Prognostic value of decline in model for end-stage liver disease score and hepatic encephalopathy in hepatitis B-related acute-on-chronic liver failure patients treated with plasma exchange.

OBJECTIVE: To investigate the prognostic value of Model for End-Stage Liver Disease (MELD) score and Hepatic Encephalopathy (HE) for short-term prognosis of Hepatitis B virus-related Acute-on-Chronic Liver Failure (HBV-ACLF) patients treated with plasma exchange (PE). METHODS: A total of 108 patients with HBV-ACLF treated with PE were retrospectively enrolled between January 2014 to December 2020. Based on survival at 28 days, patients were divided into survival (N = 87) and death groups (N = 21). Clinical data and laboratory indicators were analyzed. RESULTS: Compared with the survival group, the death group was associated with higher ACLF grade and incidence of HE. The levels of total bilirubin, prothrombin time, creatinine, blood urea nitrogen, MELD score, and Chinese Group on the Study of Severe Hepatitis B-ACLF II (COSSH II) score were significantly higher in the death group than in the survival group (p < .05). Grade 1 ACLF and the MELD score after PE treatment at one week were independent risk factors for 28-day liver transplantation-free mortality (OR = 0.062, 95%CI: 0.005-0.768; OR = 1.328, 95%CI: 1.153-1.531). A MELD score at one week of at least 25.5 was associated with a poor short-term prognosis. Of note, HE was a strong independent risk factor for a decline in MELD score at one week. (OR = 11.815, 95%CI: 3.187-43.796, p < 0.001). CONCLUSION: We found patients with HE at admission and MELD score of at least 25.5 at one week after PE treatment had a poor short-term prognosis and should prompt preparation for liver transplantation. Trial Registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT04231565). Registered 13 May 2020.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) levels are not associated with severity of liver disease and are inversely related to cholesterol in a cohort of thirty eight patients with liver cirrhosis.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is of particular importance in cholesterol metabolism with high levels contributing to hypercholesterolemia. Cholesterol and sphingolipids are low in patients with liver cirrhosis. Purpose of this study was to find associations of plasma PCSK9 with circulating cholesterol and sphingolipid species and measures of liver disease severity in patients with liver cirrhosis. METHODS: PCSK9 protein levels were determined by ELISA in systemic vein (SVP), hepatic vein (HVP) and portal vein plasma of patients with mostly alcoholic liver cirrhosis. PCSK9 and LDL-receptor protein expression were analysed in cirrhotic and non-cirrhotic liver tissues. RESULTS: Serum PCSK9 was reduced in patients with liver cirrhosis in comparison to non-cirrhotic patients. In liver cirrhosis, plasma PCSK9 was not correlated with Child-Pugh score, Model for End-Stage Liver Disease score, bilirubin or aminotransferases. A negative association of SVP PCSK9 with albumin existed. PCSK9 protein in the liver did not change with fibrosis stage and was even positively correlated with LDL-receptor protein levels. Ascites volume and variceal size were not related to PCSK9 levels. Along the same line, transjugular intrahepatic shunt to lower portal pressure did not affect PCSK9 concentrations in the three blood compartments. Serum cholesterol, sphingomyelin and ceramide levels did not correlate with PCSK9. Stratifying patients by high versus low PCSK9 levels using the median as cut-off, several cholesteryl ester species were even low in the subgroup with high PCSK9 levels. A few sphingomyelin species were also reduced in the patients with PCSK9 levels above the median. PCSK9 is highly expressed in the liver but systemic, portal and hepatic vein levels were similar. PCSK9 was not correlated with the inflammatory proteins C-reactive protein, IL-6, galectin-3, resistin or pentraxin 3. Of note, HVP PCSK9 was positively associated with HVP chemerin and negatively with HVP adiponectin levels. CONCLUSIONS: In the cohort of patients with liver cirrhosis mostly secondary to alcohol consumption high PCSK9 was associated with low levels of certain cholesteryl ester and sphingomyelin species. Positive correlations of PCSK9 and LDL-receptor protein in the liver of patients with chronic liver injury are consistent with these findings.

Predictors of 1-month and 3-months Hospital Readmissions in Decompensated Cirrhosis: A Prospective Study in a Large Asian Cohort.

INTRODUCTION AND AIM: Considered as a healthcare quality indicator, hospital readmissions in decompensated cirrhosis predispose the patients and the society to physical, social and economic distresses. Few studies involving North American cohorts have identified different predictors. The aim of this study was to determine and validate the predictors of 1-month and 3-months readmission in an Asian cohort. MATERIAL AND METHODS: We prospectively studied 281 hospitalised patients with decompensated cirrhosis at a large tertiary care public hospital in India between August 2014 and August 2016 and followed them for 3 months. Data regarding demographic, laboratory and disease related risk factors were compiled. We used multivariate logistic regression to determine predictors of readmission at 1-month and 3-months and receiver operating curves (ROC) for significant predictors to obtain the best cut-offs. RESULTS: 1-month and 3-months readmission rates in our study were 27.8% and 42.3%, respectively. Model for End stage Liver Disease (MELD) score at discharge (OR:1.24, p < 0.001) and serum sodium (OR:0.94, p-0.039) independently predicted 1-month and MELD score (OR:1.11, p-0.003), serum sodium (OR:0.94, p-0.027) and male gender (OR:2.19, p-0.008) independently predicted 3-months readmissions. Neither aetiology nor complications of cirrhosis emerged as risk factors. MELD score >14 at discharge and serum sodium < 133 mEq/L best predicted readmissions; MELD score being a better predictor than serum sodium (p - 0.0001). CONCLUSIONS: High rates of early and late readmissions were found in our study. Further, this study validated readmission predictors in Asian patients. Structured interventions targeting this risk factors may diminish readmissions in decompensated cirrhosis.

Hospital-level balloon tamponade use is associated with increased mortality for all patients presenting with acute variceal haemorrhage.

BACKGROUND & AIMS: Balloon tamponade (BT) can bridge patients to salvage therapy for uncontrollable acute variceal haemorrhage (AVH). However, data are limited regarding the reasons for, rate of and outcomes associated with Balloon tamponade use. METHODS: First, we performed an single-centre cohort study of all patients (N = 139) with oesophageal acute variceal haemorrhage from 01/2009 to 10/2015. Associations between Balloon tamponade use and adherence to four quality metrics (endoscopy within 12 hours, band-ligation, pre-endoscopy antibiotics and octreotide) were evaluated. Second, we analysed the National Inpatient Sample (2005-2011) to determine the association between in-hospital mortality for patients and their hospital's Balloon tamponade-utilization to acute variceal haemorrhage volume ratio. RESULTS: In the national cohort, 5.5% of 140 521 acute variceal haemorrhage admissions required Balloon tamponade utilization. Adjusting for patient- and hospital-level confounders, the rate of Balloon tamponade use per acute variceal haemorrhage managed at any given hospital was associated with increased mortality for all-comers with acute variceal haemorrhage. Compared to the lowest tertile, acute variceal haemorrhage admissions in the highest Balloon tamponade utilizers were associated with increased mortality of (OR1.17 95%CI (1.01-1.37). In the single-centre cohort, 14 (10.1%) patients required Balloon tamponade. Balloon tamponade utilization was significantly associated with alcohol abuse (50.4% vs 21.4%, P = .04), hepatocellular carcinoma (35.7% vs 8.8%, P = .01), higher median model for end-stage liver disease (MELD) score (26.3vs15.5, P = .002) and active bleeding during endoscopy (64.3% vs 27.5%, P = .01). Failure to provide all quality metrics was associated with a higher model for end-stage liver disease-adjusted risk of Balloon tamponade use: OR 16.7 95% CI(4.17-100.0, P < .0001). CONCLUSION: Balloon tamponade use is associated with severity of bleeding but may also implicate deficits in processes of care. Even for patients who did not need Balloon tamponade, presentation to hospitals with high Balloon tamponade utilization increases their odds of dying from acute variceal haemorrhage.

A Comparative Study of Albumin-Bilirubin Score with Child-Pugh Score, Model for End-Stage Liver Disease Score and Indocyanine Green R15 in Predicting Posthepatectomy Liver Failure for Hepatocellular Carcinoma Patients.

BACKGROUND: The albumin-bilirubin (ALBI) grade is a newly proposed model for assessing the hepatic function. This study aimed to compare the value of the ALBI score with Child-Pugh score, model for end-stage liver disease (MELD) score and indocyanine green (ICG) R15 in predicting posthepatectomy liver failure (PHLF). METHODS: Patients undergoing curative resection for hepatocellular carcinoma (HCC) between January 2014 and June 2017 were enrolled. The values of the Child-Pugh score, MELD score, ICG R15 and ALBI score in predicting PHLF were evaluated. RESULTS: A total of 473 HCC patients were enrolled. The ALBI score was identified as an independent predictor of PHLF. The AUCs for the Child-Pugh score, MELD score, ICG R15 and ALBI score in predicting PHLF were 0.665, 0.649, 0.668, and 0.745 respectively. Multivariable analyses revealed that the ALBI score was an independent predictor of PHLF regardless of the hepatectomy subgroups, but the Child-Pugh score and MELD score were not significant predictors of PHLF both in major and minor hepatectomy subgroups, and ICG R15 was only a significant predictor of PHLF in minor hepatectomy subgroup. CONCLUSION: The ALBI score showed superior predictive value of PHLF over Child-Pugh score, MELD score and ICG R15. We propose to use the ALBI score to evaluate surgical risk for HCC patients undergoing hepatic resection.

Profile and outcome of first 109 cases of paediatric acute liver failure at a specialized paediatric liver unit in India.

BACKGROUND & AIMS: The outcome of paediatric acute liver failure largely depends on age and aetiology. The aim of this work was to study the aetiological spectrum and outcome of the paediatric acute liver failure cases. METHODS: This prospective observational study included all children (<18 years age) fulfilling paediatric acute liver failure study group definition. Aetiological evaluation was done and predictive factors for poor outcome (death or liver transplantation) were analysed. RESULTS: There were 109 children in total. The commonest aetiology was viral infections (50, 45.8%) followed by metabolic liver diseases (14, 13.2%) and drug-induced liver injury (12, 11%). Viral, indeterminate and drug-induced liver injury group were older in age, had higher international normalized ratio and alanine transaminases in comparison with those with metabolic liver diseases and other aetiologies (P<.05). At 90 days from presentation, 52 (47.7%) children survived with native liver. On multivariate analysis, jaundice to encephalopathy interval >7 days (adjusted OR: 9.16, 95% CI: 1.55-53) and higher paediatric/model for end-stage liver disease scores at 72 hours (adjusted OR: 1.2, 95% CI: 1.08-1.32) were associated with poor outcome. CONCLUSION: Viral infections, indeterminate and drug-induced liver injury-related paediatric acute liver failure usually present in older children with higher international normalized ratio and alanine transaminases. Jaundice to encephalopathy interval >7 days and paediatric/model for end stage liver disease score >24 at 72 hours are associated with poor outcome.

Challenges in Patient Enrollment and Retention in Clinical Studies for Alcoholic Hepatitis: Experience of the TREAT Consortium.

The TREAT Consortium has carried out clinical studies on alcoholic hepatitis (AH) for over 4 years. We encountered problems with participant recruitment, retention, and eligibility for specific protocols. To improve our ability to carry out such trials, we reviewed recruitment screening logs, end of study logs, and surveyed study coordinators to learn the reasons for missing patients, why patients declined enrollment, and the number of patients eligible for treatment trials. Associations of the recruited subjects' demographics with their adherence to follow-up appointments were examined. Three hundred eight-seven patients (AH and heavy drinking controls) were enrolled in the observational study, and 55 AH patients were recruited into treatment trials. About half of patients identified with AH could not be recruited; no specific reason could be determined for about two-thirds of these. Among the patients who gave a reason for not participating, the most common reasons were feeling too sick to participate, desire to concentrate on abstinence, and lack of interest in research. Approximately a quarter of the AH patients met eligibility criteria for treatment trials for moderate or severe AH and we were able to recruit half to two-thirds of those eligible. Approximately 35% of participants in the observational study returned for both 6- and 12-month follow-up visits. We did not identify biopsychosocial or demographic correlates of retention in the study. This analysis revealed that attempts at recruitment into trials for AH miss some subjects because of structural issues surrounding their hospital admission, and encounter a high rate of patient refusal to participate. Nonetheless, more than half of the patients who met the eligibility criteria for moderate or severe AH were entered into clinical trials. Retention rates for the observational study are relatively low. These findings need to be accounted for in clinical trial design and power analysis.

Characteristics of liver transplant candidates delisted following recompensation and predictors of such delisting in alcohol-related liver disease: a case-control study.

Whether and when recovery beyond the need for transplant may occur in patients listed for decompensation remains unclear. This study aimed to investigate the characteristics of patients delisted following recompensation. Seventy-seven patients who were listed between 2005 and 2015 for decompensation, but later delisted following recompensation were included. Alcohol-related liver disease (ALD) was the underlying etiology in the majority (n = 47, 61%). Listing characteristics of these patients were compared with those of decompensated ALD patients who either underwent deceased donor liver transplantation or died on the waiting list. The model for end-stage liver disease (MELD) score <20 and serum albumin ≥32 g/l at listing were the only independent predictors of recompensation/delisting in ALD. The probability of recompensation was 70% when both factors were present at listing. Interestingly, about a tenth of decompensated ALD patients who died on the waiting list (median duration on waiting list 11 months) and a quarter of decompensated ALD patients who underwent living donor liver transplantation (median duration on waiting list 2 months) also had both factors at listing. In conclusion, ALD seems to be the most favorable etiology for recompensation beyond the need for transplantation. Both MELD and serum albumin at listing independently predict recompensation/delisting in ALD. It seems advisable to implement a period of observation for ALD patients with both favorable factors, before embarking on living donor liver transplantation.

Evaluation of neutrophil/leukocyte ratio and organ failure score as predictors of reversibility and survival following an acute-on-chronic liver failure event.

AIM: Acute-on-chronic liver failure (ACLF) is defined as an acute deterioration of liver disease with high mortality in patients with cirrhosis. The early mortality in ACLF is associated with organ failure and high leukocyte count. The time needed to reverse this condition and the factors affecting mortality after the early 30-day-period were evaluated. METHODS: One hundred and ninety-seven consecutive patients with cirrhosis were included. Patients were prospectively followed up for 180 days. RESULTS: ACLF was diagnosed in 54.8% of the patients. Infection was the most common precipitating event in patients with ACLF. On multivariate analysis, only the neutrophil/leukocyte ratio and Chronic Liver Failure Consortium Organ Failure (CLIF-C OF) score were associated with mortality. Hazard ratios for mortality of patients with ACLF compared with those without at different time end-points post-enrollment revealed that the relative risk of death in the ACLF group was 8.54 during the first 30-day period and declined to 1.94 during the second period of observation. The time varying effect of neutrophil/leukocyte ratio and CLIF-C score was negative (1% and 18% decline in the hazard ratio per month) while that of Model for End-Stage Liver Disease (MELD) was positive (3% increase in the hazard ratio per month). CONCLUSION: The condition of ACLF was reversible in patients who survived. During the 30-180-day period following the acute event, the probability of death in ACLF became gradually similar to the non-ACLF group. The impact of inflammatory response and organ failure on survival is powerful during the first 30-day period and weakens thereafter while that of MELD increases.

The outcomes of pediatric living donor liver transplantation using small-for-size grafts: experience of a single institute.

PURPOSE: We aimed to evaluate patients who had undergone pediatric LDLT with small-for-size graft (SFSG) and identify risk factors of graft failure to establish a preoperative graft selection strategy. METHODS: The data was collected retrospectively. SFSG was used in 14LDLTs (5.7%) of 245 LDLTs performed between May 2001 and March 2014. The mean patient age and body weight at LDLT were 12.6 ± 2.0 years and 40.5 ± 9.9 kg, respectively. The graft type was left lobe in six patients, left + caudate lobe in seven patients, and posterior segment in one patient. RESULTS: The graft survival rates in SFSG and non-SFSG groups were 78.9 and 93.1%, respectively (p = 0.045). In the univariate analysis, bleeding volume during LDLT were an independent risk factors for graft failure (p = 0.011). Graft failure was caused by sepsis in all three patients and occurred at a median of 70 postoperative days 70 (range 14-88 days). Among them, two cases showed high preoperative PELD/MELD score (PELD; 19.4 and MELD; 22, respectively). CONCLUSIONS: Pediatric LDLT using SFSG had poor outcome and prognosis, especially when it accompanies the surgical infectious complications with preoperative high PELD/MELD scores.

Glomerular filtration rate is an independent factor of mortality in patients with decompensated cirrhosis.

AIM: Although serum creatinine is included in the Model for End-Stage Liver Disease (MELD) score, it is an inaccurate marker of renal function, namely, of glomerular filtration rate ("true" GFR) in patients with decompensated cirrhosis. Our aim was to investigate the impact of MELD score and "true" GFR as determinants of survival in patients with decompensated cirrhosis. METHODS: We included all consecutive patients with decompensated cirrhosis who were admitted to our department. Renal function was assessed by creatinine- and cystatin-based estimated GFR and "true" GFR using (51) Cr-ethylenediaminetetraacetic acid. The independent factors associated with survival were evaluated. The discriminative ability of the prognostic scores (MELD and modifications of MELD score) were evaluated by using the area under the receiver-operator curve (AUC). RESULTS: One hundred and ten consecutive patients (77 men, aged 56 ± 12 years); at the end of follow up (8 months; range, 6-18), 92 patients (84%) were alive and 18 (16%) had died. In multivariate analysis, serum bilirubin (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.05-1.26; P = 0.020) and "true" GFR (HR, 0.96; 95% CI, 0.93-0.98; P = 0.003) were the only independent factors significantly associated with the outcome. The derived new prognostic model had high discriminative ability (AUC, 0.90), which was confirmed in the validation sample of 77 patients. CONCLUSION: In our cohort of patients with decompensated cirrhosis, "true" GFR and bilirubin were the independent factors of the outcome.

Survival predictors in ventricular assist device patients with prior extracorporeal life support: selecting appropriate candidates.

Several centers turn patients down for long-term ventricular assist devices (VADs) once they have received extracorporeal life support (ECLS) due to the expected poor outcome in these patients. The aim of this study was to identify survival predictors in this cohort of patients. Data of patients undergoing VAD support between January 2010 and November 2013 were retrospectively reviewed. Patients on ECLS support before implantation were considered eligible for inclusion. Outcome in survivors following long-term VAD support was compared with outcomes in nonsurvivors. Student's t-test and χ(2)-test were used as applicable. A total of 65 long-term VADs were implanted. The inclusion criteria were met by 24 patients. Eight patients did not survive the first 30 days. All preoperative characteristics were comparable between the two groups except for statistically higher Model for End-stage Liver Disease (MELD) score, bilirubin, white blood cell count, and blood urea nitrogen in nonsurvivors (P = 0.002, 0.01, 0.01, and 0.003, respectively). Stepwise discriminant analysis revealed MELD score as the most important survival predictor. Based on this analysis, an outcome predictor formula was generated. The 30-day and 1-year survival rates were 67% and 54%, respectively. In this study, we were able to determine survival predictors in VAD patients with prior ECLS support. The outcome in these patients is limited and associated with higher postoperative complications, particularly right ventricular and respiratory failure. The pre-VAD MELD score is an important predictor of poor outcome.

Comprehensive Treatment of Total Arch Replacement in a Patient With Liver Cirrhosis: A Case Report.

A 78-year-old woman with liver cirrhosis due to chronic hepatitis C visited our department for treatment of a thoracic aortic aneurysm. Her Child-Pugh classification was class A, and her model for end-stage liver (MELD) disease score was 8. As she also had thrombocytopenia associated with splenomegaly and esophageal varices, endoscopic injection sclerotherapy and partial splenic embolization were performed before total arch replacement surgery for treating esophageal varices to reduce the bleeding risk during transesophageal echocardiography and for thrombocytopenia, respectively. After endoscopic injection sclerotherapy and partial splenic embolization, the platelet count increased; hence, total arch replacement surgery was performed. By combining partial splenic embolization and endoscopic injection sclerotherapy, we were able to safely perform transesophageal echocardiography and total arch replacement surgery in the perioperative period.

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

BACKGROUND: 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. AIM: 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. METHODS: 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 ß-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). RESULTS: 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. ß-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. CONCLUSION: QTc is prolonged in cirrhosis independently of sex, age, and etiology but is correlated with severity and affected by ß-blockers and acute gastrointestinal bleeding. QTc is improved after liver Tx.

Stratified Analysis of Survival Benefit for ABO-incompatible Deceased-donor Liver Transplantation: Multicenter Propensity Score-matched Study.

Background and Aims: Liver transplantation (LT) using ABO-incompatible (ABOi) grafts can extend the donor pool to a certain extent and hence reduce the waiting time for transplantation. However, concerns of the impending prognosis associated with this option, especially for patients with liver failure and higher model for end-stage liver disease (MELD) scores, who tend to be more fragile during the waiting period before LT. Methods: Recipients undergoing LT for acute-on-chronic liver failure or acute liver failure were retrospectively enrolled at four institutions. Overall survival was compared and a Cox regression analysis was performed. Propensity score matching was performed for further comparison. Patients were stratified by MELD score and cold ischemia time (CIT) to determine the subgroups with survival benefits. Results: Two hundred ten recipients who underwent ABOi LT and 1,829 who underwent ABO compatible (ABOc) LT were enrolled. The 5-year overall survival rate was significantly inferior in the ABOi group compared with the ABOc group after matching (50.6% vs. 75.7%, p<0.05). For patients with MELD scores ≤30, using ABOi grafts achieved a comparable overall survival rate as using ABOc grafts (p>0.05). Comparison of the survival rates revealed no statistically significant difference for patients with MELD scores ≥40 (p>0.05). For patients with MELD scores of 31-39, the overall survival rate was significantly inferior in the ABOi group compared with the ABOc group (p<0.001); however, the rate was increased when the liver graft CIT was<8 h. Conclusions: For recipients with MELD scores ≤30, ABOi LT had a prognosis comparable to that of ABOc LT and can be regarded as a feasible option. For recipients with MELD scores ≥40, ABOi should be adopted with caution in emergency cases. For recipients with MELD scores of 31-39, the ABOi LT prognosis was worse. However, those patients benefited from receiving ABOi grafts with a CIT of <8 h.

DCD liver transplant in patients with a MELD over 35.

Introduction: Donation after circulatory death (DCD) liver transplantation (LT) makes up well less than 1% of all LTs with a Model for End-Stage Liver Disease (MELD)≥35 in the United States. We hypothesized DCD-LT yields acceptable ischemia-reperfusion and reasonable outcomes for recipients with MELD≥35. Methods: We analyzed recipients with lab-MELD≥35 at transplant within the UCSF (n=41) and the UNOS (n=375) cohorts using multivariate Cox regression and propensity score matching. Results: In the UCSF cohort, five-year patient survival was 85% for DCD-LTs and 86% for matched-Donation after Brain Death donors-(DBD) LTs (p=0.843). Multivariate analyses showed that younger donor/recipient age and more recent transplants (2011-2021 versus 1999-2010) were associated with better survival. DCD vs. DBD graft use did not significantly impact survival (HR: 1.2, 95%CI 0.6-2.7). The transaminase peak was approximately doubled, indicating suggesting an increased ischemia-reperfusion hit. DCD-LTs had a median post-LT length of stay of 11 days, and 34% (14/41) were on dialysis at discharge versus 12 days and 22% (9/41) for DBD-LTs. 27% (11/41) DCD-LTs versus 12% (5/41) DBD-LTs developed a biliary complication (p=0.095). UNOS cohort analysis confirmed patient survival predictors, but DCD graft emerged as a risk factor (HR: 1.5, 95%CI 1.3-1.9) with five-year patient survival of 65% versus 75% for DBD-LTs (p=0.016). This difference became non-significant in a sub-analysis focusing on MELD 35-36 recipients. Analysis of MELD≥35 DCD recipients showed that donor age of <30yo independently reduced the risk of graft loss by 30% (HR, 95%CI: 0.7 (0.9-0.5), p=0.019). Retransplant status was associated with a doubled risk of adverse event (HR, 95%CI: 2.1 (1.4-3.3), p=0.001). The rejection rates at 1y were similar between DCD- and DBD-LTs, (9.3% (35/375) versus 1,541 (8.7% (1,541/17,677), respectively). Discussion: In highly selected recipient/donor pair, DCD transplantation is feasible and can achieve comparable survival to DBD transplantation. Biliary complications occurred at the expected rates. In the absence of selection, DCD-LTs outcomes remain worse than those of DBD-LTs.

Role of Quantitation of Saline Bubble Studies in Patients with Liver Cirrhosis.

OBJECTIVE: Microbubble contrast echocardiography with a late positive signal enables the detection of intrapulmonary vascular dilation, including hepatopulmonary syndrome, in patients with end-stage liver disease. We assessed the relationship between the severity of bubble study and clinical outcome. METHODS: We retrospectively analyzed 163 consecutive patients with liver cirrhosis who underwent an echocardiogram with bubble study from 2018 to 2021. Patients who were diagnosed with a late positive signal were divided into three groups: grade 1 (1-9 bubbles), grade 2 (10-30 bubbles) and grade 3 (>30 bubbles). RESULTS: Fifty-six percent of the patients had a late positive bubble study (grade 1: 31%, grade 2: 23%, grade 3: 46%). Patients with grade 3 had a significantly higher international normalized ratio, model for end-stage liver disease score and Child-Pugh score and a lower peripheral oxygen saturation compared with patients with a negative study. In patients undergoing liver transplant (LT), survival rates were similar among the groups (3-mo: >87%, 1-y: >87%, 2-y: >83%). However, survival rate was lower in grade 3 patients without LT (3-mo: 81%, 1-y: 64%, 2-y: 39%). CONCLUSION: Patients with grade 3 had much worse mortality without LT compared with other groups. However, after LT, all grades had equal survival. Therefore, patients with grade 3 may be considered as higher priority for LT.

The positive impact of the COVID 19 pandemic on organ utilisation in liver transplantation.

Background: As the world recovers from the aftermath of devastating waves of an outbreak, the ongoing Coronavirus disease 2019 pandemic has presented a unique perspective to the transplantation community of ''organ utilisation'' in liver transplantation, a poorly defined term and ongoing hurdle in this field. To this end, we report the key metrics of transplantation activity from a high-volume liver transplantation centre in the United Kingdom over the past two years. Methods: Between March 2019 and February 2021, details of donor liver offers received by our centre from National Health Service Blood & Transplant, and of transplantation were reviewed. Differences in the activity before and after the outbreak of the pandemic, including short term post-transplant survival, have been reported. Results: The pandemic year at our centre witnessed a higher utilisation of Donation after Cardiac Death livers (80.4% vs. 58.3%, p = 0.016) with preserved United Kingdom donor liver indices and median donor age (2.12 vs. 2.02, p = 0.638; 55 vs. 57 years, p = 0.541) when compared to the pre-pandemic year. The 1- year patient survival rates for recipients in both the periods were comparable. The pandemic year, that was associated with increased utilisation of Donation after Cardiac Death livers, had an ischaemic cholangiopathy rate of 6%. Conclusions: The pressures imposed by the pandemic led to increased utilisation of specific donor livers to meet patient needs and minimise the risk of death on the waiting list, with apparently preserved early post-transplant survival. Optimum organ utilisation is a balancing act between risk and benefit for the potential recipient, and technologies like machine perfusion may allow surgeons to increase utilisation without compromising patient outcomes.

Lymphocyte-to-white blood cell ratio is associated with outcome in patients with hepatitis B virus-related acute-on-chronic liver failure.

BACKGROUND: The lymphocyte-to-white blood cell ratio (LWR) is a blood marker of the systemic inflammatory response. The prognostic value of LWR in patients with hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) remains unclear. AIM: To explore whether LWR could stratify the risk of poor outcomes in HBV-ACLF patients. METHODS: This study was conducted by recruiting 330 patients with HBV-ACLF at the Department of Gastroenterology in a large tertiary hospital. Patients were divided into survivor and non-survivor groups according to their 28-d prognosis. The independent risk factors for 28-d mortality were calculated by univariate and multivariate Cox regression analyses. Patients were divided into low- and high-LWR groups according to the cutoff values. Kaplan-Meier analysis was performed according to the level of LWR. RESULTS: During the 28-d follow-up time, 135 patients died, and the mortality rate was 40.90%. The LWR level in non-surviving patients was significantly decreased compared to that in surviving patients. A lower LWR level was an independent risk factor for poor 28-d outcomes (hazard ratio = 0.052, 95% confidence interval: 0.005-0.535). The LWR level was significantly negatively correlated with the Child-Turcotte-Pugh, model for end-stage liver disease, and Chinese Group on the Study of Severe Hepatitis B-ACLF II scores. In addition, the 28-d mortality was higher for patients with LWR < 0.11 than for those with LWR ≥ 0.11. CONCLUSION: LWR may serve as a simple and useful tool for stratifying the risk of poor 28-d outcomes in HBV-ACLF patients.

Predicting the survival benefit of liver transplantation in HBV-related acute-on-chronic liver failure: an observational cohort study.

Background: Liver transplantation (LT) is an effective therapy for acute-on-chronic liver failure (ACLF) but is limited by organ shortages. We aimed to identify an appropriate score for predicting the survival benefit of LT in HBV-related ACLF patients. Methods: Hospitalized patients with acute deterioration of HBV-related chronic liver disease (n = 4577) from the Chinese Group on the Study of Severe Hepatitis B (COSSH) open cohort were enrolled to evaluate the performance of five commonly used scores for predicting the prognosis and transplant survival benefit. The survival benefit rate was calculated to reflect the extended rate of the expected lifetime with vs. without LT. Findings: In total, 368 HBV-ACLF patients received LT. They showed significantly higher 1-year survival than those on the waitlist in both the entire HBV-ACLF cohort (77.2%/52.3%, p < 0.001) and the propensity score matching cohort (77.2%/27.6%, p < 0.001). The area under the receiver operating characteristic curve (AUROC) showed that the COSSH-ACLF II score performed best (AUROC 0.849) at identifying the 1-year risk of death on the waitlist and best (AUROC 0.864) at predicting 1-year outcome post-LT (COSSH-ACLFs/CLIF-C ACLFs/MELDs/MELD-Nas: AUROC 0.835/0.825/0.796/0.781; all p < 0.05). The C-indexes confirmed the high predictive value of COSSH-ACLF IIs. Survival benefit rate analyses showed that patients with COSSH-ACLF IIs 7-10 had a higher 1-year survival benefit rate from LT (39.2%-64.3%) than those with score <7 or >10. These results were prospectively validated. Interpretation: COSSH-ACLF IIs identified the risk of death on the waitlist and accurately predicted post-LT mortality and survival benefit for HBV-ACLF. Patients with COSSH-ACLF IIs 7-10 derived a higher net survival benefit from LT. Funding: This study was supported by the National Natural Science Foundation of China (No. 81830073, No. 81771196) and the National Special Support Program for High-Level Personnel Recruitment (Ten-thousand Talents Program).