Alcohol Use in Liver Transplant Recipients With Alcohol-related Liver Disease: A Comparative Assessment of Relapse Prediction Models.

BACKGROUND: The selection of liver transplant (LT) candidates with alcohol-related liver disease (ALD) is influenced by the risk of alcohol relapse (AR), yet the ability to predict AR is limited. We evaluate psychosocial factors associated with post-LT AR and compare the performance of high-risk alcoholism risk (HRAR), sustained alcohol use post-LT (SALT), and the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) scores in predicting relapse. METHODS: A retrospective analysis of ALD patients undergoing LT from 2015 to 2021 at a single US transplant center was performed. Risk factors associated with post-LT AR were evaluated and test characteristics of 3 prediction models were compared. RESULTS: Of 219 ALD LT recipients, 23 (11%) had AR during a median study follow-up of 37.5 mo. On multivariate analysis, comorbid psychiatric illness (odds ratio 5.22) and continued alcohol use after advice from a health care provider (odds ratio 3.8) were found to be significantly associated with post-LT AR. On sensitivity analysis, SIPAT of 30 was optimal on discriminating between ALD LT recipients with and without post-LT AR. SIPAT outperformed both the HRAR and SALT scores (c-statistic 0.67 versus 0.59 and 0.62, respectively) in identifying post-LT AR. However, all scores had poor positive predictive value (<25%). CONCLUSIONS: AR after LT is associated with comorbid psychiatric illness and lack of heeding health care provider advice to abstain from alcohol. Although SIPAT outperformed the HRAR and SALT scores in predicting AR, all are poor predictors. The current tools to predict post-LT AR should not be used to exclude LT candidacy.

Use and outcomes of hepatitis B virus-positive grafts in orthotopic liver transplantation in the United States from 1999 to 2021.

The demand for orthotopic liver transplantation (OLT) is projected to increase, which indicates a need to expand the liver donor pool. We aimed to investigate the use of hepatitis B virus (HBV)-positive grafts and the outcomes of recipients undergoing OLT with HBV-positive grafts. We conducted a retrospective cohort study analyzing all deceased donors and OLT recipients in the Organ Procurement and Transplantation Network database from January 1999 through March 2021. Donor HBV status was positive if hepatitis B surface antigen was positive or HBV nucleic acid testing was detectable. Recipients of HBV-positive allografts were matched 1:5 to recipients of HBV-negative allografts based on recipient and donor age, transplant year, recipient sex, donation after circulatory death, recipient location, and Model for End-Stage Liver Disease score at transplant. Among the 185,212 potential donors, 422 (0.2%) were HBV positive, and 265 (63%) of the HBV-positive grafts were transplanted (14 of 265 [5.3%] in HBV-positive recipients). The overall discard rate for HBV-positive donors of 37.2% (157/422) remained significantly higher than the discard rate for HBV-negative donors of 26.5% (49,026/185,212) during the study period ( p < 0.001). Recipients of HBV-positive ( n = 209) grafts had similar mortality (log-rank, p = 0.47) and graft loss (log-rank, p = 0.72) rates to the matched recipients of HBV-negative allografts ( n = 1045). The 3-year graft survival rate was 77.9% for the HBV-positive group and 79.7% in the matched HBV-negative group. Based on this analysis, transplant recipients of HBV-positive liver allografts do not experience increased rates of mortality or graft loss. One strategy that may help expand the donor pool and lower the waitlist mortality rate is using HBV-positive allografts.

Mortality in patients with end-stage liver disease above model for end-stage liver disease 3.0 of 40.

BACKGROUND AND AIMS: Since the implementation of the model for end-stage liver disease (MELD) score to determine waitlist priority for liver transplant (LT) in 2002, the score has been capped at 40. Recently, the MELD 3.0 score was proposed to improve upon MELD-Na. Here, we examine waitlist mortality and LT outcomes in patients with MELD 3.0 ≥ 40 to assess the potential impact of uncapping the score. APPROACH AND RESULTS: Adult waitlist registrations for LT from January 2016 to December 2021 were identified in the registry data from the Organ Procurement and Transplant Network. All MELD 3.0 scores were calculated at registration and thereafter. Waitlist mortality for up to 30 days was calculated as well as post-LT survival. There were 54,060 new waitlist registrations during the study period, of whom 2820 (5.2%) had MELD 3.0 ≥ 40 at listing. The 30-day waitlist mortality was high in these patients, yet it increased further in proportion with MELD 3.0 up to a score of 55 with 30-day mortality of 58.3% for MELD 3.0 of 40-44 and 82.4% for ≥50. The multivariable hazard ratio was 1.13 for each point of MELD 3.0, adjusting for several variables including acute-on-chronic liver failure. The number of LT recipients with MELD 40 at transplant increased from 155 in 2002 to 752 in 2021. Posttransplant survival was comparable across MELD strata including MELD of 35-39. CONCLUSION: MELD 3.0 scores beyond 40 are associated with increasing waitlist mortality without adversely affecting posttransplant outcome. Uncapping the MELD score in waitlist candidates may lead to greater survival benefit from LT.

Characteristics and outcomes of hepatocellular carcinoma patients with macrovascular invasion following surgical resection: a meta-analysis of 40 studies and 8,218 patients.

Background: Guidelines recommend that hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) and/or hepatic vein tumor thrombosis (HVTT) should undergo systemic therapy. However, recent data suggest that surgical resection may be beneficial in selected cases, but outcomes are heterogenous. We aimed to estimate pooled overall survival (OS), recurrence free survival (RFS) and complication rates in HCC patients with macrovascular invasion (MVI) following surgical resection. Methods: In this systematic review and meta-analysis, two investigators independently searched PubMed, Embase, and Cochrane databases from inception to Nov 10, 2020, without language restrictions, for studies reporting outcomes of adult HCC patients with MVI who underwent liver resection with curative intent. Results: We screened 8,598 articles and included 40 studies involving 8,218 patients. Among all patients with MVI, the pooled median OS was 14.39 months [95% confidence interval (CI): 10.99-18.84], 1-year OS was 54.47% (95% CI: 46.12-62.58%) and 3-year OS was 23.20% (95% CI: 16.61-31.42%). Overall, 1- and 3-year RFS were 27.70% (95% CI: 21.00-35.57%) and 10.06% (95% CI: 6.62-15.01%), respectively. Among patients with PVTT, median OS was 20.41 months in those with segmental/2nd order involvement compared to 12.91 months if 1st order branch was involved and 6.41 months if the main trunk was involved. The pooled rate of major complications was 6.17% (95% CI: 3.53-10.56%). Conclusions: Overall median survival was 14.39 months for HCC patients with MVI following resection. Median survival was higher in PVTT with segmental/2nd order involvement at 20.41 versus 6.41 months if the main trunk was involved.

Global and regional long-term survival following resection for HCC in the recent decade: A meta-analysis of 110 studies.

Surgical resection for HCC remains a major curative treatment option, but it is unclear whether there are differences in outcomes by region and whether outcomes have improved over time. We aimed to estimate pooled overall survival (OS), recurrence-free survival (RFS), and complication rates in patients with hepatocellular carcinoma (HCC) following curative surgical resection and to compare outcomes by region and by time period. In this systematic review and meta-analysis, we searched Pubmed, Embase, and Cochrane databases from inception to May 15, 2020. We selected studies reporting OS, RFS, and complications in adult patients with HCC undergoing curative surgical resection. Two authors independently searched the literature and extracted the data. We screened 6983 articles and included 110 eligible studies with 82,392 patients, with study periods spanning from 1980-2017. The global pooled 1-year and 5-year survival rates were 88.9% (95% confidence interval [CI] 87.1-90.4) and 56.2% (95% CI 52.8-59.6) for OS and 71.1% (95% CI 67.6-74.3) and 35.2% (95% CI 32.5-38.0) for RFS, respectively. Five-year OS was higher in Asia (57.03%) than in other regions (Europe 48.3%; North America 48.0%; and South America 49.5%); p = 0.002. Five-year RFS was higher in patients with hepatitis B virus versus patients with hepatitis C virus (34.8% vs. 24.1%; p = 0.02). There was no significant improvement in 5-year OS and RFS over time. The pooled rate for complications was 27.6% (95% CI 23.4-32.3), with 9.7% (95% CI 6.3-14.7) classified as major. One-year OS after surgical resection for HCC is excellent (~90%). However, 5-year OS (~55%) and RFS (~35%) are still poor, suggesting that long-term care is suboptimal. Greater efforts are required to improve survival through enhanced surveillance and preventing recurrence through antiviral therapy.

Caring for the Poor: Analysis of Nurses' Attitudes Toward the Culture of Poverty.

ABSTRACT: Living in a culture of poverty challenges people when they seek healthcare. Attitudes of healthcare workers caring for the poor can affect both return to care and subsequent health outcomes. This quality improvement project at a U.S. Midwestern hospital employed a quasi-experimental design to examine the effect of a voluntary educational intervention on nurses' attitudes toward the culture of poverty. Findings indicated a significant positive change in attitude dealing with stigmatizing statements about people living in the culture of poverty.

Increasing Trends in Transplantation of HCV-Positive Livers Into Uninfected Recipients.

The introduction of direct-acting antiviral (DAA) agents and the opioid epidemic have resulted in an increased interest in liver transplantation (LT) of organs from donors with hepatitis C virus (HCV)-related viremia.1 In March of 2015, the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) implemented a policy to perform HCV nucleic acid testing (NAT) in all HCV-seropositive donors. An open-label, single-center experience with 10 patients using a multistep informed consent reported successful transplantation of HCV-seropositive viremic (HCV-V) kidneys into HCV-seronegative recipients.2 Subsequently, a case was reported in which an HCV-V liver was transplanted into a HCV-seronegative recipient.3 In collaboration with OPTN/UNOS, we identified cases in which HCV-V deceased donor livers were transplanted into HCV-seronegative recipients.

Implementation of a Screening and Management of Overweight and Obesity Clinical Practice Guideline in an Ambulatory Care Setting.

Introduction: Obesity is a rapidly growing health problem reaching epidemic levels around the world (World Health Organization, 2014). According to the World Health Organization, the current incident rate of obesity makes it the leading risk for deaths across the globe. The United States (USA) is amidst in this growing global epidemic. The obesity epidemic is a nondiscriminatory health problem affecting millions of individuals from a variety of backgrounds and social status. One group impacted by this disease is the US military. The health-related consequences of overweight and obesity has increased our military health care expenditures and has a direct impact on our nation's military readiness (Veterans Affairs/Department of Defense, 2014). Materials and Methods: The purpose of this Doctor of Nursing Practice project was to implement the Veterans Affairs/Department of Defense's Clinical Practice Guideline on Screening and Management of Overweight and Obesity at a military treatment facility in the Midwest. The goal of the project was to reduce the incidence rate of overweight and obese active duty military service members assigned to a military installation in the Midwest. With institutional review board approval, project implementation results were analyzed with descriptive and inferential statistics (paired t- tests). Results: The goal to reduce the incident rate of overweight and obese by 5% was not achieved, but in turn the rate of overweight and obese increased by 1.57% over the 6-mo period. There were decreases in the normal with an increase in the overweight and obesity rate. This inverse outcome was unexpected and concerning. Conclusion: Based on the project's finding, there is a need to address the perceived barriers to maintaining healthy behaviors to plan future activities. An in-depth look at whether there is a knowledge deficit, a perceived lack of self-efficacy, competing life priorities preventing engagement in health promotion behaviors, or some other element influencing the motivation to change would be beneficial to understanding how to curb the growing rate of obesity. The utilization of the transtheoretical model of behavior change would make a sound theoretical framework to base such a new study, focusing on the stages of change as it relates to health promotion behaviors.

ICOS protects against mortality from acute lung injury through activation of IL-5+ ILC2s.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease causing irreversible lung scarring and loss of pulmonary function. IPF Patients suffer from a high rate of pulmonary infections and acute exacerbations of disease that further contribute to pulmonary decline. Low expression of the inducible T-cell costimulatory molecule (ICOS) in peripheral blood mononuclear cells predicts decreased survival of IPF patients, but the mechanisms by which ICOS protects are unclear. Using a model of bleomycin-induced lung injury and fibrosis, we now demonstrate that ICOS expression enhances survival from lung injury rather than regulating fibrogenesis. Of ICOS-expressing cells, type 2 innate lymphocytes (ILC2s) are the first to respond to bleomycin-induced injury, and this expansion is ICOS dependent. Interestingly, a similar decrease in ICOS+ ILCs was found in lung tissue from IPF patients. Interleukin (IL)-5, produced primarily by ILC2s, was significantly reduced after lung injury in ICOS-/- mice, and strikingly, treatment with IL-5 protected both ICOS-/- and wild-type mice from mortality. These results imply that low ICOS expression and decreased lung ILC2s in IPF patients may contribute to poor recovery from infections and acute exacerbation and that IL-5 treatment may be a novel therapeutic strategy to overcome these defects and protect against lung injury.

Weight management: A concept analysis.

AIM: There is a need to develop sound healthcare practices where patients and providers are able to succeed in meeting weight management goals. The aim of this analysis is to develop a better understanding the concept of weight management. BACKGROUND: Obesity is a rapidly growing healthcare issue, reaching epidemic levels around the world. According to the World Health Organization, the current incident rate of obesity makes it the leading risk for death across the globe. DESIGN: Walker and Avant's model for concept analysis. DATA SOURCE: A literature search was accomplished using Cumulative Index to Nursing and Allied Health, Health Source: Nursing Academic Edition, Medline, and ProQuest Health and Medical Complete. REVIEW METHODS: Keywords included weight management, weight control, weight loss, obesity, weight, and management. RESULTS: Weight management is complex concept. Strategies to develop successful weight management programs need to be multifaceted to have impact on this healthcare crisis. CONCLUSION: The critical attributes for weight management are dietary measures, physical activity, behavior modification, motivation, education, and lifelong changes. Unsuccessful weight management results in metabolic disorders and increased risk of mortality. Successful weight management practices include the prevention of weight gain, weight loss, and maintenance of ideal body weight.

Underutilization of Living Donor Liver Transplantation in the United States: Bias against MELD 20 and Higher.

Background and Aims: Utilization of living donor liver transplantation (LDLT) and its relationship with recipient Model for End-Stage Liver Disease (MELD) needs further evaluation in the United States (U.S.). We evaluated the association between recipient MELD score at the time of surgery and survival following LDLT. Methods: All U.S. adult LDLT recipients with MELD < 25 were evaluated using the 1995-2012 United Network for Organ Sharing registry. Survival following LDLT was stratified into three MELD categories (MELD < 15 vs. MELD 15-19 vs. MELD 20-24) and evaluated using Kaplan-Meier methods and multivariate Cox proportional hazards models. Results: Overall, 2,258 patients underwent LDLT. Compared to patients with MELD < 15, overall 5-year survival following LDLT was similar among patients with MELD 15-19 (80.9% vs. 80.3%, p = 0.77) and MELD 20-24 (81.2% vs. 80.3%, p = 0.73). When compared to patients with MELD < 15, there was no significant difference in long-term post-LDLT survival among those with MELD 15-19 (HR: 1.11, 95% CI: 0.85-1.45, p = 0.45) and a non-significant trend towards lower survival in patients with MELD 20-24 (HR: 1.28, 95% CI: 0.91-1.81, p = 0.16). Only 14% of LDLTs were performed in patients with MELD 20-24 and the remaining 86% in patients with MELD < 20. Conclusion: LDLT is underutilized in patients with MELD 20 and higher.

Effect of Liver Transplant on Long-term Disease-Free Survival in Children With Hepatoblastoma and Hepatocellular Cancer.

INTRODUCTION: Hepatoblastoma (HBL) and hepatocellular cancer (HCC) are the most common primary hepatic malignant neoplasms in childhood. Given the rarity of these childhood tumors and their propensity to present at advanced stages, updated long-term data are needed. OBJECTIVE: To determine the efficacy of liver transplant in children with HBL or HCC. DESIGN, PARTICIPANTS, AND SETTING: This single-institution retrospective medical record review and analysis spanned from January 1, 1997, through September 17, 2014, at Stanford University School of Medicine. A total of 40 patients younger than 18 years underwent liver transplant for treatment of HBL (n = 30) or HCC (n = 10) during the study period, with follow-up until September 17, 2014. Patients who underwent transplant for HCC included those with tumors that were greater in size than what is proposed by the Milan (a single tumor measuring ≤5 cm or ≤3 nodules measuring ≤3 cm) and University of California, San Francisco (single tumor measuring ≤6.5 cm or ≤3 nodules measuring ≤4.5 cm and a total diameter of ≤8 cm), criteria. MAIN OUTCOMES AND MEASURES: Disease-free and overall patient survival and graft survival. RESULTS: Using a Kaplan-Meier survival analysis, 1-, 5-, and 10-year disease-free survival after liver transplant was 93%, 82%, and 82%, respectively, for 30 patients with HBL and 90%, 78%, and 78%, respectively, for 10 patients with HCC. Risk factors associated with HBL recurrence after transplant included having pretreatment extent of disease stage IV lesions and a longer waiting list time and being older at the time of the transplant. Recurrence was found in 2 of 7 patients with HBL and pretransplant metastases, which were not found to be an independent risk factor for recurrence. Patients with HCC larger than the proposed Milan and University of California, San Francisco, criteria experienced good 5-year disease-free (82%) and overall (78%) survival after transplant. Being older at the time of transplant (18 vs 11 years; P = .04) and the presence of metastatic disease (1 patient vs none; P = .05) were associated with HCC tumor recurrence. CONCLUSIONS AND RELEVANCE: Liver transplant combined with chemotherapy is an excellent treatment that provides long-term disease-free survival in children diagnosed with advanced HBL and HCC. Early addition to a waiting list and aggressive multimodal therapy provide excellent results. Transplant should still be considered in children with HCC larger than the Milan and University of California, San Francisco, criteria.

Pediatric intestinal transplantation at Packard Children's Hospital/Stanford University Medical Center: report of a four-year experience.

We report a 4-year experience of a new program in pediatric intestinal transplantation. Among 50 children referred for evaluation, 27 were listed for transplantation. Two children originally listed for combined liver/small bowel transplant were changed to isolated intestinal transplant as rehabilitation efforts resulted in full recovery of hepatic function. Eighteen children received 18 grafts: 12 liver/intestine, 5 isolated intestine, and 1 multivisceral. Mean age at transplant was 3.6 year with 75% of patients aged 0 to 2 years. Five listed children died while waiting and four were still on the list. Immunotherapy included antithymocyte globulin induction and tacrolimus, sirolimus, and prednisone maintenance. At 1 year, patient and graft survivals were 75% and 67%, respectively. For isolated intestine, 1 year survivals were 100% and 75%, while for combined liver/intestine, they were 71% for both. Enteral autonomy is 100% with total parenteral nutrition stopping by 35.8 days (mean). We had two patients develop posttransplant lymphoproliferative disorder and three, exfoliative rejection, one of whom recovered completely. In conclusion, our program in pediatric intestinal transplantation has become well established with a high proportion of smaller/younger children receiving grafts. Outcomes achieved levels expected based on The Intestinal Transplant Registry and UNOS criteria, which were better than expected for isolated intestinal transplants and achievement of enteral autonomy.

Induction of tumor immunity and cytotoxic t lymphocyte responses using dendritic cells transduced by adenoviral vectors encoding HBsAg: comparison to protein immunization.

Dendritic cells (DC) are specialized antigen-presenting cells with powerful immunostimulatory properties. Their use for induction of anti-tumor immunity has been limited by several factors, including identification of appropriate tumor-associated antigens, delivery of antigens to DC, and maintaining DC in a highly activated state. Here, DC propagated in vitro were transduced with an adenoviral (Ad) vector to express hepatitis B surface antigen (HBsAg), an antigen present in hepatocellular carcinoma (HCC). Many patients with HCC demonstrate evidence of prior HBV exposure, suggesting that the presence of the virus in a quiescent state may promote tumorigenesis. Ad-HBsAg-transduced DC stimulated strong cytotoxic T lymphocyte (CTL) responses to HBsAg-expressing tumor cells, and protected mice from lethal tumor challenge. Immunity was antigen-specific, as wild-type tumor (HBsAg -) grew normally. Furthermore, DC transduced with an irrelevant vector had no effect. Vaccination with HBsAg protein, a clinically utilized preparation that confers immunity to HBV infection, did not protect against tumor challenge even though it induced a strong antibody response. These studies describe for the first time the contributions of humoral and cellular immune responses to tumor immunity induced by Ad-transduced DC compared to protein vaccination.