Evaluation of terlipressin-related patient outcomes in hepatorenal syndrome-acute kidney injury using point-of-care echocardiography.

BACKGROUND AND AIMS: Treatment of hepatorenal syndrome-acute kidney injury (HRS-AKI), with terlipressin and albumin, provides survival benefits, but may be associated with cardiopulmonary complications. We analyzed the predictors of terlipressin response and mortality using point-of-care echocardiography (POC-Echo) and cardiac and renal biomarkers. APPROACH: Between December 2021 and January 2023, patients with HRS-AKI were assessed with POC-Echo and lung ultrasound within 6 hours of admission, at the time of starting terlipressin (48 h), and at 72 hours. Volume expansion was done with 20% albumin, followed by terlipressin infusion. Clinical data, POC-Echo data, and serum biomarkers were prospectively collected. Cirrhotic cardiomyopathy (CCM) was defined per 2020 criteria. RESULTS: One hundred and forty patients were enrolled (84% men, 59% alcohol-associated disease, mean MELD-Na 25±SD 5.6). A median daily dose of infused terlipressin was 4.3 (interquartile range: 3.9-4.6) mg/day; mean duration 6.4 ± SD 1.9 days; the complete response was in 62% and partial response in 11%. Overall mortality was 14% and 16% at 30 and 90 days, respectively. Cutoffs for prediction of terlipressin nonresponse were cardiac variables [ratio of early mitral inflow velocity and mitral annular early diastolic tissue doppler velocity > 12.5 (indicating increased left filling pressures, C-statistic: 0.774), tissue doppler mitral velocity < 7 cm/s (indicating impaired relaxation; C-statistic: 0.791), > 20.5% reduction in cardiac index at 72 hours (C-statistic: 0.885); p < 0.001] and pretreatment biomarkers (CysC > 2.2 mg/l, C-statistic: 0.640 and N-terminal proBNP > 350 pg/mL, C-statistic: 0.655; p <0.050). About 6% of all patients with HRS-AKI and 26% of patients with CCM had pulmonary edema. The presence of CCM (adjusted HR 1.9; CI: 1.8-4.5, p = 0.009) and terlipressin nonresponse (adjusted HR 5.2; CI: 2.2-12.2, p <0.001) were predictors of mortality independent of age, sex, obesity, DM-2, etiology, and baseline creatinine. CONCLUSIONS: CCM and reduction in cardiac index, reliably predict terlipressin nonresponse. CCM is independently associated with poor survival in HRS-AKI.

Safety and efficacy of continuous terlipressin infusion in HRS-AKI in a transplant population.

Hepatorenal syndrome-acute kidney injury (HRS-AKI) is associated with significant morbidity and mortality. While liver transplantation is the definitive treatment, continuous terlipressin infusion for HRS-AKI may provide benefit and, as such, was assessed in a population composed of candidates for liver transplant (LT). Fifty hospitalized LT-eligible patients with HRS-AKI received a single bolus followed by continuous terlipressin infusion. Acute-on-chronic liver failure grade 3, serum creatinine (SCr)>5.0 mg/dL, or Model for End-Stage Liver Disease (MELD) ≥35 were exclusions. Fifty hospitalized patients who received midodrine and octreotide or norepinephrine for HRS-AKI served as a historical comparator cohort. Complete response (CR) was defined as a ≥30% decrease in SCr with end-of-treatment (EOT) SCr≤1.5, partial response as a ≥30% decrease in SCr with EOT SCr>1.5, and nonresponse as a <30% decrease in SCr. CR rate was significantly higher in the terlipressin cohort compared to the historical cohort (64% vs. 16%, p <0.001). Survival, while numerically higher in those who received terlipressin, was statistically similar (D30: 94% vs. 82%, p =0.12; D90: 78% vs. 68%, p =0.37). Renal replacement therapy (RRT) was more common among terlipressin NR than CR and PR (70% vs. 3% vs. 13%, p < 0.001). EOT MELD and SCr were significantly lower within terlipressin cohort (MELD: 19 vs. 25, SCr: 1.4 vs. 2.1 mg/dL, p <0.001). Sixteen of 40 terlipressin-treated patients received LT-alone (terlipressin CR in 10/16). One patient on terlipressin had a hypoxic respiratory failure that responded to diuretics; one possibly had drug-related rash. With continuous terlipressin infusion, a CR rate of 64% was observed with a favorable safety profile. Terlipressin use was associated with lower EOT MELD and SCr than the historical midodrine and octreotide/norepinephrine cohort; LT-alone was accomplished in a high proportion of complete terlipressin responders.

Perioperative Characteristics and Outcomes of Fontan Versus Non-Fontan Patients Undergoing Combined Heart-Liver Transplantation: A Retrospective Cohort Study.

OBJECTIVES: Combined heart-liver transplantation (CHLT) is becoming increasingly frequent as a maturing population of patients with Fontan-palliated congenital heart disease develop advanced liver fibrosis or cirrhosis. The authors present their experience with CHLT for congenital and noncongenital indications, and identify characteristics associated with poor outcomes that may guide intervention in high-risk patients. DESIGN: This was a single-center retrospective cohort study. SETTING: This study was conducted at Vanderbilt University Medical Center in Nashville, Tennessee. PARTICIPANTS: The study included 16 consecutive adult recipients of CHLT at the authors' institution between April 2017 and February 2022. INTERVENTIONS: Eleven patients underwent transplantation for Fontan indications, and 5 were transplanted for non-Fontan indications. MEASUREMENTS AND MAIN RESULTS: Compared with non-Fontan patients, Fontan recipients had longer cardiopulmonary bypass duration (199 v 119 minutes, p =m0.002), operative times (786 v 599 minutes, p = 0.01), and larger blood product transfusions (15.4 v 6.3 L, p = 0.18). Six of 16 patients required extracorporeal membrane oxygenation (ECMO), of whom 4 were Fontan patients who subsequently died. Patients who required ECMO had lower 5-hour lactate clearance (0.0 v 3.5 mmol/L, p = 0.001), higher number of vasoactive infusions, lower pulmonary artery pulsatility indices (0.58 v 1.77, p = 0.03), and higher peak inspiratory pressures (28.0 v 18.5 mmHg, p = 0.01) after liver reperfusion. CONCLUSIONS: Combined heart-liver transplantation in patients with Fontan-associated end-organ disease is particularly challenging and associated with higher recipient morbidity compared with non-Fontan-related CHLT. Early hemodynamic intervention for signs of ventricular dysfunction may improve outcomes in this growing high-risk population.

The novel SALT-M score predicts 1-year post-transplant mortality in patients with severe acute-on-chronic liver failure.

BACKGROUND & AIMS: Twenty-eight-day mortality ranges from 30-90% in patients with acute-on-chronic liver failure grades 2/3 (severe ACLF). Though liver transplantation (LT) has demonstrated a survival benefit, the scarcity of donor organs and uncertainty regarding post-LT mortality among patients with severe ACLF may cause hesitancy. We developed and externally validated a model to predict 1-year post-LT mortality in severe ACLF, called the Sundaram ACLF-LT-Mortality (SALT-M) score, and estimated the median length of stay (LoS) after LT (ACLF-LT-LoS). METHODS: In 15 LT centers in the US, we retrospectively identified a cohort of patients with severe ACLF transplanted between 2014-2019, followed up to Jan'2022. Candidate predictors included demographics, clinical and laboratory values, and organ failures. We selected predictors in the final model using clinical criteria and externally validated them in two French cohorts. We provided measures of overall performance, discrimination, and calibration. We used multivariable median regression to estimate LoS after adjusting for clinically relevant factors. RESULTS: We included 735 patients, of whom 521 (70.8%) had severe ACLF (120 ACLF-3, external cohort). The median age was 55 years, and 104 with severe ACLF (19.9%) died within 1-year post-LT. Our final model included age >50 years, use of 1/≥2 inotropes, presence of respiratory failure, diabetes mellitus, and BMI (continuous). The c-statistic was 0.72 (derivation) and 0.80 (validation), indicating adequate discrimination and calibration based on the observed/expected probability plots. Age, respiratory failure, BMI, and presence of infection independently predicted median LoS. CONCLUSIONS: The SALT-M score predicts mortality within 1-year after LT in patients with ACLF. The ACLF-LT-LoS score predicted median post-LT stay. Future studies using these scores could assist in determining transplant benefits. IMPACT AND IMPLICATIONS: Liver transplantation (LT) may be the only life-saving procedure available to patients with acute-on-chronic liver failure (ACLF), but clinically instability can augment the perceived risk of post-transplant mortality at 1 year. We developed a parsimonious score with clinically and readily available parameters to objectively assess 1-year post-LT survival and predict median length of stay after LT. We developed and externally validated a clinical model called the Sundaram ACLF-LT-Mortality score in 521 US patients with ACLF with 2 or ≥3 organ failure(s) and 120 French patients with ACLF grade 3. The c-statistic was 0.72 in the development cohort and 0.80 in the validation cohort. We also provided an estimation of the median length of stay after LT in these patients. Our models can be used in discussions on the risks/benefits of LT in patients listed with severe ACLF. Nevertheless, the score is far from perfect and other factors, such as patient's preference and center-specific factors, need to be considered when using these tools.

Addressing the Burden and Management Strategies for Disparities and Inequities Among Liver Transplant Professionals: The ILTS Experience.

Medical professional environments are becoming increasingly multicultural, international, and diverse in terms of its specialists. Many transplant professionals face challenges related to gender, sexual orientation or racial background in their work environment or experience inequities involving access to leadership positions, professional promotion, and compensation. These circumstances not infrequently become a major source of work-related stress and burnout for these disadvantaged, under-represented transplant professionals. In this review, we aim to 1) discuss the current perceptions regarding disparities among liver transplant providers 2) outline the burden and impact of disparities and inequities in the liver transplant workforce 3) propose potential solutions and role of professional societies to mitigate inequities and maximize inclusion within the transplant community.

Management of cardiac diseases in liver transplant recipients: Comprehensive review and multidisciplinary practice-based recommendations.

Cardiac diseases are one of the most common causes of morbidity and mortality following liver transplantation (LT). Prior studies have shown that cardiac diseases affect close to one-third of liver transplant recipients (LTRs) long term and that their incidence has been on the rise. This rise is expected to continue as more patients with advanced age and/or non-alcoholic steatohepatitis undergo LT. In view of the increasing disease burden, a multidisciplinary initiative was developed to critically review the existing literature (between January 1, 1990 and March 17, 2021) surrounding epidemiology, risk assessment, and risk mitigation of coronary heart disease, arrhythmia, heart failure, and valvular heart disease and formulate practice-based recommendations accordingly. In this review, the expert panel emphasizes the importance of optimizing management of metabolic syndrome and its components in LTRs and highlights the cardioprotective potential for the newer diabetes medications (e.g., sodium glucose transporter-2 inhibitors) in this high-risk population. Tailoring the multidisciplinary management of cardiac diseases in LTRs to the cardiometabolic risk profile of the individual patient is critical. The review also outlines numerous knowledge gaps to pave the road for future research in this sphere with the ultimate goal of improving clinical outcomes.

Global impact of the first wave of COVID-19 on liver transplant centers: A multi-society survey (EASL-ESOT/ELITA-ILTS).

BACKGROUND AND AIMS: The global impact of SARS-CoV-2 on liver transplantation (LT) practices across the world is unknown. The goal of this survey was to assess the impact of the pandemic on global LT practices. METHOD: A prospective web-based survey (available online from 7th September 2020 to 31st December 2020) was proposed to the active members of the EASL-ESOT/ELITA-ILTS in the Americas (including North, Central, and South America) (R1), Europe (R2), and the rest of the world (R3). The survey comprised 4 parts concerning transplant processes, therapy, living donors, and organ procurement. RESULTS: Of the 470 transplant centers reached, 128 answered each part of the survey, 29 centers (23%), 64 centers (50%), and 35 centers (27%) from R1, R2, and R3, respectively. When we compared the practices during the first 6 months of the pandemic in 2020 with those a year earlier in 2019, statistically significant differences were found in the number of patients added to the waiting list (WL), WL mortality, and the number of LTs performed. At the regional level, we found that in R2 the number of LTs was significantly higher in 2019 (p <0.01), while R3 had more patients listed, higher WL mortality, and more LTs performed before the pandemic. Countries severely affected by the pandemic ("hit" countries) had a lower number of WL patients (p = 0.009) and LTs (p = 0.002) during the pandemic. Interestingly, WL mortality was still higher in the "non-hit" countries in 2020 compared to 2019 (p = 0.022). CONCLUSION: The first wave of the pandemic differentially impacted LT practices across the world, especially with detrimental effects on the "hit" countries. Modifications to the policies of recipient and donor selection, organ retrieval, and postoperative recipient management were adopted at a regional or national level. LAY SUMMARY: The health emergency caused by the coronavirus pandemic has dramatically changed clinical practice during the pandemic. The first wave of the pandemic impacted liver transplantation differently across the world, with particularly detrimental effects on the countries badly hit by the virus. The resilience of the entire transplant network has enabled continued organ donation and transplantation, ultimately improving the lives of patients with end-stage liver disease.

North American Practice-Based Recommendations for Transjugular Intrahepatic Portosystemic Shunts in Portal Hypertension.

Complications of portal hypertension, including ascites, gastrointestinal bleeding, hepatic hydrothorax, and hepatic encephalopathy, are associated with significant morbidity and mortality. Despite few high-quality randomized controlled trials to guide therapeutic decisions, transjugular intrahepatic portosystemic shunt (TIPS) creation has emerged as a crucial therapeutic option to treat complications of portal hypertension. In North America, the decision to perform TIPS involves gastroenterologists, hepatologists, and interventional radiologists, but TIPS creation is performed by interventional radiologists. This is in contrast to other parts of the world where TIPS creation is performed primarily by hepatologists. Thus, the successful use of TIPS in North America is dependent on a multidisciplinary approach and technical expertise, so as to optimize outcomes. Recently, new procedural techniques, TIPS stent technology, and indications for TIPS have emerged. As a result, practices and outcomes vary greatly across institutions and significant knowledge gaps exist. In this consensus statement, the Advancing Liver Therapeutic Approaches group critically reviews the application of TIPS in the management of portal hypertension. Advancing Liver Therapeutic Approaches convened a multidisciplinary group of North American experts from hepatology, interventional radiology, transplant surgery, nephrology, cardiology, pulmonology, and hematology to critically review existing literature and develop practice-based recommendations for the use of TIPS in patients with any cause of portal hypertension in terms of candidate selection, procedural best practices and, post-TIPS management; and to develop areas of consensus for TIPS indications and the prevention of complications. Finally, future research directions are identified related to TIPS for the management of portal hypertension.

Comorbid Chronic Diseases and Survival in Compensated and Decompensated Cirrhosis: A Population-Based Study.

INTRODUCTION: The burden of liver disease is substantial and increasing; the impact of comorbid chronic diseases on the clinical course of patients with compensated and decompensated cirrhosis is not well-defined. The aim of this study was to examine the individual and additive impact of comorbid chronic diseases on mortality in patients with cirrhosis. METHODS: In this population-based study, we used Cox proportional hazards modeling with time-dependent covariates to assess the impact of comorbid chronic diseases (diabetes mellitus, chronic kidney disease, and cardiovascular disease [CVD]) on mortality in patients with cirrhosis in a large, diverse Metroplex. RESULTS: There were 35,361 patients with cirrhosis (mean age 59.5 years, 41.8% females, 29.7% non-White, and 17.5% Hispanic ethnicity). Overall, the presence of chronic comorbidities was 1 disease (28.9%), 2 diseases (17.5%), and 3 diseases (12.6%) with a majority having CVD (45%). Adjusted risk of mortality progressively increased with an increase in chronic diseases from 1 (hazard ratio [HR] 2.5, 95% confidence interval [CI] 2.23-2.8) to 2 (HR 3.27.95% CI 2.9-3.69) to 3 (HR 4.52, 95% CI 3.99-5.12) diseases. Survival of patients with compensated cirrhosis and 3 chronic diseases was similar to subsets of decompensated cirrhosis (67.7% as compared with decompensated cirrhosis with 1-3 conditions, 61.9%-63.9%). DISCUSSION: In patients with cirrhosis, a focus on comorbid chronic disease(s) as potential management targets may help avoid premature mortality, regardless of etiology. Multidisciplinary care early in the clinical course of cirrhosis is needed in addition to the current focus on management of complications of portal hypertension.

Cirrhotic cardiomyopathy: Appraisal of the original and revised criteria in predicting posttransplant cardiac outcomes.

Cardiovascular disease (CVD) significantly contributes to morbidity and mortality after liver transplantation (LT). Cirrhotic cardiomyopathy (CCM) is a risk factor for CVD after transplant. CCM criteria were originally introduced in 2005 with a revision proposed in 2020 reflecting echocardiographic technology advancements. This study assesses the two criteria sets in predicting major adverse cardiac events (MACE) after transplant. This single-center retrospective study reviewed adult LT recipients between January 1, 2009, and December 31, 2018. Patients with insufficient pre-LT echocardiographic data, prior ischemic heart disease, portopulmonary hypertension, or longitudinal care elsewhere were excluded. The primary composite outcome was MACE (arrhythmia, heart failure, cardiac arrest, and/or cardiac death) after transplant. Of 1165 patients, 210 met the eligibility criteria. CCM was present in 162 patients (77%) per the original criteria and 64 patients (30%) per the revised criteria. There were 44 MACE and 31 deaths in the study period. Of the deaths, 38.7% occurred secondary to CVD. CCM defined by the original criteria was not associated with MACE after LT (p = 0.21), but the revised definition was significantly associated with MACE (hazard ratio [HR], 1.93; 95% confidence interval, 1.05-3.56; p = 0.04) on multivariable analysis. Echocardiographic variable analysis demonstrated low septal e' as the most predictive variable for MACE after LT (HR, 3.45; p < 0.001). CCM, only when defined by the revised criteria, was associated with increased risk for MACE after LT, validating the recently revised CCM definition. Abnormal septal e', reflecting impaired relaxation, appears to be the most predictive echocardiographic criterion for MACE after LT.

Pharmacotherapy for Weight Loss in Cirrhosis and Liver Transplantation: Translating the Data and Underused Potential.

BACKGROUND AND AIMS: Thirty percent of patients with cirrhosis are obese and the prevalence of obesity increases after transplant to >40% post-transplant. There are currently four weight loss medications approved by the FDA for treatment of obesity (orlistat, phentermine-topiramate, naltrexone-bupropion, and liraglutide). The aim of this review was to investigate the data on the use of these weight loss medications and alternative medicines in patients with cirrhosis and in liver transplant recipients (LTRs). APPROACH AND RESULTS: While there is paucity of data for these medications in patients with cirrhosis and LTRs, Liraglutide appears to be generally safe in view of its pharmacokinetic properties. Phentermine-topiramate seems to have the highest weight loss potential but special consideration should be given to neuropsychiatric disorders, cardiovascular comorbidities, and drug interactions. There are emerging data on use of alternative medicines for weight loss but more data are needed. CONCLUSIONS: The use of weight loss medications is feasible in this patient population but the decision of which medication to prescribe should be individualized based on the degree of renal and hepatic impairment, other co-morbidities, and concomitant medications.

Applicability of the UK DCD risk score in the modern era of liver transplantation: A U.S. update.

BACKGROUND: Careful graft and recipient selection have resulted in improved outcomes in liver transplantation (LT) using donation after cardiac death (DCD) organs. The UK DCD Risk Score was established as a risk stratification tool to guide selection. METHODS: We evaluated the applicability of the UK DCD Risk Score in a contemporary US cohort of adult DCD LT recipients using the United Network for Organ Sharing registry (2011-2020). RESULTS: A total of 3,899 DCD LTs were included in our study (UK DCD Risk Score 0-5 points: 1,438 [36.9%], 6-10 points: 2,034 [52.2%]; 11-20 points: 427 [11.0%]). Compared to a score of 6-10 points, a score of 0-5 points was associated with decreased risk of graft loss (HR = .79, 95%CI: .68-.93, p = .004), while a score of 11-20 points was associated with increased risk of graft loss (HR = 1.26, 95%CI: 1.01-1.56, p = .04). The 5-year graft survival for patients with risk scores of 0-5, 6-10, and 11-20 were 75.9%, 71.8%, and 66.5%, respectively. The C-statistic for the UK DCD Risk Score in our contemporary cohort was .611. CONCLUSIONS: The UK DCD Risk Score demonstrates a more limited ability to differentiate recipient outcomes in the modern era of DCD LT in the US. Acceptable long-term outcomes are achievable for patients stratified to the highest-risk group.

Predictors of renal recovery in recipients of liver transplant alone who met 2017 simultaneous liver-kidney transplant criteria.

BACKGROUND: Severe renal dysfunction is common among liver transplant (LT) candidates and often prompts simultaneous liver-kidney transplantation (SLKT) consideration. In view of 2017 United Network of Organ Sharing (UNOS) criteria for SLKT, we investigated the likelihood and predictors of renal recovery among patients who met the aforementioned criteria yet received liver transplant alone (LTA). METHODS: We retrospectively analyzed relative renal recovery (RRR; increase in eGFR to >30 ml/min) in adult LTA recipients between 1/2009 and 1/2019. RESULTS: Of 1165 LT recipients, 54 met 2017 UNOS criteria, with 37 receiving LTA. RRR occurred in 84% of LTA recipients, none of whom had pre-LT eGFR <20 ml/min. Sustained RRR (>180 days) occurred in 43% of patients. While prolonged pre-LT severe renal impairment (eGFR <30 ml/min) predicted failure to have sustained RRR (HR .19 per 90-day, CI .04-.87, p < .005), having an eGFR measurement of >30 ml/min within 90 days pre-LT (HR 5.52, CI 1.23-24.79, p .01) associated with achieving sustained RRR. Sustained RRR was protective against the composite outcome of renal replacement therapy, kidney transplant, and death (HR .21, p .01). CONCLUSION: LT candidates who meet 2017 UNOS criteria for SLKT yet undergo LTA can still have relative renal recovery post-LT, exceeding 80% on short-term follow-up and 40% on long-term follow-up. eGFR trends within 90 days pre-LT can predict sustained renal recovery, which appears protective of adverse outcomes. These recovery rates advocate for applying the more restrictive criteria for SLKT outlined in this article and increasing utilization of the safety net (SN) policy for those who do not meet the proposed criteria.

Optimizing pre-donation physiologic evaluation for enhanced recovery after living liver donation - Systematic review and multidisciplinary expert panel recommendations.

BACKGROUND: While preoperative physiologic evaluation of live liver donors is routinely performed to ensure donor safety and minimize complications, the optimal approach to this evaluation is unknown. OBJECTIVES: We aim to identify predonation physiologic evaluation strategies to improve postoperative short-term outcomes, enhance donor's recovery, and reduce length of stay. We also aim to provide multidisciplinary expert panel recommendations. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: The systematic review followed PRISMA guidelines, and the recommendations were formulated using GRADE approach and experts' opinion. The search included retrospective or prospective studies, describing outcomes of physiologic evaluation predonation. The outcomes of interest were length of stay, postoperative complications (POC), recovery after donation, and mortality. PROSERO protocol ID CRD42021260662. RESULTS: Of 1386 articles screened, only three retrospective cohort studies met eligibility criteria. Two studies demonstrated no impact of age (< 70 years) on POC. Increased body mass index's (BMI) association with POC was present in one study (23.8 vs 21.7 kg/m2 , OR 1.67 (1.14-2.48), P = .01) and absent in another (< 30 vs 30-35 kg/m2 , P = .61). One study demonstrated decreased risk for postdonation subclinical hepatic dysfunction in donors with higher normal platelet count (PLT). None of the studies noted donor death. Given the scarce data on predonation physiologic testing, the expert panel recommended a battery of tests to guide clinical practice and future investigations. CONCLUSION: Advancing age (60-69 years) is not a contraindication for liver donation. There is insufficient evidence for a specific predonation BMI cut-off. Abbreviated predonation physiologic testing is recommended in all candidates. Comprehensive testing is recommended in high-risk candidates while considering the pretest probability in various populations (Quality of evidence; Low to Very Low | Grade of Recommendation; Strong).

Waitlist mortality and post-liver transplant outcomes of pediatric patients with hepatocellular carcinoma and hepatoblastoma in the United States.

BACKGROUND: Liver transplantation (LT) is offered in cases of advanced disease for both pediatric patients with hepatoblastoma (HBL) and those with hepatocellular carcinoma (HCC). Current United States organ allocation priorities differ between the two groups. METHODS: We retrospectively examined the waitlist and posttransplant outcomes of pediatric LT candidates with HBL and HCC using the United Network for Organ Sharing registry (February 2002 to September 2020). RESULTS: Six hundred sixty-eight children with HBL and 95 children with HCC listed for first LT were identified. Patients with HBL were younger (p < .001), had lower laboratory Model for End-stage Liver Disease (MELD)/Pediatric End-stage Liver Disease (PELD) scores (p < .001), and had lesser proportion with encephalopathy (p = .01). Patients with HCC had an increased risk of waitlist mortality in univariable (unadjusted subdistribution hazard ratio [sHR] = 4.37, 95% confidence interval [CI], 2.01-9.51, p < .001) and multivariable competing risk regression (adjusted sHR = 3.08, 95% CI 1.13-8.37, p = .03) accounting for age and laboratory MELD/PELD score. Five hundred ninety-five children underwent LT for HBL and 76 for HCC. Patients transplanted for HBL had a significantly higher proportion with status 1B exception (71.3% vs. 7.9%, p < .001). No difference was observed in patient (unadjusted log-rank test, p = .52; adjusted hazard ratio [HR] = 0.77, 95% CI, 0.40-1.48, p = .43) or graft survival (unadjusted log-rank test, p = .93; adjusted HR = 0.74, 95% CI 0.42-1.33, p = .32) between HCC and HBL recipients. CONCLUSION: Waitlist mortality for pediatric LT candidates with HCC is significantly higher than for HBL, while posttransplant patient and graft survival are similar. This highlights an opportunity to improve equitable prioritization for children with HCC who may have reduced access to size-appropriate deceased donor organs and less effective bridge-to-transplant therapies.

Cirrhotic Cardiomyopathy Predicts Posttransplant Cardiovascular Disease: Revelations of the New Diagnostic Criteria.

The diagnostic criteria for cirrhotic cardiomyopathy (CCM) were recently revised to reflect the contemporary advancements in echocardiographic technology. This study evaluates the prevalence of CCM, according to the new criteria, and its impact on posttransplant cardiovascular disease (CVD). This is a single-center retrospective matched cohort study of liver transplantation (LT) recipients who underwent LT between January 1, 2008 and November 30, 2017. A total of 3 cohorts with decompensated cirrhosis (nonalcoholic steatohepatitis, alcohol-related liver disease, or other etiologies) were matched based on age, sex, and year of transplant after excluding patients listed without evidence of hepatic decompensation. CCM was defined, according to 2020 criteria, as having diastolic dysfunction, left ventricular ejection fraction ≤50%, and/or a global longitudinal strain (GLS) absolute value <18%. The study echocardiographers were blinded to the clinical data. Posttransplant CVD included new coronary artery disease, congestive heart failure, atrial and ventricular arrhythmia, and stroke. The study included 141 patients of whom 59 were women. The mean age at LT was 57.8 (±7.6) years. A total of 49 patients (34.8%) had CCM. Patients with CCM were at an increased risk for post-LT CVD (hazard ratio, 2.57; 95% confidence interval, 1.2-5.5; P = 0.016). Changes in CCM individual parameters pretransplant, such as GLS, early diastolic transmitral flow to early diastolic mitral annular velocity, and left atrial volume index were associated with an increased risk for posttransplant CVD. CCM, defined by the new diagnostic criteria, affects approximately one-third of decompensated LT candidates. CCM predicts an increased risk for new CVD following LT. Studies into addressing and follow-up to mitigate these risks are needed.

Triple-Phase Computed Tomography May Replace Dual-Energy X-ray Absorptiometry Scan for Evaluation of Osteoporosis in Liver Transplant Candidates.

Assessment of bone density is an important part of liver transplantation (LT) evaluation for early identification and treatment of osteoporosis. Dual-energy X-ray absorptiometry (DXA) is currently the standard clinical test for osteoporosis; however, it may contribute to the appointment burden on LT candidates during the cumbersome evaluation process, and there are limitations affecting its accuracy. In this study, we evaluate the utility of biomechanical analysis of vertebral images obtained during dual-energy abdominal triple-phase computed tomography (TPCT) in diagnosing osteoporosis among LT candidates. We retrospectively reviewed cases evaluated for LT between January 2017 and March 2018. All patients who underwent TPCT within 3 months of DXA were included. The biomechanical computed tomography (BCT) analysis was performed at a centralized laboratory (O.N. Diagnostics, Berkeley, CA) by 2 trained analysts blinded to the DXA data. DXA-based osteoporosis was defined as a T score ≤-2.5 at the hip or spine. BCT-based osteoporosis was defined as vertebral strength ≤4500 N for women or ≤6500 N for men or trabecular volumetric bone mineral density ≤80 mg/cm3 . Comparative data were available for 91 patients who had complete data for both DXA and BCT: 31 women and 60 men, age 54 ± 11 years (mean ± standard deviation), mean body mass index 28 ± 6 kg/m2 . Using DXA as the clinical reference, sensitivity of BCT to detect DXA-defined osteoporosis was 83.3% (20/24 patients) and negative predictive value was 91.7%; specificity and positive predictive value were 65.7% and 46.5%, respectively. BCT analysis of vertebral images on triple-phase computed tomography, routinely obtained during transplant evaluation, can reliably rule out osteoporosis in LT candidates. Patients with suspicion of osteoporosis on TPCT may need further evaluation by DXA.

Mortality Determinants in Children with Biliary Atresia Awaiting Liver Transplantation.

OBJECTIVE: To determine risk factors for waitlist mortality in children with biliary atresia listed for liver transplantation. STUDY DESIGN: There were 2704 children with biliary atresia (<12 years of age) listed for a first liver transplant (2002-2018) in the United Network for Organ Sharing database. Fine-Gray regression models for competing risks analysis (main risk = waitlist mortality/delisting owing to too sick; competing risk = liver transplantation) were implemented to identify risk factors for waitlist mortality. RESULTS: The median waitlist time was 83 days (IQR, 34-191). The cumulative incidence of waitlist mortality was 5.2%. In multivariable analysis (n = 2253), increasing bilirubin level (P < .001), portal vein thrombosis (P = .03), and ventilator dependence (P < .001) at listing were associated with a higher risk, whereas weight ≥10 kg at listing (P = .009) was associated with a lower risk of waitlist mortality. When ascites at listing was included in multivariable analysis (n = 1376), it was associated with a higher risk for the composite outcome (P = .03). Encephalopathy at listing was not associated with waitlist mortality (n = 1376; P = .15). CONCLUSIONS: These parameters can be used to more objectively prioritize children with biliary atresia awaiting liver transplantation and identify children with biliary atresia-related end-stage liver disease at high-risk of mortality.

Redefining Cirrhotic Cardiomyopathy for the Modern Era.

Cirrhotic cardiomyopathy (CCM) is cardiac dysfunction in patients with end-stage liver disease in the absence of prior heart disease. First defined in 2005 during the World Congress of Gastroenterology, CCM criteria consisted of echocardiographic parameters to identify subclinical cardiac dysfunction in the absence of overt structural abnormalities. Significant advancements in cardiovascular imaging over the past 14 years, including the integration of myocardial deformation imaging into routine clinical practice to identify subclinical cardiovascular dysfunction, have rendered the 2005 CCM criteria obsolete. Therefore, new criteria based on contemporary cardiovascular imaging parameters are needed. In this guidance document, assembled by a group of multidisciplinary experts in the field, new core criteria based on contemporary cardiovascular imaging parameters are proposed for the assessment of CCM. This document provides a critical assessment of the diagnosis of CCM and ongoing assessment aimed at improving clinical outcomes, particularly surrounding liver transplantation. Key points and practice-based recommendations for the diagnosis of CCM are provided to offer guidance for clinicians and identify gaps in knowledge for future investigations.

Liver chemistries in glycogenic hepatopathy associated with type 1 diabetes mellitus: A systematic review and pooled analysis.

BACKGROUND & AIMS: Glycogenic hepatopathy (GH) in type 1 diabetes-mellitus (T1DM) is characterized by hepatomegaly and perturbations of liver chemistries (LC) that have not been well studied. Furthermore, misdiagnosis with other hepatic complications of T1DM, such as nonalcoholic fatty liver disease, has been described. We perform a systematic review of biopsy-proven GH reports in T1DM patients to identify LC patterns. METHODS: A systematic review identified reports of biopsy-proven GH in patients with T1DM. We excluded GH with other liver diseases, Mauriac syndrome, or GH without T1DM. Two reviewers screened and extracted studies and assessed their methodological quality. LC elevation magnitude, AST-to-ALT ratio, R-ratio to designate hepatocellular, cholestatic or mixed pattern of hepatic injury, and evolution of transaminases after glycemic control were analyzed. RESULTS: A total of 192 patients were included, with median age of 20 years, 73% adults, 66% females, median duration of T1DM before diagnosis 10 years, median adult body mass index 21 kg/m2 , median HbA1c 12%, at least one episode of diabetic ketoacidosis 70%, and hepatomegaly 92%. ALT and AST showed moderate-to-severe elevation in 78% and 76%, respectively, AST/ALT >1 in 71% and hepatocellular to mixed pattern of hepatic injury in 81%. Transaminase improvement with glycemic control was the rule, regardless of other factors in multilinear regression analysis. CONCLUSION: GH tends to have AST-predominant elevation with a median of 13 times the upper normal limit and R-ratio >2, which may distinguish it from other etiologies of AST-predominant LC elevation, and in the appropriate clinical context, may obviate invasive tests.