World J Surg DOI 10.1007/s00268-015-3086-5
ORIGINAL SCIENTIFIC REPORT
Quality of Life After Living Donor Hepatectomy for Liver Transplantation Abu Bakar Hafeez Bhatti1 • Haseeb Zia1 • Faisal Saud Dar1 • Mariam Qasim Zia2 Amara Nasir2 • Farah Saif2 • Abdul WahabYousafzai3 • Farah Imtiaz4 • Mohammad Salih5 • Najmul Hassan Shah5
•
Ó Socie´te´ Internationale de Chirurgie 2015
Abstract Background Living donor liver transplantation (LDLT) involves healthy individuals undergoing voluntary major hepatic resection. LDLT program only started in 2012 in Pakistan and its impact on donor’s quality of life (QOL) post resection is not known. The objective of this study was to determine health-related QOL in donors who underwent hepatectomy in country’s first liver transplant program. Methods A total of 60 donors who underwent hepatectomy between 2012 and 2014 with a minimum follow-up of 6 months were included in the study. Short form (SF-36) and Profile of mood states (POMS-65) was used to assess QOL. In addition scores were compared between patients who did and did not develop complications. Result Mean time duration between hepatectomy and administration of questionnaire was 15 ± 5.1 months. Median age was 28 (19–45) years. Mean BMI was 24.4 ± 3.7. A total of 7 (11.6 %) Grade 3 and above complications were observed in donors. Donors exceeded a score of 90 in 6 out of 8 evaluated categories on SF-36. The highest mean score was recorded for emotional role limitation 95.5 ± 17.1 and lowest for energy 84.8 ± 17.5. The mean score for anger was 6.6 ± 7.5. Donors also did well on the POMS vigor score with a mean of 22.7 ± 5. No significant difference in scores was observed between donors with and without complications for any of the categories except tension. Donors who developed complications post-operatively had a significantly low mean tension score of 1.5 versus 3.8 for donors without complications. Conclusion Acceptable post donation QOL was achieved and surgical complications did not adversely affect SF-36 and POMS scores.
Introduction & Abu Bakar Hafeez Bhatti [email protected] 1
Department of HPB and Liver Transplantation, Shifa International Hospital, Islamabad, Pakistan
2
Shifa College of Medicine, Islamabad, Pakistan
3
Department of Psychiatry, Shifa International Hospital, Islamabad, Pakistan
4
Shifa International Hospital, Islamabad, Pakistan
5
Department of Hepatology and Gastroenterology, Shifa International Hospital, Islamabad, Pakistan
Living donor liver transplantation (LDLT) is the only viable treatment option for patients with liver failure in countries like Pakistan where cadaveric donors are not available. According to World Health Organization, health comprises of physical, mental, and social attributes. Health-related quality of life (HRQOL) questionnaires are effective means of assessing mental and psychosocial aspects of well-being [1]. Donor hepatectomy for liver transplantation is one of the most challenging procedures performed on healthy individuals and carries certain serious complication and minor albeit significant mortality
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World J Surg
risks [2]. Since donors are individuals in state of normal psychosocial health; return to pre donation quality of life (QOL) is of paramount importance. It has been shown that HRQOL in liver transplant recipients is acceptable and improves over time [3]. A systematic review identified 13 studies reporting on short form (SF-36) scores in LDLT donors [4]. Only two of these had a sample size [60 and a control group was present in nine studies. Median time duration was 12 months. The authors concluded that donors do return to their baseline QOL. Although data on QOL in donors have generally been limited, a number of studies with larger sample size have been published in recent years [5–10]. All these studies demonstrate acceptable donor QOL at various time intervals after donation. Liver transplantation in Pakistan is a recent development and the first transplant program only began in 2012. In a low resource country with population over 180 million and a health budget comprising only 1.3 % of gross national product; assurance of adequate QOL after hepatectomy is skeptical [11].The current study aims to report QOL outcomes from a population which remains rather under-reported in medical literature. This study was carried out with the objective to determine HRQOL in individuals who underwent donor hepatectomy for liver transplant in the country’s first indigenous liver transplant program.
Methods We retrospectively reviewed donors who underwent hepatectomy for liver transplantation at Shifa International Hospital between April 2012 and July 2014. A total of 96 living donors underwent hepatectomy during this period. The first donor hepatectomy was performed in April 2012. Following is the distribution of hepatectomies over 6 months periods; April–Sep 2012 (9 LDLT’s), October 2012–March 2013 (15), April 2013–September 2013(21), October 2013–March 2014 (22). The interviews were conducted in the month of August/September 2014. Donors who underwent hepatectomy until February 2014 were included. Sixty patients with a minimum follow-up of 6 months post-operation were included in the study to be evaluated for QOL. Basic criteria for donor selection were (1) Age 18–45 years (2) Body mass index 20–30 (3) Compatible blood group (4) Radiological and biochemical evaluation and eligibility in terms of graft function, quality, and size (5) Clearance from cardiology, nephrology, and gastroenterology (6) Psychological evaluation and clearance. The mode of communication was predominantly phone calls and in rare instances emails and one to one interviews were utilized.
123
Consent was taken from the donors and purpose of interview was explained. The interview was conducted by one of the three authors (MQZ, AN, FS). We used SF-36 and Profile of Mood State POMS-65 as instruments for assessment of QOL. The questionnaires were prepared in two different languages (English and Urdu) to accommodate donors with different language proficiencies. Due to language barrier of two donors, a Pushto translator was arranged. All questions were explained in detail. The SF-36 questionnaire covered both physical and mental aspects of donors and included questions evaluating (1)Physical functioning (PF) (2) physical role limitation (RP) (3) emotional role limitation (RE) (4)energy (E) (5) emotional well-being (EWB) (6)social functioning (SF) (7) pain (P), and (8) general health (GH). For each question, score ranged from 0 to 100 with increasing score representative of better function. POMS-65 was used to assess post-operative psychiatric health of donors and included variables of tension, depression, anger, fatigue, confusion, and vigor. A lower score for all variables in POMS-65 was representative of better function except vigor. A higher vigor score corresponded with better QOL outcome. POMS has been shown to have acceptable test–retest validity and reliability [12]. Total mood disturbance (TMD) was calculated by adding scores for Tension, Depression, Anger, Fatigue, and Confusion and subtracting them from the vigor score. Categorical variables were represented as frequencies and percentages. For interval variables with standard distribution, means were calculated while medians were calculated for variables with skewed distribution. T test was used as test of significance for interval variables. A P value \0.05 was considered statistically significant. We also calculated the physical composite score (PCS) and mental composite score (MCS) of our donors against a standardized mean of 50 and standard deviation of 10 from the previously published norms [13].A meeting was arranged with psychiatrist for all donors with significant complaints and SF-36 scores of 40 or less. SF-36 and POMS scores were compared between donors who did and did not develop complications. All grade 3 and above complications on Clavien–Dindo grading system were included. We were unable to comment on Grade 1 and 2 complications considering data were extracted from patient files and minor complications could go unnoticed. All Statistical analysis was performed on SPSS version 20.
Results Mean time duration between hepatectomy and administration of questionnaire was 15 ± 5.1 months. Median age was 28 (19–45) years. Mean BMI was 24.4 ± 3.7.
World J Surg Table 1 Donor characteristics Number
Percent
Male
36
60
Female
24
40
Gender
Education Attended school
43
71
Did not
17
29
Marital status Married
28
47
Not married
32
53
Son Sister
17 8
28 13
Nephew
7
12
Brother
6
10
Daughter
5
8
Wife
3
5
Mother
1
2
Others
13
22
Relationship
Fig. 1 Mean SF-36 scores in 60 individuals who underwent donor hepatectomy
Residence Punjab
32
53
Khyber Pakhtoonkhaw
8
13
Sind
10
17
Balochistan
1
2
Federal Capital
8
13
Kashmir
1
2
[40 30–40
3 19
7 31
\30
38
62
Age groups
Fig. 2 Physical composite scores (PCS) and mental composite scores (MCS) of donors
Donor male to female ratio was 1.5:1. The most common relationship between recipient and donor was that of father and son in 17 patients (28 %). Thirteen (22 %) patients received liver grafts from far off relatives. Majority of donors were residents of Punjab 32(53 %) and Sind 10 (17 %). Out of total, 38(62 %) donors were less than 30 years of age as shown in Table 1. Figure 1 depicts donor mean SF-36 scores 6 months after operation. Donors exceeded a score of 90 in 6 out of 8 evaluated categories. A score \90 was seen for E and P. The highest mean score was recorded for RE = 95.5 ± 17.1 and lowest for E = 84.8 ± 17.5. Mean PCS and MCS was 55.4 and 58.4 as shown in Fig. 2. On POMS evaluation, a mean score\5 was recorded for all negative attributes except anger. The mean score for anger was 6.6 ± 7.5. Donors also did well on the POMS
vigor score with a mean of 22.7 ± 5 as shown in Fig. 3. Mean TMD score was -1.4. A total of 7 (11.6 %) complications were observed in donors. These include bile leak (4), incisional hernia (1), pneumonia (1), and intra-abdominal collection (1). All complications were managed successfully and there were no donor deaths. We compared mean SF-36 and POMS scores between patients with and without complications. No significant difference was observed for any of the categories except tension. Donors who developed complications post-operatively had a significantly low mean tension score of 1.5 versus 3.8 for donors without complications as shown in Table 2. No significant difference in donor SF-36 (94.9 versus 93.7) was noted based on whether the recipient was alive or not at the time of
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World J Surg Table 2 Mean SF-36 and POMS scores in patients with and without complications Complication
Mean score
P value
Yes
86.4
0.5
No
92.2
Yes
85.7
No
94.3
Emotional role limitation
Yes
85.7
0.4
Energy
No Yes
96.8 88
0.7
No
84.4
Yes
95.4
No
91.5
Yes
94.6
No
94.8
Yes
83.5
No
89.7
Yes
85
No
90.8
Yes
1.5
No
3.8
Depression
Yes
2
0.3
Anger
No Yes
4 6.5
0.9
No
6.6
Yes
2.8
No
3.6
Confusion
Yes
2.5
No
3.4
Vigor
Yes
23.4
No
22.6
SF-36 variables Physical function Physical role limitation
Emotional well-being Social function Pain Fig. 3 Mean POMS-65 scores in 60 individuals who underwent donor hepatectomy
interview. Similarly, no significant difference in mean scores was observed for various POMS categories.
General health
123
0.2 0.9 0.6 0.6
POMS variables Tension
Discussion A complication rate of 11.6 % in the current study is comparable with previous reports [5, 14–17].No significant difference in physical and mental health was observed in patients who did and did not develop complications. Mean tension score, however, was significantly different and donors who developed complications experienced less tension. Majority of donors achieved near normal SF-36 and POMS scores. SF-36 is a widely used tool to assess health status, is not disease specific and deals with both physical and mental aspects of well-being [18]. In our donors, mean SF-36 scores were higher than previously reported [2, 8, 19, 20]. The PCS and MCS were also better. We believe that stringent pre-operative psychiatric evaluation with exclusion of patients with Axis 1 diagnosis, younger age, and successful post donation outcomes with low pre donation expectation produced a heightened sense of well-being. It can be argued that impressive scores were achieved simply because of the method employed to fill the questionnaires. In order to complete questionnaires, telephonic interview/ one to one meeting with donors was conducted and it is possible that donors were obliged to respond positively in front of members of transplant team. SF-36 and POMS should ideally be completed by the patient either accompanied by the interviewer or alone. The authors initially
0.5
Fatigue
0.02*
0.7 0.4 0.7
* P \ 0.05
planned to have face to face interviews conducted. However, 59/60 donors refused to come for an interview. Primary reasons were financial burden of travel and difficulty in getting days off from work. It is important to note that majority of our donors were from areas far away from Islamabad. In fact some belonged to regions where there is ongoing political turmoil. It should also be noted that donors who went to school and received education till grade 5 were listed as educated in our survey. It was very difficult for them to complete these extensive forms alone without any guidance. Three donors were outside Pakistan at the time interviews were conducted. They completed the survey forms alone and posted them back to us. Nevertheless, we undertook some important steps to reduce bias in our methodology.
World J Surg
1)
2)
3)
4)
We ensured that donors were not pushed for time at the time of interview. All telephonic interviews were conducted after a pre interview call where donors were asked to specify a suitable time when they could spend around 60 min on telephonic conversation. The interviews were conducted by medical students (MQZ, AN, FS) shadowing liver transplant team at the time of study. They were not directly responsible for patient care and outcomes and it is unlikely that their interpretation of donor responses would introduce bias in the study. Questions in SF-36 and POMS tools are multiple response questions (well categorized) and are not in YES/NO format. Donors were given all options in each and every question and asked to describe the option that best represented their condition. If they were unsure about something, they were called back after a few days. Donors with very high score ([90) were re-surveyed to ensure their response was correct and persistent.
The current study also identified a group of patients with low SF-36 scores and high POMS scores. These patients were referred for formal psychological evaluation and support was sought. Development of post-operative complications in donors did not significantly affect SF-36 scores in our patients and points toward recuperative ability of donors to move on with their life and resume their everyday responsibilities. On POMS scores, a low tension score was observed in donors with prior surgical complications. We believe that coming out from the anxiety and tension of a major surgical complication after voluntary hepatectomy probably endorsed their self-belief of having successfully survived a major stress situation. This resulted in them being better at tension scores. Mean anger scores were higher in our donors. We specifically asked for contributing factors in individuals with higher anger scores. Less than expected gratitude shown by recipients and in rare instances recipient death was contributory. Takada and colleagues reported QOL outcomes in 578 LDLT donors using SF-36 scores. They reported superior donor outcomes when compared with normal Japanese population. However, prolongation of symptoms did lower mental health and social functioning [21].Similarly, another recent study on donor outcomes reported better outcomes in donors post donation than normal population [22]. Compared to SF-36, very few studies have applied POMS to assess QOL. POMS is used to assess transient changes in mood and evaluates expected performance levels in athletes. In recent years, it has also been used in clinical settings but its use in surgical patients is rather limited [19].We used POMS in addition to SF-36 due to
relatively younger donor cohort. POMS revealed a higher than normal mean anger score in our cohort. Despite excellent scores on SF-36, a high anger score on POMS evaluation points toward utility of this questionnaire in assessing transient changes in patients post-surgery. There is scarcity of studies assessing QOL in surgical patients in Pakistan [23, 24]. This aspect has generally been ignored and not considered important. Being the first liver transplant program in Pakistan where the only mode of donation happens to be a living donor, assessment and maintenance of QOL becomes extremely significant. Donors are healthy individuals and expected to return to normal life after certain recovery period of donation. Their physical, mental, and emotional health must be in balance to face every day challenges of a relatively resource limited environment in developing countries. There were certain limitations of the study. Pre donation SF-36 and POMS scores in donors could not be determined due to cross-sectional nature of the study. These instruments have not been used previously in Pakistani population undergoing surgery and we are unaware of mean scores in normal Pakistani population. However, comparing donor QOL with our general population might give a false impression of donor’s well-being. Donors were congratulated before and after the operation for demonstrating great kindness and humanity by the family and close ones. Being the first transplant program in the country, they also received huge social and electronic media coverage. They repeatedly had to give interviews regarding their experience. We believe that such encouragement and attention definitely played an important role in improving their SF-36 and POMS scores post-operatively. Experience of general population was obviously not as out-standing as our donors. We also believe that sociopolitical environment is not the same in 4 provinces of Pakistan. People in Khyber Pakhtoonkhaw and Balochistan face security issues every day. Many from these areas have been displaced and currently labeled as internally displaced persons (IDP’s). It is very difficult to conduct surveys’ of such types in these regions. Since a number of our donors were from these regions, comparing their QOL with normal population from other provinces where things are much better would not give a true reflection. A pre-operative QOL score would have explained the results of our study better. Generally, QOL is not given the desired importance in LDLT setting. For a new center, trying to embark upon a major undertaking this meant addressing multiple social, political, and economic issues. HRQOL was not given its desired importance in the beginning. The design of our study is cross-sectional. Obviously, it was not possible to have pre-operative QOL assessed once the donor had undergone a surgical procedure. We only assessed grade 3 and above complications on
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Clavien system for the purpose of this study. Generally, our donor complication rate is very low, probably because we are very careful in selecting our donors. Since donor’s data were gathered retrospectively, we found it very difficult to accurately identify and collect data regarding minor complications from hand written notes. To avoid any falsification in our results, we avoided reporting grade 1 and 2 complications. Assessment of HRQOL at 6 months post donation might be considered by some a pre-mature assessment of well-being. It is important to note that 43/60 (71 %) donors had completed 1-year post donation at the time of interview. A systematic review on QOL in LDLT donors has shown that donors do return to their baseline QOL levels around 6 months after operation. So, 6 months might not be an inappropriate time to conduct these studies [5]. Nevertheless, a separate study with longer follow-up should be able to determine long-term QOL in LDLT donors. Being the first liver transplant program, we believe it was important to assess psychosocial issues of our donors early and make necessary interventions. This is also acceptable because it has been shown repeatedly that donor’s HRQOL does not deteriorate but improves over time [19, 25].
Conclusion The current study demonstrates impressive short-term HRQOL in Pakistani individuals undergoing donor hepatectomy. Donors can have a normal QOL after complex surgical procedures in developing countries with multi-disciplinary evaluation pre-operatively and protocolized follow-up. HRQOL studies not only allow us to determine QOL, but also help in identification of patients in need of physical and psychosocial support. In addition to SF-36, POMS questionnaire might be an effective tool to determine quality of health status in comparatively younger donors.
References 1. Bruner DW (1998) In search of the ‘‘quality’’ in quality-of-life research. Int J Radiat Oncol Biol Phys 31:191–192 2. Chan SC, Liu CL, Lo CM, Lam BK, Lee EW, Fan ST (2006) Donor quality of life before and after adult-to-adult right liver live donor liver transplantation. Liver Transpl 12:1529–1536 3. Humar A (2003) Donor and recipient outcomes after adult living donor liver transplantation. Liver Transpl 9:S42–S44 4. Parikh ND, Ladner D, Abecassis M, Butt Z (2010) Quality of life in donors after living donor liver transplantation: a review of the literature. Liver Transpl 16:1352–1358 5. DuBay DA, Holtzman S, Adcock L et al (2009) Adult right-lobe living liver donors: quality of life, attitudes and predictors of donor outcomes. Am J Transplant 9:1169–1178
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6. Azoulay D, Bhangui P, Andreani P et al (2011) Short- and longterm donor morbidity in right lobe living donor liver transplantation: 91 consecutive cases in a European Center. Am J Transplant 11:101–110 7. Ladner DP, Dew MA, Forney S et al (2015) Long-term quality of life after liver donation in the adult to adult living donor liver transplantation cohort study (A2ALL). J Hepatol 62:346–353 8. Jin SG, Xiang B, Yan LN et al (2012) Quality of life and psychological outcome of donors after living donor liver transplantation. World J Gastroenterol 18:182–187 9. Kousoulas L, Emmanouilidis N, Klempnauer J, Lehner F (2011) Living-donor liver transplantation: impact on donor’s health-related quality of life. Transplant Proc 43:3584–3587 10. Toyoki Y, Ishido K, Kudo D et al (2012) Donor quality of life after living donor liver transplantation: single-institute experience. Transplant Proc 44:341–343 11. Rizvi SA, Naqvi SA, Zafar MN, Akhtar SF (2013) A kidney transplantation model in a low-resource country: an experience from Pakistan. Kidney Int Suppl 3:236–240 12. McNair DM, Lorr M, Droppleman LF (2005) POMS. Profile of mood states manual. Multi Health Systems Inc, New York 13. Ware JEKMGB (2000) SF-36 Health survey: Manual and interpretation guide. Quality Metric Incorporated, Lincoln, RI 14. Hashikura Y, Ichida T, Umeshita K et al (2009) Japanese Liver Transplantation Society. Donor complications associated with living donor liver transplantation in Japan. Transplantation 88:110–114 15. Brown RS Jr, Russo MW, Lai M et al (2003) A survey of liver transplantation from living adult donors in the United States. N Engl J Med 348:818–825 16. Umeshita K, Fujiwara K, Kiyosawa K et al (2003) Japanese Liver Transplantation Society. Operative morbidity of living liver donors in Japan. Lancet 362:687–690 17. Middleton PF, Duffield M, Lynch SV et al (2006) Living donor liver transplantation–adult donor outcomes: a systematic review. Liver Transpl 12:24–30 18. Chen PX, Yan LN (2011) Health-related quality of life in living liver donors after transplantation. Hepatobiliary Pancreat Dis Int 10:356–361 19. Ishizaki M, Kaibori M, Matsui K, Kwon AH (2012) Change in donor quality of life after living donor liver transplantation surgery: a single-institution experience. Transplant Proc 44:344–346 20. Tumin M, Abdul Talib Abdul Mutalib M, MohdSatar N et al (2014) A comparison of donor and control group quality of life. Ann Transplant 19:112–118 21. Takada Y, Suzukamo Y, Oike F et al (2012) Long-term quality of life of donors after living donor liver transplantation. Liver Transpl 18:1343–1352 22. Kawagishi N, Takeda I, Miyagi S, Sato K, Ohuchi N (2014) Donors’ quality of life evaluated by short form-36 analysis after living donor liver transplantation in a single-center experience. Transplant Proc 46:675–677 23. Nisar N, Zehra N, Haider G, Munir AA, Sohoo NA (2008) Frequency, intensity and impact of premenstrual syndrome in medical students. J Coll Physicians Surg Pak 18:481–484 24. Barolia R, Ali F, Jaffar S (2012) Coronary artery bypass grafting: quality of life of patients in Karachi. Br J Nurs 21:349–355 25. Schulz KH, Kroencke S, Beckmann M et al (2009) Mental and physical quality of life in actual living liver donors versus potential living liver donors: a prospective, controlled, multicenter study. Liver Transpl 15:1676–1687
ORIGINAL SCIENTIFIC REPORT
Quality of Life After Living Donor Hepatectomy for Liver Transplantation Abu Bakar Hafeez Bhatti1 • Haseeb Zia1 • Faisal Saud Dar1 • Mariam Qasim Zia2 Amara Nasir2 • Farah Saif2 • Abdul WahabYousafzai3 • Farah Imtiaz4 • Mohammad Salih5 • Najmul Hassan Shah5
•
Ó Socie´te´ Internationale de Chirurgie 2015
Abstract Background Living donor liver transplantation (LDLT) involves healthy individuals undergoing voluntary major hepatic resection. LDLT program only started in 2012 in Pakistan and its impact on donor’s quality of life (QOL) post resection is not known. The objective of this study was to determine health-related QOL in donors who underwent hepatectomy in country’s first liver transplant program. Methods A total of 60 donors who underwent hepatectomy between 2012 and 2014 with a minimum follow-up of 6 months were included in the study. Short form (SF-36) and Profile of mood states (POMS-65) was used to assess QOL. In addition scores were compared between patients who did and did not develop complications. Result Mean time duration between hepatectomy and administration of questionnaire was 15 ± 5.1 months. Median age was 28 (19–45) years. Mean BMI was 24.4 ± 3.7. A total of 7 (11.6 %) Grade 3 and above complications were observed in donors. Donors exceeded a score of 90 in 6 out of 8 evaluated categories on SF-36. The highest mean score was recorded for emotional role limitation 95.5 ± 17.1 and lowest for energy 84.8 ± 17.5. The mean score for anger was 6.6 ± 7.5. Donors also did well on the POMS vigor score with a mean of 22.7 ± 5. No significant difference in scores was observed between donors with and without complications for any of the categories except tension. Donors who developed complications post-operatively had a significantly low mean tension score of 1.5 versus 3.8 for donors without complications. Conclusion Acceptable post donation QOL was achieved and surgical complications did not adversely affect SF-36 and POMS scores.
Introduction & Abu Bakar Hafeez Bhatti [email protected] 1
Department of HPB and Liver Transplantation, Shifa International Hospital, Islamabad, Pakistan
2
Shifa College of Medicine, Islamabad, Pakistan
3
Department of Psychiatry, Shifa International Hospital, Islamabad, Pakistan
4
Shifa International Hospital, Islamabad, Pakistan
5
Department of Hepatology and Gastroenterology, Shifa International Hospital, Islamabad, Pakistan
Living donor liver transplantation (LDLT) is the only viable treatment option for patients with liver failure in countries like Pakistan where cadaveric donors are not available. According to World Health Organization, health comprises of physical, mental, and social attributes. Health-related quality of life (HRQOL) questionnaires are effective means of assessing mental and psychosocial aspects of well-being [1]. Donor hepatectomy for liver transplantation is one of the most challenging procedures performed on healthy individuals and carries certain serious complication and minor albeit significant mortality
123
World J Surg
risks [2]. Since donors are individuals in state of normal psychosocial health; return to pre donation quality of life (QOL) is of paramount importance. It has been shown that HRQOL in liver transplant recipients is acceptable and improves over time [3]. A systematic review identified 13 studies reporting on short form (SF-36) scores in LDLT donors [4]. Only two of these had a sample size [60 and a control group was present in nine studies. Median time duration was 12 months. The authors concluded that donors do return to their baseline QOL. Although data on QOL in donors have generally been limited, a number of studies with larger sample size have been published in recent years [5–10]. All these studies demonstrate acceptable donor QOL at various time intervals after donation. Liver transplantation in Pakistan is a recent development and the first transplant program only began in 2012. In a low resource country with population over 180 million and a health budget comprising only 1.3 % of gross national product; assurance of adequate QOL after hepatectomy is skeptical [11].The current study aims to report QOL outcomes from a population which remains rather under-reported in medical literature. This study was carried out with the objective to determine HRQOL in individuals who underwent donor hepatectomy for liver transplant in the country’s first indigenous liver transplant program.
Methods We retrospectively reviewed donors who underwent hepatectomy for liver transplantation at Shifa International Hospital between April 2012 and July 2014. A total of 96 living donors underwent hepatectomy during this period. The first donor hepatectomy was performed in April 2012. Following is the distribution of hepatectomies over 6 months periods; April–Sep 2012 (9 LDLT’s), October 2012–March 2013 (15), April 2013–September 2013(21), October 2013–March 2014 (22). The interviews were conducted in the month of August/September 2014. Donors who underwent hepatectomy until February 2014 were included. Sixty patients with a minimum follow-up of 6 months post-operation were included in the study to be evaluated for QOL. Basic criteria for donor selection were (1) Age 18–45 years (2) Body mass index 20–30 (3) Compatible blood group (4) Radiological and biochemical evaluation and eligibility in terms of graft function, quality, and size (5) Clearance from cardiology, nephrology, and gastroenterology (6) Psychological evaluation and clearance. The mode of communication was predominantly phone calls and in rare instances emails and one to one interviews were utilized.
123
Consent was taken from the donors and purpose of interview was explained. The interview was conducted by one of the three authors (MQZ, AN, FS). We used SF-36 and Profile of Mood State POMS-65 as instruments for assessment of QOL. The questionnaires were prepared in two different languages (English and Urdu) to accommodate donors with different language proficiencies. Due to language barrier of two donors, a Pushto translator was arranged. All questions were explained in detail. The SF-36 questionnaire covered both physical and mental aspects of donors and included questions evaluating (1)Physical functioning (PF) (2) physical role limitation (RP) (3) emotional role limitation (RE) (4)energy (E) (5) emotional well-being (EWB) (6)social functioning (SF) (7) pain (P), and (8) general health (GH). For each question, score ranged from 0 to 100 with increasing score representative of better function. POMS-65 was used to assess post-operative psychiatric health of donors and included variables of tension, depression, anger, fatigue, confusion, and vigor. A lower score for all variables in POMS-65 was representative of better function except vigor. A higher vigor score corresponded with better QOL outcome. POMS has been shown to have acceptable test–retest validity and reliability [12]. Total mood disturbance (TMD) was calculated by adding scores for Tension, Depression, Anger, Fatigue, and Confusion and subtracting them from the vigor score. Categorical variables were represented as frequencies and percentages. For interval variables with standard distribution, means were calculated while medians were calculated for variables with skewed distribution. T test was used as test of significance for interval variables. A P value \0.05 was considered statistically significant. We also calculated the physical composite score (PCS) and mental composite score (MCS) of our donors against a standardized mean of 50 and standard deviation of 10 from the previously published norms [13].A meeting was arranged with psychiatrist for all donors with significant complaints and SF-36 scores of 40 or less. SF-36 and POMS scores were compared between donors who did and did not develop complications. All grade 3 and above complications on Clavien–Dindo grading system were included. We were unable to comment on Grade 1 and 2 complications considering data were extracted from patient files and minor complications could go unnoticed. All Statistical analysis was performed on SPSS version 20.
Results Mean time duration between hepatectomy and administration of questionnaire was 15 ± 5.1 months. Median age was 28 (19–45) years. Mean BMI was 24.4 ± 3.7.
World J Surg Table 1 Donor characteristics Number
Percent
Male
36
60
Female
24
40
Gender
Education Attended school
43
71
Did not
17
29
Marital status Married
28
47
Not married
32
53
Son Sister
17 8
28 13
Nephew
7
12
Brother
6
10
Daughter
5
8
Wife
3
5
Mother
1
2
Others
13
22
Relationship
Fig. 1 Mean SF-36 scores in 60 individuals who underwent donor hepatectomy
Residence Punjab
32
53
Khyber Pakhtoonkhaw
8
13
Sind
10
17
Balochistan
1
2
Federal Capital
8
13
Kashmir
1
2
[40 30–40
3 19
7 31
\30
38
62
Age groups
Fig. 2 Physical composite scores (PCS) and mental composite scores (MCS) of donors
Donor male to female ratio was 1.5:1. The most common relationship between recipient and donor was that of father and son in 17 patients (28 %). Thirteen (22 %) patients received liver grafts from far off relatives. Majority of donors were residents of Punjab 32(53 %) and Sind 10 (17 %). Out of total, 38(62 %) donors were less than 30 years of age as shown in Table 1. Figure 1 depicts donor mean SF-36 scores 6 months after operation. Donors exceeded a score of 90 in 6 out of 8 evaluated categories. A score \90 was seen for E and P. The highest mean score was recorded for RE = 95.5 ± 17.1 and lowest for E = 84.8 ± 17.5. Mean PCS and MCS was 55.4 and 58.4 as shown in Fig. 2. On POMS evaluation, a mean score\5 was recorded for all negative attributes except anger. The mean score for anger was 6.6 ± 7.5. Donors also did well on the POMS
vigor score with a mean of 22.7 ± 5 as shown in Fig. 3. Mean TMD score was -1.4. A total of 7 (11.6 %) complications were observed in donors. These include bile leak (4), incisional hernia (1), pneumonia (1), and intra-abdominal collection (1). All complications were managed successfully and there were no donor deaths. We compared mean SF-36 and POMS scores between patients with and without complications. No significant difference was observed for any of the categories except tension. Donors who developed complications post-operatively had a significantly low mean tension score of 1.5 versus 3.8 for donors without complications as shown in Table 2. No significant difference in donor SF-36 (94.9 versus 93.7) was noted based on whether the recipient was alive or not at the time of
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World J Surg Table 2 Mean SF-36 and POMS scores in patients with and without complications Complication
Mean score
P value
Yes
86.4
0.5
No
92.2
Yes
85.7
No
94.3
Emotional role limitation
Yes
85.7
0.4
Energy
No Yes
96.8 88
0.7
No
84.4
Yes
95.4
No
91.5
Yes
94.6
No
94.8
Yes
83.5
No
89.7
Yes
85
No
90.8
Yes
1.5
No
3.8
Depression
Yes
2
0.3
Anger
No Yes
4 6.5
0.9
No
6.6
Yes
2.8
No
3.6
Confusion
Yes
2.5
No
3.4
Vigor
Yes
23.4
No
22.6
SF-36 variables Physical function Physical role limitation
Emotional well-being Social function Pain Fig. 3 Mean POMS-65 scores in 60 individuals who underwent donor hepatectomy
interview. Similarly, no significant difference in mean scores was observed for various POMS categories.
General health
123
0.2 0.9 0.6 0.6
POMS variables Tension
Discussion A complication rate of 11.6 % in the current study is comparable with previous reports [5, 14–17].No significant difference in physical and mental health was observed in patients who did and did not develop complications. Mean tension score, however, was significantly different and donors who developed complications experienced less tension. Majority of donors achieved near normal SF-36 and POMS scores. SF-36 is a widely used tool to assess health status, is not disease specific and deals with both physical and mental aspects of well-being [18]. In our donors, mean SF-36 scores were higher than previously reported [2, 8, 19, 20]. The PCS and MCS were also better. We believe that stringent pre-operative psychiatric evaluation with exclusion of patients with Axis 1 diagnosis, younger age, and successful post donation outcomes with low pre donation expectation produced a heightened sense of well-being. It can be argued that impressive scores were achieved simply because of the method employed to fill the questionnaires. In order to complete questionnaires, telephonic interview/ one to one meeting with donors was conducted and it is possible that donors were obliged to respond positively in front of members of transplant team. SF-36 and POMS should ideally be completed by the patient either accompanied by the interviewer or alone. The authors initially
0.5
Fatigue
0.02*
0.7 0.4 0.7
* P \ 0.05
planned to have face to face interviews conducted. However, 59/60 donors refused to come for an interview. Primary reasons were financial burden of travel and difficulty in getting days off from work. It is important to note that majority of our donors were from areas far away from Islamabad. In fact some belonged to regions where there is ongoing political turmoil. It should also be noted that donors who went to school and received education till grade 5 were listed as educated in our survey. It was very difficult for them to complete these extensive forms alone without any guidance. Three donors were outside Pakistan at the time interviews were conducted. They completed the survey forms alone and posted them back to us. Nevertheless, we undertook some important steps to reduce bias in our methodology.
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1)
2)
3)
4)
We ensured that donors were not pushed for time at the time of interview. All telephonic interviews were conducted after a pre interview call where donors were asked to specify a suitable time when they could spend around 60 min on telephonic conversation. The interviews were conducted by medical students (MQZ, AN, FS) shadowing liver transplant team at the time of study. They were not directly responsible for patient care and outcomes and it is unlikely that their interpretation of donor responses would introduce bias in the study. Questions in SF-36 and POMS tools are multiple response questions (well categorized) and are not in YES/NO format. Donors were given all options in each and every question and asked to describe the option that best represented their condition. If they were unsure about something, they were called back after a few days. Donors with very high score ([90) were re-surveyed to ensure their response was correct and persistent.
The current study also identified a group of patients with low SF-36 scores and high POMS scores. These patients were referred for formal psychological evaluation and support was sought. Development of post-operative complications in donors did not significantly affect SF-36 scores in our patients and points toward recuperative ability of donors to move on with their life and resume their everyday responsibilities. On POMS scores, a low tension score was observed in donors with prior surgical complications. We believe that coming out from the anxiety and tension of a major surgical complication after voluntary hepatectomy probably endorsed their self-belief of having successfully survived a major stress situation. This resulted in them being better at tension scores. Mean anger scores were higher in our donors. We specifically asked for contributing factors in individuals with higher anger scores. Less than expected gratitude shown by recipients and in rare instances recipient death was contributory. Takada and colleagues reported QOL outcomes in 578 LDLT donors using SF-36 scores. They reported superior donor outcomes when compared with normal Japanese population. However, prolongation of symptoms did lower mental health and social functioning [21].Similarly, another recent study on donor outcomes reported better outcomes in donors post donation than normal population [22]. Compared to SF-36, very few studies have applied POMS to assess QOL. POMS is used to assess transient changes in mood and evaluates expected performance levels in athletes. In recent years, it has also been used in clinical settings but its use in surgical patients is rather limited [19].We used POMS in addition to SF-36 due to
relatively younger donor cohort. POMS revealed a higher than normal mean anger score in our cohort. Despite excellent scores on SF-36, a high anger score on POMS evaluation points toward utility of this questionnaire in assessing transient changes in patients post-surgery. There is scarcity of studies assessing QOL in surgical patients in Pakistan [23, 24]. This aspect has generally been ignored and not considered important. Being the first liver transplant program in Pakistan where the only mode of donation happens to be a living donor, assessment and maintenance of QOL becomes extremely significant. Donors are healthy individuals and expected to return to normal life after certain recovery period of donation. Their physical, mental, and emotional health must be in balance to face every day challenges of a relatively resource limited environment in developing countries. There were certain limitations of the study. Pre donation SF-36 and POMS scores in donors could not be determined due to cross-sectional nature of the study. These instruments have not been used previously in Pakistani population undergoing surgery and we are unaware of mean scores in normal Pakistani population. However, comparing donor QOL with our general population might give a false impression of donor’s well-being. Donors were congratulated before and after the operation for demonstrating great kindness and humanity by the family and close ones. Being the first transplant program in the country, they also received huge social and electronic media coverage. They repeatedly had to give interviews regarding their experience. We believe that such encouragement and attention definitely played an important role in improving their SF-36 and POMS scores post-operatively. Experience of general population was obviously not as out-standing as our donors. We also believe that sociopolitical environment is not the same in 4 provinces of Pakistan. People in Khyber Pakhtoonkhaw and Balochistan face security issues every day. Many from these areas have been displaced and currently labeled as internally displaced persons (IDP’s). It is very difficult to conduct surveys’ of such types in these regions. Since a number of our donors were from these regions, comparing their QOL with normal population from other provinces where things are much better would not give a true reflection. A pre-operative QOL score would have explained the results of our study better. Generally, QOL is not given the desired importance in LDLT setting. For a new center, trying to embark upon a major undertaking this meant addressing multiple social, political, and economic issues. HRQOL was not given its desired importance in the beginning. The design of our study is cross-sectional. Obviously, it was not possible to have pre-operative QOL assessed once the donor had undergone a surgical procedure. We only assessed grade 3 and above complications on
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Clavien system for the purpose of this study. Generally, our donor complication rate is very low, probably because we are very careful in selecting our donors. Since donor’s data were gathered retrospectively, we found it very difficult to accurately identify and collect data regarding minor complications from hand written notes. To avoid any falsification in our results, we avoided reporting grade 1 and 2 complications. Assessment of HRQOL at 6 months post donation might be considered by some a pre-mature assessment of well-being. It is important to note that 43/60 (71 %) donors had completed 1-year post donation at the time of interview. A systematic review on QOL in LDLT donors has shown that donors do return to their baseline QOL levels around 6 months after operation. So, 6 months might not be an inappropriate time to conduct these studies [5]. Nevertheless, a separate study with longer follow-up should be able to determine long-term QOL in LDLT donors. Being the first liver transplant program, we believe it was important to assess psychosocial issues of our donors early and make necessary interventions. This is also acceptable because it has been shown repeatedly that donor’s HRQOL does not deteriorate but improves over time [19, 25].
Conclusion The current study demonstrates impressive short-term HRQOL in Pakistani individuals undergoing donor hepatectomy. Donors can have a normal QOL after complex surgical procedures in developing countries with multi-disciplinary evaluation pre-operatively and protocolized follow-up. HRQOL studies not only allow us to determine QOL, but also help in identification of patients in need of physical and psychosocial support. In addition to SF-36, POMS questionnaire might be an effective tool to determine quality of health status in comparatively younger donors.
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