Aspirin for Metabolic Dysfunction-Associated Steatotic Liver Disease Without Cirrhosis: A Randomized Clinical Trial.

Importance: Aspirin may reduce severity of metabolic dysfunction-associated steatotic liver disease (MASLD) and lower the incidence of end-stage liver disease and hepatocellular carcinoma, in patients with MASLD. However, the effect of aspirin on MASLD is unknown. Objective: To test whether low-dose aspirin reduces liver fat content, compared with placebo, in adults with MASLD. Design, Setting, and Participants: This 6-month, phase 2, randomized, double-blind, placebo-controlled clinical trial was conducted at a single hospital in Boston, Massachusetts. Participants were aged 18 to 70 years with established MASLD without cirrhosis. Enrollment occurred between August 20, 2019, and July 19, 2022, with final follow-up on February 23, 2023. Interventions: Participants were randomized (1:1) to receive either once-daily aspirin, 81 mg (n = 40) or identical placebo pills (n = 40) for 6 months. Main Outcomes and Measures: The primary end point was mean absolute change in hepatic fat content, measured by proton magnetic resonance spectroscopy (MRS) at 6-month follow-up. The 4 key secondary outcomes included mean percentage change in hepatic fat content by MRS, the proportion achieving at least 30% reduction in hepatic fat, and the mean absolute and relative reductions in hepatic fat content, measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF). Analyses adjusted for the baseline value of the corresponding outcome. Minimal clinically important differences for study outcomes were not prespecified. Results: Among 80 randomized participants (mean age, 48 years; 44 [55%] women; mean hepatic fat content, 35% [indicating moderate steatosis]), 71 (89%) completed 6-month follow-up. The mean absolute change in hepatic fat content by MRS was -6.6% with aspirin vs 3.6% with placebo (difference, -10.2% [95% CI, -27.7% to -2.6%]; P = .009). Compared with placebo, aspirin treatment significantly reduced relative hepatic fat content (-8.8 vs 30.0 percentage points; mean difference, -38.8 percentage points [95% CI, -66.7 to -10.8]; P = .007), increased the proportion of patients with 30% or greater relative reduction in hepatic fat (42.5% vs 12.5%; mean difference, 30.0% [95% CI, 11.6% to 48.4%]; P = .006), reduced absolute hepatic fat content by MRI-PDFF (-2.7% vs 0.9%; mean difference, -3.7% [95% CI, -6.1% to -1.2%]; P = .004]), and reduced relative hepatic fat content by MRI-PDFF (-11.7 vs 15.7 percentage points; mean difference, -27.3 percentage points [95% CI, -45.2 to -9.4]; P = .003). Thirteen participants (32.5%) in each group experienced an adverse event, most commonly upper respiratory tract infections (10.0% in each group) or arthralgias (5.0% for aspirin vs 7.5% for placebo). One participant randomized to aspirin (2.5%) experienced drug-related heartburn. Conclusions and Relevance: In this preliminary randomized clinical trial of patients with MASLD, 6 months of daily low-dose aspirin significantly reduced hepatic fat quantity compared with placebo. Further study in a larger sample size is necessary to confirm these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT04031729.

Liver Transplant in Patients With Autoimmune Hepatitis: A Large Single-Center Study.

OBJECTIVES: Autoimmune hepatitis is a rare indication for liver transplant in Western countries. Our goal was to identify characteristics and long-term outcomes of patients who underwent liver transplant for autoimmune hepatitis-related end-stage liver disease at our center. MATERIALS AND METHODS: Adult patients who underwent primary liver transplant from January 2007 to March 2022 at Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran, were enrolled in our study. RESULTS: Among 1107 patients enrolled in our study, mean age was 45.94 ± 12.43 years (range, 16-73 years) and 423 (38.2%) female patients were included. Autoimmune hepatitis was the underlying cause of cirrhosis in 177 patients (experimental group); the other 930 patients did not have autoimmune hepatitis (control group). All patients were followed for a median of 60 ± 40.3 months (range, 3-187 months) after transplant. In the experimental group, patient survival rates at 1 month, 1 year, and 3 years were 87%, 81%, and 78%, which were not significantly different between the 2 groups (P = .445). Recurrence of autoimmune hepatitis was detected in 8 patients (4.5%) in the experimental group. Acute allograft rejection was more significantly detected in the patients with recurrence of autoimmune hepatitis than in patients without recurrence of autoimmune hepatitis. CONCLUSIONS: Liver transplant in patients with autoimmune hepatitis is safe and is associated with good outcomes.

Effect of Donors' Biliary Variation on Postoperative Biliary Complications in Living Donor Liver Transplantation: A Single-Center Observational Study in Vietnam.

BACKGROUND: Our study aims to evaluate the biliary anatomy variation according to the Varotti classification and its correlation with surgical outcomes for both donors and recipients undergoing living donor liver transplants (LDLTs). METHODS: A retrospective analysis of 150 LDLT cases performed at a single center in Vietnam with preoperative radiologic evaluations and intraoperative surgical assessments to identify biliary variant anatomy. Postoperative biliary complications were documented and analyzed. Statistical analysis was performed to determine any significant associations between biliary variations and post-transplant outcomes. RESULTS: One hundred fifty cases of LDLT at 108 Military Central Hospital from October 2017 to December 2022 were included in our study. Among the donors, the mean age was 30.89 ± 7.23, with male predominance (77.3%). The prevalence of type 1 biliary anatomy was 84.67%. Type 2, 3a, 3b, 4a, and 4b accounted for 5.33%, 2.67%, 5.33%, 0.67%, and 1.33% of cases, respectively. Donors' complications were witnessed in 7 cases (4.67%), and all needed intervention (Clavien-Dindo grade 3). Biliary complications were found in 36 (24.0%) recipients, with 22 (14.67%) cases of biliary stenosis and 16 (10.67%) cases of biliary leak, including 2 cases encountering both complications. Age, gender, graft type, preoperative liver function, biliary variant anatomy, number of graft orifices, Model for End-Stage Liver Disease score, and blood loss were not significant risk factors for recipients' biliary complications. Cold ischemia time significantly increased the biliary complication rate. CONCLUSIONS: This study shows that biliary variant anatomy is common in living liver donors. Such variations should not be a contraindication to liver donation. However, accurate pre- and intraoperative radiologic and surgical evaluations are fundamental for a careful reconstruction plan.

Cardiac Reverse Remodeling and Changes in Heart Failure Indices After Transcatheter Tricuspid Valve Replacement in Adults With Congenital Heart Disease.

BACKGROUND: There are limited data about changes in cardiac function (cardiac reverse remodeling) and heart failure indices after transcatheter tricuspid valve-in-valve replacement (TT-VIVR). The purpose of this study was to evaluate cardiac reverse remodeling and temporal changes in heart failure indices after TT-VIVR in adults with congenital heart disease. METHODS: Retrospective cohort study of adults with congenital heart disease that underwent TT-VIVR and had >6 months of follow-up (January 1, 2011, to April 30, 2023). Echocardiographic indices of cardiac remodeling and heart failure indices (New York Heart Association class, NT-proBNP (N-terminal pro-brain natriuretic peptide), glomerular filtration rate, and model for end-stage liver disease excluding international normalized ratio score) were assessed preintervention and at 1-, 3-, and 5-year postintervention. RESULTS: Of 39 patients (age 39 [32-46] years), 14 (36%) and 25 (64%) received Melody valve and Sapien valve prosthesis, respectively. At 1-year post-TT-VIVR, there was a temporal improvement in right atrial reservoir strain (17±8% versus 22±8%, P<0.001), right atrial volume (81 [59-108] versus 63 [48-82] mL/m2, P<0.001), right atrial pressure (12±4% versus 6±4%, P<0.001), and right ventricular global longitudinal strain (-15±7% versus -20±7%, P<0.001). Similarly, there was a temporal improvement in NT-proBNP, glomerular filtration rate, model for end-stage liver disease excluding international normalized ratio score, and New York Heart Association class. The temporal improvements in heart failure indices and valve function were maintained at 3- and 5-year post-TT-VIVR. CONCLUSIONS: Considering the significant mortality risk associated with reoperations for tricuspid valve replacement, these data suggest favorable outcomes after TT-VIVR, and support TT-VIVR as a viable alternative to surgical tricuspid valve replacement, especially in high-risk patients.

Chronic Liver Disease - What's New?

Chronic liver disease (CLD) is a persistent public health burden, with over one billion cases reported worldwide. In most cases, the progression of CLD is slow and undulating with end-stage liver disease developing at variable time points depending on the underlying etiology of the disease. The concept of reversibility or halting progression to end stage liver disease is recent and various medications are in the pipeline which influence the progression of CLD. Non-invasive tests for monitoring of CLD may have the potential to avoid the morbidity and mortality related to invasive procedures. However, their applicability and validation in pediatrics requires further development and a coordinated effort by large pediatric liver centres. Recent advances in metabolomics and modern molecular technologies have led to an understanding of the interaction between gut microbiome liver axis and gut dysbiosis contributing to liver diseases. In the future, modifying the gut microbiome has the potential to change the outcome and significantly reduce the morbidity associated with CLD. This article focuses on newer modalities and concepts in the management of CLD, which may help develop strategies to prevent its progression to end-stage liver disease and associated morbidity/mortality.

Indocyanine green clearance tests to assess liver transplantation outcomes: a systematic review.

BACKGROUND: Liver transplantation (LT) is the gold standard for end-stage liver disease, yet postoperative complications challenge patients and physicians. Indocyanine green (ICG) clearance, a quantitative dynamic test of liver function, is a rapid, reproducible, and reliable test of liver function. This study aimed to systematically review and summarize current literature analyzing the association between ICG tests and post-LT outcomes. METHODS: This systematic review was conducted according to PRISMA guidelines. MEDLINE and Cochrane Library, as main databases, and other sources were searched until August 2022 to identify articles reporting the prognostic value of postoperative ICG tests associated with outcomes of adult LT recipients.Risk of bias of included articles was assessed using Quality In Prognosis Studies tool. Methodological quality varied from low to high across risk of bias domains. RESULTS: Six studies conducted between 1994 and 2018 in Europe, America, and Asia were included. The study population ranged from 50 to 332 participants. ICG clearance on the first postoperative day was associated with early allograft dysfunction, graft loss, 1-month and 3-month patient survival probability, prolonged ICU, and hospital stay. The dichotomized ICG plasma disappearance rate (PDR) provided a strong association with medium-term and long-term outcomes: PDR less than 10%/min with 1-month mortality or re-transplantation (odds ratio: 7.89, 95% CI 3.59-17.34, P <0.001) and PDR less than 16.0%/min with 3-month patient survival probability (hazard ratio: 13.90, 95% CI 4.67-41.35, P <0.01). The preoperative model for end-stage liver disease and body mass index were independent prognostic factors for early allograft dysfunction, early complications, and prolonged ICU stay; post-LT prothrombin time and INR were independently associated with graft loss and bilirubin with a prolonged hospital stay. CONCLUSION: This review shows that ICG clearance tests are associated with graft function recovery, suggesting that a potential prognostic role of ICG test, as an aid in predicting the post-LT course, could be considered.

Role of intelligent/interactive qualitative and quantitative analysis-three-dimensional estimated model in donor-recipient size mismatch following deceased donor liver transplantation.

BACKGROUND: Donor-recipient size mismatch (DRSM) is considered a crucial factor for poor outcomes in liver transplantation (LT) because of complications, such as massive intraoperative blood loss (IBL) and early allograft dysfunction (EAD). Liver volumetry is performed routinely in living donor LT, but rarely in deceased donor LT (DDLT), which amplifies the adverse effects of DRSM in DDLT. Due to the various shortcomings of traditional manual liver volumetry and formula methods, a feasible model based on intelligent/interactive qualitative and quantitative analysis-three-dimensional (IQQA-3D) for estimating the degree of DRSM is needed. AIM: To identify benefits of IQQA-3D liver volumetry in DDLT and establish an estimation model to guide perioperative management. METHODS: We retrospectively determined the accuracy of IQQA-3D liver volumetry for standard total liver volume (TLV) (sTLV) and established an estimation TLV (eTLV) index (eTLVi) model. Receiver operating characteristic (ROC) curves were drawn to detect the optimal cut-off values for predicting massive IBL and EAD in DDLT using donor sTLV to recipient sTLV (called sTLVi). The factors influencing the occurrence of massive IBL and EAD were explored through logistic regression analysis. Finally, the eTLVi model was compared with the sTLVi model through the ROC curve for verification. RESULTS: A total of 133 patients were included in the analysis. The Changzheng formula was accurate for calculating donor sTLV (P = 0.083) but not for recipient sTLV (P = 0.036). Recipient eTLV calculated using IQQA-3D highly matched with recipient sTLV (P = 0.221). Alcoholic liver disease, gastrointestinal bleeding, and sTLVi > 1.24 were independent risk factors for massive IBL, and drug-induced liver failure was an independent protective factor for massive IBL. Male donor-female recipient combination, model for end-stage liver disease score, sTLVi ≤ 0.85, and sTLVi ≥ 1.32 were independent risk factors for EAD, and viral hepatitis was an independent protective factor for EAD. The overall survival of patients in the 0.85 < sTLVi < 1.32 group was better compared to the sTLVi ≤ 0.85 group and sTLVi ≥ 1.32 group (P < 0.001). There was no statistically significant difference in the area under the curve of the sTLVi model and IQQA-3D eTLVi model in the detection of massive IBL and EAD (all P > 0.05). CONCLUSION: IQQA-3D eTLVi model has high accuracy in predicting massive IBL and EAD in DDLT. We should follow the guidance of the IQQA-3D eTLVi model in perioperative management.

[Application Value of Novel Coagulation Markers in Predicting Postoperarative Complications in the Early Stage After Liver Transplantation].

Objective: To investigate the relationship between thrombin-antithrombin complex (TAT), plasmin-α 2-plasmininhibitor complex (PIC), soluble thrombomodulin (sTM), and tissue plasminogen activator-inhibitor complex (tPAIC) and postoperative complications in the early stage after liver transplantation (LT). Methods: We analyzed the perioperative clinical data, including plasma TAT, PIC, sTM, and tPAIC, of 130 post-LT patients admitted to the intensive care unit (ICU), West China Hospital, Sichuan University between December 2021 and November 2022. Patients were divided into two groups, a complication group and a non-complication group, according to whether they experienced complications of Clavien-Dindo (CD) grade Ⅲb and above within 30 days after the surgery. Univariate analysis and binary multivariate logistic regression models were used to determine the risk factors for complications within 30 days post-LT. Results: The incidence of complications of CD grade Ⅲb and above within 30 days post-LT was 33.1% (43/130). Patients in the complication group had significantly higher scores for the Model for End-Stage Liver Disease (MELD), operative time, intraoperative red blood cell transfusion volume, intraoperative plasma transfusion volume, and plasma TAT, PIC, sTM and tPAIC measured at the time of admission to ICU after the operation than those in the non-complication group did (all P<0.05). Logistic regression showed that for every single U of red blood cells transfused during the transplant surgery, the probabilities of complications within 30 days post-LT increased by 15.1% (95% confidence interval [ C I]: 1.070-1.239, P<0.001) and for the increase of every single TU/mL of plasma sTM measured upon post-LT admission to ICU, the probabilities of complications increased by 13.7% (95% CI: 1.060-1.220, P<0.001). Conclusion: Plasma sTM measured upon admission to ICU after LT is an independent risk factor for complications within 30 days post-LT, and additional assessment of sTM may help predict complications in the early stage post-LT.

Survival benefit of living-donor liver transplantation in patients with a model for end-stage liver disease over 30 in a region with severe organ shortage: a retrospective cohort study.

BACKGROUND: The benefits of living-donor liver transplantation (LDLT) in patients with a high Model for End-stage Liver Disease (MELD) score (who have high waitlist mortality) are unclear. Regional availability of deceased-donor organs must be considered when evaluating LDLT benefits. The authors aimed to compare the survival benefit of intended-LDLT to awaiting deceased-donor liver transplantation (DDLT) in patients with a MELD score greater than or equal to 30 in a region with severe organ shortage. MATERIALS AND METHODS: This retrospective review included 649 patients with a MELD score greater than or equal to 30 placed on the liver transplantation waitlist. They were divided into intended-LDLT ( n =205) or waiting-DDLT ( n =444) groups based on living-donor eligibility and compared for patient survival from the time of waitlisting. Post-transplantation outcomes of transplant recipients and living donors were analyzed. RESULTS: Intended-LDLT patients had higher 1-year survival than waiting-DDLT patients (53.7 vs. 28.8%, P <0.001). LDLT was independently associated with lower mortality [hazard ratio (HR), 0.62; 95% CI, 0.48-0.79; P <0.001]. During follow-up, 25 patients were de-listed, 120 underwent LDLT, 170 underwent DDLT, and 334 remained on the waitlist. Among patients undergoing transplantation, the risk of post-transplantation mortality was similar for LDLT and DDLT after adjusting for pretransplantation MELD score (HR, 1.86; 95% CI, 0.73-4.75; P =0.193), despite increased surgical complications after LDLT (33.1 vs. 19.4%, P =0.013). There was no mortality among living-donors, but 4.2% experienced complications of grade 3 or higher. CONCLUSIONS: Compared to awaiting DDLT, LDLT offers survival benefits for patients with a MELD score greater than or equal to 30, while maintaining acceptable donor outcomes. LDLT is a feasible treatment for patients with a MELD score greater than or equal to 30 in regions with severe organ shortages.

Early period intensive care follow-up after liver transplantation in children: a single center experience.

BACKGROUND: Liver transplantation (LT) is a well-established, life-saving treatment for children with irreversible acute and chronic liver failure (LF). We aimed to evaluate the factors associated with morbidity and mortality in the early period of LT in children by reviewing our pediatric intensive care unit (PICU) experience. METHODS: We reviewed children`s medical records followed in the PICU after LT between May 2015-August 2021, including demographic parameters, indications for LT, operative variables, respiratory and circulatory support requirements, LT-related complications and survival. RESULTS: During this period, 40 pediatric patients who underwent LT were evaluated. LT was performed in 35 (87.5%) cases of chronic liver disease and 5 (12.5%) cases of acute liver failure. Twenty-four patients had chronic liver failure due to cholestatic liver disease. The patients` Pediatric Risk of Mortality (PRISM) III score was 18.82±SD (2-58) at PICU admission. 1-year survival was 87.5%, and overall survival was 85%. Younger age, low body weight, preoperative pediatric end-stage liver disease (PELD), and model for end-stage liver disease (MELD) values of 20 and higher were important risk factors for unfavorable outcomes after living donor liver transplantation (LDLT). These risk factors are both associated with technically more challenging vascular and bile duct reconstruction and higher complication rates, and increased mortality during the early period after LT. CONCLUSIONS: The early period of optimum PICU management in pediatric LT recipients is crucial for successful outcomes, which is also related to the patients` characteristics, disease severity scores, and surgical procedures.

Prevalence and Risk Factors of Post-chemoembolization Syndrome After Chemo-Embolization for Hepatocellular Carcinoma in Thailand.

BACKGROUND: The data regarding the incidence of post-embolization syndrome after transarterial chemoembolization for hepatocellular carcinoma in Thailand are scarce. Therefore, this study aimed to determine the prevalence and predictors of post-embolization syndrome after transarterial chemoembolization for hepatocellular carcinoma in Thailand. METHODS: This retrospective study collected data from patients undergoing transarterial chemoembolization for five years. Post-embolization syndrome was defined as fever and/or abdominal pain, and/or nausea or vomiting that occurred within three days after the transarterial chemoembolization procedure for hepatocellular carcinoma or hospital discharge. Pre-defined predictors for post-embolization syndrome were explored using Poisson regression analysis. RESULTS: Of the 298 patients and 739 transarterial chemoembolization procedures, the incidence of post-embolization syndrome was 68.1% (203/298) and the incidence density was 53.9% (398/739). Tumor size, Barcelona Clinic Liver Cancer stages, and dose of chemotherapy showed no association with the occurrence of PES. However, a model for end-stage liver disease score was the only predictor for post-embolization syndrome [adjusted IRR 0.91 (0.84-0.98); p = 0.01]. There were three patients developing fever after transarterial chemoembolization due to infection. CONCLUSION: Post-embolization syndrome was common in patients undergoing transarterial chemoembolization for hepatocellular carcinoma. Patients with a lower model for end-stage liver disease scores were at increased risk of post-embolization syndrome. This study highlights the burden of post-embolization syndrome among patients with hepatocellular carcinoma receiving transarterial chemoembolization.

Liver transplant outcomes using late allocation grafts.

Post-cross clamp late allocation (LA) liver allografts are at increased risk for discard for many reasons including logistical complexity. Nearest neighbor propensity score matching was used to match 2 standard allocation (SA) offers to every 1 LA liver offer performed at our center between 2015 and 2021. Propensity scores were based on a logistic regression model including recipient age, recipient sex, graft type (donation after circulatory death vs. donation after brain death), Model for End-stage Liver Disease (MELD), and DRI score. During this time, 101 liver transplants (LT) were performed at our center using LA offers. In comparing LA and SA offers, there were no differences in recipient characteristics including indication for transplant ( p = 0.29), presence of PVT ( p = 0.19), TIPS ( p = 0.83), and HCC status ( p = 0.24). LA grafts came from younger donors (mean age 43.6 vs. 48.9 y, p = 0.009) and were more likely to come from regional or national Organ Procurement Organizations (OPOs) ( p < 0.001). Cold ischemia time was longer for LA grafts (median 8.5 vs 6.3 h, p < 0.001). Following LT, there were no differences between the 2 groups in intensive care unit ( p = 0.22) and hospital ( p = 0.49) lengths of stay, need for endoscopic interventions ( p = 0.55), or biliary strictures ( p = 0.21). Patient (HR 1.0, 95% CI, 0.47-2.15, p = 0.99) and graft (HR 1.23, 95% CI, 0.43-3.50, p = 0.70) survival did not vary between the LA and SA cohorts. One-year LA and SA patient survival was 95.1% and 95.0%; 1-year graft survival was 93.1% and 92.1%, respectively. Despite the additional logistical complexity and longer cold ischemia time, LT outcomes utilizing LA grafts are similar to those allocated by means of SA. Improving allocation policies specific to LA offers, as well as the sharing of best practices between transplant centers and OPOs, are opportunities to further help minimize unnecessary discards.

Comparison of Liver Transplant Outcomes in Biliary Atresia Patients, Considering Whether They Underwent the Kasai Procedure Beforehand: A Single Center Analysis of 72 Patients.

BACKGROUND: This study examines the results of liver transplantation (LT) in patients with biliary atresia, considering whether they underwent the Kasai procedure beforehand. LT and determine postoperative and long-term graft outcomes. METHODS: This single-center, retrospective study included 72 pediatric patients diagnosed with postpartum biliary atresia who underwent LT between 2010 and 2022. We included patients who underwent LT either after or without the Kasai procedure and compared the demographic data of the patients with various factors, such as the Pediatric End-Stage Liver Disease scores and laboratory values. RESULTS: The study included 72 patients, with 39 of them being female (54.2%) and 33 of them being male (45.8%). Of the 72 patients in the study, 47 (65.3%) had undergone the Kasai procedure, and 25 (34.7%) had not. The preoperative and postoperative month 1 bilirubin values were lower in patients who underwent the Kasai procedure and were higher in postoperative months 3 and 6. Preoperative bilirubin values, postoperative month 3 bilirubin values, and preoperative albumin values were higher in patients who developed mortality (P < .05). Cold ischemia time was longer in patients who developed mortality (P < .05). CONCLUSIONS: Our study showed a higher mortality rate in patients who underwent the Kasai procedure. The results also showed that LT was more effective in children, as patients with Kasai had higher mean bilirubin values and higher preoperative albumin values than patients without Kasai.

Effect of Prophylactic Antibiotics on Mortality in Severe Alcohol-Related Hepatitis: A Randomized Clinical Trial.

Importance: The benefits of prophylactic antibiotics for hospitalized patients with severe alcohol-related hepatitis are unclear. Objective: To determine the efficacy of amoxicillin-clavulanate, compared with placebo, on mortality in patients hospitalized with severe alcohol-related hepatitis and treated with prednisolone. Design, Setting, and Participants: Multicenter, randomized, double-blind clinical trial among patients with biopsy-proven severe alcohol-related hepatitis (Maddrey function score ≥32 and Model for End-stage Liver Disease [MELD] score ≥21) from June 13, 2015, to May 24, 2019, in 25 centers in France and Belgium. All patients were followed up for 180 days. Final follow-up occurred on November 19, 2019. Intervention: Patients were randomly assigned (1:1 allocation) to receive prednisolone combined with amoxicillin-clavulanate (n = 145) or prednisolone combined with placebo (n = 147). Main Outcome and Measures: The primary outcome was all-cause mortality at 60 days. Secondary outcomes were all-cause mortality at 90 and 180 days; incidence of infection, incidence of hepatorenal syndrome, and proportion of participants with a MELD score less than 17 at 60 days; and proportion of patients with a Lille score less than 0.45 at 7 days. Results: Among 292 randomized patients (mean age, 52.8 [SD, 9.2] years; 80 [27.4%] women) 284 (97%) were analyzed. There was no significant difference in 60-day mortality between participants randomized to amoxicillin-clavulanate and those randomized to placebo (17.3% in the amoxicillin-clavulanate group and 21.3% in the placebo group [P = .33]; between-group difference, -4.7% [95% CI, -14.0% to 4.7%]; hazard ratio, 0.77 [95% CI, 0.45-1.31]). Infection rates at 60 days were significantly lower in the amoxicillin-clavulanate group (29.7% vs 41.5%; mean difference, -11.8% [95% CI, -23.0% to -0.7%]; subhazard ratio, 0.62; [95% CI, 0.41-0.91]; P = .02). There were no significant differences in any of the remaining 3 secondary outcomes. The most common serious adverse events were related to liver failure (25 in the amoxicillin-clavulanate group and 20 in the placebo group), infections (23 in the amoxicillin-clavulanate group and 46 in the placebo group), and gastrointestinal disorders (15 in the amoxicillin-clavulanate group and 21 in the placebo group). Conclusion and Relevance: In patients hospitalized with severe alcohol-related hepatitis, amoxicillin-clavulanate combined with prednisolone did not improve 2-month survival compared with prednisolone alone. These results do not support prophylactic antibiotics to improve survival in patients hospitalized with severe alcohol-related hepatitis. Trial Registration: ClinicalTrials.gov Identifier: NCT02281929.

[Risk Factors and Prognosis of Delirium After Liver Transplantation].

Objective: To analyze the incidence, the onset time, and the risk factors of delirium after liver transplantation (LT). Methods: The clinical data of 211 patients who underwent LT at Third Xiangya Hospital, Central South University between January 2019 and December 2021 were collected to investigate the incidence and the onset time of postoperative delirium. Univariate analysis and multivariate logistic regression analysis were conducted to analyze the risk factors of delirium and to analyze the effect of delirium on clinical outcomes. Results: The incidence of delirium was 20.4% (43/211) and the median interval between LT and the onset of delirium was 19 hours. Univariate analysis showed that the preoperative Model for End-Stage Liver Disease (MELD) score≥22, preoperative length-of-stay≥7, liver cancer, preoperative hepatic encephalopathy, infections within 2 months before LT, preoperative lymphocyte value<0.5×10 9 L －1, massive amount of intraoperative red blood cell infusion, and carbapenem antibiotics use for 3 days or longer were associated with postoperative delirium. Multivariate logistic regression analysis showed that preoperative infections within 2 months before LT (odds ratio [ OR]=2.597, 95% confidence interval [ CI]: 1.135-5.944, P=0.024), preoperative MELD score≥22 ( OR=2.967, 95% CI: 1.104-7.975, P=0.031), and preoperative hepatic encephalopathy ( OR=4.700, 95% CI: 2.043-10.602, P<0.001) were independent risk factors for delirium after LT, while carbapenems antibiotics use for 3 days or longer ( OR=0.192, 95% CI: 0.083-0.441, P<0.001) was a protective factor for postoperative delirium among LT recipients. Regarding clinical outcomes, patients with delirium had longer postoperative ICU length-of-stays than those without delirium did ( P=0.025). Conclusion: There is a high incidence of postoperative delirium among patients who undergo LT and the onset time of delirium after LT is early. Risk factors include preoperative infections, high MELD score, and hepatic encephalopathy. On the other hand, the use of carbapenems can help prevent delirium.

Artificial intelligence, machine learning, and deep learning in liver transplantation.

Liver transplantation (LT) is a life-saving treatment for individuals with end-stage liver disease. The management of LT recipients is complex, predominantly because of the need to consider demographic, clinical, laboratory, pathology, imaging, and omics data in the development of an appropriate treatment plan. Current methods to collate clinical information are susceptible to some degree of subjectivity; thus, clinical decision-making in LT could benefit from the data-driven approach offered by artificial intelligence (AI). Machine learning and deep learning could be applied in both the pre- and post-LT settings. Some examples of AI applications pre-transplant include optimising transplant candidacy decision-making and donor-recipient matching to reduce waitlist mortality and improve post-transplant outcomes. In the post-LT setting, AI could help guide the management of LT recipients, particularly by predicting patient and graft survival, along with identifying risk factors for disease recurrence and other associated complications. Although AI shows promise in medicine, there are limitations to its clinical deployment which include dataset imbalances for model training, data privacy issues, and a lack of available research practices to benchmark model performance in the real world. Overall, AI tools have the potential to enhance personalised clinical decision-making, especially in the context of liver transplant medicine.

Predictors and management of post-banding ulcer bleeding in cirrhosis: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Post-banding ulcer bleeding (PBUB) is an understudied complication of oesophageal varices endoscopic band ligation (EBL). This systematic review with meta-analysis aimed at: (a) evaluating the incidence of PBUB in patients with cirrhosis treated with EBL in primary or secondary prophylaxis or urgent treatment for acute variceal bleeding and (b) identifying predictors of PBUB. METHODS: We conducted a systematic review of articles in English published in 2006-2022 using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Searches were made in eight databases including Embase, PubMed and Cochrane Library. Random-effects meta-analysis was used to determine the incidence, mean interval and predictors of PBUB. RESULTS: Eighteen studies (9034 patients) were included. The incidence of PBUB was 5.5% (95% CI 4.3-7.1). The mean time for it to occur was 11 days (95% CI 9.94-11.97). Model for End-stage Liver Disease (MELD) score (OR 1.162, 95% CI 1.047-1.291) and EBL done in emergency setting (OR 4.902, 95% CI 2.99-8.05) independently predicted post-ligation ulcer bleeding. Treatment included drugs, endoscopic procedures and transjugular intrahepatic portosystemic shunt. Refractory bleeding was treated with self-expandable metallic stents or balloon tamponade. Mortality was on average 22.3% (95% CI 14.1-33.6). CONCLUSIONS: Patients with high MELD score and receiving EBL in an emergency setting are more prone to develop PBUB. Prognosis is still poor and the best therapeutic strategy to address remains to be ascertained.

Reassessing Geographic, Logistical, and Cold Ischemia Cutoffs in Liver Transplantation.

INTRODUCTION: Liver acceptance patterns vary significantly between transplant centers. Data pertaining to outcomes of livers declined by local and regional centers and allocated nationally remains limited. PROJECT AIM: The objective was to compare post-liver transplant outcomes between liver allografts transplanted as a result of national and local-regional allocation. DESIGN: This was a retrospective evaluation of 109 nationally allocated liver allografts used for transplant by a single center. Outcomes of nationally allocated grafts were compared to standard allocation grafts (N = 505) during the same period. RESULTS: Recipients of nationally allocated grafts had lower model for end stage liver disease scores (17 vs 22, P = .001). Nationally allocated grafts were more likely to be post-cross clamp offers (29.4% vs 13.4%, P = .001) and have longer cold ischemia times (median hours 7.8 vs 5.5, P = .001). Early allograft dysfunction was common (54.1% vs 52.5%, P = .75) and did not impact hospital length of stay (median 5 vs 6 days, P = .89). There were no differences in biliary complications (P = .11). There were no differences in patient (P = .88) or graft survival (P = .35). In a multivariate model, after accounting for differences in cold ischemia time and posttransplant biliary complications, nationally allocated grafts were not associated with increased risk for graft loss (HR 0.9, 95% CI 0.4-1.8). Abnormal liver biopsy findings (33.0%) followed by donor donation after circulatory death status (22.9%) were the most common reasons for decline by local-regional centers. CONCLUSION: Despite longer cold ischemia times, patient and graft survival outcomes remain excellent and comparable to those seen from standard allocation grafts.

Postoperative Outcomes in 415 Patients Following Liver Transplantation Using Extended Donor Criteria: A Study from a Single Center in Germany.

BACKGROUND Because of the massive organ shortage worldwide, marginal organs are increasingly being considered. The aim of this study was to present a comprehensive analysis of donor-related factors clinically supposed to influence the outcome after liver transplantation. This study from a single center in Germany aimed to evaluate postoperative outcomes in 415 patients following liver transplantation using extended donor criteria. MATERIAL AND METHODS Extended donor criteria (EDC) were considered according to the official guidelines issued through the German Medical Association. Other factors and the Eurotransplant Donor Risk Index (ET-DRI) were also considered. Correlation studies, logistic regression, and Kaplan-Meier-estimator were used to evaluate the outcome. RESULTS The postoperative outcomes with or without EDC were comparable. Other factors had an impact on early allograft failure (EAD), including male donors (χ²=14.135, P=0.0001). Other donor-unrelated factors, like cold ischemia time, also had an impact on EAD (r=0.135, P=0.010), especially in patients with model for end-stage liver disease (MELD) <25 (ß=0.001, P=0.008). ET-DRI was a crucial factor in estimating overall and allograft survival after liver transplantation. CONCLUSIONS The findings from this study support the possibility of liver transplantation using organs obtained by EDC. Other factors, like donor sex and cold ischemic time, are not part of the EDC, although they have an impact on EAD. Organs obtained by EDC continue to be an option to address the organ shortage.

A Single-Center's Early Surgical Outcomes of Living Donor Liver Transplantation.

BACKGROUND: Living donor liver transplantation (LDLT) has become an increasingly common surgical option because the number of cadaveric donors is insufficient to fulfill the organ needs of patients facing end-stage cirrhosis. Many centers are investigating different surgical techniques to achieve lower complication rates. We aimed to examine our complication rates in light of demographic data, graft data, and perioperative findings as a single-center experience. METHODS: The study included one hundred and three patients who underwent LDLT for end-stage liver cirrhosis. Demographic data; sex; age; blood group; Model for End-Stage Liver Disease score; Child score; etiology; liver side; graft-to-recipient weight ratio; hepatic artery, portal vein, and bile anastomosis type rates; anhepatic phase; cold ischemia time; operation time; and blood product transfusion rates were analyzed. Biliary complications in patients with single or multiple biliary anastomoses, right or left liver transplants, and with or without hepatic artery thrombosis were analyzed statistically. RESULTS: There was no significant difference in biliary complications between patients who underwent single or multiple bile anastomosis (P = .231) or patients receiving right lobe and left lobe transplants (P = .315). Although there was no statistically significant difference in the rate of portal vein thrombosis between the regular and reconstructed portal vein anastomosis groups (P = .693), the postoperative portal vein thrombosis rate was statistically higher in patients with left lobe transplants (P = .044). CONCLUSIONS: Vascular and biliary complication rates can be reduced with increasing experience.