ANALYTICAL AND QUANTITATIVE CYTOPATHOLOGY AND HISTOPATHOLOGY

1. 42
Analytical and Quantitative Cytopathology and Histopathology®
0884-6812/20/4202-0042/$18.00/0 © Science Printers and Publishers, Inc.
Analytical and Quantitative Cytopathology and Histopathology®
OBJECTIVE: To explore the long-term postoperative
health-related quality of life (HRQoL) of liver transplant
recipients in Southwest China. Survivors’ physical re-
habilitation and psychological changes at 3 stages were
used to investigate parameters of their life and assess
long-term outcomes of liver transplant among the sub-
jects, especially those living more than 10 years postop-
eratively.
STUDY DESIGN: Data were collected using Medi-
cal Outcomes Study Short Form 36 (MOS SF-36) for
self-reported HRQoL variables at 3 stages over 8 years.
Changes in all dimensions of HRQoL were analyzed
every 4 years. Disease-related information of the sub-
jects was obtained from the Transplantation Center
database.
RESULTS: Compared with a reference general popula-
tion, the liver transplant recipients showed significantly
worse HRQoL scores for all SF-36 domains (p<0.05).
However, scores improved postoperatively in subsequent
years. Patients living for more than 10 years postopera-
tively showed significant improvements in health status.
Despite aging and reductions in somatic function and
physical activity, the long-term survivors showed their
mental health scores improved, indicating improved psy-
chological conditions in patients.
CONCLUSION: Liver transplant recipients demon-
strated gradual HRQoL development. Patients living for
more than 10 years postoperatively showed high mental
health scores, suggesting improvement in their psycho-
logical condition. (Anal Quant Cytopathol Histpathol
2020;42:42–48)
Keywords: end stage liver disease, health-related
quality of life, liver transplant, liver transplantation,
organ transplant, organ transplantation, patient-
reported outcome, quality of life, transplant recipi-
ents, treatment outcome.
Since Professor Thomas Starzl performed the first
orthotopic liver transplantation in 1963, liver trans-
Longitudinal Study on Quality of Life in Liver
Transplant Recipients in Southwest China
Kai Zhou, M.D., Li Lai, M.D., Ph.D., Jiping Li, M.D., Yanli Luo, M.D., Jiabo Cui, M.D.,
Xiaoling Yang, M.D., and Zhonghua Hu, M.D., Ph.D.
From the Department of Emergency, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province; the Schools
of Nursing, Sichuan University, Chengdu Medical College, and Chengdu University of Traditional Chinese Medicine; and West China
Hospital, Sichuan University, Chengdu, China.
Kai Zhou is Professor, Department of Emergency, The Affiliated Hospital of Southwest Medical University.
Li Lai is Professor, School of Nursing, Sichuan University, Chengdu Medical College, and West China Hospital, Sichuan University.
Jiping Li is Professor, School of Nursing, Sichuan University, and West China Hospital, Sichuan University.
Yanli Luo is Professor, Department of Nursing, West China Hospital, Sichuan University.
Jiabo Cui is Professor, Department of Nursing, West China Hospital, Sichuan University.
Xiaoling Yang is Professor, Department of Nursing, West China Hospital, Sichuan University.
Zhonghua Hu is Professor, School of Nursing, Chengdu University of Traditional Chinese Medicine.
Address correspondence to: Jiping Li, M.D., School of Nursing, Sichuan University, Guoxue Xiang No. 37, Wuhou District, 610041,
Chengdu, China (jp_li@163.com).
Financial Disclosure: The authors have no connection to any companies or products mentioned in this article.

2. Volume 42, Number 2/April 2020 43
Quality of Life in Liver Transplant Recipients
plantation has become an effective treatment for
end-stage liver disease.1 China has the highest
incidence of liver disease in the world, accounting
for one-third of all liver disease.2 Among liver dis-
eases, common end-stage liver disease is character-
istically associated with hepatitis B virus infection.
Although liver transplantation was first performed
in China in the 1970s, the procedure was not effec-
tively developed until the late 1990s.3 With surgical
and postoperative intensive care improvements,
there are no significant differences in the one- and
five-year survival rates of liver transplant recipi-
ents between Chinese centers and other advanced
liver transplant centers around the world. As
patients can survive long after surgery, criteria for
evaluating therapeutic efficacy are not restricted to
survival indicators, and quality of life has become
the subject of intense research.4
Liver transplantation is a successful procedure
for treating end-stage liver disease,1 with survival
rates exceeding 85% at 5 years in most centers.5
According to the China Liver Transplant Reg-
istry (CLTR), 26,941 liver transplant operations
were performed from January 1993 to May 2014.
The short-term outcomes for liver transplantation
have been documented, but the long-term effects
on the survivors have not been closely examined.
This study evaluated changes in the health-related
quality of life (HRQoL) of liver transplant recipi-
ents by assessing their daily activities, social perfor-
mance, and psychological status.
Materials and Methods
Study Design and Sample
This study followed a longitudinal, descriptive
design that was repeated during the 8-year peri­
od from 2006 to 2014. HRQoL measures were as-
sessed through self-administered questionnaires
sent to patients after consent was obtained via tele-
phone or an in-person interview.
Patients who underwent liver transplantation
before November 2006 in a liver transplant center
in southwest China and who were still being fol-
lowed by the same center were enrolled. Eligible
patients were required to meet the following cri-
teria: (1) underwent liver transplant, (2) survived
for more than 3 months after liver transplant,
(3) aged 14 years or older, (4) were lucid and able
to communicate, (5) understood the purpose of the
study and the procedures involved, and (6) pro­
vided informed consent. The exclusion criteria were
(1) evidence of dementia and (2) known history of
a psychiatric disorder. There were 141, 225, and 66
recipients who met the eligibility criteria for this
study in 2006, 2010, and 2014, respectively.
Study Instruments
HRQoL was evaluated using the Medical Out-
comes Study Short Form 36 (SF-36).6 SF-36 is a
36-item questionnaire covering the following 8
components of HRQoL: Physical Functioning, Role
Limitations Due to Physical Health, Body Pain,
General Health, Vitality, Social Function, Role Lim-
itations Due to Emotional Health, and Mental
Health. Responses were scored according to stan-
dard formulas for all 8 scale profiles. Norm-based
scores range from 0 to 100, with a mean of 50 and
a standard deviation of 10. The scores allow for the
direct comparison of individual scales with each
other and with national data, with lower scores
indicating a greater limitation in function.7
Demographic data, including gender, age, edu-
cation level, family income, and marital status,
were collected from liver transplant recipients.
Data regarding clinical characteristics were collect-
ed from the Transplantation Center database and
included the duration since liver transplant and the
type of liver disease, as well as other data.
Statistical Analysis
For the collected data, numerical scores assigned
to each question answer score are expressed as
the mean±SD. Multivariate and univariate anal-
yses of variance were used to evaluate the main
and interaction effects of transplantation, time
after transplantation, and SF-36 domain scores.
Independent t tests were performed to compare
SF-36 scales between liver transplant recipients
and a reference general population (RGP). The
Mann-Whitney U test was used to compare the
SF-36 scores of different groups of recipients. For
the same group of liver transplant recipients who
survived over different time points, the repeated
measures of variance was used to compare the
scores of HRQoL. Data analysis was performed
using the statistical software package SPSS, ver-
sion 19.0 (SPSS, Inc.). A probability value of p<0.05
was taken to represent a significant difference.
Results
Demographic and Clinical Characteristics
In 2006, a total of 141 liver transplant patients were
surveyed. Four years later, 225 patients were in-
vited to join the study; of those, 99 patients had

3. 44 Analytical and Quantitative Cytopathology and Histopathology®
Zhou et al
been followed from the beginning in 2006. In 2014,
we contacted only the patients who were on the
previous survey list and who survived for more
than 10 years after liver transplantation. There-
fore, 66 long-term survivors were enrolled in this
study. The demographic characteristics of the 3
groups are shown in Table I.
Comparison of HRQoL at the Same Stages After
Liver Transplant in 2010 and 2006
Newly added recipients in the first, second, and
fifth postoperative year were compared with pa­
tients in the same postoperative period in 2006.
A relatively long recovery period after liver
transplantation is required, and we suspect that
patients may need to recover for 1 or 2 years. At
this stage, patient HRQoL has an excellent rela­
tionship with the surgical technique and the post-
operative rehabilitation support provided by the
hospital.
To better understand the effect of postopera-
tive care and support on patient quality of life,
the new patients included in 2010 were select-
ed and split into 3 subgroups as follows: 1 year
(2006, n=51; 2010, n=30), 2 years (2006, n=51;
2010, n=20), and 5 years (2006, n=39; 2010, n=76),
according to survival time after surgery. The
HRQoL of these subgroups was compared with
that of patients who had survived for the same
periods after liver transplantation in 2006.
The results showed higher scores in most SF-36
domains in the 2010 liver transplant group than in
the 2006 liver transplant group. The HRQoL of the
liver transplant recipients improved over 4 years,
as shown in Figures 1–3.
Comparison of HRQoL at 3 Stages
We tracked the same group of liver transplant
recipients on the name list in 2006; however,
some of those patients died or lost contact. In all,
141, 99, and 66 patients from the 2006, 2010, and
2014 groups were invited to join the long-term
follow-up study. The longitudinal HRQoL data
of the liver transplant recipient groups were col-
lected and compared. The data showed statistical-
ly significant differences in the scores for each
dimension among the 3 stages (p<0.05) (Table II).
Comparison of Liver Transplant Patient HRQoL with
That of the RGP
The liver transplant patient HRQoL data were
compared with those of the RGP. The population
in Southwest China was sampled using SF-36 in
2001 following a random design, and the final
group consisted of 2,249 participants.4 The 2006
liver transplant recipients showed significantly
worse HRQoL in all SF-36 domains as compared
with later liver transplant recipients and the RGP
(p<0.05) (Figure 4). Comparing the 2010 data with
that of 2014, there was no significant difference
Table I Demographic Characteristics of the Three Groups
2006 2010 2014
N=141 N=225 N=66
Gender, M/F 115/556 186/39 53/13
Age, mean±SD 44.91±9.82 48.73±10.28 53.47±9.52
Education (year
at school)
<6 10 (7.1%) 15 (6.7%) 4 (6.1%)
7–12 73 (51.8%) 92 (40.9%) 29 (43.9%)
>13 58 (41.1%) 118 (52.4%) 33 (50.0%)
Marital status
Unmarried 6 (4.2%) 12 (5.3%) 3 (4.5%)
Married 128 (90.8%) 211 (93.8%) 59 (89.4%)
Divorced 7 (5.0%) 2 (0.9%) 4 (6.1%)
Cause of disease
Benign 103 (73.1%) 167 (74.2%) 52 (78.8%)
Malignant 38 (26.9%) 58 (25.8%) 14 (21.2%)
Postoperation
(no. of years)
<1 51 (36.2%) 30 (13.3%) 0 (0%)
1~2 51 (36.2%) 19 (8.4%) 0 (0%)
3~5 21 (14.9%) 65 (28.9%) 0 (0%)
6~9 18 (12.8%) 106 (47.1%) 0 (0%)
≥10 0 (0%) 5 (2.1%) 66 (100%)
Figure 1 HRQoL at 1 year after liver transplant, 2006 and 2010.
*p<0.05.
BP = Body Pain, GH = General Health, MH = Mental Health,
PF = Physical Functioning, RE = Role Limitations Due to
Emotional Health, RP = Role Limitations Due to Physical Health,
SF = Social Function, VT = Vitality.

4. Volume 42, Number 2/April 2020 45
Quality of Life in Liver Transplant Recipients
in HRQoL except for the Role Limitations Due
to Emotional Health dimension. Compared with
the 2006 HRQoL score, all dimensions of quality
of life 4 years and 8 years later were significantly
improved (p<0.05) (Figure 4).
In order to explore the relationship between
HRQoL score and survival time in liver transplant
recipients, we divided patients into 2 groups—sur-
viving and deceased—to compare the 8 domains
of quality of life. It was found that recipients
enrolled in 2006 and who had died 4 years later
reported significantly lower scores in General
Health, Vitality, Role Limitations Due to Emotion­
al Health, and Mental Health domains than those
who had survived (p<0.05).
Continuing to track the following 4 years until
2014, the difference in the quality of life scores
between the surviving and deceased groups that
existed before was no longer apparent. Recipients
living in 2014 showed no significant difference in
HRQoL as compared to the scores of the deceased
group (p>0.05).
Comparison of Long-Term Survivors’ HRQoL
The same group of recipients who survived over
the 3 time points and living more than 10 years
after liver transplantation was tracked. The repeat-
ed measures of variance was used to compare the
HRQoL scores of the long-term survivors in 2006,
2010, and 2014, respectively.
We took into consideration that this group of
recipients had aged as their survival time pro-
gressed, which may have an impact on their health
status. Differences were adjusted for age so that
the “age” variable was controlled for as a covari-
ance when we performed statistical analysis.
The scores of the 4 dimensions of physical
HRQoL in this group of patients were found to be
relatively stable, and only Role Limitations Due
to Emotional Health and Mental Health domain
scores showed significant differences at the 3 time
points, with significantly higher scores in 2010 and
2014 (p<0.05) (Figure 5).
Discussion
Many studies have confirmed that most HRQoL
domains improve after transplantation because
patients listed for liver transplant have a poor
quality of life.8 However, few studies have focused
on the long-term outcomes in the years following
surgery in liver transplant recipients. Our study
followed liver transplant recipients for 8 years to
integrate an overall perception of HRQoL after liv­
er transplantation with physical and mental health
changes.
Improvement of HRQoL in Recent Liver Transplant
Recipients
By analyzing the data from 2010, we found that
most HRQoL domains were improved in 2010
liver transplant recipients as compared with ear-
lier liver transplant recipients.
Since liver transplantation surgery in this center
was first carried out in the late 1990s, the surgical
technique was not perfect at the early stages. How-
ever, the technique was improving and followed
Figure 2 HRQoL at 2 years after liver transplant, 2006 and
2010. *p<0.05.
BP = Body Pain, GH = General Health, MH = Mental Health,
PF = Physical Functioning, RE = Role Limitations Due to
Emotional Health, RP = Role Limitations Due to Physical Health,
SF = Social Function, VT = Vitality.
Figure 3 HRQoL at 5 years after liver transplant, 2006 and
2010. *p<0.05.
BP = Body Pain, GH = General Health, MH = Mental Health,
PF = Physical Functioning, RE = Role Limitations Due to
Emotional Health, RP = Role Limitations Due to Physical Health,
SF = Social Function, VT = Vitality.

5. 46 Analytical and Quantitative Cytopathology and Histopathology®
Zhou et al
other transplant centers in the world until there
was no significant difference of the liver transplant
surgical outcome data shown in 2004. The main
evaluation index was the 1-year and 5-year sur-
vival rates of the patients. Therefore, new patient
data collected in 2010 were divided into postoper-
ative 1-, 2-, and 5-year groups and compared with
patients in the same period in 2006.
Three groups of recipients, those within 1, 2,
and 5 years after the operation, exhibited higher
HRQoL scores in 2010 than in 2006. At least half
of the domains associated with physical health
and social performance improved 1 year after the
operation in 2010 (p<0.05) (Figure 1). Significant
progress was observed in Physical Functioning,
Body Pain, Vitality, and Social Function. In addi-
tion, at least 3 domains were increased at 2 and 5
years after the operation in 2010 (p<0.05), includ­
ing Body Pain, General Health, and Social Function
(Figures 2 and 3). These results are likely due to the
development of surgical techniques which led to
more rapid recovery of recipient physical strength
and greater pain relief, both of which allow patients
to return to society more quickly. We have reason
Table II Comparison of HRQoL for the Survivors
2006 2010 2014
SF-36 N=141 N=99 N=66 F p Value
PF 77.61±19.52 87.34±11.70 59.90±16.12 52.99 <0.01
RP 48.94±43.70 77.89±36.44 85.61±33.99 25.92 <0.01
BP 60.64±16.76 77.63±12.25 81.71±12.28 62.55 <0.01
GH 53.77±19.15 64.65±17.80 63.89±19.38 11.53 <0.01
VT 63.94±17.82 73.63±14.81 76.89±12.52 19.09 <0.01
SF 66.51±22.34 89.34±18.95 88.48±18.00 44.99 <0.01
RE 62.88±41.99 78.25±35.31 90.91±27.76 13.91 <0.01
MH 66.92±14.90 68.58±13.68 80.81±14.31 21.66 <0.01
BP = Body Pain, GH = General Health, MH = Mental Health, PF = Physical Functioning, RE = Role Limitations Due to Emotional Health, RP = Role Limita-
tions Due to Physical Health, SF = Social Function, VT = Vitality.
Figure 4
Comparison of HRQoL with
reference general population
(RGP). Post hoc test: *HRQoL
scores compared with RGP,
p<0.01. ∆HRQoL scores
compared with 2014, p<0.01.
BP = Body Pain, GH =
General Health, MH = Mental
Health, PF = Physical
Functioning, RE = Role
Limitations Due to Emotional
Health, RP = Role Limitations
Due to Physical Health, SF =
Social Function, VT = Vitality.

6. Volume 42, Number 2/April 2020 47
Quality of Life in Liver Transplant Recipients
to conclude that Physical Functioning, Body Pain,
Vitality, and Social Function form a cluster and
that reducing physical discomfort can directly im-
prove the patient’s social life.
In the meantime, it was believed that the post­
operative patient care and medical treatments
were helpful. We also found that the majority of
recipients suffered from complex symptoms and
the patients complained of physical discomfort,
resulting in their inability to return to work.9
Over the next 4 years the medical staff followed
standard procedures to monitor patients and de-
livered consulting services by multiple methods,
such as Internet tools, face-to-face consulting, and
regular health education. The results show that
improvements in the postoperative management
strategy helped relieve distress and improve the
health status of patients.
Longitudinal Follow-Up Study of Long-Term HRQoL
Among the patients who were followed for 8
years, significant differences were found in the
HRQoL among the 3 analyzed stages (p<0.05)
(Table II). As a general trend, improved patient
status was observed with increasing survival
time.
Compared with the RGP, the HRQoL of liver
transplant recipients was still inferior after the life-
saving operation. All SF-36 domain scores were
significantly lower in liver transplant recipients.
These results are similar to those of other studies,
such as that of Whiting et al,10 which showed sig­
nificant deficiencies in organ recipients as com-
pared with the general population on physical
scales. Jacobsen et al11 explained that the diseases
and the effects of treatment combinations (e.g.,
complications from immunosuppressive agents)
were likely to decrease HRQoL.
While some studies have reported that HRQoL
only increased initially after the operation and
did not last in the long term, this study revealed
a different result regarding postoperative HRQoL
changes.12 We observed a gradual improvement
of HRQoL over the long term in liver transplant
recipients.
It was found that all aspects of quality of life
improved significantly after 4 years compared
with 2006, which indicated that the quality of life
of the recipients was gradually improved as the
survival time increased. However, continuing to
follow-up of the next 4 years, the improvement
became less obvious. Only Role Limitations Due
to Emotional Health was still improving (p<0.05)
(Figure 4).
Despite the Physical Functioning score drop-
ping significantly in 2014, this dimension of
HRQoL did not show a difference after the age
variable was adjusted for (Figure 5). In fact, the
greatest improvements in HRQoL occurred in the
group of long-term survivors. The Role Limita-
tions Due to Emotional Health and Mental Health
scores of the patients were significantly better
than before, indicating that the psychological con­
dition of these patients was very good.
These patients have had a long time to adapt
to their posttransplant status. They have achieved
psychological and emotional stability by accept-
ing their bodily integrity and have developed an
effective coping mechanism to address physical
problems due to medical complications. Most of
the patients survived for more than 10 years post-
operatively, which could be due in part to a sense
of optimism. Some patients even felt that their
health conditions were better than those of their
contemporaries.
Although a portion of the recipients were not
included in the analysis due to loss of contact,
there were also at least 10 patients who were
unwilling to answer the questionnaire and others
who had died. Nevertheless, the followed recip-
ients showed very positive long-term outcomes
after liver transplantation.
Figure 5 HRQoL of the long-term liver transplant recipients
2006, 2010, and 2014. *p<0.05
BP = Body Pain, GH = General Health, MH = Mental Health,
PF = Physical Functioning, RE = Role Limitations Due to
Emotional Health, RP = Role Limitations Due to Physical Health,
SF = Social Function, VT = Vitality.

7. 48 Analytical and Quantitative Cytopathology and Histopathology®
Zhou et al
Conclusion
Although their lives had been successfully pro-
longed, liver transplant recipients suffered im-
paired HRQoL during the first postoperative
stage. Fortunately, HRQoL measures improved
gradually when the recipients recovered from the
surgery and accepted their conditions after liver
transplantation. The long-term survivors report-
ed a more satisfying quality of life with greatly
improved mental health.
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