Research

Adherence in Liver Transplant Recipients

 What is adherence?

Adherence can be defined as the extent to which the patient’s behaviour matches the recommendations agreed upon with the health care provider. Nonadherence therefore is the degree to which the patient’s behaviour deviates from this agreement. Adherence after liver transplantation refers to a variety of health behaviours, including the taking, timing and dosing of immunosuppressive medication, taking medication for other co-occurring conditions, attending clinic appointments, self-monitoring for symptoms of infection and rejection, undergoing blood work and other tests, as well as performing health behaviours such as regular exercise, controlling calorie intake, limited (if any) alcohol use, abstaining from tobacco or illicit drug use, and avoiding exposure to the sun. This clearly illustrates that transplant recipients need to adhere to a multifactorial, complex, and lifelong regimen.1

 Incidence of nonadherence in adult liver recipients:

A recent study investigating the incidence of nonadherent behaviour in a sample of 103 adult liver recipients used a self-report anonymised questionnaire which was specifically designed to assess nonadherence with the transplant medical regimen.2 

Almost half (46%) of these adult recipients reported nonadherent behaviour specifically relating to the intake of immunosuppressive drugs (see figure 1 below).

 Other behaviours such as smoking, alcohol intake and nonadherence to general medical prescriptions were also evident in this study (see figure 2 below).

Nonadherence in paediatric and adolescent liver recipients:

Research has found nonadherent behaviour to be four times higher among paediatric and adolescent liver transplant patients versus adults3 with a prevalence rate across studies ranging from 10% to 70%.4-14 Adherence to advice on medication and lifestyle may be undermined by experimental risk taking during adolescence and may be perceived as less important than, or in conflict with, normative developmental tasks such as becoming more independent. 

 Among paediatric liver recipients greater psychological distress due to low self-esteem, social adjustment problemsand behavioural difficulties and a stressful or unsupportive family environment are often associated with reduced adherence to medical regimens.15

Another factor that can negatively influence adherence, particularly for young female recipients is the impact of immunosuppressant-related side effects on the body such as excessive hair growth and obesity.16  The table below outlines the factors found to be associated with nonadherence in adult and paediatric transplant recipients.

Table 1: Factors associated with nonadherence in adult and paediatric transplant recipients:

Adult liver recipients

 

Paediatric liver recipients

Pre-transplant nonadherence

Psychological distress

High cost of medication

Social adjustment problems

Young age (<40 years)

Behavioural problems

Psychiatric disorders

Dysfunctional family environment

Conviction that the medication is harmful

Educational limitations

Side effects of medication

Physical functioning limitations

Poor social support

Side effects of medications

Lower conscientiousness

Females (19-21 years)

Higher education levels

From single-parent household

 A study17 conducted in 2008 investigated the prevalence of nonadherence in a sample of 111 adolescent liver recipients aged between 12 and 21 years.  Overall, 45% were found to be nonadherent with one or more elements of the medical regimen (see figure 3 below).  Nonadherent patients were more likely to be female, older (>18 years), and from a single-parent household.

Measures to promote adherence in both adult and paediatric liver transplant recipients:

Recent research states that one of the more effective ways of improving adherence in transplant patients is by simplifying the doses of immunosuppressive medication.18 This can be done by a physician for example, by prescribing Advograf instead of Prograf as this means a patient will only have to take 1 single dose per day instead two.

The interventions listed below are also found to be effective in improving liver recipients’ adherence to the medical regimen:19-21

·         Counselling on immunosuppressive medication in the hospital

·         Educational intervention with paediatric patients

·         Increasing the frequency of clinical visits for nonadherent patients

·         Providing a dedicated psychoeducational service

Overall however, the evidence states that the most effective interventions to improve adherence are those that involve a combination of the above strategies to form a multicomponent intervention.22

 Health care providers dealing with liver transplant patients therefore need to be able to use all available means to improve patients’ adherence. As multicomponent interventions are evidenced to be the most effective approach to improve patient adherence, multidisciplinary measures developed by professional educators, supported by psychologists, and coordinated by physicians are warranted.

References:

1. Laederach-Hofmann K. & Bunzel B.  (2000). Noncompliance in organ transplant recipients: a literature review. General Hospital Psychiatry, 22, 412-424. 

 2. Lazzaro S., Germani G., Borella V., Gnoato F., Rupolo G., Cillo U, et al. (2010).  Assessment of adherence to medical regimen after solid organ transplantation: the experience of Padova University Hospital [abstract]. Liver Transplantation, 16, (suppl 1) S183.

3. Shemesh E., Shneider B., Savitzky J., Arnott L., Gondolesi, G., Krieger N., et al. (2004).  Medication adherence in pediatric and adolescent liver transplant recipients. Pediatrics, 113, 825-832.

 4. Fredericks E., Magee J., Opipari-Arrigan L., Shieck V., Well A. & Lopez M.  (2008). Adherence and health-related quality of life in adolescent liver transplant recipients. Pediatric Transplantation, 12, 289-299.

 5. Shemesh E., Shneider B., Savitzky J., Arnott L., Gondolesi, G., Krieger N., et al. (2004).  Medication adherence in pediatric and adolescent liver transplant recipients. Pediatrics, 113, 825-832.

 6. Annunziato R., Emre S., Shneider B., Barton C., Dugan C. & Shemesh E. Adherence and medical outcomes in pediatric liver transplant recipients who transition to adult services. (2007). Pediatric Transplantation, 11, 608-614.

 7. Avitzur Y., De Luca E., Cantos M., Jimenez-Rivera C., Jones N., Fecteau A., et al. (2004).  Health status ten years after pediatric liver transplantation—looking beyond the graft. Transplantation, 78, 566-573.

 8. Berquist R., Berquist W., Esquivel C., Cox K., Wayman K. & Litt I. Adolescent non-adherence: prevalence and consequences in liver transplant recipients. (2006). Pediatric Transplantation, 10, 304-310.

 9. Bueno J., Medina A., Ortega J., Escartin A., Bello M., BilbaoI., et al. (2007).  Liver transplantation in childhood with more than 10 years of follow-up: analysis of a single-centre experience. Transplant Proceedings, 39, 2288-2289.

 10. Falkenstein K., Flynn L., Kirkpatrick B., Casa-Melley A. & Dunn S. (2004).  Non-compliance in children post-liver transplant. Who are the culprits?  Pediatric Transplantation, 8, 233-236.

 11. Fredericks M., Lopez M., Magee J., Shieck V. & Opipari- Arrigan L.  (2007).  Psychological functioning, nonadherence and health outcomes after pediatric liver transplantation. American Journal of Transplantation, 7, 1974-1983.

 12. Rumbo C., Shneider B. &  Emre S. (2004).  Utility of azathioprine metabolite measurements in post-transplant recurrent autoimmune and immune-mediated hepatitis. Pediatric Transplantation, 8, 571-575.

 13. Shemesh E., Annunziato R., Shneider B., Dugan C.,Warshaw J., Kerkar N. & Emre S. (2008). Improving adherence to medications in pediatric liver transplant recipients.  Pediatric Transplantation, 12, 316-323.

 14. Venkat V., Nick T., Wang Y. & Bucuvalas J. (2008).  An objective measure to identify pediatric liver transplant recipients at risk for late allograft rejection related to non-adherence. Pediatric Transplantation, 12, 67-72.

 15. Laederach-Hofmann K. & Bunzel B. (2000).  Noncompliance in organ transplant recipients: a literature review. General Hospital Psychiatry, 22, 412-424.

 16. Fredericks E., Magee J., Opipari-Arrigan L., Shieck V., Well A. & Lopez M.  (2008). Adherence and health-related quality of life in adolescent liver transplant recipients. Pediatric Transplantation, 12, 289-299.

17. Berquist R., Berquist W., Esquivel C., Cox K., Wayman K., Litt I  (2008). Non-adherence to post-transplant care: prevalence, risk factors and outcomes in adolescent liver transplant recipients. Pediatric Transplantation, 12, 194-200.

18. Germani G., Borella V., Gnoato F., Lazzaro S., Senzolo M., Russo P., et al. (2010).  Does once-daily tacrolimus (Advagraf) increase adherence to immunosuppressive therapy in liver transplanted patients [abstract] Liver Transplantation, 16, (suppl 1), S230.

 19. Shemesh E., Annunziato R., Shneider B., Dugan C., Warshaw J., Kerkar N. & Emre S.  (2008). Improving adherence to medications in pediatric liver transplant recipients. Pediatric Transplantation, 12, 316-323.  

 20. Annunziato R., Emre S., Shneider B., Dugan C., Aytaman Y., McKay M. & Shemesh E.  (2008). transitioning health care responsibility from caregivers to patient: a pilot study aiming to facilitate medication adherence during this process. Pediatric Transplantation, 12, 309-315.

21. Klein A., Otto G. &  Kramer I. (2009).  Impact of a pharmaceutical care program on liver transplant patients’ compliance with immunosuppressive medication: a prospective, randomised, controlled trial using electronic monitoring. Transplantation, 87, 839-847.

 22.   Burra, P., Germani, G.,Gnoato, F., Lazzaro, S., Paolo Russo, F.,Cillo, U., & Senzolo, M.  (2011).  Adherence in Liver Transplant Recipients.  Liver Transplantation, 17, 760–770.