the high recurrence rate. There is currently no proper tool for stratifying relapse risk. Herein, we investigated prognostic factors before hepatectomy in patients with a single large hepatocellular carcinoma (HCC). Material and methodsWe retrospectively identified 119 patients who underwent liver resection for a single large HCC in 2 tertiary academic French centres and collected pre- and post-operative clinical, biological and radiological features. The primary outcome was overall survival at five years. Secondary outcomes were recurrence-free survival at five years and prognostic factors for recurrence. ResultsA total of 84% of the patients were male, and the median age was 66 years old (IQR 58–74). Thirty-nine (33%) had Child–Pugh A cirrhosis, and the mean Model for End-Stage Liver Disease (MELD) score was 6 (6–6). The aetiology of liver disease was predominantly alcohol-related (48%), followed by nonalcoholic steatohepatitis (22%), hepatitis B (18%) and hepatitis C (10%). The mean tumour size was 70 mm (55–110). The median overall survival was 72.5 months (IC 95%: 56.2-88.7), and the five-year overall survival was 55.1 ± 5.5%. The median recurrence-free survival was 26.6 months (95% CI: 16.0-37.1), and the five-year recurrence-free survival rate was 37.8 ± 5%. In multivariate analysis, preoperative prognostic factors for recurrence were baseline alpha-fetoprotein (AFP) > 7 ng/mL (p<0.001), portal veinous invasion (p=0.003) and cirrhosis (p=0.020). Using these factors, we created a simple recurrence-risk scoring system that classified three groups with distinct disease-free survival medians (p<0.001): no risk factors (65 months), 1 risk factor (36 months), and ≥2 risk factors (8.9 months). ConclusionLiver resection is the only curative option for large HCC, and we confirmed that survival could be acceptable in experienced centres. Recurrence is the primary issue of surgery, and we proposed a simple preoperative score to help identify patients with the most worrisome prognosis and possible candidates for combined therapy.