Transplant Selection: Disease Severity and Psychosocial Evaluation.

Association of Type of Induction with Posttransplant Lymphoproliferative Disorders

Liver transplantation for alcoholic hepatitis in the United States: Excellent outcomes with profound temporal and geographic variation in frequency.

Previous studies have found inconsistent associations between pre-transplant dialysis modality and subsequent post-transplant survival. We aimed to examine this relationship using the instrumental variable method and to compare the results with standard Cox regression. We included 29 088 patients (age >20 years) from 16 European national or regional renal registries who received a first kidney transplant between 1 January 1999 and 31 December 2008 and were on dialysis before transplantation for a period between 90 days and 10 years. Standard multivariable Cox regression examined the association of individually assigned pre-transplant dialysis modality with post-transplant patient and graft survival. To decrease confounding-by-indication through unmeasured factors, we applied the instrumental variable method that used the case-mix adjusted centre percentage of peritoneal dialysis (PD) as predictor variable. Standard analyses adjusted for age, sex, primary renal disease, donor type, duration of dialysis, year of transplantation and country suggested that PD before transplantation was associated with better patient [hazard ratio, HR (95% CI) = 0.83 (0.76-0.91)] and graft survival (HR (95% CI) 0.90 (0.84-0.96)) when compared with haemodialysis (HD). In contrast, the instrumental variable analysis showed that a 10% increase in the case-mix adjusted centre percentage of patients on PD was neither associated with post-transplant patient survival [HR (95% CI = 1.00 (0.97-1.04)] nor with graft survival [HR (95% CI) = 1.01 (0.98-1.04)]. The instrumental variable method failed to confirm the associations found in standard Cox regression between pre-transplant dialysis modality and patient and graft survival after transplantation. The lack of association in instrumental variable analysis may be due to better control of residual confounding.

As hepatology providers, we assemble a toolbox of interventions to treat acute and chronic liver diseases with a goal to prevent fibrosis progression, HCC, and hepatic decompensation while also improving the quality of life and survival of our patients (Figure 1). This toolbox has been built based on our experiences during clinical training and the practice of routine patient care. We are comfortable with a diverse set of tools, from antivirals to immunosuppressive medications, vasoactive medications to beta-blockers, as well as performing interventions such as endoscopy, banding, paracentesis, and liver biopsies. Hepatology providers have accepted that in the setting of chronic liver disease, we are primarily responsible for prescribing interventions, which treat the underlying liver insult and follow-up on outcomes and side effects using a multidisciplinary approach. Yet, when it comes to the management of alcohol use disorder (AUD) in the setting of alcohol-associated liver disease (ALD), our discipline seems to have made an exception. Although treatment of AUD has been identified as a quality metric in the care of patients with liver disease,1 rates of AUD treatment in those with ALD are astonishingly low,2,3 and current societal recommendations are to refer elsewhere for AUD management once identified.4,5 Why has this culture evolved among hepatology providers? Is it a lack of knowledge and/or comfort in AUD treatment? Do patients with AUD and their providers have difficulty accessing the tools when needed? Importantly, can social stigma and sociocultural considerations influence patient participation in AUD treatment? The answer is all of the above.FIGURE 1: The hepatology toolbox—how do we include alcohol use disorder treatment?.DESPITE THE BENEFIT, TREATMENT OF AUD IN ALD RARELY HAPPENS It is universally agreed that alcohol abstinence is the cornerstone of ALD management, as it is associated with improved liver-related outcomes3 and is cost-effective and even cost-saving in those with ALD cirrhosis.6 Yet despite this, 2 large cohort studies of individuals with AUD and ALD cirrhosis have shown that only ~15% receive AUD behavioral therapy and a mere 1% receive pharmacotherapy.2,3 Why are AUD treatment rates so low? To begin, data have suggested that apart from psychiatry and addiction medicine, physicians receive minimal training in AUD identification and management and do not feel equipped to treat it. Surveys by GI/hepatology providers suggest that almost all screen universally for frequency and quality of alcohol consumption; however, almost half never/rarely screen for AUD, and 70% never/rarely prescribe AUD therapy.7 The most common provider-perceived barriers to prescribing AUD pharmacotherapy were lack of training, unfamiliarity, and lack of time. Other studies have identified patient-perceived barriers, including lack of apparent benefit to treatment, financial and insurance obstacles, and access to transportation.8 However, in addition to these hurdles, other patient-related barriers are faced disproportionately by those most vulnerable in society. SOCIOCULTURAL AND EQUITY CONSIDERATIONS INFLUENCING DELIVERY OF AUD/ALD THERAPY A significant proportion of individuals with AUD/ALD are from historically underrepresented racial/ethnic, sex/gender, and sociocultural groups9 and those vulnerable in their social determinants of health, creating additional barriers to AUD treatment (Figure 2). These disparities are complex and historically rooted in patterns of systemic discrimination and socioeconomic disadvantage.10 Overall, AUD treatment is most effective as a combination of pharmacologic and behavioral interventions, yet most studies evaluating AUD treatment underrepresent those of diverse cultural, racial/ethnic, and sex/gender backgrounds and have not been designed to address important dimensions of diversity. In considering those vulnerable in social determinants of health, pharmacologic treatments require public and/or private insurance to cover costs, while in addition to cost, behavioral therapy also requires significant time and social resources to participate. These include the ability to take time from work in those employed and/or the ability to delay home obligations if caring for dependents. Individuals must also secure transportation and be in proximity to AUD behavioral treatment, or if able to be delivered remotely, have access to technological resources for participation. Finally, culturally and linguistically appropriate AUD services are required to provide safe and equitable access to AUD treatment to all but are not universally accessible. Moving forward, these important aspects of diversity will need to be considered in the development and delivery of AUD services.FIGURE 2: Barriers to alcohol use disorder treatment in vulnerable populations.SPECIAL CONSIDERATIONS FOR WOMEN AND YOUTHS Women and youths have been identified as populations experiencing a disproportionate increase in harm from AUD/ALD and have emerged as priority groups in need of AUD treatment.11,12 Women and youths with AUD have a high prevalence of co-morbid mental health conditions and have experienced mental, physical, and/or sexual abuse, which can impact participation and outcomes of treatment. Although outcomes of AUD treatment are comparable between sexes, women are less likely to receive treatment than men.12 Unique factors among women that can influence participation in AUD treatment include issues surrounding motherhood, such as the need for childcare to participate and perceived or experienced social stigma creating fear of the involvement of child protective services if AUD is disclosed.12 Further, no AUD pharmacotherapy has been shown to be safe for women who are pregnant or breastfeeding, limiting treatment options during this time. Similarly, for youths, no pharmacotherapies are FDA-approved to treat AUD in those ≤18 years of age, and no trials of AUD treatment among youths with ALD have been conducted. Despite the knowledge that most adults with AUD began using alcohol during the teenage years, the majority of efforts developed to treat AUD have not focused on identification and intervention during adolescence, which may be a key time for behavioral change. Further, the delivery of AUD behavioral therapy for youths is best if the family and caregivers partake, which again will be dependent on the ability of not only the individuals but also their social circle to participate. POTENTIAL SOLUTIONS Several provider, hospital, research, and societal solutions to address barriers in AUD management in ALD are outlined in Figure 3. On an individual GI/Hepatology provider level, the universal implementation of standardized screening tools for AUD to all patients with ALD at the time of the first clinical encounter should be straightforward to implement. In addition to this, the delivery of an AUD pharmacotherapy curriculum to GI/Hepatology trainees, nurses, and clinicians could empower them with the knowledge and skills to initiate AUD pharmacotherapy among their ALD patients. This would be especially important in settings where access to addiction medicine is limited. From a hospital level, providing language and transportation services to facilitate access to AUD behavioral therapy would be specifically helpful to engage vulnerable populations. Further, universal and quick access to inpatient and outpatient addiction medicine consultative services, social work, and psychiatry are essential. From an academic level, the development of studies, which evaluate AUD treatment and outcomes among those with advanced ALD, are needed in addition to the inclusion of previously understudied and vulnerable populations as outlined above. From a society level, it is vital to address the stigma attached to a diagnosis of AUD to empower patients to seek appropriate help without worry about judgment or discrimination. This could involve public education campaigns that emphasize AUD as a disease as opposed to a personal choice and highlight how appropriate treatment of AUD can lead to disease remission and improve other alcohol-associated harms including ALD.FIGURE 3: Potential solutions to address disparities in AUD treatment among those with ALD. Abbreviations: ALD, alcohol-associated liver disease; AUD, alcohol use disorder.CONCLUSIONS AND FUTURE CONSIDERATIONS AUD is a preventable cause of liver-related morbidity and mortality, and AUD treatment is associated with improved outcomes, especially among those with ALD. Yet the use of AUD treatment in those with ALD is discouragingly low due to the paucity of well-executed clinical trials and patient and provider barriers, with additional unique barriers faced by underrepresented and vulnerable members of society. As hepatology providers caring for these patients, our discipline needs to begin gathering AUD treatment tools to put in our toolbox. Importantly, these tools will need to incorporate considerations surrounding stigma, culture, diversity, and equity in order to provide the best care for our diverse patient population.

New Challenges in Addiction Medicine: COVID-19 Infection in Patients With Alcohol and Substance Use Disorders-The Perfect Storm.

Intersection of Coronavirus Disease 2019 and Alcohol-associated Liver Disease: A Review of Emerging Trends and Implications

The Effect of New Acuity Circle Policy on Simultaneous Liver and Kidney Transplantation in the United States

Although a set period of abstinence is no longer a requirement for transplant consideration in many liver transplantation programs, it is imperative to use valid monitoring tools to detect ongoing alcohol use in candidates for transplant. Urinary ethyl glucuronide (EtG) is an objective measure of alcohol use. This single-center retrospective study aims to describe the psychosocial characteristics of patients with alcohol-associated liver disease (ALD) who provided positive EtG tests in the pretransplant phase. Data were collected between May 1, 2018, and November 30, 2021, for all patients with ALD referred to our transplantation program (n = 497). Psychosocial characteristics and transplant outcomes were recorded for all patients. Patients with a positive EtG test were compared to patients who did not have a positive EtG test. A backward logistic regression analysis was performed to assess the factors associated with a positive EtG test. Of the 497 patients evaluated, 40 (8%) provided a positive EtG test, including at the initial clinic visit (n = 20), during medical evaluation (n = 14), and while on the waitlist (n = 6). Severe alcohol use disorder ( p < 0.01), consuming <10 daily standard drinks ( p = 0.011), and longer duration of daily alcohol use ( p = 0.028) were significantly associated with a positive EtG test. Psychiatric comorbidity and previous treatment for alcohol use disorder were not significantly associated with positive tests. A minority of patients with ALD provided a positive urine EtG in the pretransplant phase. Alongside clinical interviews, biomarker testing is an objective tool to identify ongoing alcohol use in patients with ALD.

Orthotopic liver transplantation (OLT) is a lifesaving therapy for patients with irreversible liver damage caused by autoimmune liver diseases (AutoD) including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). Currently, it is unclear how access to transplantation differs among patients with various etiologies of liver disease. Our aim is to evaluate the likelihood of transplant and the long-term patient and graft survival after OLT for each etiology for transplantation from 2000 to 2021. We conducted a large retrospective study of United Network for Organ Sharing (UNOS) liver transplant patients in five 4-year eras with five cohorts: AutoD (PBC, PSC, AIH cirrhosis), alcohol-related liver disease (ALD), hepatocellular carcinoma (HCC), viral hepatitis, and nonalcoholic steatohepatitis (NASH). We conducted a multivariate analysis for probability of transplant. Intent-to-treat (ITT) analysis was performed to assess the 10-year survival differences for each listing diagnosis while accounting for both waitlist and post-transplant survival. Across all eras, autoimmune conditions had a lower adjusted probability of transplant of 0.92 (0.92, 0.93) compared to ALD 0.97 (0.97, 0.97), HCC 1.08 (1.07, 1.08), viral hepatitis 0.99 (0.99, 0.99), and NASH 0.99 (0.99, 1.00). Patients with AutoD had significantly better post-transplant patient and graft survival than ALD, HCC, viral hepatitis, and NASH in each and across all eras (p-values all < 0.001). Patients with AutoD had superior ITT survival (p-value < 0.001, log rank test). In addition, the waitlist survival for patients with AutoD compared to other listing diagnoses was improved with the exception of ALD, which showed no significant difference (p-value = 0.1056, log rank test). Despite a superior 10-year graft and patient survival in patients transplanted for AutoD, patients with AutoD have a significantly lower probability of receiving a liver transplant compared to those transplanted for HCC, ALD, viral hepatitis, and NASH. Patients with AutoD may benefit from improved liver allocation while maintaining superior waitlist and post-transplant survival. Decreased access in spite of appropriate outcomes for patients poses a significant risk for increased morbidity for patients with AutoD.

Barriers to the management of alcohol use disorder and alcohol-associated liver disease: strategies to implement integrated care models

Background.Alcohol-associated liver disease (ALD) is the leading indication for liver transplantation (LT) in the United States. Alcohol use disorder relapse can lead to graft failure and the need for liver retransplantation (re-LT). Despite the rising incidence of LT for ALD, the practice of re-LT for recurrent ALD is not well understood. We aimed to define the practice of re-LT for recurrent ALD during the last 20 y.Methods.Using the US national transplant registry, adults who underwent re-LT for recurrent ALD were compared with LT recipients who died from recurrent ALD and propensity score–matched re-LT recipients with non-ALD indications. All groups had at least 1-y survival of their primary graft. Kaplan-Meier analysis was used to calculate 1- and 5-y survivals.Results.Between 2000 and 2020, 74 re-LTs were performed for recurrent ALD (1.0% of all re-LTs). There was an increase in recurrent ALD re-LT practice from 2017 to 2020 versus 2014 to 2016 (20 versus 2). At the time of re-LT, patients with recurrent ALD had a significant decrease in body mass index (median 25.1 versus 28.8 kg/m2; P < 0.001) versus the index LT. Patient and graft survivals were similar between patients who underwent re-LT for ALD and non-ALD (56.4% versus 56.9% 5-y graft survival, P = 0.96; 62.8% versus 59.0% 5-y patient survival, P = 0.58).Conclusions.The practice of re-LT for recurrent ALD is uncommon in the United States. Graft and patient survivals seem to be acceptable and support the occasional practice of re-LT for recurrent ALD should the patient be deemed an appropriate candidate.

Given the importance of understanding COVID-19-positive donor incidence and acceptance, we characterize chronological and geographic variations in COVID-19 incidence relative to COVID-19-positive donor acceptance. Data on deceased donors and recipients of liver and kidney transplants were obtained from the UNOS database between 2020 and 2023. Hierarchical cluster analysis was used to assess trends in COVID-19-positive donor incidence. Posttransplant graft and patient survival were assessed using Kaplan-Meier curves. From among 38429 deceased donors, 1517 were COVID-19 positive. Fewer kidneys (72.4%vs. 76.5%, p < 0.001) and livers (56.4%vs. 62.0%, p < 0.001) were used from COVID-19-positive donors versus COVID-19-negative donors. Areas characterized by steadily increased COVID-19 donor incidence exhibit the highest transplantation acceptance rates (92.33%), followed by intermediate (84.62%) and rapidly increased (80.00%) COVID-19 incidence areas (p = 0.016). Posttransplant graft and patient survival was comparable among recipients, irrespective of donor COVID-19 status. Regions experiencing heightened rates of COVID-19-positive donors are associated with decreased acceptance of liver and kidney transplantation. Similar graft and patient survival is noted among recipients, irrespective of donor COVID-19 status. These findings emphasize the need for adaptive practices and unified medical consensus in navigating a dynamic pandemic.

Blue Notes

Alcohol-associated liver disease (ALD) is a rapidly rising indication for liver transplantation. Early studies showed comparable post-transplant outcomes but emerging data suggest long-term survival benefits in ALD, thus warranting an analysis of waitlist and post-transplant outcomes. Medline and Embase were searched from inception to 16 May 2025. Kaplan-Meier curves were extracted to reconstruct individual participant data for pooled survival analysis of time-to-event outcomes using a random effects model. Cox regression-generated hazard ratios (HRs) for survival outcomes, and odds ratios (ORs) for post-transplant complications were obtained using pairwise meta-analyses. 50 articles (382,614 patients) were included in the meta-analysis. 6-month, 1- and 2-year waitlist survival in ALD patients was 79.7%, 72.7% and 63.8%, compared to 81.7%, 72.9% and 61.3% in non-ALD patients. 1-, 3-, 5- and 10-year post transplant patient survival was 91.3%, 83.0%, 76.1% and 60.2% in ALD, and 90.3%, 82.8%, 76.9% and 66.4% in non-ALD. Waitlist (HR: 1.021, 95% CI: 0.519-2.009, p = 0.95) and post-transplant survivals (HR: 0.914, 95% CI: 0.805-1.039, p = 0.17) were comparable between ALD and non-ALD patients. ALD patients had a higher risk of de novo malignancy post-transplant (OR: 2.194, 95% CI: 1.534-3.139, p < 0.001). In this reconstructed individual patient data meta-analysis, waitlist survival was comparable between ALD and non-ALD patients. While early post-transplant patient survival was similar, long-term survival remained inferior in ALD, partly attributed to increased de novo malignancy. These findings highlight the need for improved candidate selection, addiction care, and cancer surveillance to maximise long-term outcomes in the growing ALD transplant population.

Survival in Allosensitized Children After Listing for Cardiac Transplantation