Transplant Psychiatry

Annotated Abstracts of Journal Articles
2014, 2nd Quarter

Transplant Psychiatry

Annotations by Paula Zimbrean, MD, FAPM
June 2014

  1. New-onset cognitive dysfunction impairs the quality of life in patients after liver transplantation
  2. Longitudinal study of cognitive and academic outcomes after pediatric liver transplantation
  3. Predictors of post-traumatic psychological growth in the late years after lung transplantation

PUBLICATION #1 — Transplant Psychiatry
New-onset cognitive dysfunction impairs the quality of life in patients after liver transplantation

Tryc AB, Pflugrad H, Goldbecker A, et al
Liver Transpl 2014 Jul; 20(7):807-14

ANNOTATION (Paula Zimbrean)

The Finding: Fifty patients were investigated prospectively pre-OLT, at 6 months, and at 12 months after OLT. A battery of psychometric tests was used: the Psychometric Hepatic Encephalopathy Score (PHES), the Inhibitory Control Test (ICT), and the critical flicker frequency (CFF) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).

The HE group performed significantly worse on all tests in comparison with the non-HE group before OLT (PHES, P<0.01; ICT, P<0.04; CFF, P<0.01). Six months after OLT, the HE group still had lower mean scores for CFF (P<0.04) and PHES (P<0.09) in comparison with the non-HE group. Over time, the patients in the HE group improved on RBANS (T1 versus T3, P<0.06), whereas a cognitive decline was measured with RBANS for the non-HE group (T1 versus T2, P<0.02; T1 versus T3, P<0.02). Twelve months after OLT, no significant differences between the groups were detectable. Approximately 70% of the patients showed a decline in cognition exceeding 10% in at least one cognitive domain. HE-related cognitive dysfunction was mostly resolved within the first 6 months after OLT, and no patient was diagnosed with MHE according to PHES and ICT-Targets 12 months after OLT.

Strength and Weaknesses: The strengths of the study consist in its prospective design, extensive cognitive battery and length of follow-up (12 months). All patients received a standard triple-immunosuppression regimen after OLT, which took away one possible confounding factor. The main limitation of the study consists in lack of information about the possible causes of cognitive decline posttransplantation.

Relevance: This study is addressing the important topic of cognitive impairment post-liver transplantation. Liver transplant patients often suffer from cognitive impairment related to hepatic encephalopathy while on the transplant waiting list; however, they often have significant risk factors for other cognitive disorders: long history of alcohol abuse, cardiovascular disease, medications, and age. Differentiating reversible from progressive cognitive decline pre- and post-liver transplantation is often extremely difficult. This study brings valuable information regarding the evolution of the HE after liver transplantation and raises attention to the cognitive decline posttransplantation which is not related to HE. The findings of the study suggest that one year after OLT, cognitive dysfunctions in transplant patients are not residual symptoms but instead are new-onset cognitive disturbances.


Patients after orthotopic liver transplantation (OLT) may show cognitive dysfunction. To date, it has not been clear whether this dysfunction is due to residual hepatic encephalopathy (HE) or new-onset cognitive disturbances. Just as little is known about the course and clinical significance. In this prospective, observational study, 50 patients on the waiting list for OLT were examined in an outpatient setting before OLT and 6 and 12 months after OLT with the Psychometric Hepatic Encephalopathy Score, the Inhibitory Control Test, and the critical flicker frequency for the diagnosis of HE; in addition, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used as a tool for the measurement of global cognitive function. The Short Form 36 health survey was used to assess health-related quality of life. Twelve months after OLT, cognitive dysfunction characteristic of HE had resolved, but a secondary cognitive decline became apparent and had features different from those known with HE. Approximately 70% of the patients deteriorated in at least 1 cognitive domain of RBANS. This cognitive decline was related to neither a history of HE nor a history of alcohol abuse, but it was accompanied by a decline in the quality of life. In conclusion, OLT improves HE but is frequently followed by new-onset cognitive dysfunction, which can interfere with the quality of life.

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PUBLICATION #2 — Transplant Psychiatry
Longitudinal study of cognitive and academic outcomes after pediatric liver transplantation

Sorensen LG, Neighbors K, Martz K, Zelko F, Bucuvalas JC, Alonso EM; Studies of Pediatric Liver Transplantation (SPLIT) Research Group and the Functional Outcomes Group (FOG).
J Pediatr 2014 Jul; 165(1):65-72

ANNOTATION (Paula Zimbrean)

The Finding: 144 pediatric liver transplantation survivors were assessed for cognitive status and IQ at the time of the transplant (T1) and 2 years posttransplantation (T2). Patients completed the Wechsler Preschool and Primary Scale of Intelligence, 3rd edition (WPPSI-III) at T1, and the Wechsler Intelligence Scales for Children, 4th edition (WISC-IV) and Wide Range Achievement Test, 4th edition (WRAT-4): Word Reading and Math Computation at T2. Of the original 144 patients tested at the first time point, 93 (65%) completed testing at T2.

At T2, more patients scored below expected levels compared with the normal distribution on goodness of fit analyses for WISC-IV FSIQ (P=.01), VC (P=.003), and WM (P=.01). T1 results, overall means at T2 were uniformly within the average range on IQ testing; however, significantly more liver transplant recipients than expected had below average functioning on most variables. Household status and parent education had an important influence in both models. Single parent household at the time of transplantation predicted a FSIQ that was 10 points lower than patients with two adult care-providers and was associated with a four-fold increased risk of FSIQ ≤85. Having a primary care provider with a college education was protective. Two medical factors were significant: growth failure at transplant (more than 2 SDs below the 50th percentile for weight at liver transplantation) and higher transfusion requirements during the surgery predicted to have a lower FSIQ.

Strengths and Weaknesses: This is a longitudinal prospective study of 20 pediatric liver transplantation centers. Adequate measures were used to assess cognitive status and IQ. Participants were carefully assessed for hearing impairment, which could have skewed the findings. The primary limitation of this study was attrition between T1 and T2 (65%). Different IQ measures at T1 and T2 because of the lower age limit of the WISC-IV can also limit the analysis but were necessary due to the known age-related appropriateness of the tests. The study focused on 5-6 years of age group, so no information is available about the cognitive evolution of liver transplant recipients in other age groups.

Relevance: This study is addressing an important clinical issue of childhood liver transplant survivors: the academic and cognitive long term functioning. Findings suggest that early education and/or medical intervention should be considered for liver recipients in the 5-6 years of age group.


Objective: To determine the evolution of cognitive and academic deficits and risk factors in children after liver transplantation.

Study Design: Patients ≥2 years after liver transplantation were recruited through Studies of Pediatric Liver Transplantation. Participants age 5-6 years at Time 1 completed the Wechsler Preschool and Primary Scale of Intelligence, 3rd edition, Wide Range Achievement Test, 4th edition, and Behavior Rating Inventory of Executive Function (BRIEF). Participants were retested at age 7-9 years, Time 2 (T2), by use of the Wechsler Intelligence Scales for Children, 4th edition, Wide Range Achievement Test, 4th edition, and BRIEF. Medical and demographic variables significant at P ≤ .10 in univariate analysis were fitted to repeated measures modeling predicting Full Scale IQ (FSIQ).

Results: Of 144 patients tested at time 1, 93 (65%) completed T2; returning patients did not differ on medical or demographic variables. At T2, more participants than expected had below-average FSIQ, Verbal Comprehension, Working Memory, and Math Computation, as well as increased executive deficits on teacher BRIEF. Processing Speed approached significance. At T2, 29% (14% expected) had FSIQ = 71-85, and 7% (2% expected) had FSIQ ≤70 (P = .0001). A total of 42% received special education. Paired comparisons revealed that, over time, cognitive and math deficits persisted; only reading improved. Modeling identified household status (P < .002), parent education (P < .01), weight z-score at liver transplantation (P < .03), and transfusion volume during liver transplantation (P < .0001) as predictors of FSIQ.

Conclusions: More young liver transplantation recipients than expected are at increased risk for lasting cognitive and academic deficits. Pretransplant markers of nutritional status and operative complications predicted intellectual outcome.

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PUBLICATION #3 — Transplant Psychiatry
Predictors of post-traumatic psychological growth in the late years after lung transplantation

Fox KR1, Posluszny DM, DiMartini AF, et al
Clin Transplant 2014 Apr; 28(4):384-93

ANNOTATION (Paula Zimbrean)

The Finding: 64 lung recipients who participated in an earlier study during the first two years posttransplant were assessed for posttraumatic growth (PTG) and interpersonal resources. The following battery of tests was administered: 10-item Posttraumatic Growth Inventory–Short Form (PTGI-SF) Life Orientation Test, Sense of Mastery Scale Recipients, Caregiver Support Scale, and the Friend Support Scale. Responders who were female, had less education, experienced panic disorder early posttransplant, and had higher social support from friends at the long-term follow-up assessment had significantly higher PTG. Individuals with poorer perceived general health at the follow-up assessment experienced less PTG.

Strengths and Weaknesses: The study had a high response rate among those contacted (90%) and subjects were assessed long after the transplantation (average of 8.1 yrs. posttransplant, range: 6.5–11.0). The assessments of depression and anxiety for the first 2 years for transplant had high reliability and validity, being done through SCID. The limitations of the study consist in the relatively small sample coming from a single site, thus limiting generalizability. There was also no assessment of mental health status or additional trauma between two years posttransplantation and the time of the PTG assessment. In addition, there was no analysis of medical factors such as rehospitalization, infections as potential predictors for PTG.

Relevance: Although there is evidence about symptoms of posttraumatic stress disorder posttransplantation, there is very little information about the PTG following the life-changing event of organ transplantation. This study is starting to fill this gap in knowledge. More information about PTG will enable clinicians to optimize the mental health care provided posttransplantation.


Background: Although lung transplantation improves quality of life, most psychosocial research focuses on adverse psychological and social functioning outcomes. Positive effects, particularly in the late-term years as physical morbidities increase, have received little attention. We provide the first data on a psychological benefit – post-traumatic growth (PTG) – and we focused on long-term (>5 yrs.) survivors.

Methods: Among 178 patients from a prospective study of mental health during the first two yrs. post-transplant, we recontacted survivors 6-11 yrs. post-transplant. We assessed PTG (i.e., positive psychological change resulting from the transplant) and examined its relationship to other patient characteristics with multivariable regression analyses.

Results: Sixty-four patients (86% of survivors) were assessed (M = 8.1 yrs. post-transplant, SD = 1.2). Mean PTG exceeded the scale’s midpoint (M = 38.6, SD = 10.0; scale midpoint = 25). Recipients experiencing greater PTG were female (p = 0.022), less educated (p = 0.014), and had a history of post-transplant panic disorder (p = 0.005), greater friend support (p = 0.048), and better perceived health (p = 0.032). Neither other pre- or post-transplant mood and anxiety disorders nor transplant-related morbidities (acute rejection, bronchiolitis obliterans syndrome) predicted PTG.

Conclusions: PTG exceeded levels observed in other chronic disease populations, suggesting that lung transplantation may uniquely foster positive psychological change in long-term survivors. PTG occurs despite physical and psychiatric morbidities. Whether PTG promotes other positive post-transplant psychosocial outcomes deserves attention.

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