A systematic review of the factors significantly influencing the quality of life of living liver donors

doi:10.21203/rs.3.rs-1653375/v1

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A systematic review of the factors significantly influencing the quality of life of living liver donors

https://doi.org/10.21203/rs.3.rs-1653375/v1

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Background Several reviews have summarized data on the medical outcomes and psychosocial status of living liver donors. However, a systematic review or synthesis of evidence on factors significantly influencing quality of life in living liver donors has not been conducted. With this systematic review, we aimed to synthesize the literature on predictors of or factors influencing quality of life in living liver donors post donation.

Methods PubMed, Embase, CINHAL with full text, Web of Science and ProQuest Dissertations & Theses databases were searched for studies. The methodological quality of the individual studies was examined using a modified version of the National Institutes of Health Quality Assessment Tool. Factors influencing the four quality of life dimensions of physical functioning, psychological state, and social function and environment were extracted.

Results The search yielded 6576 records, and a total of 16 articles (11 studies) were included in the systematic review. Four types of independent influencing factors, sociodemographic, donation-related, health-related, and psychosocial, were extracted from the included studies. Old age, recipient death, recent donation, postoperative complications experienced by donors, and donor concerns about their own well-being were consistently identified by several studies as negative influencing factors on physical function. Female donor, low education levels, longer hospital stay and/or more hospital visits due to donation, poor recipient outcome, recent donation, predonation concerns regarding their own well-being, and first-degree relative and spouse/partner donors were reported in several studies as negative predictors for psychological status. Factors affecting social function were considered by only two included articles.

Conclusions The significant influencing factors summarized in our study provided convenient information for clinical practitioners to formulate precise interventions. Donors with these risk factors can be regarded as a vulnerable group and targeted interventions should be carried out to minimize possible negative effects.

living donors

liver transplantation

quality of life

systematic review

Global Transplant Observatory data (http://www.transplant-observatory.org/) reports that 34 047 liver transplantations were completed in 2018 worldwide and 19.2% of them were from living liver donors. Living donor liver transplantation is not only the optimal treatment option for end-stage liver disease, but also mitigates the scarcity of deceased donor organs. Liver donors are healthy individuals who undergo a major surgical operation with no medical benefit. For this reason, researchers have not only analyzed the clinical outcomes of the procedure but have also sought to comprehensively understand the quality of life (QoL) of liver donors [1, 2]. The World Health Organization defines QoL as individuals’ perceptions of their position in life in the context of the culture and value systems in which they reside, in relation to their goals, expectations, standards, and concerns [3]. QoL is a multidimensional concept that is typically assessed as personal self-reported physical functioning, psychological state, social relationships, and environmental aspects [4, 5].

Living liver donation does have impact on the QoL of liver donors. Our previous meta-analysis found that compared with predonation, obvious declined physical functioning was presented in liver donors for a considerably long time. Impaired social and psychological QoL affected donors for a shorter time after their donation [6]. Many researchers recommended that long-term routine follow-up and necessary intervention are essential for living liver donors [7].

The QoL of living liver donors has been confirmed to be influenced by multiple factors. For example, the published studies have reported that female sex [8–10], education level of less than a bachelor’s degree [11, 12], experiencing complications [13], longer postdonation hospitalization [9, 10, 14], and recipient death [10–12, 15] were predictors of poor physical- and mental-health-related QoL. Old age has been found to be both a good and poor predictor for the physical and mental health of liver donors [16]. A comprehensive understanding of these positive and negative impacts on the QoL of living liver donors could be helpful to both clinical practitioners and donors. Specifically, for clinicians to monitor donors with elevated risk factors and set targeted interventions for them could be helpful. Donors with psychosocial factors should be treated as a vulnerable group in need of increased attention and further assessment before and after donation. Data on positive and negative factors influencing QoL are critical for donor informed consent and to ensure relevant psychological interventions are provided in advance

Several reviews have summarized the data on medical outcomes and the psychosocial status of living liver donors [7, 17, 18]. However, systematic review or synthesis of the evidence on predictors or factors influencing their QoL is still absent. In this systematic review, we synthesized the literature on predictors of QoL and factors influencing QoL in living liver donors. Our focus was beyond physical functioning, psychological status, social relationships, and environmental aspects were also encompassed.

The systematic review was registered on PROSPERO, and the information is available at http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42022303475.

Search strategies

Five databases: PubMed, Embase, CINHAL with full text, Web of Science, and ProQuest Dissertations & Theses were searched for studies published between date of database inception and November 2021. In addition, the references of included studies were searched manually. We used a combination of Medical Subject Headings (MeSH) or Emtree term with the text words to retrieve references from the databases. The specific search strategy using PubMed as an example is presented in the Supplementary Material section (see supplementary material). Minor changes in search strategy were required to adapt the search to the other databases (e.g., keywords related to “quality of life” and “liver transplantation” were only used when searching the ProQuest Dissertations & Theses database and CINHAL because of the limited number of studies in these databases). Potential unpublished studies were retrieved from System for Information on Grey Literature (SIGLE) database (http://opensigle.inist.fr/).

Inclusion and exclusion criteria

Cross-sectional and longitudinal studies on the QoL of living liver donors and its influencing factors were included. Eligibility of studies for inclusion was based on the following criteria: (1) Living liver donors must have been enrolled in the study after the donation; (2) Studies must have analyzed the factors affecting donor QoL using multivariate analysis; (3) The self-reports of donor QoL had to be based on four domains as defined in our previous study [6]: physical functioning (physical activity, physical symptom, pain and fatigue), psychological status (e.g., feelings, worries, and tension), social relationships (social activity; relationships with relatives, friends, and others; and social support), and environment (physical safety and security, home environment, living condition, work satisfaction, financial resources, leisure activities, and physical environment); and (4) Included articles had to be published in English. Articles were excluded if they were conference proceedings, abstracts only, commentaries, editorials, reviews, newsletters, or research protocols.

Selection of studies

First, the articles retrieved from the databases were imported into Endnote X9 Software, a reference management software program with which duplicates could be removed. Then two authors independently screened the titles of the remaining records for relevance to the review topic. Articles unrelated to the review topic were deleted directly. We reviewed the full text of articles that potentially met the inclusion criteria, for f

Data extraction

We created a data extraction form that extracted the following data from each included article: study characteristics (first author, publication year, country), sample size, donor–recipient type, age, surgical techniques, assessment tool(s), data collection periods and points, complications, and information pertaining to the study’s methodological quality. The independent influencing factors on QoL of the living liver donors were also extracted.

Methodological quality assessments

The methodological quality of each individual study was evaluated by two authors ndependently and discrepancies were discussed by all authors until consensus was reached. A modified version of the National Institutes of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies (http://www.nhlbi.nih.gov/health-pro/guidelines/in-develop/cardiovascular-risk-reduction/tools/cohort) was employed, which contains eight items with possible answers “yes”, “no”, “cannot determine”, “not applicable” or “not reported”. Six items (items 6, 7, 8, 9, 10, and 12) were removed because they were of relevance to cohort studies. Adjustment for confounding was considered sufficient if studies adjusted for at least one sociodemographic variable (e.g., age). The adequacy of sample size was judged by whether it reached at least 15 times the number of independent variables.

Synthesis of results

We synthesized the study results using a narrative approach. The significant influencing factors were grouped into four categories: physical function, psychological status, social relationships, and environment-related QoL.

Search process

The systematic search yielded 6,576 records, of which 1,429 were screened as duplicates. A total of 5,081 records were excluded based on their titles and abstracts against the eligibility criteria, leaving 1,838 records for screening. The full text of 66 articles was further assessed and 50 were excluded. The excluded articles included 43 that only described the current QoL of liver donors without regression analysis, 6 that were not related to the QoL of liver donors, and an article that included liver donation candidates. Sixteen papers representing 11 studies were finally included in our systematic review (Fig. 1).

Characteristics of the included studies

The articles came from the following countries: USA (5), Japan (4), China (2), Canada (1), Poland (1), South Korea (1), Singapore (1), and Germany (1). The data from 3,783 living liver donors were analyzed finally. Most (n = 12) of the included articles reported on the adoption of the 36-Item Short-Form Health Survey (SF-36) to assess QoL. The other assessment instruments included the WHOQOL–Brief Scale (WHOQOL-BREF), the Functional Assessment of Chronic Illness Therapy–Fatigue Scale (FACIT-F), Brief Pain Inventory (BPI), International Physical Activity Questionnaire (IPAQ), donation-specific instruments for social relationship and financial outcomes, visual analog scale for pain, Living Liver Donor Quality of Life Scale (LLD-QOLL), and a six-question survey containing an item on self-esteem (Table 1).

Table 1

The characteristics of the included studies
Author, year, country	Sample size	Donor-recipient type	Age	Surgery techniques	Quality of life assessment tool(s)	Data collection period	Data collection point	Complication
Butt, 2018, USA	297 donors were enrolled; 245 of them provided complete data	Adult-to-adult l	Mean age at donation: 36.79 years	Right lobe hepatectomies: 84% Laparoscopic surgery: 35%	FACIT-F BPI SF-36	February to July 2011 and on January 31, 2014	1 month prior to donation and at 3, 6, 12, and 24 months after donation	During the first month after donation, 19.2% had 1 or more postoperative complications
Dew, 2016, USA	517 donors were enrolled; 507 of them provided complete data	Adult-to-adult	Aged 19 to 61 years at donation	Unclear	SF-36	Unclear	Liver donors who donated 3 to 10 years post donation	78(15%) donors reported current donation-related medical problems. Of them, hernia was the most common problem: 17(22%); gastrointestinal/digestive issues (nausea, fat and food intolerances): 17(22%); chronic diarrhea: 8(10%) and problems with scar tissue and adhesions: 7(9%).
Dew, 2018, USA	517 donors were enrolled; 424 of them provided complete data	Adult-to-adult	Aged 19 to 61 years at donation	Unclear	SF-36	The research was conducted in 2009 to 2014	517 donors averaged almost 6 years post donation at enrollment; They were assessed 3 times (at enrollment, and twice annually thereafter).	The overall complication rate was 28.7%, of them: Grade I: 33(8.9%); Grade II: 71(19.2%) Grade III: 2(0.5%)
DiMartini, 2017, USA	297 were enrolled; of 271 were interviewed at least once; of 245 interviewed at both pre- and post-donation	Adult-to-adult	Mean age at donation: 36.79 years	Donating right lobe 84.1%; left lobe or left lateral segment: 35.9%	Donation-specific instruments for social relationship Donation-specific instruments for financial outcomes	February to July 2011 and on January 31, 2014	Pre-donation and at 3, 6, 12 and 24 months post-donation	Complications during the first month post-donation ≤ 1: 52 (19.2%)
DuBay, 2009, Canada	204 donors invited to participate, 143 donors provided sufficient data	Adult-to-adult or pediatric	Mean age 41.7 ( range: 20–66) year	Right-Lobe	SF-36	unclear	Median 27 (3–84) months post donation	Donor in-hospital complication (≥ Grade II): 19 (13%); Donor postdischarge complications (≥ Grade II) : (26 (18%)
Fukuda, 2014, Japan	100 response rate: 81%	Adult-to- pediatric (Mother/father/grandfather/aunt 51/47/1/1)	Mean age 35.4 years	Left lateral segment 68 (68.0%) Hyper-reduced left lateral segment 19 (19.0%) Left lobe 11 (11.0%) Right lobe 2 (2.0%	SF-36	unclear	Clinic visits at 1, 3, 6, and 12 months, and then annually, post-surgery	The overall complication rate was 13.0%, of them: Grade I: 7( 7%); Grade II: 3(3%) Grade IIIa: 3( 3%) Two donors with grade IIIa complications developed hematemesis due to a duodenal ulcer 3 months and 4 months after the donation, respectively
Janik, 2019, Poland	101 donors	Adult-to-adult or pediatric	The median age of patients was 36.8 (range:24–59) years	Unclear	IPAQ SF-36	unclear	Included donors more than 6 months post donation (range 7-169 months post donation)	The total complication rate for the procedure at around 4.5%, with the major complication wound infections
Ladner, 2015, USA	Included HRQOL data from 374 donors	Adult-to-adult	Mean age at evaluation for donation was 38.0 (range: 18.2–62.7) years	Unclear	SF-36	Donors enrolled in the A2ALL study who donated between 1998 and 2010. Clinical, laboratory, hospitalization, complication and HRQOL data were collected between 2004 and 2013	Pre-donation evaluation, 3 months post donation, 1 year post-donation, and every year thereafter up to a maximum of 8 years	Complication occurred before study end point (374 donors): Grade I:57(15.2%); Grade II: 95(25.4%) Grade III: 2(0.5%)
Lee, 2012, South Korea	102 donors	Adult-to-adult or pediatric	Mean age was 28.9 years	Right lobe:92.2% Left lobe, left lateral lobe: 7.8%	Visual analogue scale for pain	From March 1 to August 30, 2009	Within 6 months post donation	These complications occurred in 16 (15.7%) donors: of them wound inflammation (2.0%, n = 2), transient compressive neuropathic symptom (1.0%, n = 1), digestive disorders (11.8%, n = 12), and other (1.0%, n = 1)
Morooka, 2019, Japan	449 donors responded the survey, 374 of them were included in the final analysis	77 (20.6%) donated to children aged < 18 years, while 292 (78.1%) donated to adults.	Mean age was 45.1 years	Unclear	SF-36 V2 LLD-QOLL Scale	Unclear	Included donors more than a year postdonaotion	A total of 7.2% experienced complications including surgical site infection and hernia.
Noma, 2011, Japan	30 donors	Adult-to-adult	Mean age was 42.2 (range: 22–63) years	Unclear	WHOQOL-BREF PTCA	November 2001 through July 2003	Pre-donation and several years post donation	Unclear
Shi, 2021, China	436 donors agreed to participate, 382 donors provided the effective questionnaires.	Parental donors accounted for 99.2%	Median age 32.0, (Interquartile range: 28.25, 36.00) years	Right lobe: 1(0.5%) Left lobe: 9(2.3%) Left lateral lobe: 372(97.4%)	SF-36 V1	August 2017 to February 2019	The median number of months post-donation was 25 (IQR: 13–48); at a minimum of 1-month post donation	The overall complication rate was 8.4%, of them: Grade I: 7(1.8%); Grade II: 20(5.2%) Grade IIIa: 5(1.3%)
Sotiropoulos, 2011, Germany	83 of 84 agreed donors responded the survey	Adult-to-adult	Median age of 36 (range: 23–63) years	All were right hepatectomy	The survey consisted of 6 questions and one of them was used to assess the self-esteem (better-similar-worst after donation)	August 1998 and June 2007	Median donor follow-up was 69 months (range 46–128 months)	The overall complication rate was 15.7%, of them: grade I: 3 (3.6%) grade II 3 (3.6%) grade IIIa: 1 (1.2%) grade IIIb: 6 (7.2%).
Takada, 2012, Japan	578 of the 997 donors who were sent the questionnaire responded	Adult-to-adult or pediatric	Mean age at the time of response was 45.6 years	Right lobe: 211 (36.5) ; Left lobe: 367(63.5%)	SF-36 V2	SF-36 version 2 questionnaire	The mean years after donation was 6.8 ± 3.4	The incidence of postoperative complications in 163 (28.2%): Grade I: 117(20.2%); Grade II: 17(2.9%) Grade III or high: 29(5.0%)
Yuen, 2018, Singapore	32 parent donors who met inclusion criteria, 27 responded to the questionnaires	Parents donor	Median age 33.0, (range: 24.0-51.0) years	Left lobe: 8 (29.6%); Left lateral segment: 19 (70.4%)	SF-36 V2	Between January 2000 and December 2015	Unclear	The overall complication rate was 29.6%, of them: Grade I: 3 (11.1%) Grade II: 4 (14.8%) Grade III: 1 (3.7%)
Weng, 2019, Taiwan China	102 donors agreed to participate, 68 donors provided the effective questionnaires.	Mixed	Mean age was 31.6 (range: 20–53) years	A right-lobe hepatectomy	SF-36	August 2013 to December 2015	Assessed at Pre-donation and at 3, 6 and 12 months post-donation	The overall complication rate was 23.5%, of them: Grade I: 9 (13.2%) Grade II: 7 (10.3%)
Abbreviations: ACSA: Anamnestic Comparative Self-Assessment Scale; BPI: Brief Pain Inventory; CLDQ: Chronic Liver Disease Questionnaire; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue Scale; IPAQ: International Physical Activity Questionnaire; LLD-QOLL: Living Liver Donor Quality of Life Scale; PACT: Psychosocial assessment of Candidates for Transplantation Scale; PRIME-MD: Primary Care Evaluation of Mental Health Disorders; SF-36: 36-Item Short-Form Health Survey; WHOQOL-26: World Health Organization Quality-of-Life Assessment-26

Methodological quality

Table 2 shows the methodological quality risks for each study. Only four studies satisfied all the assessment items. Most of the studies failed to meet questions 5 and 8, which were about sample size justification and confounding variables. The sample size in 6 of 16 papers met the quality requirement of being 15 times that of the independent variable. Only three of the included papers indicated a method used for controlling confounders.

Table 2

Methodological quality of the included studies
Author, year	1.Was the research question or objective in this paper clearly stated?	2. Was the study population clearly specified and defined?	3. Was the participation rate of eligible persons at least 50%?	4. Were all the subjects selected or recruited from the same or similar populations (including the same time period)? Were inclusion and exclusion criteria for being in the study prespecified and applied uniformly to all participants?	5. Was a sample size justification, power description, or variance and effect estimates provided?	6. Were the outcome measures (dependent variables) clearly defined, valid, reliable, and implemented consistently across all study participants?	7. Was loss to follow-up after baseline 20% or less?	8. Were key potential confounding variables measured and adjusted statistically for their impact on the relationship between exposure(s) and outcome(s)?
Butt, 2018	Yes	Yes	Yes	Yes	No	Yes	Yes	Yes
Dew, 2016	Yes	Yes	Yes	Yes	Yes	Yes	Yes	No
Dew, 2018	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
DiMartini, 2017	Yes	Yes	Yes	Yes	No	Yes	Yes	Yes
DuBay, 2009	Yes	Yes	Yes	Yes	No	Yes	Yes	No
Fukuda, 2014	Yes	No	Yes	Yes	No	Yes	Yes	No
Janik, 2019	Yes	Yes	Yes	Yes	No	Yes	Yes	No
Ladner, 2015	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Lee, 2012	Yes	No	Cannot determine	Yes	No	Yes	No	No
Morooka, 2019	Yes	Yes	Yes	Yes	Yes	Yes	Yes	No
Noma, 2011	Yes	Yes	No	Yes	No	Yes	No	No
Takada, 2012	Yes	Yes	Yes	Yes	Yes	Yes	Yes	No
Yuen, 2018	Yes	Yes	Yes	Yes	No	Yes	Yes	No
Sotiropoulos, 2011	Yes	Yes	Yes	Yes	No	No	Yes	No
Shi, 2021	Yes	Yes	Yes	Yes	No	Yes	Yes	No
Weng, 2019	Yes	Yes	No	Yes	No	Yes	No	No

Overall status of living liver donors

The overall rate for complications experienced by donors in the included studies ranged from 7.2% to 41.1%. Among them, the Clavien Grade Ⅰ complication rate was reported to be 3.6% to 20.2%, Grade Ⅱ was 2.9% to 25.4%, and Grade Ⅲ or higher was 0.5% to 5.0% (Table 1). Figure 2 shows a physical component summary score and mental component summary score for the SF-36 in our included articles. Eight articles provided the mean physical component summary score and/or mental component summary score, and six of them reported a similar or significantly better physical component summary score and/or mental component summary score among living liver donors when compared with local healthy controls or standardized scores.

Factors influencing QoL of living liver donors

A variety of risk factors related to the QoL of living liver donors were identified across the studies. Detailed information can be found in Table 3 and table S1. These risk factors were grouped into sociodemographic, donation-related, health-related, and psychosocial characteristics (Table 3 and supplementary material table S1-S3).

Table 3

Independently influencing factors of quality of life of living liver donors
Influencing factors		Physical functioning		Psychological status		Social/environmental domain
Influencing factors		+/-	Articles	+/-	Articles	+/-	Articles
Sociodemographic characteristics	Female	-	Butt, 2018	-	Butt, 2018 Janik, 2019 Morooka, 2019 Takada, 2012
	Donors age	-	Janik, 2019 ^a Morooka, 2019 ^a Takada, 2012 ^a	-	Butt, 2018 ^a Janik, 2019 ^a	+	DiMartini, 2017 ^a
				་	DuBay, 2009 ^a Morooka, 2019 ^a Sotiropoulos, 2011 ^b
	Young recipients age					-	Morooka, 2019
	Married/had a long term partner before donation	-	Butt, 2018
	Low education level (less than a bachelor’s degree/ Graduate degree)	-	Ladner, 2015	-	Ladner, 2015 Weng, 2019 DuBay, 2009 ^c
	Hispanic ethnicity	-	Ladner, 2015
Donation related characteristics	Longer hospital stay/hospitalized/ more times hospital visits due to donation surgery	-	Butt, 2018 Morooka, 2019	-	Butt, 2018 Dew, 2016	-	Takada, 2012 DiMartini, 2017
	Recipient health status (death/ complication/ severity of liver disease preoperation)	-	Butt, 2018 ^d Ladner, 2015 ^d	-	Butt, 2018 ^d Ladner, 2015 ^d Morooka, 2019 ^d Weng, 2019 ^d	-	DiMartini, 2017 ^d Morooka, 2019 ^d
		+	Yuen, 2018 ^e
	Short time post donation	-	Butt, 2018 ^f Fukuda, 2014 ^g Ladner, 2015 ^f Shi, 2021 Weng 2019	-	Butt, 2018 ^f Fukuda, 2014 ^g DiMartini, 2017 ^f	-	DiMartini, 2017 ^f
	Postoperative complications experienced by donors	-	Butt, 2018 Takada, 2012	-	Takada, 2012	-	Takada, 2012
		+(absence of complication)	Weng 2019	(absence of complication)	Sotiropoulos, 2011
	Encouraged or discouraged to make a donation decision	- (discouraged)	Butt, 2018			+ (Encouraged)	Takada, 2012
	Predonation concerns regarding their own well-being	-	Dew, 2018 Fukuda, 2014	-	Dew, 2018 DuBay, 2009 Fukuda, 2014
	Ambivalence to donate			- (high lever)	Butt, 2018 DiMartini, 2017	- (low level)	DiMartini, 2017^h
	First-degree relative donors and spouse/partner donors			-	Butt, 2018 DiMartini, 2017	+	DiMartini, 2017
	The boy recipients	-	Shi, 2021
	Number of analgesics use associated with postoperative pain	-	Lee, 2012
	The more days rest from work related to donation	-	Takada, 2012
	Anticipation that life would be more worthwhile after donation	-	Butt, 2018
	Anticipated long term health effects from donation	-	Butt, 2018
	The number of months until recovery to the preoperative health status					-	Takada, 2012
	Preoperative prediction of long time off work(> 3 months) / Concern about missing work/ Having a technical or clerical or lower-level position					-	DiMartini, 2017
	Predonation concerns about who would pay donation costs					-	DiMartini, 2017
Health related characteristics	High BMI	-	Butt, 2018 ^h	-	DiMartini, 2017 ⁱ
	Predonation pain/fatigue	-	Butt, 2018
Psychosocial characteristics	Better predonation PCS and/or MCS	+	Butt, 2018	+	Weng 2019
	Lower pre-donation MCS			-	Butt, 2018
	Household income	-	Butt, 2018 ^j			-	DiMartini, 2017^k
		+	Butt, 2018 ^j
	Trait anxiety at the survey time	-	Lee, 2012
	Past or present psychiatric diagnosis	-	DuBay, 2009
Note: +, positive; -, negative; BMI: body mass index; PCS: physical component summary score;
MCS: mental component summary score
^a Old
^b Young age
^c Graduate degree
^d Recipient death as the outcome
^e Donors’ recipient with complication of Clavien-Dindo grade III or IV
^f 3 and 6 months postdonation
^g Time to donation was > 4 weeks
^h Donors with BMI of 25.0-29.9 kg/m2 compared with those with BMI of ≤ 24.9 kg/m²
ⁱ BMI ≤ 30
^j Higher household income
^k Lower household income

Sociodemographic characteristics

Female One article [19] identified that being a female donor was associated with more physical symptoms, pain, and fatigue post donation and four articles [19–22] reported that female donors had a poor psychological status and more worries.

Donor age Three articles [20–22] confirmed that older-aged donors had poor physical function; however, inconsistency was found in the relationship between donor age and psychological status, with two studies separately reporting that older age of donors was associated with an increase in health-related worries [19] and poor mental state [20] in donors. Another two articles [21, 23] showed that old age was a positive predictor of better psychological status, whereas one article [24] found that younger donors had an improved self-esteem. Regarding social function, one article [25] reported that older donor age was a positive factor for an improved relationship between donor and recipient.

Recipients age One article found that child recipients were the negative factor for social function (lack of understanding of donors health) [21].

Education One [26] and three [11, 23, 26] articles identified that a low level of education (less than a bachelor’s degree) was an independent influencing factor for poor physical and psychological QoL, respectively.

Ethnicity and marital status One article [26] found that Hispanic ethnicity was associated with poor physical function and another article [19] reported that being married prior to donation was associated with higher fatigue.

Donation-related characteristics

Length of hospital stay and number of hospitalizations/hospital visits related to donation surgery Six articles [19, 21, 22, 25, 27] determined that longer hospital stays, being hospitalized during the first month after donation, and more frequent hospital visits related to the donation were independent risk factors in living liver donors for all four domains of QoL ^[23], including having more physical problems, pain, and fatigue; more health-related worries and stress [19]; more after-effects [21], significantly impaired mental health [27]; poor social function [22] ; a greater burden of postdonation costs and decreased income due to the donation [25].

Recipient outcome (death/complication/ severity of liver disease preoperation) Two articles reported that recipient death was a factor associated with poor physical function in donors [26] and continuing physical symptoms (physically not “back to normal”, pain, and fatigue) [19]. One article indicated that donors with a recipient with Clavien-Dindo grade III or IV complications were more likely to have higher role-physical score in SF-36. In terms of psychological status, four articles indicated that the death of the recipient was a negative factor influencing the psychological status of the donor [11, 21, 26] and was like to induce physical stress in the donor [19]. In terms of social function, one article indicated that donors whose recipients died were less likely to report being held in high esteem by the recipient’s family or receiving gratitude from them [25] and had low satisfaction of liver donation [21].

Time from donation Recent donation was determined as a negative predictor for all three QoL domains. A total five articles [6, 11, 19, 26, 28] identified that recent donation was a negative predictor of physical QoL of living liver donors, especially within 6 months post donation [19, 26], during which time living liver donors were likely to have lower levels of vitality and more physical problems (unable to perform some physical activities, slower than expected recovery, higher levels of abdominal/back pain, and more fatigue). In terms of psychological status, three articles [19, 25, 28] reported that recent donation was associated with lower mental component summary score and more worry (about their recipient). In addition, one article [25] reported that recent donors (3 months and 6 months post donation) bore a higher financial burden (decreased income, burdensome medical expenses, job change or modification due to donation).

Postdonation complications Two articles [19, 22] reported that postoperative complications experienced by donors was a risk factor for poor physical function and induced high levels of abdominal and back pain. One article [22] found that living liver donors with two or more complications were more likely to have both poor mental and poor socially related QoL. Donors with no postoperative complication were obviously likely to have had better physical function and higher satisfaction and this was supported by two articles [11, 24].

Donation decision One article [22] found that donors encouraged by someone to donate were more likely to report improved family relationships; another article [19] showed that donors who were discouraged from donating by someone were likely to have more physical symptoms.

Concern for own well-being Concern by living liver donors about their own well-being predonation was a negative predictor for both their physical and psychological QoL; this was identified in two [9, 28] and three articles [9, 23, 28], respectively.

Ambivalence about donating Two articles [19, 25] reported that living liver donors with high levels of ambivalence about donating were more likely to worry about their recipient’s and their own health. One article [25] found that donors with low levels of ambivalence about donation experienced greater decrease in income due to donation.

Donor–recipient relationship Two articles [19, 25] reported that first-degree relative donors and spouse/partner donors were more likely to report donation as being physically stressful and were more worried about their recipients. In contrast, one article [25] indicated that donors donating to first-degree relatives or a spouse/partner were more likely to report being held in high esteem and having gratitude expressed by their families.

Other factors Other independent influencing factors for poor physical function of donors included having a male child recipient [6], use of analgesics associated with postoperative pain [29], taking more days off work for reasons related to donation [22], anticipation that life would be more worthwhile after donation, [19] and anticipation of long-term health effects [19]. Other negative influencing factors for social function included the number of months until recovery to preoperative health status [22]; preoperative prediction of a long time off work (> 3 months); concern about missing work; working in a technical, clerical, or lower-level position [25]; and having predonation concern about who would pay donation costs [25].

Health-related characteristics

Body mass index One article [19] reported that donors with high body mass index (BMI) (25.0–29.9 kg/m²) were more likely to report being unable to do some physical activities after donation and another article [25] found that donors with BMI < 30 had more worries about their recipients.

Predonation physical symptoms One article [19] found that donors with abdominal/back pain or fatigue before donation were more likely to experience the same symptoms post donation.

Psychosocial characteristics

Predonation physical component summary score and mental component summary score Two articles [11, 19] identified that high physical component summary and/or mental component summary scores predonation were a positive factor for donors having fewer physical symptoms, lower levels of abdominal or back pain, and better mental health post donation. One article [19] found that lower predonation mental component summary score was independently associated with both physical and mental issues in donors, such as health-related worries, not feeling physically back to normal, and feeling physically stressed.

Household income One article [19] identified that higher household income was a negative factor for postoperative recovery but a positive factor for abdominal/back pain, and another one [25] reported that donors with lower household income were more likely to report postdonation costs as a burden.

Trait anxiety One article [29] indicated that trait anxiety was associated with significant postoperative pain; another article [16] reported that past or present psychiatric diagnosis was a negative predictor of the psychological function of living liver donors.

A study from Noma et al. [30] that did not classify QoL into different domains showed that recipient age at onset of hepatic disease was positively associated with the mean health-related QoL of donors, whereas a high depression score of recipients (Beck Depression Inventory) was negatively associated with mean QoL score.

This systematic review summarized the factors significantly influencing the QoL of living liver donors. Sixteen articles from eight countries were included. Although the included studies and previous syntheses of the evidence reported that the overall QoL of living liver donors is good, they were still affected by invasive surgery and postdonation complications, and aspects of QoL were indeed impaired among the donors in our review. We extracted four kinds of factors influencing QoL: sociodemographic, donation-related, health-related, and psychosocial.

Of the negative factors, some could be modified; however, others were fixed. Being female, low education levels, old age, recent donation, recipient death, and being a first-degree relative or spouse/partner donor were consistently determined by several articles as factors negatively influencing donor physical function or psychological status. Living liver donors with fixed characteristics identified as negatively associated with reduced QoL should be treated as a vulnerable group (e.g., females, low education levels). Strict screening of physical and mental aspects of functioning is essential, with closer attention paid to vulnerable groups before and after donation. The transplant team can also give additional attention to living liver donors at vulnerable time points such as after recent donation (especially within 6 months post donation) and to donors who have recently experienced recipient death.

Recipient complications, postoperative complications experienced by donors, predonation physical or psychological status (e.g., physical component summary score/ mental component summary score, concerns regarding their own well-being) can be regarded as modifiable factors. Great advances in the technology of living liver transplantation such as the use of laparoscopic donor hepatectomy are important measures to protect the safety of donors. Purely laparoscopic donor hepatectomy has been confirmed as a feasible and safe method, even for donors with anatomical variations [31]. Studies have found that living liver donors who undergo pure laparoscopic donor hepatectomy do not require admission into the intensive care unit or intraoperative transfusion of blood, and complication rates, length of hospital stay, and number of hospitalizations are also reduced [31, 32]. In addition, donors operated using a pure laparoscopic approach have greater wound satisfaction, which may also benefit donor mental health [1]. Furthermore, poor physical component summary score and mental component summary score indicate that evaluation and targeted intervention are essential to improving physical and psychological status predonation.

Social function is an essential QoL domain, but it has received little attention in the study of QoL of living liver donors. This may be because of a lack of effective tools to assess social function. Only two of the studies included in our review focused on factors influencing social QoL. The study from Japan analyzed three components of the SF-36: physical component summary, mental component summary, and role/social component summary score. role/social component summary score includes the role-physical, role-emotional, and social-functioning subscales of SF-36 [22]. Another study assessed social and environmental related QoL using self-developed assessment questionnaires [25]. Both of these studies mainly concerned the family relationships and financial issues. Unexpected postdonation issues, such as the living liver donor requiring more recovery time or experiencing complications, a long hospital stay, or frequent hospitalizations, may worsen socially related QoL. They may also cause donation-related financial strain (e.g., burdensome postdonation costs, loss of income). Donation-related physical function, psychological status, and social function may be mutually affected. Poor social function may influence the physical and psychological aspects of QoL because medical treatment postdonation may be restricted due to impaired social roles, decreased income, and the burden of donation-related medical expenses. The social and environmental related QoL of donors should be treated as equally as important as other aspects. A specific social function assessment tool should be developed for use with living donors, in a future study.

Limitations

This systematic review had some limitations. First, a limited number of studies could be included and many of them were of small sample size, which limited the strength of evidence. Second, the majority of the studies adopted cross-sectional designs, so causality in the relationships between potential risk factors and QoL could not be established. Consequently, the influencing factors summarized in this review reflect associations rather than causations. Third, in the majority of the studies the SF-36 was used to assess QoL. Although the SF-36 is widely recognized as an effective QoL measurement tool, it is not targeted to living liver donors. Only one of the included studies used a donor-specific QoL assessment tool. Finally, we were unable to merge data in a meta-analysis because of the limited statistics that the included studies provided; hence this is merely a systematic review in which the existing evidence is reviewed narratively.

Many factors potentially contribute to decreased QoL of living liver donors. We summarized these factors, providing convenient information enabling clinical practitioners to formulate precise interventions. Potential donors need to be informed of all possible outcomes after donation. Vulnerable groups of donors and donors at time points of heightened vulnerability deserve increased attention, and by identifying these, specific interventions can be carried out for modifiable risk factors to minimize possible negative effects. Social function is also an important element in the QoL of donors and requires greater attention from both clinicians and researchers. On the one hand, development of a valid assessment tool is necessary for measuring donation-related outcomes. On the other hand, helping donors to activate their social support system, not only their healthcare team but also their family, friends, and even other donors, may benefit donors in dealing with potential risks and issues. Strong evidence will depend on multicenter, prospective, and longitudinal studies being conducted in the future, to confirm causality between potential factors and the QoL of living liver donors.

QoL

Quality of Life

SF-36

36-Item Short-Form Health Survey

Ethics approval and consent to participate: Not applicable (this is a systematic review )

Consent for publication: Not applicable.

Availability of data and materials: All data generated or analysed during this study are included in this published article.

Competing interests: The authors declare that they have no competing interests

Funding: This work was supported by National Natural Science Foundation of China (grant number 71603272 and grant number 71974008); Fundamental Research Funds for the Central Universities (grant number BMU2021YJ025)

Authors’ Contribution: ZJ Z: Protocol/project development; YX S and HM Z: Data summary, prepared tables and figures, wrote the main manuscript text; YR F and M C: Literature retrieval, data extraction. All authors reviewed the manuscript

Acknowledgements: Not applicable.

Lee JM, Shehta A, Lee KW, Hong SK, Cho JH, Yi NJ, Suh KS: Donor wound satisfaction after living-donor liver transplantation in the era of pure laparoscopic donor hepatectomy. Surg Endosc 2021, 35(5):2265–2272.
Raza MH, Kim MH, Ding L, Fong T-L, Romero C, Genyk Y, Sher L, Emamaullee J: Long-Term Financial, Psychosocial, and Overall it Check for updates Health-Related Quality of Life After Living Liver Donation. Journal of Surgical Research 2020, 253:41–52.
Orley J, Saxena S, Herrman H: Quality of life and mental illness. Reflections from the perspective of the WHOQOL. Br J Psychiatry 1998, 172:291–293.
The World Health Organization, Quality of Life Assessment (WHOQOL): development and general psychometric properties. Soc Sci Med 1998, 46(12):1569–1585.
The WHOQOL Group, Development of the World Health Organization WHOQOL-BREF quality of life assessment. Psychol Med 1998, 28(3):551–558.
Shi Y, Liu C, Zhang H, Huang Y, Sun M, Wang W, Shang S: Changes in the quality of life of living liver donors: A meta-analysis. International Journal of Nursing Studies 2020, 109:N.PAG-N.PAG.
Dew MA, Butt Z, Humar A, DiMartini AF: Long-Term Medical and Psychosocial Outcomes in Living Liver Donors. American Journal of Transplantation 2017, 17(4):880–892.
Janik MK, Księżopolska A, Kostrzewa K, Kobryń K, Moskwa M, Raszeja-Wyszomirska J, Kornasiewicz O, Patkowski W, Milkiewicz P, Krawczyk M et al: Long-Term Health-Related Quality of Life in Living Liver Donors. Ann Transplant 2019, 24:45–51.
Dew MA, Butt Z, Liu Q, Simpson MA, Zee J, Ladner DP, Holtzman S, Smith AR, Pomfret EA, Merion RM et al: Prevalence and Predictors of Patient-Reported Long-term Mental and Physical Health After Donation in the Adult-to-Adult Living-Donor Liver Transplantation Cohort Study. Transplantation 2018, 102(1):105–118.
Butt Z, DiMartini AF, Liu Q, Simpson MA, Smith AR, Zee J, Gillespie BW, Holtzman S, Ladner D, Olthoff K et al: Fatigue, Pain, and Other Physical Symptoms of Living Liver Donors in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study. Liver Transpl 2018, 24(9):1221–1232.
Weng LC, Huang HL, Lee WC, Tsai YH, Wang WS, Chen KH: Health-related quality of life of living liver donors 1 year after donation. Hepatobiliary Surg Nutr 2019, 8(1):1–9.
Ladner DP, Dew MA, Forney S, Gillespie BW, Brown RS, Jr., Merion RM, Freise CE, Hayashi PH, Hong JC, Ashworth A et al: Long-term quality of life after liver donation in the adult to adult living donor liver transplantation cohort study (A2ALL). J Hepatol 2015, 62(2):346–353.
Takada Y, Suzukamo Y, Oike F, Egawa H, Morita S, Fukuhara S, Uemoto S, Tanaka K: Long-term quality of life of donors after living donor liver transplantation. Liver Transpl 2012, 18(11):1343–1352.
Dew MA, DiMartini AF, Ladner DP, Simpson MA, Pomfret EA, Gillespie BW, Merion RM, Zee J, Smith AR, Holtzman S et al: Psychosocial Outcomes 3 to 10 Years After Donation in the Adult to Adult Living Donor Liver Transplantation Cohort Study. Transplantation 2016, 100(6):1257–1269.
Chandran B, Bharathan VK, Shaji Mathew J, Amma B, Gopalakrishnan U, Balakrishnan D, Menon RN, Dhar P, Vayoth SO, Surendran S: Quality of life of liver donors following donor hepatectomy. Indian J Gastroenterol 2017, 36(2):92–98.
DuBay DA, Holtzman S, Adcock L, Abbey SE, Greenwood S, Macleod C, Kashfi A, Renner EL, Grant DR, Levy GA et al: Cosmesis and body image after adult right lobe living liver donation. Transplantation 2010, 89(10):1270–1275.
Zhong J, Lei J, Wang W, Yan L: Systematic review of the safety of living liver donors. Hepato-Gastroenterology 2013, 60(121):252–257.
Parikh ND, Ladner D, Abecassis M, Butt Z: Quality of life for donors after living donor liver transplantation: a review of the literature. Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 2010, 16(12):1352–1358.
Butt Z, DiMartini AF, Liu Q, Simpson MA, Smith AR, Zee J, Gillespie BW, Holtzman S, Ladner D, Olthoff K et al: Fatigue, Pain, and Other Physical Symptoms of Living Liver Donors in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study. Liver transplantation 2018, 24(9):1221–1232.
Janik MK, Księżopolska A, Kostrzewa K, Kobryń K, Moskwa M, Raszeja-Wyszomirska J, Kornasiewicz O, Patkowski W, Milkiewicz P, Krawczyk M et al: Long-Term Health-Related Quality of Life in Living Liver Donors. Annals of transplantation 2019, 24:45–51.
Morooka Y, Umeshita K, Taketomi A, Shirabe K, Yoshizumi T, Yamamoto M, Shimamura T, Oshita A, Ohdan H, Kawagishi N et al: Long-term donor quality of life after living donor liver transplantation in Japan. Clinical transplantation 2019, 33(6):1.
Takada Y, Suzukamo Y, Oike F, Egawa H, Morita S, Fukuhara S, Uemoto S, Tanaka K: Long-term quality of life of donors after living donor liver transplantation. Liver transplantation 2012, 18(11):1343–1352.
Dubay DA, Holtzman S, Adcock L, Abbey S, Greenwood S, MacLeod C, Kashfi A, Jacob M, Renner EL, Grant DR et al: Adult right-lobe living liver Ddonors: Quality of life, attitudes and predictors of donor outcomes. American Journal of Transplantation 2009, 9(5):1169–1178.
Sotiropoulos GC, Radtke A, Molmenti EP, Schroeder T, Baba HA, Frilling A, Broelsch CE, Malago M: Long-Term Follow-Up After Right Hepatectomy for Adult Living Donation and Attitudes Toward the Procedure. Annals of Surgery 2011, 254(5):694–701.
DiMartini A, Dew MA, Liu Q, Simpson MA, Ladner DP, Smith AR, Zee J, Abbey S, Gillespie BW, Weinrieb R et al: Social and Financial Outcomes of Living Liver Donation: A Prospective Investigation Within the Adult-to-Adult Living Donor Liver Transplantation Cohort Study 2 (A2ALL-2). American Journal of Transplantation 2017, 17(4):1081–1096.
Ladner DP, Dew MA, Forney S, Gillespie BW, Brown RS, Merion RM, Freise CE, Hayashi PH, Hong JC, Ashworth A et al: Long-term quality of life after liver donation in the adult to adult living donor liver transplantation cohort study (A2ALL). Journal of hepatology 2015, 62(2):346–353.
Dew MA, DiMartini AF, Ladner DP, Simpson MA, Pomfret EA, Gillespie BW, Merion RM, Zee J, Smith AR, Holtzman S et al: Psychosocial Outcomes 3 to 10 Years After Donation in the Adult to Adult Living Donor Liver Transplantation Cohort Study. Transplantation 2016, 100(6):1257–1269.
Fukuda A, Sakamoto S, Shigeta T, Uchida H, Hamano I, Sasaki K, Kanazawa H, Loh DL, Kakee N, Nakazawa A et al: Clinical outcomes and evaluation of the quality of life of living donors for pediatric liver transplantation: a single-center analysis of 100 donors. Transplantation proceedings 2014, 46(5):1371–1376.
Lee SH, Lim KC, Jeon MK, Kim IO, Jeong JS, Hong JJ, Ha HS: Post-operative pain and its inflencing factors among living liver donors. Liver Transplantation 2012, 18:S250.
Noma Si, Hayashi A, Uehara M, Uemoto S, Murai T: Comparison between psychosocial long-term outcomes of recipients and donors after adult-to-adult living donor liver transplantation. Clinical transplantation 2011, 25(5):714–720.
Han ES, Suh KS, Lee KW, Yi NJ, Hong SK, Lee JM, Hong KP, Tan MY: Advances in the surgical outcomes of 300 cases of pure laparoscopic living donor right hemihepatectomy divided into three periods of 100 cases: a single-centre case series. Ann Transl Med 2021, 9(7):553.
Li H, Zhang JB, Chen XL, Fan L, Wang L, Li SH, Zheng QL, Wang XM, Yang Y, Chen GH et al: Different techniques for harvesting grafts for living donor liver transplantation: A systematic review and meta-analysis. World J Gastroenterol 2017, 23(20):3730–3743.

No competing interests reported.

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A systematic review of the factors significantly influencing the quality of life of living liver donors

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Abstract

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Introduction

Methods

Search strategies

Inclusion and exclusion criteria

Selection of studies

Data extraction

Methodological quality assessments

Synthesis of results

Results

Search process

Characteristics of the included studies

Methodological quality

Overall status of living liver donors

Factors influencing QoL of living liver donors

Sociodemographic characteristics

Donation-related characteristics

Health-related characteristics

Psychosocial characteristics

Discussion

Conclusion

Abbreviations

Declarations

References

Additional Declarations

Supplementary Files

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