Post-transplant outcomes and financial burden of donation after circulatory death donor liver transplant after the implementation of acuity circle policy.

BACKGROUND: After implementation of the Acuity Circles (AC) allocation policy, use of DCD liver grafts has increased in the United States. METHODS: We evaluated the impact of AC on rates of DCD-liver transplants (LT), their outcomes, and medical costs in a single practice. Adult LT patients were classified into three eras: Era 1 (pre-AC, 1/01/2015-12/31/2017); Era 2 (late pre-AC era, 1/01/2018-02/03/2020); and Era 3 (AC era, 05/10/2020-09/30/2021). RESULTS: A total of 520 eligible LTs were performed; 87 were DCD, and 433 were DBD. With each successive era, the proportion of DCD increased (Era 1: 11%; Era 2: 20%; Era 3: 24%; p < .001). DCD recipients had longer ICU stays, higher re-admission/re-operation rates, and higher incidence of ischemic cholangiopathy compared to those with DBD. Direct, surgical, and ICU costs during first admission were higher with DCD than DBD (+8.0%, p < .001; +4.2%, p < .001; and +33.3%, p = .001). DCD-related costs increased after Era 1 (Direct: +4.9% [Era 2 vs. 1] and +12.4% [Era 3 vs. 1], p = .04; Surgical: +17.7% and +21.7%, p < .001). In the AC era, there was a significantly higher proportion of donors ≥50 years, and more national organ sharing. Compared to DCD from donors <50 years, DCD from donors ≥50 years was associated with significantly higher total direct, surgical, and ICU costs (+12.6%, p = .01; +9.5%, p = .01; +84.6%, p = .03). CONCLUSIONS: The proportion of DCD-LT, especially from older donors, has increased after the implementation of AC policies. These changes are likely to be associated with higher costs in the AC era.

A New Look at Precipitants of Overt Hepatic Encephalopathy in Cirrhosis.

BACKGROUND AND AIMS: Overt hepatic encephalopathy (HE) is a major cause of significant morbidity and mortality in patients with liver cirrhosis. We examined the frequency and profile of the precipitating factors resulting in hospitalizations for overt HE. METHODS: We conducted both retrospective and prospective studies to identify clinical precipitants of overt HE in patients with cirrhosis. The retrospective study patients were hospitalized at a large urban safety-net hospital, and the prospective study included the patients admitted at a liver transplant center. RESULTS: There were a total of 149 patients with cirrhosis and overt HE (91 males, mean age 55.3 ± 8.6 years) in the retrospective group and 45 patients (27 males, mean age 58.3 ± 8.2 years) in the prospective group of the study. The average MELD score was 16 ± 6.8 in the retrospective group and 22.7 ± 7.2 in the prospective group. Dehydration (46-76%), acute kidney injury (32-76%), lactulose nonadherence (about 50%), constipation (about 40%), and infections (20-42%) were the most frequently identified precipitants for hospitalization in retrospective and prospective groups. Multiple precipitants were identified in 60 (40.3%) patients in the retrospective group and 34 (76%) patients in the prospective group. CONCLUSIONS: Multiple concurrent precipitating factors were identified in the majority of patients with overt HE requiring hospitalization. Dehydration due to various causes was the most common precipitant of overt HE, followed by acute kidney injury (AKI), constipation, and infections. Prevention of dehydration, AKI, and constipation by close outpatient monitoring may be an effective measure to prevent hospitalization for overt HE in patients with cirrhosis.

Acute onset nitrofurantoin-induced autoimmune hepatitis after urinary tract infection treatment.

Key Clinical Message: This case signifies the importance of recognizing DIAIH within the context of antibiotic therapy, especially in older adults and even shortly after common drug exposures for treating UTI. Abstract: Various drugs can induce immune-mediated liver damage and in rare instances may lead to autoimmune hepatitis. Here we report an 84-year-old woman who developed autoimmune hepatitis less than 3 weeks after treatment for urinary tract infection with the antibiotic nitrofurantoin. She presented with jaundice, right upper quadrant abdominal pain, nausea, and vomiting. In the absence of a history of an autoimmune disorder or elevated liver enzymes in the past; elevated liver enzymes after a short course of Nitrofurantoin and the presence of smooth muscle antibodies strongly suggested autoimmune hepatitis, which was confirmed through biopsy sample analysis. The patient scored 7 points on the Naranjo adverse reaction probability scale. The patient's rapid recovery within 1 month of prednisone therapy supports the association of liver damage with nitrofurantoin use.

Clinical characteristics of new-onset diabetes after liver transplantation and outcomes.

Background: We aimed to identify the characteristics of new-onset diabetes after liver transplantation (LT) (NODAT) and investigate its impacts on post-transplant outcomes. Methods: Adult LT patients between 2014 and 2020 who used tacrolimus as initial immunosuppression and survived 3 months at least were evaluated. Patients who developed NODAT within 3 months after LT were classified as NODAT group. Also, patients were further classified as history of diabetes before LT (PHDBT) and non-diabetes (ND) groups. Patient characteristics, post-LT outcomes, and cardiovascular and/or pulmonary complications were compared. Results: A total of 83, 225, and 263 patients were classified into NODAT, PHDBT, and ND groups. The proportion of cholestatic liver disease and rejection within 90 days were higher in NODAT group. Mean serum tacrolimus concentration trough level in the first week after LT was 7.12, 6.12, and 6.12 ng/mL (p < 0.001). Duration of corticosteroids was significantly longer in NODAT compared to PHDBD or ND (416, 289, and 228 days, p < 0.001). Three-year graft and patient survival were significantly worse in NODAT than ND (80.5% vs. 95.0%, p < 0.001: 82.0% vs. 95.4%, p < 0.001) but similar to PHDBT. Adjusted risks of 3-year graft loss and patient death using Cox regression analysis were significantly higher in NODAT compared to ND (adjusted hazard ratio [aHR] 3.41, p = 0.004; aHR 3.61, p = 0.004). Incidence rates of cardiovascular or pulmonary complications after LT in NODAT were significantly higher than ND but similar to PHDBT. Conclusion: Higher initial tacrolimus concentration and early rejection might be risk factors for NODAT. NODAT was associated with worse post-transplant outcomes.

Improved Waitlist Outcomes in Liver Transplant Patients With Mid-MELD-Na Scores Listed in Centers Receptive to Use of Organs Donated After Circulatory Death.

BACKGROUND: Liver transplant (LT) using organs donated after circulatory death (DCD) has been increasing in the United States. We investigated whether transplant centers' receptiveness to use of DCD organs impacted patient outcomes. METHODS: Transplant centers were classified as very receptive (group 1), receptive (2), or less receptive (3) based on the DCD acceptance rate and DCD transplant percentage. Using organ procurement and transplantation network/UNOS registry data for 20 435 patients listed for LT from January 2020 to June 2022, we compared rates of 1-y transplant probability and waitlist mortality between groups, broken down by model for end-stage liver disease-sodium (MELD-Na) categories. RESULTS: In adjusted analyses, patients in group 1 centers with MELD-Na scores 6 to 29 were significantly more likely to undergo transplant than those in group 3 (aHR range 1.51-2.11, P < 0.001). Results were similar in comparisons between groups 1 and 2 (aHR range 1.41-1.81, P < 0.001) and between groups 2 and 3 with MELD-Na 15-24 (aHR 1.19-1.20, P < 0.007). Likewise, patients with MELD-Na score 20 to 29 in group 1 centers had lower waitlist mortality than those in group 3 (scores, 20-24: aHR, 0.71, P = 0.03; score, 25-29: aHR, 0.51, P < 0.001); those in group 1 also had lower waitlist mortality compared with group 2 (scores 20-24: aHR0.69, P = 0.02; scores 25-29: aHR 0.63, P = 0.03). One-year posttransplant survival of DCD LT patients did not vary significantly compared with donation after brain dead. CONCLUSIONS: We conclude that transplant centers' use of DCD livers can improve waitlist outcomes, particularly among mid-MELD-Na patients.

Splenic Artery Embolism in Liver Transplant Patients: A Single-Center Experience.

BACKGROUND: Hypersplenism, portal hypertension, and ascites have been seen after liver transplants. Patients are usually treated medically with refractory patients potentially undergoing splenectomy. Splenic artery embolism (SAE) is an alternative that can be performed to limit the surgical intervention that may have the benefit of improving portal hypertension. Few studies have studied the effect on main portal vein (MPV) velocities and hepatic artery resistive indices (HARIs) which may be beneficial as markers of portal hypertension. PURPOSE: This study aims to evaluate the efficacy and safety of interventional radiology (IR)-guided SAE for the management of portal hypertension in patients who have had liver transplants. METHODS: A retrospective analysis was conducted on liver transplant patients who had undergone IR-guided SAE post-transplant at a single tertiary transplant center from 2012 to 2022. The primary outcome of intervention efficacy was quantified by peak HARIs and MPV velocities. Ultrasound with Doppler obtained before and after the intervention was reviewed for these parameters. Secondary outcomes included adverse events at the time of the procedure and within one year of the procedure, the need for splenectomy, and spleen size. RESULTS: Twenty-eight patients met the criteria for inclusion. The mean age of patients was 52.5 years (21-71 years) and the time after transplant was 149.5 days (2-1588 days). About 96.4% of SAEs were technically successful (n=27). Twenty-one patients had MPV velocities available, and 24 had peak HARIs available. In these patients, HARIs decreased by an average of 0.063 (95% CI 0.014-0.112) after SAE. MPV velocity decreased by an average of 47.2 cm/s (95% CI 27.3-67.1) after SAE. About 10.4% of patients (n=3) developed a procedure-related complication, all of which were femoral access site aneurysms. No (0) patients suffered from bleeding, infections, or abscesses after the procedure. About 10.7% of patients (n=3) required splenectomy after SAE: one splenectomy was due to technical failure and two were due to refractory symptoms. CONCLUSION: We performed one of the first analyses on MPV and RI and showed that our patients saw an improvement post-embolization with a theoretical improvement in portal hypertension. The complication rate and risk of infection seem to be acceptable risks, making SAE a feasible option for management.

Takotsubo Cardiomyopathy Following Liver Transplantation: A Report of 2 Cases.

PURPOSE: Takotsubo cardiomyopathy, also called apical ballooning syndrome, is characterized by regional left ventricular systolic dysfunction that resembles myocardial infarction in its initial presentation; however, it lacks angiographic evidence of coronary artery disease. We evaluated the incidence of takotsubo cardiomyopathy following liver transplant at a diverse urban transplant program. METHODS: This is a retrospective review of patients transplanted at a single center between 2017 and 2019. Here we report 2 cases of takotsubo cardiomyopathy that developed after liver transplantation. RESULTS: A 65-year-old woman diagnosed with alcoholic cirrhosis underwent a brain-dead donor liver transplant. The postoperative course was complicated by stroke, pulmonary hypertension, and a left internal jugular thrombus. Six months following transplant, the patient developed takotsubo cardiomyopathy with congestive hepatopathy and died of heart failure complications despite maximal medical care. The second case was a 65-year-old woman with alcoholic cirrhosis admitted for a living donor liver transplant. The postoperative period involved recurrent seizures and elevated troponins with markedly reduced ejection fraction, which were appropriately managed. The patient recovered well with supportive care and was discharged to a rehabilitation facility shortly after. CONCLUSION: We present a series of patients with takotsubo cardiomyopathy after liver transplantation. The diagnosis depends on the clinical presentation and findings on electrocardiography, echocardiography, and cardiac enzymes. Our patients met the Mayo Clinic diagnostic criteria and were appropriately managed according to guidelines. Our report highlights the possibility of pulmonary hypertension contributing to the development of takotsubo cardiomyopathy. Additional studies are needed to establish a definite correlation.

Risk Factors and Outcomes of Intracardiac Thrombosis During Orthotopic Liver Transplantation.

BACKGROUND: Intracardiac thrombosis incidence during orthotopic liver transplantation is estimated at 0.36% to 6.2% with mortality up to 68%. We aimed to evaluate risk factors and outcomes related to intracardiac thrombosis during orthotopic liver transplantation. MATERIALS AND METHODS: A comprehensive retrospective data review of 388 patients who underwent orthotopic liver transplantation at an urban transplant center from January 2013 to October 2016 was obtained. RESULTS: Six patients were found to have documented intracardiac thrombosis; 4 cases were recognized during the reperfusion stage and 1 during pre-anhepatic stage. All allografts were procured from decreased donors with a median donor age of 44 years (interquartile range, 35.25-49.75) and the cause of death was listed as cerebrovascular accident in 5 donors. Preoperative demographic, clinical, laboratory, and historical risk factors did not differ in patients with thrombosis. None had a prior history of trans-jugular intrahepatic portosystemic shunt or gastrointestinal bleeding. Three patients had renal injury, but no intraoperative hemodialysis was performed. Transesophageal echocardiographic findings included elevated pulmonary artery pressure (1/6), right ventricular strain (1/6), and pulmonary artery thrombus (1/6). Three patients died intraoperatively. Tissue plasminogen activator alone was given to 1 patient who did not survive, intravenous heparin only to 1 patient with resolution, and a combination of both was used in 2 patients with clot resolution achieved. CONCLUSION: Cardiac thrombosis should be considered in patients having hemodynamic compromise during liver transplantation. Transesophageal echocardiography is a useful diagnostic tool. Intracardiac thrombosis treatment remains challenging; however, using both thrombolytics and heparin could achieve better results.

Hepatorenal syndrome.

Acute kidney injury (AKI) secondary to hepatorenal syndrome (HRS) is an ominous complication of end-stage liver disease (ESLD). In HRS, splanchnic and peripheral vasodilatation with reduction in effective arterial volume causes activation of mechanisms leading to intense renal vasoconstriction and functional AKI. HRS is a diagnosis of exclusion and all other causes of AKI (especially prerenal azotemia) have to be considered and excluded. Spontaneous bacterial peritonitis (SBP) frequently precipitates HRS and should be ruled out in all ESLD patients presenting with AKI. Prompt therapy of SBP with intravenous antibiotics and albumin lessens the risk of developing HRS. Combined use of intravenous albumin, splanchnic and/or peripheral vasoconstrictors, and renal replacement therapy (RRT) are only bridges to early liver transplantation (or combined liver-kidney transplantation in selected patients). Transplantation is the only definitive way of improving the long-term prognosis. Close collaboration between hospitalists/internists managing HRS patients and hepatology and nephrology consultants is critically important.

Frequent Offenders and Patterns of Injury.

Given the liver's role in drug metabolism, it is uniquely sensitive to potential drug-induced liver injury (DILI) despite inherent protective mechanisms. In this article, we focus on the most common causes of DILI and their patterns of injury. Although not comprehensive, we attempt to cover several classes of commonly used drugs, and their associated patterns of injury and management.