Futility and poor outcomes are not the same thing: A clinical perspective of refined outcomes definitions in liver transplantation.

The term "futility" in liver transplantation is used inappropriately and inaccurately, as it is frequently applied to patient populations with suboptimal outcomes that are often not truly "futile." The term "futile" is used interchangeably with poor outcomes. Not all poor outcomes fulfill a definition of futility when considering all viewpoints. Definitions of "futility" are variable throughout the medical literature. We review futility in the context of liver transplantation, encompassing various viewpoints, with a goal to propose focused outcome definitions, including futility, that encompass broader viewpoints, and improve the utilization of "futility" to truly futile situations, and improve communication between providers and patients/families. Focused, appropriate definitions will help the transplant community develop better models to more accurately predict and avoid futile transplants, and better predict an individual patient's posttransplant outcome.

Sleep disturbances in chronic liver disease.

Sleep disturbances are common in chronic liver disease and significantly impact patient outcomes and quality of life. The severity and nature of sleep disturbances vary by liver disease etiology and severity. While there is ongoing research into the association between liver disease and sleep-wake dysfunction, the underlying pathophysiology varies and, in many cases, is poorly understood. Liver disease is associated with alterations in thermoregulation, inflammation, and physical activity, and is associated with disease-specific complications, such as HE, that may directly affect sleep. In this article, we review the relevant pathophysiologic processes, disease-specific sleep-wake disturbances, and clinical management of CLD-associated sleep-wake disturbances.

De novo hepatitis B infection following liver transplantation with core antibody positive grafts: The role of surface antibody status in guiding long-term prophylaxis.

Liver transplantation (LT) with hepatitis B core antibody (anti-HBc) positive grafts to hepatitis B surface-antigen (HBsAg) negative recipients is safe and has likely contributed to improvements in organ access over the years. The incidence of de novo hepatitis B infection (HBV) in these instances is low with appropriate prophylaxis and is affected by recipient immunologic status. There is debate as to whether hepatitis B surface antibody (anti-HBs) positivity may safely inform prophylaxis discontinuation post-LT. In this retrospective study of all hepatitis B surface antigen (HBsAg) negative recipients of anti-HBc positive organs at three large academic centers between January 2014 and December 2019, nine LT recipients discontinued prophylaxis after developing anti-HBs antibodies 1 year or later post-LT. Three of the nine patients (33%) developed de novo HBV, defined by positive HBsAg or hepatitis B virus (HBV) DNA, during the study period. The remaining six patients had no evidence of HBV infection after a mean follow-up of 37 months. The patients without de novo HBV had higher anti-HBs titers at the time of prophylaxis discontinuation and were less likely to have negative anti-HBs at the time of transplant or negative anti-HBc at any time point. These results suggest that quantitative anti-HBs titer thresholds rather than qualitative anti-HBs positivity at 1 year or later after LT should be used to identify patients at decreased risk of de novo infection and help guide prophylaxis duration.

Hepatitis B Virus Reactivation in Non-Liver Solid Organ Transplantation: Incidence and Risk Analysis.

INTRODUCTION: Hepatitis B virus reactivation (HBVr) can occur in solid organ transplant (SOT) recipients with previously inactive hepatitis B virus (HBV) infection. Previous studies have reported that HBVr is generally less than 10% in nonliver SOT recipients with past HBV infection. METHODS: We conducted a retrospective study from January 2018 to August 2023 at Mayo Clinic sites in Arizona, Florida, and Minnesota. We examined the antiviral prophylaxis strategy used and the characteristics of HBVr in hepatitis B core antibody-positive (HBcAb +) nonliver SOT adult recipients. Past HBV infection was defined as HBcAb + / hepatitis B surface antigen (HBsAg) -. Chronic HBV infection was defined as HBcAb + / HBsAg +. RESULTS: A total of 180 nonliver SOT recipients were identified during the study period. Indefinite antiviral prophylaxis was utilized in 77 recipients, and none developed HBVr after transplantation. In 103 recipients without antiviral prophylaxis, the incidence of HBVr was 12% (12/97) and 33% (2/6) in those with past HBV infection and chronic HBV infection. The incidence of HBVr in patients with past HBV infection is 16% (8/50), 15% (3/20), and 5% (1/22) in kidney, heart, and lungs, respectively. HBVr was more frequent in those who received alemtuzumab. Among 14 recipients with HBVr, none had HBV-associated liver failure or death. CONCLUSIONS: Our study observed a higher rate of HBVr (12%) in nonliver SOT recipients with past HBV infection compared to the previous studies. Further studies are needed to identify predictors of HBVr in nonliver SOT recipients and optimize antiviral prophylaxis guidance.

The Frequency and Impact of Adverse Childhood Experiences on Mood, Alcohol Relapse, and Outcomes in Liver Transplantation: A Retrospective Cohort Study.

BACKGROUND: Adverse childhood experiences (ACEs) are associated with the development of negative health behaviors and medical illnesses. ACE's association with poor health outcomes has been well documented in the general population; however, this relationship remains less clear in liver transplant (LT) recipients. OBJECTIVE: The aims of this study were to determine the prevalence of ACE and the influence of ACE on LT outcomes. METHODS: A retrospective electronic medical record review of all LT recipients over 11 years at an academic LT center. Demographic, diagnostic, and disease characteristics were extracted and compared for a history of ACE. Associations between a history of ACE and extracted variables were statistically tested using Student's t-test, chi-square tests, or Fisher's exact test, where appropriate. Graft and patient survival were tested using log-rank tests. RESULTS: Of the 1172 LT recipients, 24.1% endorsed a history of ACE. Females (P = 0.017) and recipients with lower levels of education (P < 0.001) had a higher frequency of ACE. Those with a history of ACE had a higher prevalence of hepatitis C virus (P < 0.001) and higher pretransplant body mass index (P < 0.001). Recipients with a history of ACE had higher prevalence of mood (P < 0.001), anxiety (P < 0.001), post traumatic stress disorder (P < 0.001), alcohol use (P < 0.001), and cannabis use (P < 0.001) disorders, as well as higher Patient Health Questionnaire-9 (P < 0.001) and General Anxiety Disorder-7 (P < 0.001) scores pre- and post-transplant. Those with ACE had a higher incidence of recorded relapses to alcohol by 3 years post-transplant (P = 0.027). Mean lab values, graft survival, and patient survival were not significantly different between those with and without a history of ACE except for total bilirubin at 6 months (P = 0.021). CONCLUSIONS: One-quarter of LT recipients have experienced ACE. ACE was associated with a history of psychiatric diagnoses, substance use disorders, elevated Patient Health Questionnaire-9 and General Anxiety Disorder-7 scores, and a higher prevalence of relapse to alcohol use after transplant. This population may benefit from increased/improved access to appropriate mental health and substance use services and support in the peri- and post-transplant period.

Celiac artery mesenteric fat measurement with endosonography (CAMEUS) reliably correlates with obesity and related comorbidities.

Background: Visceral fat represents a metabolically active entity linked to adverse metabolic sequelae of obesity. We aimed to determine if celiac artery mesenteric fat thickness can be reliably measured during endoscopic ultrasound (EUS), and if these measurements correlate with metabolic disease burden. Methods: This was a retrospective analysis of patients who underwent celiac artery mesenteric fat measurement with endosonography (CAMEUS) measurement at a tertiary referral center, and a validation prospective trial of patients with obesity and nonalcoholic steatohepatitis who received paired EUS exams with CAMEUS measurement before and after six months of treatment with an intragastric balloon. Results: CAMEUS was measured in 154 patients [56.5% females, mean age 56.5 ± 18.0 years, body mass index (BMI) 29.8 ± 8.0 kg/m2] and was estimated at 14.7 ± 6.5 mm. CAMEUS better correlated with the presence of non-alcoholic fatty liver disease (NAFLD) (R2 = 0.248, P < 0.001) than BMI (R2 = 0.153, P < 0.001), and significantly correlated with metabolic parameters and diseases. After six months of intragastric balloon placement, the prospective cohort experienced 11.7% total body weight loss, 1.3 points improvement in hemoglobin A1c (P = 0.001), and a 29.4% average decrease in CAMEUS (-6.4 ± 5.2 mm, P < 0.001). CAMEUS correlated with improvements in weight (R2 = 0.368), aspartate aminotransferase to platelet ratio index (R2 = 0.138), and NAFLD activity score (R2 = 0.156) (all P < 0.05). Conclusions: CAMEUS is a novel measure that is significantly correlated with critical metabolic indices and can be easily captured during routine EUS to risk-stratify susceptible patients. This station could allow for EUS access to sampling and therapeutics of this metabolic region.

Cancer Surveillance in Solid Organ Transplant Recipients With a Pretransplant History of Malignancy: Multidisciplinary Collaborative Expert Opinion.

With improved medical treatments, the prognosis for many malignancies has improved, and more patients are presenting for transplant evaluation with a history of treated cancer. Solid organ transplant (SOT) recipients with a prior malignancy are at higher risk of posttransplant recurrence or de novo malignancy, and they may require a cancer surveillance program that is individualized to their specific needs. There is a dearth of literature on optimal surveillance strategies specific to SOT recipients. A working group of transplant physicians and cancer-specific specialists met to provide expert opinion recommendations on optimal cancer surveillance after transplantation for patients with a history of malignancy. Surveillance strategies provided are mainly based on general population recurrence risk data, immunosuppression effects, and limited transplant-specific data and should be considered expert opinion based on current knowledge. Prospective studies of cancer-specific surveillance models in SOT recipients should be supported to inform posttransplant management of this high-risk population.