Abdominal CT and MRI Findings of Portal Hypertension in Children and Adults with Fontan Circulation.

Background Portal hypertension in the Fontan circulation is a function of elevated systemic venous pressure and liver fibrosis. Purpose To quantify the prevalence of radiologic evidence of portal hypertension and elevated VAST score (one point each for varices, ascites, splenomegaly, and thrombocytopenia) of 2 or greater in children and adults with Fontan circulation and to determine the association with hemodynamics and adverse outcomes. Materials and Methods This was a retrospective study of individuals with Fontan circulation who underwent abdominal MRI or CT for focal liver lesion surveillance between January 2012 and December 2019. Portal hypertension was defined as the presence of at least two of the following: varices, ascites, or splenomegaly. Fontan deterioration was defined as a composite of heart failure signs or symptoms requiring diuretic escalation, placement of a ventricular assist device, heart transplant, or death. Relationships between variables and the composite end point were assessed using univariable and multivariable logistic regression. Results A total of 123 patients (age range, 9-55 years; 32 children) were evaluated (median age, 23 years; IQR, 17-30 years; 63 male patients). Median time since diagnosis of Fontan circulation was 16 years (IQR, 12-23 years). Twenty-five of the 123 patients (20%) had radiologic evidence of portal hypertension, and 34 (28%) had a VAST score of 2 or greater. Fontan deterioration occurred in 25 of the 123 patients (20%); median follow-up duration was 0.4 year (IQR, 0.1-3.1 years). Compared with patients who had Fontan circulation without deterioration, patients with Fontan deterioration were more likely to have moderate or severe ventricular systolic dysfunction (P < .01), moderate or severe atrioventricular valve regurgitation (P < .01), higher Fontan pressure (P = .01), radiologic evidence of portal hypertension (P < .01), and VAST score of 2 or greater (P < .01). Conclusion Radiologic evidence of portal hypertension at abdominal imaging in children and adults with Fontan circulation was associated with higher venous pressures and an increased risk for Fontan deterioration. These characteristics may be used to identify patients who warrant comprehensive hemodynamic evaluation. © RSNA, 2022.

Developing an adolescent and adult Fontan Management Programme.

Patients with single-ventricle CHD undergo a series of palliative surgeries that culminate in the Fontan procedure. While the Fontan procedure allows most patients to survive to adulthood, the Fontan circulation can eventually lead to multiple cardiac complications and multi-organ dysfunction. Care for adolescents and adults with a Fontan circulation has begun to transition from a primarily cardiac-focused model to care models, which are designed to monitor multiple organ systems, and using clues from this screening, identify patients who are at risk for adverse outcomes. The complexity of care required for these patients led our centre to develop a multidisciplinary Fontan Management Programme with the primary goals of earlier detection and treatment of complications through the development of a cohesive network of diverse medical subspecialists with Fontan expertise.

Expanding the Donor Pool: First Use of Hepatitis B Virus Nat Positive Solid Organ Allografts Into Seronegative Recipients.

OBJECTIVES: The aim of this study was to assess the 1-year safety and effectiveness of HBV Nucleic Acid Test positive (HBV NAT+) allografts in seronegative kidney transplant (KT) and liver transplant (LT) recipients. SUMMARY BACKGROUND DATA: Despite an ongoing organ shortage, the utilization of HBV NAT+ allografts into seronegative recipients has not been investigated. METHODS: From January 2017 to October 2020, a prospective cohort study was conducted among consecutive KT and LT recipients at a single institution. Primary endpoints were post-transplant HBV viremia, graft and patient survival. RESULTS: With median follow-up of 1-year, there were no HBV-related complications in the 89 HBV NAT+ recipients. Only 9 of 56 KTs (16.1%) and 9 of 33 LTs (27.3%) experienced post-transplant HBV viremia at a median of 185 (KT) and 269 (LT) days postoperatively. Overall, viremic episodes resolved to undetected HBV DNA after a median of 80 days of entecavir therapy in 16 of 18 recipients. Presently, 100% of KT recipients and 93.9% of LT recipients are HBV NAT- with median follow-up of 13 months, whereas 0 KT and 8 LT (24.2%) recipients are HBV surface antigen positive indicating chronic infection. KT and LT patient and allograft survival were not different between HBV NAT+ and HBV NAT- recipients (P > 0.05), whereas HBV NAT+ KT recipients had decreased waitlist time and pretransplant duration on dialysis (P < 0.01). CONCLUSIONS: This is the largest series describing the transplantation of HBV NAT+ kidney and liver allografts into HBV seronegative recipients without chronic HBV viremia or decreased 1-year patient and graft survival. Increasing the utilization of HBV NAT+ organs in nonviremic recipients can play a role in decreasing the national organ shortage.

Pulmonary Vascular Resistance Predicts Mortality and Graft Failure in Transplantation Patients With Portopulmonary Hypertension.

Portopulmonary hypertension (POPH) is a pulmonary vascular disease associated with significant morbidity and mortality in those with liver disease, conferring a higher mortality in patients awaiting liver transplantation (LT). Although not a transplant indication, patients with POPH can experience significant clinical improvement following LT, and those maintaining a mean pulmonary artery pressure (MPAP) <35mm Hg and a pulmonary vascular resistance (PVR) <5 Woods units (WU) are granted additional listing points to expedite LT. The effect of POPH on posttransplant outcomes such as mortality and graft failure, however, is not well defined. We performed a retrospective cohort study of the US Organ Procurement and Transplantation Network database of all adult patients who underwent LT between January 1, 2006, and December 1, 2020. Using adjusted accelerated failure time models, we examined the relationship between a diagnosis of POPH and outcomes following LT and the relationship between pre-LT hemodynamics and post-LT survival (alive with a functioning graft) in patients with POPH. Compared with those undergoing transplants without exception points, patients with POPH had comparable post-LT survival rates but were significantly more likely to have graft failure. Both pre-LT MPAP and PVR predicted post-LT survival in POPH, with a pre-LT PVR of ≥1.6 WU, more than doubling the hazard for mortality (death or a nonfunctioning graft; coefficient, 2.01; standard error, 0.85; hazard ratio, 2.21; P = 0.02). POPH may confer a significantly higher risk of post-LT graft failure compared with patients with cirrhosis without POPH, and a pre-LT PVR of ≥1.6 WU may predict post-LT survival. Further investigation into the relationship between pre-LT hemodynamics, right ventricular function, and post-LT outcomes of mortality and graft failure in POPH is needed.

Relation of Magnetic Resonance Elastography to Fontan Circulatory Failure in a Cohort of Pediatric and Adult Patients.

Elevated magnetic resonance elastography (MRE)-derived liver stiffness may be associated with worse outcomes in people with Fontan circulation. We sought to evaluate the association between liver stiffness and Fontan failure or portal hypertension. Single center cross-sectional retrospective study of people with Fontan circulation who underwent MRE between 2011 and 2020. The cohort was divided into adult (age ≥ 21 years) and pediatric (< 21 years) groups. Fontan circulatory failure (FF) was defined as any of the following: death, transplantation, ventricular assist device, heart failure symptoms requiring escalation of diuretics. Radiologic portal hypertension was defined as the presence of one or more of the following: splenomegaly, ascites, or gastrointestinal varices. 128 patients were included (average age = 22.6 ± 8.7 years) and 58 (45%) were children. Median liver stiffness was 4.3 kPa (interquartile range (IQR) 3.8-5.8) for the entire cohort. Thirty patients (23%) developed FF (16 adults, 14 children). Liver stiffness was higher in adults with FF compared to those without FF (4.9 (IQR 4.0-6.0) vs. 4.2 (IQR 3.8-4.7) kPa, p = 0.04). There was no difference in liver stiffness between pediatric patients with and without FF (4.4 (IQR 4.1-5.4) vs. 4.4 (IQR 3.8-5.0), p = 0.5). Adults with radiologic portal hypertension and adults with moderate or severe atrioventricular valve regurgitation had higher liver stiffness than adults without. MRE-derived liver stiffness is associated with atrioventricular valve regurgitation, portal hypertension, and poor clinical outcomes in adults with Fontan circulation. There was no association between liver stiffness and FF in pediatric patients. This difference may be due to the progressive nature of Fontan-associated liver disease.

Safety and Efficacy of Budesonide for Liver Transplant Immune Suppression: Results of a Pilot Phase 2a Trial.

Despite adverse effects like hyperglycemia, new-onset diabetes after transplant (NODAT), and infectious complications, corticosteroid use remains an important part of liver transplantation (LT) immune suppression. Budesonide, a synthetic corticosteroid, undergoes extensive first-pass hepatic metabolism with only 10% systemic bioavailability, providing an opportunity for an improved toxicity-therapeutic ratio. Although effective in the treatment of autoimmune hepatitis, the effects of budesonide for LT immune suppression are unknown. We conducted a single-center phase 2a trial to study the safety and efficacy of budesonide immunosuppressive therapy. From July 2017 to November 2018, 20 patients undergoing a first LT received budesonide tapering doses (from 9 to 3 mg) for 12 weeks. Patients were compared with matched control patients who received prednisone from the same time period. Additionally, both groups received calcineurin inhibitors and mycophenolate mofetil. Outcome measures at week 24 included rates of biopsy-proven acute cellular rejection (ACR), NODAT (hemoglobin A1c >6.4%), and infectious complications. In the budesonide arm, 1 patient developed ACR at week 5 and was removed from the study. Another patient stopped the study drug at week 8 due to persistent nausea. Rates of ACR were similar between the budesonide and control groups (5% versus 5%, P = 1.00). Three patients in the control group developed NODAT versus none in the budesonide group (15% versus 0%; P = 0.23). There were 6 infections in the control group compared with none in the budesonide group (30% versus 0; P = 0.02). These pilot data suggest that budesonide has the potential to be a safe and effective alternative to prednisone for LT immune suppression while reducing steroid-induced infections and NODAT. Randomized controlled trials are required to validate these findings.

Use of Hepatitis C Nucleic Acid Test-Positive Liver Allografts in Hepatitis C Virus Seronegative Recipients.

Because of underutilization of liver allografts, our center previously showed that hepatitis C virus (HCV) antibody-positive/nucleic acid test (NAT)-negative livers when transplanted into HCV nonviremic recipients were safe with a 10% risk of HCV transmission. Herein, we present our single-center prospective experience of using HCV NAT+ liver allografts transplanted into HCV NAT- recipients. An institutional review board-approved matched cohort study was conducted examining post- liver transplantation (LT) outcomes of HCV- patients who received HCV NAT+ organs (treatment group) compared with matched recipients with HCV NAT- organs (matched comparator group) between June 2018 to October 2019. The primary endpoint was success of HCV treatment and elimination of HCV infection. The secondary outcomes included the 30-day and 1-year graft and patient survival as well as perioperative complications. There were 32 recipients enrolled into each group. Because of 1 death in the index admission, 30/31 patients (97%) were given HCV treatment at a median starting time of 47 days (18-140 days) after LT. A total of 19 (63%) patients achieved sustained virological response at week 12 (SVR12). Another 6 patients achieved end-of-treatment response, while 5 remained on therapy and 1 is yet to start treatment. No HCV treatment failure has been noted. There were no differences in 30-day and 1-year graft and patient survival, length of hospital stay, biliary or vascular complications, or cytomegalovirus viremia between the 2 groups. In this interim analysis of a matched cohort study, which is the first and largest study to date, the patients who received the HCV NAT+ organs had similar outcomes regarding graft function, patient survival, and post-LT complications.

Clinical Implications of Donor Warm and Cold Ischemia Time in Donor After Circulatory Death Liver Transplantation.

The use of donation after circulatory death (DCD) liver allografts has been constrained by limitations in the duration of donor warm ischemia time (DWIT), donor agonal time (DAT), and cold ischemia time (CIT). The purpose of this study is to assess the impact of longer DWIT, DAT, and CIT on graft survival and other outcomes in DCD liver transplants. The Scientific Registry of Transplant Recipients was queried for adult liver transplants from DCD donors between 2009 and 2015. Donor, recipient, and center variables were included in the analysis. During the study period, 2107 patients underwent liver transplant with DCD allografts. In most patients, DWIT and DAT were <30 minutes. DWIT was <30 minutes in 1804 donors, between 30 and 40 minutes in 248, and >40 minutes in 37. There was no difference in graft survival, duration of posttransplant hospital length of stay, and readmission rate between DCD liver transplants from donors with DWIT <30 minutes and DWIT between 30 and 40 minutes. Similar outcomes were noted for DAT. In the multivariate analysis, DAT and DWIT were not associated with graft loss. The predictors associated with graft loss were donor age, donor sharing, CIT, recipient admission to the intensive care unit, recipient ventilator dependence, Model for End-Stage Liver Disease score, and low-volume transplant centers. Any CIT cutoff >4 hours was associated with increased risk for graft loss. Longer CIT was also associated with a longer posttransplant hospital stay, higher rate of primary nonfunction, and hyperbilirubinemia. In conclusion, slightly longer DAT and DWIT (up to 40 minutes) were not associated with graft loss, longer posttransplant hospitalization, or hospital readmissions, whereas longer CIT was associated with worse outcomes after DCD liver transplants.

Hepatitis C transmission from seropositive, nonviremic donors to non-hepatitis C liver transplant recipients.

Breakthroughs in hepatitis C virus (HCV) treatment and rising rates of intravenous drug use have led to an increase in the number of organ donors who are HCV antibody-positive but serum nucleic acid test (NAT)-negative. The risk of HCV transmission from the liver grafts of these donors to recipients is unknown. To estimate the incidence of HCV transmission, we prospectively followed 26 consecutive HCV antibody-negative (n = 25) or NAT-negative (n = 1) transplant recipients who received a liver graft from donors who were HCV antibody-positive but serum NAT-negative between March 2016 and March 2017. HCV transmission was considered to have occurred if recipients exhibited a positive HCV PCR test by 3 months following transplantation. Drug overdose was listed as the cause of death in 15 (60%) of the donors. One recipient died 18 days after transplantation from primary graft nonfunction and was excluded. Of the remaining 25 recipients, HCV transmission occurred in 4 (16%), at a median follow-up of 11 months, all from donors who died of drug overdose. Three of these patients were treated with direct-acting antiviral therapy, with two achieving a sustained virologic response and one an end-of-treatment response. One patient with HCV transmission died after a complicated postoperative course and did not receive antiviral therapy. CONCLUSION: In this prospective cohort of non-HCV liver recipients receiving grafts from HCV antibody-positive/NAT-negative donors, the incidence of HCV transmission was 16%, with the highest risk conferred by donors who died of drug overdose; given the availability of safe and highly effective antiviral therapies, use of such organs could be considered to expand the donor pool. (Hepatology 2018;67:1673-1682).

Transplanting organs from hepatitis B positive donors: Is it safe? Is it ethical?

Liver transplant centres throughout the USA face a huge shortage of liver organs for their wait-listed patients. Various types of innovations are being considered for expansion of this donor pool. Organs that were previously deemed to be high risk are now being considered for transplantation. For the last 25 years, hepatitis B core antibody (anti-HBc+) organs have been used for liver transplantation. While the initial transplantations did reveal a high incidence of de novo hepatitis (DNH) in the recipients, the medical knowledge and experience have evolved and this risk has been markedly decreased. In this paper, medical literature evaluating the safety of such organ transplants has been reviewed. There is strong evidence to suggest that using anti-HBc+ organs with appropriate prophylaxis after transplant is a safe practice with good patient and graft survivals. In the second half of the paper, we discuss whether it is ethical to use anti-HBc+ organs. We argue that the use of such organs is in compliance with the principles of medical ethics and that society at large benefits from the use of these organs. Hence, we recommend that the use of such organs is both safe and ethical and this practice should be continued in the future.

Impact of recipient morbid obesity on outcomes after liver transplantation.

The aim of this study was to analyze the impact of morbid obesity in recipients on peritransplant resource utilization and survival outcomes. Using a linkage between the University HealthSystem Consortium and Scientific Registry of Transplant Recipients databases, we identified 12 445 patients who underwent liver transplantation (LT) between 2007 and 2011 and divided them into two cohorts based on recipient body mass index (BMI; <40 vs. ≥40 kg/m²). Recipients with BMI ≥40 comprised 3.3% (n = 416) of all LTs in the studied population. There were no significant differences in donor characteristics between two groups. Recipients with BMI ≥40 were significant for being female, diabetic, and with NASH cirrhosis. Patients with a BMI ≥40 had a higher median MELD score, limited physical capacity, and were more likely to be hospitalized at LT. BMI ≥40 recipients had higher post-LT length of stay and were less often discharged to home. With a median follow-up of 2 years, patient and graft survival were equivalent between the two groups. In conclusion, morbidly obese LT recipients appear sicker at time of LT with an increase in resource utilization but have similar short-term outcomes.

The Use of Pre-Endoscopic Metoclopramide Does Not Prevent the Need for Repeat Endoscopy: A U.S. Based Retrospective Cohort Study.

BACKGROUND: Peptic ulcer disease (PUD) can cause upper gastrointestinal bleeding (UGIB), often needing esophagogastroduodenoscopy (EGD). Second-look endoscopies verify resolution, but cost concerns prompt research on metoclopramide's efficacy compared to erythromycin. METHODS: We analyzed the Diamond Network of TriNetX Research database, dividing UGIB patients with PUD undergoing EGD into three groups: metoclopramide, erythromycin, and no medication. Using 1:1 propensity score matching, we compared repeat EGD, post-EGD transfusion, and mortality within one month in two study arms. RESULTS: Out of 97,040 patients, 11.5% received metoclopramide, 3.9% received erythromycin, and 84.6% received no medication. Comparing metoclopramide to no medication showed no significant difference in repeat EGD (10.1% vs. 9.7%, p = 0.34), transfusion (0.78% vs. 0.86%, p = 0.5), or mortality (1.08% vs. 1.08%, p = 0.95). However, metoclopramide had a higher repeat EGD rate compared to erythromycin (9.4% vs. 7.5%, p = 0.003), with no significant difference in transfusion or mortality. CONCLUSIONS: The need to repeat EGD was not decreased with pre-EGD use of metoclopramide. If a prokinetic agent is to be used prior to EGD, erythromycin shows superior reduction in the need of repeat EGD as compared to metoclopramide.

SARS-CoV-2 Infection Is an Independent Risk Factor for Decompensation in Cirrhosis Patients.

BACKGROUND: SARS-CoV-2 causes varied gastrointestinal symptoms. Cirrhosis patients face higher mortality rates from it, especially those with decompensated cirrhosis. This study examines SARS-CoV-2's impact on decompensation in previously compensated cirrhotic patients. METHODS: We analyzed the Global Collaborative Network, comprising 98 healthcare organizations across sixteen countries, using TriNetX's deidentified research database. Compensated cirrhosis patients were split into two groups: one with SARS-CoV-2-positive patients and another testing negative. Using a 1:1 propensity score matching model based on baseline characteristics and comorbidities, we created comparable cohorts. We then assessed decompensation, mortality, and GI bleed at 1 and 3 months. RESULTS: Out of 252,631 identified compensated cirrhosis patients, 27.3% (69,057) tested SARS-CoV-2-positive, while 72.6% (183,574) remained negative. Post PSM, 61,963 patients were in each group. SARS-CoV-2-positive patients showed significantly higher decompensation rates (4.4% vs. 1.9% at 1 month; 6% vs. 2.6% overall). Rates of complications, like ascites, SBP, HE, and HRS, increased notably. Mortality (2.5% vs. 1.7% at 1 month; 3.6% vs. 2.7% at 3 months) and GI bleed (1.3% vs. 0.9% at 1 month; 1.9% vs. 1.2% at 3 months) were also elevated in SARS-CoV-2 patients. CONCLUSIONS: SARS-CoV-2 increases decompensation over 2-fold in compensated cirrhosis patients and raises mortality and increases rates of complications at 1 and 3 months.

Use of proton pump inhibitors improves outcomes in mild acute pancreatitis: A nationwide cohort study.

Previous studies showed a potential anti-inflammatory effect of proton pump inhibitors (PPI) as well as possible inhibition of pancreatic secretion. This presents the question of their possible use in acute pancreatitis (AP). Current clinical evidence does not address the role of PPI and the present review for possible therapeutic use and safety is lacking. Therefore, our study aims to address the role of PPI in the management of AP and their association with the different outcomes of AP. We queried the Diamond Network through TriNetX-Research Network. This network included 92 healthcare organizations. Patients with mild AP with Bedside Index of Severity in Acute Pancreatitis (BISAP) score of Zero regardless of etiology were divided into 2 cohorts; 1st cohort included patients on PPI, and 2nd cohort included patients not on any PPI. Patients with BISAP score equal to or more than 1 or on PPI prior to the study date were excluded. Two well-matched cohorts were created using 1:1 propensity-scored matching model between cohorts. We compared the incidence of intensive care unit admission, mortality, and other associated complications. A total of 431,571 patients met the inclusion criteria. Of those, 32.9% (n = 142,062) were on PPI, and 67% (n = 289,509) were not on any PPI. After propensity matching, the sample included 115,630 patients on PPI vs 115,630 patients not on PPI. The PPI group had a lower rate of mortality (3.7% vs 4.4%, P < .001), a lower rate of intensive care unit admission (3.9% vs 5.5%, P < .001), a lower rate of necrotizing pancreatitis (1.1% vs 1.9%, P < .001), a lower rate of Hospital-Acquired Pneumonia (3.6% vs 4.9%, P < .001), a lower rate of respiratory failure (2.8% vs 4.2%, P < .001), and a lower rate of acute kidney injury (6.9% vs 10.1%, P < .001). There was no statistical difference in the rate of Clostridium difficile infection between the 2 cohorts (0.9% vs 0.8%, P = .5). The use of PPI in mild AP with a BISAP-score of zero is associated with reduced pancreatitis-related complications and improved mortality. Prospective studies are needed to confirm these findings.

Safety of DOACs in patients with Child-Pugh Class C cirrhosis and atrial fibrillation.

Background: Anticoagulation (AC) is used for stroke prevention in atrial fibrillation (AF). Direct Oral Anticoagulants (DOACs) are safe in patients with AF without cirrhosis, they are hardly studied in patients with advanced cirrhosis. Our study evaluates the safety and outcomes of DOACs in patients with Child-Pugh class C cirrhosis (CPC). Methods: We queried TriNetX Database. Patients with CPC and AF were divided into three cohorts: patients on DOACs, no AC, and warfarin. Three study arms were created using a 1:1 propensity score matching system (PSM). Results: Totally 16 029 patients met the inclusion criteria. Of those, 20.2% (n = 3235) were on DOACs, 47.1% (n = 7552) were not on AC, and 32.7% (n = 5242) were on warfarin. First arm comparing AC versus no AC, a statistically significant benefit was identified in 3-year mortality risk (47% vs 71%, P < 0.0001) and transplant status (17% vs 5%, p < 0.0001) with AC. However, no significant difference was identified regarding intracranial hemorrhage and GI bleeding risk. Second arm comparing patients on DOACs versus no AC, we identified mortality benefit (40% vs 72%, P < 0.0001) and a higher transplant rate (9% vs 3.2%, P < 0.0001) with DOACs. Intracranial hemorrhage rates (6% vs 4%, P = 0.03) were higher in patients on DOACs. Third arm comparing patients on DOACs versus Warfarin, a statistically significant lower risk of intracranial hemorrhage (6.6% vs 8.7%, P = 0.004) and GI bleed (2% vs 2.4%, P < 0.0001) were identified in patients on DOACs. Conclusion: Anticoagulation is safe in patients with CPC with AF and may provide a mortality benefit. DOACs are a safer alternative to warfarin.

Daptomycin-Induced Acute Liver Failure: A Rare Case Report.

Acute liver failure (ALF) is characterized by severe liver injury, encephalopathy, and impaired coagulation/synthetic function. Drug-induced liver injury (DILI) can rarely, in a dose-dependent manner, lead to ALF. This article presents a rare case of daptomycin-induced acute liver failure in a patient with no prior liver disease. A 73-year-old male with multiple comorbidities including heart failure, diabetes, and chronic kidney disease received daptomycin treatment for diabetic left foot osteomyelitis. Five days after starting therapy, he developed weakness, jaundice, and drowsiness, leading to ICU admission. Physical examination and labs revealed hepatomegaly, elevated liver enzymes and abnormal ultrasound findings. Autoimmune and infectious causes were ruled out. Daptomycin was discontinued, and the patient's labs showed significant improvement within three days. One week after recovery from acute liver failure, he experienced cardiogenic shock due to worsening of his underlying heart failure and was transferred to the Cardiac ICU before ultimately being discharged to inpatient hospice care. To our best knowledge, this is the first reported case of daptomycin-induced acute liver failure, presenting with massive liver enzyme elevations, synthetic dysfunction, and encephalopathy. The Naranjo scale score suggests a probable causal relationship between daptomycin and liver injury. While a few cases of daptomycin-induced liver injury have been reported, there are no previous reports of acute liver failure. The rapid development of liver failure following daptomycin administration and subsequent recovery after discontinuation is noteworthy. However, various confounding factors and the mechanism of daptomycin-induced liver failure remain unclear. Further research is needed to identify predisposing factors and better understand this rare complication. While rare, this care also raises caution to follow liver function closely while prescribing daptomycin.

Relation of Liver Volume to Adverse Cardiovascular Events in Adolescents and Adults With Fontan Circulation.

Elevated central venous pressure in those with Fontan circulation causes liver congestion and hepatomegaly. We assessed if liver volume by magnetic resonance imaging (MRI) is associated with adverse cardiovascular outcomes. Retrospective study of 122 patients with Fontan circulation who were >10 years old and had a liver MRI with magnetic resonance elastography. Liver volume (ml) was measured by manual segmentation from axial T2-weighted images and was indexed to body surface area. The composite outcome included death, heart transplant, ventricular assist device placement, or nonelective cardiovascular hospitalization. The median age at the time of MRI was 18.9 (interquartile range 15.8 to 25.9) years, and 47% of the patients were women. The mean indexed liver volume was 1,133 ± 180 ml/m2. Indexed liver volume was not significantly associated with age, years since Fontan, or with liver stiffness (r = 0.15, p = 0.10), but was positively correlated with Fontan pressure (r = 0.32, p = 0.002). Over a median follow-up of 2.1 (0.8 to 4.2) years, 32 patients (26%) experienced the composite outcome. Higher indexed liver volume was associated with a greater hazard for the composite outcome (hazard ratio per 1 SD increase = 1.74, 95% confidence interval 1.27 to 2.35, p = 0.0004) but increased liver stiffness was not significantly associated with the composite outcome (hazard ratio per 1 SD increase 1.44, 95% confidence interval 0.90 to 2.21, p = 0.11). In conclusion, greater liver volume indexed to body surface area is associated with unfavorable hemodynamics and adverse outcomes in patients with Fontan circulation. Liver volume may be a useful, simple imaging biomarker in adolescents and adults with Fontan circulation.

Predictors of outcomes following liver transplant in hepatopulmonary syndrome: An OPTN database analysis.

Hepatopulmonary syndrome (HPS) is a type of pulmonary vascular disease occurring exclusively in those with underlying liver disease, associated with significant mortality in patients awaiting liver transplantation (LT). LT is curative in HPS, and these patients are granted Model for End Stage Liver Disease (MELD) exception points to expedite LT. The purpose of this study is to use multivariable competing risk Accelerated Failure Time models and propensity matching to examine the relationship between pre-LT hypoxemia and post-LT outcomes in HPS. We performed a retrospective cohort study of UNOS/OPTN database of all adult patients undergoing LT between January 1, 2006 and January 12, 2020. Pre-LT PaO2 was significantly associated with post-LT mortality in HPS, with each 1 mmHg increase in PaO2 significantly decreasing the risk of post-LT mortality (coefficient 0.039, HR = 0.95, p = 0.001). HPS patients with a pre-LT PaO2 < 54 mmHg demonstrated increased mortality following LT as compared to matched non-HPS cirrhotic patients. We conclude that HPS patients with a PaO2, 54 mmHg are at increased risk of post-LT mortality and may identify high-risk patients who would benefit from additional resources during LT, and that the effects of HPS MELD exception points to optimize post-LT outcomes should be continuously re-evaluated.