A Meta-Analysis of Cumulative Incidence of Hepatocellular Carcinoma After the Fontan Operation.

BACKGROUND: Hepatic complications are increasingly recognized after the Fontan operation. The development of hepatocellular carcinoma (HCC) is associated with high mortality when diagnosed, but its incidence and risk factors are poorly understood. We conducted a systematic review and meta-analysis of the cumulative incidence of HCC after Fontan and associated risk factors. METHODS: We searched PubMed, CINAHL, and MEDLINE databases for articles reporting the cumulative incidence of HCC after Fontan operation on March 21, 2023. A single-arm random effects meta-analysis was conducted to assess cumulative incidence at 10, 20, and 30 years after Fontan. Meta-analysis of the difference of the medians was used to assess the influence of risk factors on the development of HCC. RESULTS: Four studies including a total of 1320 patients reported cumulative incidence. The cumulative incidence of HCC at 10, 20, and 30 years after Fontan was 0% (95% CI 0.00-0.01), 2% (0.01-0.06), and 7% (0.03-0.17) respectively. Seven studies including 6,250 patients reported overall incidence of HCC and associated risk factors. At a median 18.4 (IQR 11.9-24.9) years of follow-up, incidence of HCC was 2% (0.01-0.04). Only use of anticoagulation was associated with a lower risk of HCC (RR 0.3, 95% CI 0.1-0.88). DISCUSSION: By 30 years after Fontan, cumulative incidence of HCC is high (7%). Risk of HCC development prior to 10 years post-Fontan is low (0%), though the decision to defer HCC surveillance in this period may require future investigation based on larger studies. Screening with ultrasound every 6 months starting 20 years post-Fontan is reasonable, however, further research regarding timing, cost-effectiveness, additional risk factors associated with HCC risk, and different screening modalities is required.

Performance of a Prospective Anticoagulation Stratification Algorithm After Liver Transplantation.

Venous thromboembolism (VTE) occurs in 0.4% to 15.5% and bleeding occurs in 20% to 35% of patients after liver transplantation (LT). Balancing the risk of bleeding from therapeutic anticoagulation and risk of thrombosis in the postoperative period is challenging. Little evidence exists regarding the best treatment strategy for these patients. We hypothesized that a subset of LT patients who develop postoperative deep vein thromboses (DVTs) could be managed without therapeutic anticoagulation. We implemented a quality improvement (QI) initiative using a standardized Doppler ultrasound-based VTE risk stratification algorithm to guide parsimonious implementation of therapeutic anticoagulation with heparin drip. Methods: In a prospective management QI initiative for DVT management, we compared 87 LT historical patients (control group; January 2016-December 2017) to 182 LT patients (study group; January 2018-March 2021). We analyzed the rates of immediate therapeutic anticoagulation after DVT diagnosis within 14 d of LT, clinically significant bleeding, return to the operating room, readmission, pulmonary embolism, and death within 30 d of LT before and after the QI initiative. Results: Ten patients (11.5%) in the control group and 23 patients (12.6%; P = 0.9) in the study group developed DVTs after LT. Immediate therapeutic anticoagulation was used in 7 of 10 and 5 of 23 patients in the control and study groups, respectively (P = 0.024). The study group had lower odds of receiving immediate therapeutic anticoagulation after VTE (21.7% versus 70%; odds ratio = 0.12; 95% confidence interval, 0.019-0.587; P = 0.013) and a lower rate of postoperative bleeding (8.7% versus 40%; odds ratio = 0.14, 95% confidence interval, 0.02-0.91; P = 0.048). All other outcomes were similar. Conclusions: Implementing a risk-stratified VTE treatment algorithm for immediate post-LT patients appears to be safe and feasible. We observed a decrease in the use of therapeutic anticoagulation and a lower rate of postoperative bleeding without adverse impacts on early outcomes.

Implementation of Incidental Liver Lesion Clinically Integrated Workflow Increases Compliance With ACR Follow-Up Guidelines, Closing Care Gaps.

OBJECTIVE: Follow established management guidelines from the ACR and improve adherence to follow-up recommendations for incidental liver lesions (ILLs) for all patients undergoing CT abdomen and pelvis with contrast (CTAPw) examinations, with advocacy from a multidisciplinary care team. METHODS: A mandatory structured radiology reporting module was developed for use in CTAPw reports for ILL recommendations. Data from the electronic medical record describing patients with radiology-reported ILLs and their clinical risk diagnosis categories were tabulated in a queryable electronic database. A nurse co-ordinator initiated workflow to communicate the need for ILL follow-up MRI to ordering physicians and primary care providers. MRIs were ordered by the ILL team. An interactive process was undertaken with continuous review to improve identification of eligible patients and adherence to recommendations. RESULTS: During the initial launch phase from December 2020 to March 2021, 1,577 ILLs were detected on 20,667 CTAPw examinations, and for those with the characterize now recommendation, 36 of 114 (31.6%) received follow-up in 30 days. Between January 2021 and June 2022, 117,520 CTAPws were performed and 4,371 ILLs were detected. Using the ILL workflow, in the MRI now cohort, follow-up occurred within 30 days in 202 of 542 (36.2%) patients, and a total of 368 of 542 (67.9%) patients have completed their follow-up to date. DISCUSSION: Using a focused effort to close a gap in ILL care, adherence to follow-up recommendations improved over the long term, although there remains a gap in adherence to short-term interventions. A multidisciplinary approach, radiology reporting, and software solutions were leveraged to improve a complex process.

Nonalcoholic fatty liver disease: impact on healthcare resource utilization, liver transplantation and mortality in a large, integrated healthcare system.

BACKGROUND AND AIMS: NAFLD is the most prevalent liver disease globally, affecting 20% of the world population. Healthcare resource utilization (HRU) attributable to NAFLD has been difficult to define. METHODS: We performed a case control study on NAFLD patients from 2005 to 2015 in a large integrated healthcare system with an affiliated insurance company that prospectively captures HRU information. Outcomes encompassed costs, liver transplantation and mortality rates. RESULTS: There were 17,085 patients, of which 4512 were NAFLD cases and 12,573 were non-NAFLD controls. The cohorts were similar in age and gender distribution (p > 0.05). The NAFLD cohort had a younger mean age of death (60.9 vs. 63.3, p = 0.004) and had over twice the number of annual healthcare visits (14.6 vs. 7.1). The increased overall annual overall cost attributable to NAFLD (in 2015 $) was $449/year. Overall, NAFLD was independently associated with 17% higher annual attributable healthcare costs. More advanced NAFLD (FS 3-4) was associated with a 40% increase in median annual healthcare costs (vs. FS 0-2). The strongest predictors of HRU among patients with NAFLD were advanced fibrosis and medical co-morbidities. The rate of liver transplantation was 18 times greater (0.054%/year) in the NAFLD compared with the non-NAFLD cohort, while mortality rate was 1.7 times greater. CONCLUSIONS: Within a large, integrated healthcare system a diagnosis of NAFLD is independently associated with a 17% overall excess in HRU and a several-fold increase liver transplantation and mortality. Although the dollar amounts will change over time and between healthcare systems, the proportional need for HRU will have broad applicability and implications.

Liver and Kidney Recipient Selection of Hepatitis C Virus Viremic Donors: Meeting Consensus Report From the 2019 Controversies in Transplantation.

The development of multiple highly effective and safe direct-acting antivirals to treat hepatitis C virus (HCV) has resulted in greater ease and confidence in managing HCV infection in transplant recipients that in turn has impacted the solid organ transplant community as well. In the United States, the opioid epidemic has increased the number of overdose deaths with a concomitant increase in younger HCV viremic donors after brain death being identified. At the same time, a decrease in HCV viremic transplant candidates has led to a growing interest in exploring the use of HCV viremic liver and kidney donor allografts in HCV-negative recipients. To date, experience with the use of HCV viremic liver and kidney allografts in HCV-negative recipients is limited to a few small prospective research trials, case series, and case reports. There are also limited data on recipient and donor selection for HCV viremic liver and kidney allografts. In response to this rapidly changing landscape in the United States, experts in the field of viral hepatitis and liver and kidney transplantation convened a meeting to review current data on liver and kidney recipient selection and developed consensus opinions related specifically to recipient and donor selection of HCV viremic liver and kidney allografts.

Split liver transplantation is utilized infrequently and concentrated at few transplant centers in the United States.

Split liver transplantation (SLT) is 1 strategy for maximizing the number of deceased donor liver transplants. Recent reports suggest that utilization of SLT in the United States remains low. We examined deceased donor offers that were ultimately split between 2010 and 2014. SLTs were categorized as "primary" and "secondary" transplants. We analyzed allocation patterns and used logistic regression to evaluate factors associated with secondary split discard. Four hundred eighteen livers were split: 54% from adult, 46% from pediatric donors. Of the 227 adult donor livers split, 61% met United Network for Organ Sharing "optimal" split criteria. A total of 770 recipients (418 primary and 352 secondary) were transplanted, indicating 16% discard. Ninety-two percent of the 418 primary recipients were children, and 47% were accepted on the first offer. Eighty-seven percent of the 352 secondary recipients were adults, and 7% were accepted on the first offer. Of the 352 pairs, 99% were transplanted in the same region, 36% at the same center. In logistic regression, shorter donor height was associated with secondary discard (odds ratio 0.97 per cm, 95% CI 0.94-1.00, P = .02). SLT volume by center was not predictive of secondary discard. Current policy proposals that incentivize SLT in the United States could increase the number of transplants to children and adults.

Receipt of a pediatric liver offer as the first offer reduces waitlist mortality for adult women.

In liver transplantation, adults with small stature have a greater susceptibility to waitlist mortality. This may explain the persistent waitlist mortality disparity that exists for women. We hypothesized that women who receive early offers of pediatric donor livers have improved waitlist survival, and that preferentially offering these organs to women mitigates this sex-based disparity. We analyzed donor liver offers from 2010 to 2014. Adult candidates who received a first offer that ranked within the first three match run positions from the donors' perspective were classified based on gender and whether they received a pediatric versus adult offer. We used competing risks regression to associate first offer type and waitlist mortality. A total of 8,101 waitlist candidates received a first offer that was ranked within the first three match run positions: 5.6% (293/5,202) men and 6.2% (179/2,899) women received a pediatric donor liver as their first offer. In multivariable analyses, compared with adult-first men, adult-first women (subhazard ratio [sHR] 1.33, 95% confidence interval 1.17-1.51, P < 0.01) had an increased pretransplant mortality risk while pediatric-first men and pediatric-first women had noninferior risks of morality. Pediatric-to-adult and adult-to-adult recipients had similar risks of graft failure and posttransplant mortality. CONCLUSION: Our study examines allograft selection by donor age, recipient sex, and in effect size as a means to address disparities in waitlist mortality. We found that women who received a pediatric donor liver as the first offer had a lower risk of waitlist mortality compared with those who receive adult offers. Our data provides a simple approach to mitigating the increased waitlist mortality experienced by women by incorporating donor and recipient size as variables into organ allocation. (Hepatology 2018).

A Concentric Neighborhood Solution to Disparity in Liver Access That Contains Current UNOS Districts.

BACKGROUND: Policymakers are deliberating reforms to reduce geographic disparity in liver allocation. Public comments and the United Network for Organ Sharing Liver and Intestinal Committee have expressed interest in refining the neighborhoods approach. Share 35 and Share 15 policies affect geographic disparity. METHODS: We construct concentric neighborhoods superimposing the current 11 regions. Using concepts from concentric circles, we construct neighborhoods for each donor service area (DSA) that consider all DSAs within 400, 500, or 600 miles as neighbors. We consider limiting each neighborhood to 10 DSAs and use no metrics for liver supplies and demands. We change Model for End-Stage Liver Disease (MELD) thresholds for the Share 15 policy to 18 or 20 and apply 3- and 5-point MELD proximity boosts to enhance local priority, control travel distances, and reduce disparity. We conduct simulations comparing current allocation with the neighborhoods and sharing policies. RESULTS: Concentric neighborhoods structures provide an array of solutions where simulation results indicate that they reduce geographic disparity, annual mortalities, and the airplane travel distances by varying degrees. Tuning of the parameters and policy combinations can lead to beneficial improvements with acceptable transplant volume loss and reductions in geographic disparity and travel distance. Particularly, the 10-DSA, 500-mile neighborhood solution with Share 35, Share 15, and 0-point MELD boost achieves such while limiting transplant volume losses to below 10%. CONCLUSIONS: The current 11 districts can be adapted systematically by adding neighboring DSAs to improve geographic disparity, mortality, and airplane travel distance. Modifications to Share 35 and Share 15 policies result in further improvements. The solutions may be refined further for implementation.

Share 35 changes in center-level liver acceptance practices.

Share 35 was implemented to provide improved access to organs for patients with Model for End-Stage Liver Disease (MELD) scores ≥ 35. However, little is known about the impact of Share 35 on organ offer acceptance rates. We evaluated all liver offers to adult patients who were ultimately transplanted between January 1, 2011 and December 31, 2015. The analyses focused on patients ranked in the top 5 positions of a given match run and used multilevel mixed-effects models, clustering on individual wait-list candidate and transplant center. There was a significant interaction between Share 35 era and MELD category (P < 0.001). Comparing offers to MELD score ≥ 35 patients, offers after Share 35 were 36% less likely to be accepted compared with offers to MELD score ≥ 35 patients before Share 35 (adjusted odds ratio, 0.64). There was no clinically meaningful difference in the donor risk index of livers that were declined for patients with an allocation MELD score ≥35 in the pre- versus post-Share 35 era. Organ offer acceptance rates for patients with an allocation MELD ≥ 35 decreased in every region after Share 35; the magnitude of these changes was bigger in regions 2, 3, 4, 5, 6, 7, and 11, compared with regions 8 and 9 that had regional sharing in place before Share 35. There were significant changes in organ offer acceptance rates at the center level before versus after Share 35, and these changes varied across centers (P < 0.001). In conclusion, in liver transplantation candidates achieving a MELD score ≥ 35, liver acceptance of offers declined significantly after implementation of Share 35. The alterations in behavior at the center level suggest that practice patterns changed as a direct result of Share 35. Changes in organ acceptance under even broader organ sharing (redistricting) would likely be even greater, posing major logistical and operational challenges, while potentially increasing discard rates, thus decreasing the total number of transplants nationally. Liver Transplantation 23 604-613 2017 AASLD.

Interpreting Outcomes in DCDD Liver Transplantation: First Report of the Multicenter IDOL Consortium.

BACKGROUND: In the United States, 5% of adult liver transplant recipients receive a graft donation after circulatory determination of death (DCDD). Concerns for ischemic cholangiopathy (IC), a disease of diffuse intrahepatic stricturing limits broader DCDD use. Single-center reports demonstrate large variation in outcomes. METHODS: Retrospective deidentified data collected between 2005 and 2013 were entered electronically by 10 centers via a Research Electronic Data Capture database. Our primary outcome was development of intrahepatic biliary strictures consistent with IC. RESULTS: Within 6 months post-DCDD transplant, 162 (21.8%) patients developed a biliary stricture, of which 88 (11.8%) exhibited intrahepatic structuring consistent with IC. Unadjusted 6-month IC rate among the 10 centers varied significantly (P = 0.006) from 6.3% to 25.9%. The only factor associated with increased risk of IC within 6 months was Roux-en-Y hepaticojejunostomy (vs duct-to-duct) (odds ratio, 3.06; 95% confidence interval, 1.52-6.16; P = 0.002). Graft failure by 6 months was more than 3 times higher for DCDD recipients with IC (odds ratio for IC, 3.36; 95% confidence interval, 1.95-5.79). CONCLUSIONS: This first report of the large combined experience with DCDD from the Improving DCDD Outcomes in Liver Transplant consortium demonstrates significant differences in IC among centers, the importance of biliary strictures as a risk factor for graft failure, and does not validate other risk factors for IC found in smaller studies.

Epidemiology and Healthcare Resource Utilization Associated With Children With Short Bowel Syndrome in the United States.

BACKGROUND: There is a lack of large database research relating to the epidemiology and health resource utilization associated with short bowel syndrome (SBS) in the United States. METHODS: We analyzed the Kids' Inpatient Database for the year 2012 and utilized International Classification of Diseases, Ninth Revision, and Clinical Modification ( ICD-9-CM) diagnosis codes to identify patients 0-3 years of age with SBS, who were matched by age and sex to children without SBS. The study variables included patient and hospital demographics, All Patient Refined Diagnosis Related Groups, in-hospital mortality, hospital length of stay, and hospitalization costs. We also determined the most frequent ICD-9-CM diagnostic and procedural codes associated with SBS. RESULTS: Children with SBS demonstrated a higher rate of mortality than that of children without SBS (1.6% vs 0.7%; P < .001). Children with SBS also experienced a longer length of stay (median days [interquartile range]: 8 [15] vs 2 [3]; P < .001) and higher hospital costs ($17,000 [$34,000] vs $3000 [$5000]; P < .001). The most frequent medical diagnoses associated with SBS were infection (62%), anemia (29%), and liver disease (17%). Children with SBS also demonstrated more severe illness as assessed by an All Patient Refined Diagnosis Related Group score of 3 or 4 (94.30% vs 16.20%; P < .001). CONCLUSIONS: Children hospitalized with SBS have a high severity of illness and experience complicated inpatient courses related to their disease. Our study represents the first use of national U.S. data to study the epidemiology and health resource utilization associated with SBS.

Liver transplant center variability in accepting organ offers and its impact on patient survival.

BACKGROUND & AIMS: Despite an allocation system designed to give deceased-donor livers to the sickest patients, many transplantable livers are declined by U.S. transplant centers. It is unknown whether centers vary in their propensities to decline organs for the highest priority patients, and how these decisions directly impact patient outcomes. METHODS: We analyzed Organ Procurement and Transplantation Network (OPTN) data from 5/1/07-6/17/13, and included all adult liver-alone waitlist candidates offered an organ that was ultimately transplanted. We evaluated acceptance rates of liver offers for the highest ranked patients and their subsequent waitlist mortality. RESULTS: Of the 23,740 unique organ offers, 8882 (37.4%) were accepted for the first-ranked patient. Despite adjusting for organ quality and recipient severity of illness, transplant centers within and across geographic regions varied strikingly (p<0.001) in the percentage of organ offers they accepted for the highest priority patients. Among all patients ranked first on waitlists, the adjusted center-specific organ acceptance rates ranged from 15.7% to 58.1%. In multivariable models, there was a 27% increased odds of waitlist mortality for every 5% absolute decrease in a center's adjusted organ offer acceptance rate (adjusted OR: 1.27, 95% CI: 1.20-1.32). However, the absolute difference in median 5-year adjusted graft survival was 4% between livers accepted for the first-ranked patient, compared to those declined and transplanted at a lower position. CONCLUSION: There is marked variability in center practices regarding accepting livers allocated to the highest priority patients. Center-level decisions to decline organs substantially increased patients' odds of dying on the waitlist without a transplant.

Rising Incidence of Clostridium difficile Related Discharges among Hospitalized Children in the United States.

Using a national database, we report an increasing trend in Clostridium difficile incidence among hospitalized children in the United States from 2003 to 2012. The incidence rate of CDI increased from 24.0 to 58.0 per 10,000 discharges per year (P<0.001) across all age groups, with the greatest increase in children 15 years and older. Infect. Control Hosp. Epidemiol. 2015;37(1):104-106.

mHealth Clinic Appointment PC Tablet: Implementation, Challenges and Solutions.

BACKGROUND: Patients requiring daily intravenous (IV) home parenteral nutrition (HPN) would benefit from in-home professional observation to improve self-care, to assess, detect and prevent serious complications. AIMS: The study aims are to assess the viability and utility of conducting mobile healthcare (mHealth) videoconference assessments with patients managing lifelong daily 12-hour IV nutrition infusions in their homes. The challenges and solutions to implementing mobile personal computer (PC) tablet based clinic appointments are described. METHODS: A wireless Apple iPad Mini™ mobile touch-screen tablet computer with 5 mega-pixel camera was loaned to patients. Each tablet had Polycom RealPresence software and a fourth generation (4G) mobile telecommunications data plan. These supported audio-visual mobile videoconferencing encrypted connections between health professionals in their offices and HPN patients and their family members in their homes. Patients' and professionals' evaluations of their mHealth clinic experiences are collected. RESULTS: Patients (mean age = 41.9, SD = 2.8 years) had been prescribed 12-hour home parenteral nutrition (HPN) infusions daily due short bowel disorders. Patients had been on HPN from 1 to 10 years (M=4, SD=3.6). Evaluation of clinic appointments revealed that 100% of the patients (n=45) and the professionals (n=6) indicated that they can clearly hear and easily see one another. The mHealth audio-visual interactions were highly rated by patients and family members. Professionals highly rated their ability to obtain a medical history and visual inspection of patients. Several challenges were identified and recommendations for resolutions are described. DISCUSSION: All patients and professionals highly rated the iPad mHealth clinic appointments for convenience and ease of communicating between homes and offices. An important challenge for all mHealth visits is the clinical professional's ability to make clinically accurate judgments about what they observed and heard from the patients. Following our solutions for obtaining clear visuals with the iPad can improve ability to make clinical assessments.