Journal Article Annotations
2021, 3rd Quarter

Transplant Psychiatry

Annotations by Sarah R. Andrews, MD
September, 2021

Results of Early Transplantation for Alcohol-Related Cirrhosis: Integrated Addiction Treatment with Low Rate of Relapse.
Transplant-related trauma, personal growth and alcohol use outcomes in a cohort of patients receiving transplants for alcohol associated liver disease.

PUBLICATION #1 — Transplant Psychiatry

Results of Early Transplantation for Alcohol-Related Cirrhosis: Integrated Addiction Treatment with Low Rate of Relapse.

Lauren Carrique, Jill Quance, Adrienne Tan, Susan Abbey, Isabel Sales, Les Lilly, Mamatha Bhat, Zita Galvin, Mark Cattral, Anand Ghanekar, Ian McGilvray, Trevor Reichman, Gonzalo Sapisochin, Blayne Sayed, Markus Selzner, Marie-Josée Lynch, Nazia Selzner

Abstract: Gastroenterology. 2021 Aug 8;S0016-5085(21)03342-4. doi: 10.1053/j.gastro.2021.08.004.

Background & aims:
In 2018, our team initiated a prospective pilot program to challenge the paradigm of the “6-month rule” of abstinence for patients with alcohol-related liver disease (ALD) requiring transplant. Our pilot involved an in-depth examination of patients’ alcohol use, social support, and psychiatric comorbidity, as well as the provision of pre- and post-transplantation addiction treatment.

Methods:
Patients with ALD were assessed for inclusion in the pilot by a multidisciplinary team. Relapse prevention therapy was provided directly to all patients deemed to meet the program’s inclusion criteria. Random biomarker testing for alcohol was used pre and post transplantation.

Results:
We received 703 referrals from May 1, 2018 to October 31, 2020. After fulfilling the program’s criteria, 101 patients (14%) were listed for transplantation and 44 (6.2%) received transplants. There were no significant differences in survival rates between those receiving transplants through the pilot program compared with a control group with more than 6 months of abstinence (P = .07). Three patients returned to alcohol use during an average post-transplantation follow-up period of 339 days. In a multivariate analysis, younger age and lower Model for End-Stage Liver Disease scores at listing were associated with an increased likelihood of a return to alcohol use (P < .05); length of abstinence was not a predictor.

Conclusions:
Our prospective program provided direct monitoring and relapse prevention treatment for patients with ALD and with less than 6 months of abstinence and resulted in a reduction of post-transplantation return to drinking. This pilot study provides a framework for the future of more equitable transplant care.

Keywords:
6 Months of Abstinence; Alcohol Use Disorder; Alcohol-Related Liver Disease; Biomarker Monitoring; Relapse Prevention Therapy.

Annotation

The finding:
This prospective pilot study, based in Canada, challenges the 6-month-rule of abstinence for transplant in patients with alcohol-associated liver disease. Between May 2018 and October 2020, 703 referrals were made for liver transplant. Of these referrals, 14% were listed and 6% received transplants. There was no significant difference in survival rate among patients who had six months of sobriety prior to transplant compared to those who did not. Length of abstinence was not a predictor for returning to alcohol use, but younger age and lower Model for End-Stage Liver Disease (MELD) scores were. There was no significant difference with non-pilot patients with greater than six months of abstinence versus alcohol-liver disease pilot patients in return to alcohol use.

Strength and weaknesses:
This study is one of the first to pilot early liver transplantation beyond acute alcohol-associated hepatitis to include alcohol-related liver disease. One notable weakness of the study is the need for ongoing follow-up data to assess for sustained abstinence.

Relevance:
As the rate for early transplantation in acute alcohol-associated hepatitis has increased, this study focuses on more equitable transplant care for all patients with alcohol-related liver disease and how relapse prevention therapy and monitoring biomarkers can assist in decreased relapse rates and improving survival. This study is relevant for consulting transplant psychiatrists to better understand how to evaluate patients for transplant: simply suggesting abstinence for six months may not be as predictive of good clinical outcomes as other markers, such as MELD score.

PUBLICATION #2 — Transplant Psychiatry

Transplant-related trauma, personal growth and alcohol use outcomes in a cohort of patients receiving transplants for alcohol associated liver disease.

Katherine M Kruckenberg, Neeta Shenai, Mary Amanda Dew, Galen Switzer, Christopher Hughes, Andrea F DiMartini

Abstract: Gen Hosp Psychiatry. Sep-Oct 2021;72:73-80. doi: 10.1016/j.genhosppsych.2021.07.005. Epub 2021 Jul 17.

Background:
Previous studies suggested that depressive symptoms and sleep quality may be important for long-term clinical outcomes following cardiothoracic transplant. Few studies, however, have systematically examined objective markers of these behavioral factors among ambulatory transplant recipients, or their association with clinical outcomes.

Methods:
We examined sleep quality and depressive symptoms with subsequent clinical outcomes (hospitalizations and death) in a sample of 66 lung or heart transplant recipients using a single-center, prospective cohort study. Recipients were assessed at approximately 6 months post-transplant and completed one week of actigraphy assessment to examine sleep quality and self-report measures of mood (Centers for Epidemiologic Studies of Depression [CESD]). Recipients were followed for clinical outcomes.

Results:
At 6-months following transplantation, recipients spent the majority of daytime activity at a sedentary level (61% of daily activity [SD = 10]) and elevated depressive symptoms were common (subclinical = 17%, mild = 12%, or moderate = 8%). Over a median follow-up of 4.5 years (IQR = 0.9, 5.1), 51 participants (77%) had at least one unplanned hospitalization and 11 (17%) participants died. In addition, sleep efficiency measurements suggested that a subset of participants exhibited suboptimal sleep (mean efficiency = 87% [SD = 7]). Poorer sleep quality, indexed by lower sleep efficiency and greater sleep fragmentation, was associated with greater depressive symptoms (r’s = 0.37-0.50, P < .01). Better sleep quality at 6-months (HR = 0.75 [0.60, 0.95], P = .015), including sleep efficiency (HR = 0.74 [0.56, 0.99], P = .041) and sleep fragmentation (HR = 0.71 [0.53, 0.95], P = .020) were associated with lower risk of hospitalization or death. Compared with individuals without elevated depressive symptoms or sleep difficulties, individuals with either factor (HR = 1.72 [1.05, 2.81], P = .031) or both factors (HR = 2.37 [1.35, 4.18], P = .003) exhibited greater risk of clinical events in adjusted analyses.

Conclusions:
Sleep quality is associated with depressive symptoms among cardiothoracic transplant recipients and enhances the prognostic association between biobehavioral risk factors and clinical outcomes.

Keywords:
Actigraphy; Depressive symptoms; Sleep quality.

Annotation

The finding:
This prospective cohort study evaluated depressive symptoms and sleep patterns among 66 lung or heart transplant patients for several years post-transplant. At six months following transplantation, patients were more likely to be sedentary and over one-third had increased depressive symptoms. Impaired quality of sleep was associated with increased depressive symptoms while better sleep quality was associated with less risk of hospitalization or death.

Strength and weaknesses:
The strength of this study was identifying the importance of sleep quality and transplant outcomes. Objective outcome measures improved internal validity: sleep quality was assessed from actigraphy-based data, which has been shown to be comparable in validity and reliability to polysomnography. Depressive symptoms were measured using the Centers for Epidemiologic Study of Depression (CESD). However, one weakness is that these data rely on association and do not show causation. The sample size is small, and the investigators lacked sleep data for recipients prior to transplant. It remains unclear how interventions on sleep might correlate with clinical outcomes.

Relevance:
C-L psychiatrists managing patients pre- and post- heart or lung transplant should carefully assess sleep symptoms, which correlate with both psychiatric and medical outcomes. It may well be that improving patients’ sleep may not only improve quality of life but also prolong life.