American Journal of Transplantation 2011; 11: 101–110Wiley Periodicals Inc.

C© 2010 The AuthorsJournal compilation C© 2010 The American Society of

Transplantation and the American Society of Transplant Surgeons

doi: 10.1111/j.1600-6143.2010.03284.x

Short- and Long-term Donor Morbidity in Right LobeLiving Donor Liver Transplantation: 91 ConsecutiveCases in a European Center

D. Azoulaya,b,c,*, P. Bhanguia, P. Andreania,

C. Sallouma, V. Karama, E. Hotia, G. Pascala,

R. Adama,b,d, D. Samuela,b,d, Ph. Ichaia,d,

F. Salibab,d and D. Castainga,b,d

aAP-HP Hopital Paul Brousse, Centre Hepato-Biliaire,Villejuif, FrancebUniversite Paris-Sud, Villejuif, FrancecInserm, Unite 1004, Villejuif, FrancedInserm, Unite 785, Villejuif, France*Corresponding author: Daniel Azoulay,daniel.azoulay@pbr.aphp.fr

The lack of use of a common grading system in re-porting morbidity impedes estimation of the true riskto a right lobe living donor (RLLD). We report out-comes in 91 consecutive RLLD’s using the validated5-tier Clavien grading and a quality of life (QOL) ques-tionnaire. The median follow-up was 79 months. Thedonors were predominantly female (66%), 22 (24%) re-ceived autologous blood transfusions. Fifty-three com-plications occurred in 43 donors (47% morbidity), 19(37%) were ≥ Grade III, biliary fistula (14%) was themost common. There was no donor mortality. Two in-traoperative complications could not be graded andtwo disfiguring complications in female donors weregraded as minor. Two subgroups (first 46 vs. later 45donors) were compared to study the presence if any, ofa learning curve. The later 45 donors had lesser autol-ogous transfusions, lesser rehospitalization and no re-operation and a reduction in the proportion of ≥ GradeIII (major) complications (24% vs. 50%; p = 0.06). In thelong term, donors expressed an overall sense of wellbeing, but some sequelae of surgery do restrain theircurrent lifestyle. Our results warn against lackadaisicalvigilance once RLLD hepatectomy becomes routine.

Key words: Morbidity, outcomes, quality of life, rightlobe liver donation

Abbreviations: RLLD, right lobe living donor; QOL,quality of life; LDLT, living donor liver transplantation;RLLDLT, right lobe living donor liver transplantation;CT, computerized tomography; MR, magnetic reso-nance; GRWR, graft-to-recipient weight ratio; IOUS, in-traoperative ultrasound; CUSA, Cavitronic UltrasoundAspirator; MHV, middle hepatic vein; IC, intermediatecare; ICU, intensive care unit; CNS, central nervous sys-tem; DVT, deep vein thrombosis; NIDDK, National In-

stitute of Diabetes and Digestive Kidney Disease; BMI,body mass index; PVT, portal vein thrombosis; CBD,common bile duct; LT, liver transplantation.

Recieved 23 June 2010, revised 06 August 2010 andaccepted for publication 11 August 2010

Introduction

Living donor liver transplantation (LDLT) is a therapy whosefeasibility depends to a great extent on the integrity of aperson other than the patient himself, i.e. the donor; and isa procedure which may jeopardize the donors’ health, andeven his life.

The first successful adult LDLT (left liver graft) was reportedby Makuuchi et al. (1) in Japan in 1993, it was performeddue to the absence of cadaveric grafts in that country. Thefirst right lobe LDLT (RLLDLT) was reported by the groupof Fan from Hong Kong in 1996 (2), and has today becomethe most widely used procedure for adult LDLT in Westerncountries (3–5).

The initial success in recipients and low donor morbidityrates led to a rapid expansion of adult-to-adult LDLT’s (3,4);however five right lobe living donor (RLLD) deaths between1999 and 2002 (two in USA and three in Europe), led toa more cautious approach to the use of this procedure(6). Subsequently, there was a decline in the number ofLDLT’s performed in the Western world after 2001–2002(European Liver Transplant Registry 2005 [www.eltr.org];United Network for Organ Sharing [www.unos.org]). It wasalso shown that morbidity is statistically correlated to theextent of the hepatectomy and complications are signifi-cantly higher after right donor hepatectomy (25%) as com-pared to left donor hepatectomy or lobectomy (10%) (7).

Fifteen years after the first RLLDLT was performed, thedebate on “probable risks to a donor” still continues. Afrank and accurate disclosure regarding the risks and ben-efits of RLLDLT can be provided to interested parties onlyif principal problems like underreporting of technical com-plications, a short donor follow-up and lack of reporting oflong-term quality of life (QOL) in the donors are overcome(8). A common validated grading system to report donor

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Table 1: Clavien grading of surgical complications10

Grade Definition

Grade I Any deviation from the normal postoperativecourse without the need for pharmacologicaltreatment or surgical, endoscopic andradiological interventions

Allowed therapeutic regimen are drugs asantiemetics, antipyretics, analgesics, diuretics,electrolytes and physiotherapy. This grade alsoincludes wound infections opened at thebedside

Grade II Requiring pharmacological treatment with drugsother than such allowed for Grade Icomplications

Blood transfusions and total parenteral nutritionare also included

Grade III Requiring surgical, endoscopic or radiologicalintervention

Grade IIIA Intervention not under general anaesthesiaGrade IIIB Intervention under general anaesthesiaGrade IV Life threatening complication (including CNS

complications)1 requiring IC/ICU managementGrade IVA Single organ dysfunction (including dialysis)Grade IVB Multi organ dysfunctionGrade V Death of a patient1Brain haemorhage, ischaemic stroke, subarachnoidal bleeding,but excluding transient ischaemic attacks.CNS = central nervous system; IC = intermediate care; ICU =intensive care unit.

outcomes is a must to be able to compare worldwide out-comes. Recently, some studies have used the validatedClavien grading (9,10) to classify and report the post oper-ative morbidity in living donors (11–21), only one of thesebeing a European series (14).

Our study was aimed at reporting short and long-termdonor outcomes with RLLDLT in a European centre us-ing the 5-tier Clavien grading system described in 2004(10) (Table 1).

Materials and Methods

From January 2000 to December 2009, we performed 91 consecutiveRLLDLT’s at the Centre Hepatobiliaire, Villejuif, France. Before we startedthe adult-to-adult LDLT programme, 1288 liver resections and 1531 cadav-eric orthotopic liver transplants (including 80 split liver transplants and 21domino transplants) were done at our centre. Between 2000 and 2009(study period), 1645 liver resections and a total of 1088 liver transplants (in-cluding 167 split liver transplants, 113 domino transplants) were performed.We reviewed the patient demographics, operative details, post operativecomplications and follow-up from our prospectively maintained database. Inaddition, a QOL study was done to determine the realistic long-term impactof liver donation on donor lifestyle.

Donor selection and evaluation

The RLLD’s were accepted only after a stringent selection process(Figure 1), starting with an initial evaluation process (initial health-screening,blood tests, viral serology, imaging studies and medical and psychiatric as-

sessment) by health-care professionals independent of the transplantationteam. The first 12 donors in our series underwent a conventional arteri-ography to assess vascular anatomy, this was later replaced by triphasiccomputerized tomography (CT) and MR angiography to assess vascularanatomy and perform volumetry (OSIRIS imaging software (Digital Imag-ing Unit, University Hospital of Geneva, Geneva, Switzerland). A residualliver/body-weight ratio ≥ 0.7 and graft-to-recipient weight ratio (GRWR) of ≥0.8 were considered acceptable (24). All donors underwent a magnetic res-onance cholangiography (MRCP) to study the biliary anatomy. Liver biopsywas performed selectively in patients in whom liver steatosis was sus-pected (but not definitely proven on imaging studies), and in those withserum liver enzyme abnormalities. Absolute exclusion criteria were; un-derlying medical condition likely to increase the complication risk, positivehepatitis serology, underlying liver disease, inadequate graft size, macrovac-uolar steatosis >30% and abnormal biliary anatomy (e.g. branches to leftlobe arising from right duct). Three autotransfusion units were drawn fromall donors before surgery.

We went ahead with the RLLDLT only when all the senior doctors involved(surgeons, hepatologists, and anaesthesists) agreed to the same, thus itwas a consensus decision rather than a majority decision to proceed withthe right donor hepatectomy.

Surgical technique of right lobe donor hepatectomy

A right subcostal incision with midline extension (if required) was used. Anintraoperative cholangiography was performed to verify biliary anatomy anddetermine whether there were any biliary anomalies missed on preopera-tive MRCP (or in the first 12 cases where MRCP and MR angiography werenot performed), that could preclude resection. Intraoperative ultrasound(IOUS) was used to define the line of parenchymal transection, which wasthen performed without inflow occlusion using Cavitronic Ultrasound Aspi-rator (CUSA), drip bipolar and monopolar diathermy, with suture ligation forlarger vessels. The right lobe was harvested excluding MHV in 70 cases(77%). The right bile duct and the hilar plate were divided sharply after two-thirds of the parenchymal dissection had been completed. The right hepaticartery, right portal vein and the hepatic veins were clamped and divided,and the graft was removed and flushed with cold University of Wiscon-sin solution (Viaspan; Dupont, Wilmington, DE). A cell-saver (red blood cellscavenging device) was routinely used. Hemostasis was achieved with elec-trocoagulation or suture ligation depending on the size of the pedicles, a 30Fr abdominal drain was systematically placed before closure.

Postoperative care and follow up

Donors were managed in an intensive care step-down unit (ICU) for thefirst 48 h, and then in a regular surgical ward. Daily haematological andbiochemical investigations were done. Doppler US was done every dayduring the ICU stay and every 3rd day during the stay in the surgical wardto assess vessel integrity and flow. DVT prophylaxis was started on the dayof the operation and continued for 1 month post operatively (prophylacticdose of low-molecular weight heparin). All the donors were closely followedat our center till date. During the first year; at 1, 3, 6 months and 1 year,donors had blood investigations and an abdominal ultrasound; a CT scanwas done at 1 month, 6 months and 1 year. After the first year; the donorswere evaluated yearly (or at least their detailed health status was confirmedby telephonic conversation in case they were not able to personally cometo our center for examination).

Clavien grading of complications

Clavien’s 5-tier grading (10) was used in preference to his original version,which had only four grades (9). The most serious and seminal complica-tion was considered if simultaneous or multiple complications occured.The onset of the complication was defined as the time when the resultingorgan dysfunction was detected or the corrective treatment was started.

102 American Journal of Transplantation 2011; 11: 101–110

Donor Morbidity in Right Lobe Living Donors

Figure 1: Donor cohort.

Distinctions of Clavien IIIa and b were not used for analysis because patientsare given sedation under anesthesiologist supervision for essentially all ra-diological, endoscopic or other invasive procedures at our centre. We notedevery complication that affected the donors’ day to day life postoperativelyand till date.

Sub groups

In order to evaluate the presence if any of a learning curve over the years, thepatient cohort was further divided into two subgroups; the first 46 and later45 donors. The patient demographics, operative details and postoperativemorbidity were compared between the two groups.

QOL assessment

To assess the long-term impact on QOL in donors, a cross-sectional analy-sis was done. A questionnaire based on the one used by National Instituteof Diabetes and Digestive and Kidney Disease (NIDDK), Pittsburgh (23) anddeveloped from standardized instruments was used. Five domains of QOL:measures of disease (physical symptoms), psychologic status (emotionaldistress), personal function (working capacity and handicap), social androle function (social interaction) and general health perception were stud-ied. Two native French speakers translated the NIDDK-QOL questionnairefrom English to French with appropriate cultural adaptations, in collaborationwith a specialist in subjective measures in health, and organ-transplantationsurgeons. A back-translation to English was then performed by anothertranslator; a method validated according to the standard methodology(25).

Statistical analysis

Continuous variables are presented as mean with standard deviation andanalyzed by the Student’s t-test. Categorical variables are presented asproportions and analyzed by Chi-square test. A p-value ≤ 0.05 is consideredstatistically significant. All statistics were performed using Stat View 5.0software for Windows (SAS Institute, Cary, NC).

Results

The mean follow-up was 77 ± 29 months (median 79months, range = 6–121 months).

Donor selection

Forty-five potential donors were excluded during initialscreening (Figure 1). Four donors were refused by ourteam due to very sick potential recipients, while recipientsthemselves refused 11 donors (donation from child to par-ent). Socioeconomic conditions, psychological status, al-cohol abuse, ABO incompatibility, or inadequate remnantliver on volumetry led us to exclude 30 other potentialdonors. The donor who was refused due to his unsta-ble psychological status incidentally committed suicide ayear later. Eight donors were excluded due to steatosis on

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Table 2: Donor characteristics over time

All patients Period 1 Period 2 p-Value (Period 1n = 91 n = 46 n = 45 vs. Period 2)

Age at donation (mean ± SD) 39 ± 13 yrs 39 ± 13 yrs 39 ± 12 yrs 0.84Sex

No of females (percentage) 60 (66%) 29 (63%) 31 (68%) 0.56Relation to recipient

Biologically related 64 (70.3%) 32 (69.6%) 32 (71.1%) 0.76Parent 10 5 5Child 25 12 13Sibling 28 15 13Other biological 1 0 1

Not biologically related 27 (29.7%) 14 (30.4%) 13 (28.9%) 0.14Spouse 26 14 12Close friend 1 0 1

Body Mass Index (mean ± SD) 23.62 ± 4.1 kg/m2 23.35 ± 3.6 kg/m2 23.91 ± 4.6 kg/m2 0.91Remnant left liver to body weight 0.78 ± 0.17 0.81 ± 0.16 0.77 ± 0.18 0.26

ratio (mean ± SD)

liver biopsy. For cancer recipient’s, the donor operation wasstarted only after exploratory laparotomy including frozensection analysis of any suspect extrahepatic nodule/lesion.Three scheduled donor hepatectomies were cancelled af-ter exploratory laparotomy in cancer recipient’s revealedextrahepatic disease. There were no aborted donor opera-tions (‘no-go’ hepatectomies). Thus 91 of the 147 potentialdonors (61.9%) finally underwent right lobe donor hepate-ctomy.

Donor characteristics and operative details

(Tables 2 and 3)

The mean donor age was 39 ± 13 years, and 66%were females. All 91 RLLDLT’s were ABO-compatible. Themean remnant liver/body weight ratio in the donors was0.78 ± 0.17.

The mean operative time was 283 ± 45 min, estimated in-traoperative blood loss was 702 ± 593 mL, and 22 patients(24.2%) received autologous transfusion. The mean lengthof hospitalization was 13 ± 5 days, 1 donor had to be rehos-pitalized on the 21st day posthepatectomy and operatedfor biliary peritonitis. Overall 19 patients (21%) were re-hospitalized during the entire follow-up period. We werevery liberal in our rehospitalization policy for the donors,

two donors were hospitalized as they complained of ab-dominal pain, three for pain with fever, one for chest paindue to oesophagitis, one each for abdominal wall abscessand haematoma and seven donors for ultrasound guidedaspiration of abdominal or pleural collections. Two donorswere hospitalized for check cholangiography (one donorwho had primary repair of an intraoperative bile duct injuryfor T-tube cholangiography before its removal; the otherdonor for a contrast study through a percutaneous drain in-troduced for postoperative biliary fistula, to verify absenceof a persitent biliary communication).

First 46 versus the second 45 donors: The mean donorage, BMI, sex distribution, remnant left liver/body weightratio were similar between the two groups. Fewer donorsreceived autologous blood tranfusions in the later period ascompared to the first period (13.3% vs. 34.8%, p < 0.01).The mean post operative hospital stay was comparable,and there was a trend towards lesser rehospitalization inthe later period (13.3% vs. 28.3%, p = 0.08).

Donor complications

All donors (Table 4): Forty-three out of 91 donors devel-oped 53 complications (morbidity rate of 47.3%). Howeveronly 51 of these complications could be graded as per the

Table 3: Donor outcomes over time

All patients Period 1 Period 2 p-Value (Period 1n = 91 n = 46 n = 45 vs. Period 2)

Operative time (mean ± SD) 283 ± 45 min 288 ± 49 min 278 ± 41 min 0.30Intraoperative blood loss (mean ± SD) 702 ± 593 mL 767 ± 677 mL 637 ± 470 mL 0.32Autologous transfusions (%) 22 (24.2%) 16 (34.8%) 6 (13.3%) <0.01

0 units 69 30 391 unit 13 7 62–3 units 9 9 0

Hospital stay (mean ± SD) 13 ± 5 days 12 ± 3 days 14 ± 6 days 0.08Reoperation for operative complications (%) 1 (1.1%) 1 (2.2%) 0 1.00Number of patients rehospitalized (%) 19 (21%) 13 (28.3%) 6 (13.3%) 0.08

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Table 4: Donor complications graded by Clavien system10

53 complications in all 91 patients No of(51 graded as per Clavien grading) Donors (%) Grade I Grade II Grade III Grade IV

Intraoperative complications 2 (2.2%) – – – –Haemorrhage due to slipped hepatic vein clamp 1 – – – –Common bile duct transection 1 – – – –Biliary 13 (14.3%)Bile leak/biloma 13 – 9 4 –Abdominal 9 (9.9%)Sterile sub-phrenic collection requiring aspiration 5 – – 5 –Gastric paresis 2 2 – – –Abdominal wall abscess/haematoma 2 1 – 1 –Cardiopulmonary 9 (9.9%)Pneumonia 3 – 3 – –Pleural effusion requiring pleurocenthesis 6 – – 6 –Hepatic 7 (7.7%)Ascites (>500 cc/24 h > 3 days) 5 5 – – –Liver failure 2 – – – 2Vascular 2 (2.2%)Portal vein thrombosis 1 1 – – –Middle hepatic vein thrombosis 1 1 – – –Others 11 (12.1%)Urinary tract infection 5 – 5 – –Infected T tube 1 1 – – –Blood culture positive 1 – 1 – –Arm lymphangitis 1 1 – – –Depression 1 – 1 – –Accidental finger amputation during post op physiotherapy 1 – – 1 –Alopecia areata in a female patient 1 1 – – –Total 13 19 17 2

Clavien classification as two complications were intraop-erative and there is no provision for grading these. Biliarycomplications (bile leak and biloma) accounted for the ma-jority of postoperative complications (13 patients, 14.3%).Liver failure characterized by either flapping tremors (en-cephalopathy) or as defined by the 50:50 criteria (26) oc-cured in two patients (2.2%) [the remnant liver to bodyweight ratios in these two patients were 0.56 and 0.78];and one patient each developed portal vein thrombosis(PVT) and middle hepatic vein thrombosis (MHV), bothwere successfully treated with anticoagulation therapy.

Thirty-two of the 51 complications (63%) were Grade I-II (minor), 17 (33%) were Grade III and 2 (4%) wereGrade IV. There was no donor mortality (Grade V). The twointraoperative complications which could not be gradedwere as follows. In one donor, the MHV stump clampslipped which led to profuse haemorrhage, necessitatingtotal vascular exclusion of the remnant liver for 10 min andautologous transfusion of 3 units. The other patient hadan intraoperative CBD injury which was repaired primar-ily with an end to end biliobiliary anastomosis and T-tubedrainage. Both these patients had an uneventful post op-erative recovery and no long-term sequelae.

Two female donors had disfiguring complications. Onedonor developed coronal alopecia as a result of position

during surgery (pressure-induced alopecia areata). Thoughthis is classified as Grade I, the significant impact of thiscomplication on the QOL of a previously healthy femaledonor is obvious. Another female donor had an accidentalinjury to one of her fingers during post operative physio-therapy which necessitated a finger amputation (Grade IIIcomplication). Though this complication was not directlyrelated to the surgical procedure itself, it occured duringher recovery from the surgery.

First 46 versus second 45 donors (Table 5): Twenty-twopatients (47.8%) suffered a total of 26 complications inthe first period whereas 21 patients (46.7%) suffered 25complications in the later period. Most of the complica-tions in both periods were Clavien Grade I/II. There wasa decrease in the incidence of ≥ Grade III complicationsin the later period as compared to the first period (24%vs. 50%, p = 0.055) (Table 5). The incidence of biliary, car-diopulmonary and abdominal complications was similar inthe two periods. There was a trend towards decreasinghepatic complications (ascites, liver failure) during the laterperiod (8% vs. 26.9%, p = 0.14).

QOL assessment

A summary of the responses from 51 donors on variousaspects of their QOL is presented in Table 6A and B.

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Table 5: Donor complications in the two periods

Complications in the two groups Period 1 Period 2 p-Value (Period 1as per Clavien grading 22 patients 21 patients vs. Period 2)

Total number of complications (51) 26 25Clavien Grade I-II 13 (50%) 19 (76%) 0.06Clavien Grade III/IV 11/2 (50%) 6/0 (24%)Biliary Fistula 7 (26.9%) 6 (24%) 0.81Abdominal 5 (19.2%) 4 (16%) 1.00Subphrenic collection drained 3 2Gastric Paresis 1 1Abd wall abscess/haematoma 1 1Cardiopulmonary 4 (15.4%) 5 (20%) 0.73Pneumonia 1 2Pleural effusion requiring pleurocenthesis 3 3Hepatic 7 (26.9%) 2 (8%) 0.14Ascites (> 500cc /24h > 3 days) 4 1Liver failure (encephalopathy) 2 –Portal vein thrombosis 1 –Middle hepatic vein thrombosis 1Others 3 (11.5%) 8 (32%) 0.08Infected T tube 1 –Urinary tract infection 0 5Blood culture positive – 1Depression – 1Arm lymphangitis – 1Finger amputation/Localized alopecia 2 –

Table 6: Donor quality of life (QOL)

(A) Parameters (n = 51 donors) Yes No

Social StatusPresent state of health causing problems with social life

(going out, seeing friends)– 4% 96%

WorkReturned to predonation occupation – 86% 14%Post donation health status responsible for inability to

perform type/quantity of work desired– 6% 94%

HealthHealth status compared to before donation Same or better 94% 6%Your overall health rating at present Good to excellent 85% 15%Current health status limits vigorous activity (running,

heavy lifting, sports)– 22% 78%

SymptomsFatigue or lack of energy Considerable to severe 14% 86%Abdominal pains or discomfort Considerable to severe 16% 84%Bowel problems(constipation/diarrhoea) Considerable to severe 14% 86%Anxiety/Nervousness Considerable to severe 18% 82%Change in facial appearance Considerable to severe 6% 94%Fluid retention/swelling of ankles Considerable to severe 10% 90%

(B) Parameters (n = 51 donors) Yes No

Level of satisfaction with present capacity to work Satisfied to completely satisfied 86% 14%Level of satisfaction with present health status Satisfied to completely satisfied 86% 14%Level of satisfaction with family life Satisfied to completely satisfied 96% 4%Level of satisfaction with life as a whole Satisfied to completely satisfied 96% 4%Level of satisfaction as regards the liver donation Satisfied to completely satisfied 96% 4%Do you regret your decision to donate 0% 100%Given the same situation will you donate again 98% 2%

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Functional status (Table 6A): Ninety-six per cent ofdonors have returned to their previous level of social activ-ity and an equal proportion to their predonation occupation.6% of patients felt that they were unable to perform thedesired type or quantity of work, post donation. 85% ratetheir present health status as good to excellent, whereas6% feel that the donation may have worsened it in someway. 22% of the donors felt that their capacity to performvigorous activity including running, lifting heavy weights orsport was limited post surgery. 15% of donors continue tohave irregular bowel habits and 18% suffer from anxietyand nervousness which they consider a consequence oftheir surgery. A decrease in sexual activity was reportedby 9% of donors.

Overall satisfaction (Table 6B): The overall level of satis-faction as regards present capacity to work, health statusand family life was estimated as 86%, 86% and 96%, re-spectively. Ninety-six per cent of donors were satisfied,very satisfied or completely satisfied with the entire dona-tion process and their current lifesyle.

None of the donors regretted their decision to donateand 98% of donors would donate again if required andfeasible.

Discussion

Our study revealed a 47.3% donor morbidity rate usingthe validated Clavien 5-tier grading system after a medianfollow up of 79 months. The overall rate of ≥ Grade III(major) complications was 37.3%. When the post operativemorbidity in the first 46 patients was compared to that inthe later 45 patients, the overall complication rate remainedthe same (47.8% vs. 46.6%, p = 0.78), and there was adecrease in the proportion of ≥ Grade III complications inthe later 45 patients (24% vs. 50%, p = 0.055). Donationdid have long-term effects on the donor QOL.

The whole basis of LDLT rests on the equipose of riskand benefit to the donor and recipient, respectively, donorsafety being the primary concern (7,27). We have beenupholding the policy that donors deserve treatment of thehighest standards, and two surgeons with an experienceof more than 20 years in liver surgery and involved in theLT programme at our center since its inception, performedall 91 right lobe LDLT’s at our center.

In 2002, Beavers et al. (8) could find only 12 detailed re-ports on RLLD morbidity out of 211 articles on the subject.Morbidity rates varied widely (0–67%), and this demon-strated that the definition of morbidity is not straightfor-ward. Clavien et al. (9) proposed a grading system for re-porting negative outcomes in solid organ transplantationand adapted it to liver transplantation in 1994. Since then,authors used modified versions of this grading to reportdonor outcome (28,29), none of these versions were vali-dated. A modified 5-tier Clavien grading was proposed in2004 (10), and this was later validated in 6336 patients.Grade III and IV complications are seldom missed, as pa-tients either need some form of anaesthesia (for interven-tions, Grade III complications), or need IC/ICU manage-ment for life threathening (Grade IV) complications. Weused this grading in our series to evaluate morbidity, as itis simple and reproducible.

Twelve studies used the Clavien grading to report RLLDmorbidity; 2 of these used the 4-tier grading (11,12)whereas 10 used the 5-tier grading (13–22). Two of thelatter series (19,20) reported results in both right and leftdonor hepatectomies and interpretation of RLLD morbiditywas difficult, whereas 1 series (21) had few donors (< 40).In these series, overall donor morbidity ranged from 20%to 78.3% and 0% to 65% of the complications were graded≥ Grade III (Table 7, 13–18,22).

Among the Western series, the Mayo Clinic group(13) reported an overall morbidity of 35% with 64%

Table 7: Major series on right liver donor outcomes which used the 5-tier Clavien grading

Proportion Biliary Vascular HepaticFirst author, Donor Donor of ≥ Grade III complication1 complication2 complication3 Donoryear of publication number morbidity complications rate rate rate mortality4

Western seriesB. Gali (13) 40 35% 64% 15% 4% 0% 0S. Gruttadauria (14) 75 30.6% 65% 9.3% 3% 4% 0J.W. Marsh (15) 121 20% 54% 6% 2% 0.8% 0Present series, (2010) 91 47.3% 37% 14.3% 2.2% 7.7% 0

Eastern seriesS.C. Chan (16) 200 20.5% 22% 2.5% 1% 0.5% 1 (0.5%)T. Iida (17) 500 44.2% 17% 12.2% 0.2% 1.8% 1 (0.2%)A. Azzam (18) 311 33.4% 35% 13% 0.3% 1.2% 1 (0.3%)N.J. Yi (22) 83 78.3% 1% 11% 0.3% 4.8% 0 (0%)

1Biliary complications: Biliary fistula/Stricture/Cholestasis.2Vascular complications: Portal Vein Thrombosis, Hepatic Vein Thrombosis, Deep Vein Thrombosis, Haemoperitoneum.3Hepatic complications: Liver failure, Encephalopathy, Significant ascites, Prolonged hyperbilirubinemia.4At least 11 donor deaths were reported in literature in other Western series (Ref. 6).

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complications graded ≥Grade III. Marsh et al. (15) notedonly Grade II–V complications (20% overall morbidity); notconsidering the Grade I complications could have led toan underestimation of the actual incidence. The only Eu-ropean series (from Italy) (14) reported a 30.6% overallmorbidity with 65% of the complications graded ≥GradeIII. The reported right lobe donor morbidity in Europe isabout 46% (www.eltr.org) (6).

Our overall morbidity rate was 47.3%, which was higherthan most of the other series. We also included intraoper-ative complications in these. There is no provision in theClavien grading for including intra operative complicationsand there is a definitive need to do so (PA Clavien, personalcommunication). The proportion of ≥ Grade III complica-tions in our series was 37.3% which is midway in thespectrum (17–65%) of studies using the 5-tier classifica-tion (Table 7).

In spite of some variation between series, the morbidityrate in most series is superior to 30% and at least 20% ofthe complications are major (Table 7). Chan et al. (16) vali-dated in their recent study the current standards to achieveas regards donor morbidity and mortality rate (20% and0.5%, respectively). The results of our study and the othercomparable studies illustrate that, even with a high levelof experience in liver surgery, it is not always possible toattain these standards. More importantly, increasing expe-rience does not always result in better outcome. In themost recent Asian series by Iida et al. from Japan (17)(Table 7), there was no improvement in the donor morbid-ity results over time when they compared their results overthree periods. Yi et al. (22), emphasized in their study thatdonor morbidity must be noted prospectively, and with thisstrategy they found an overall morbidity of 78.3% in rightliver donors in the Asian setting.

The study by Marsh et al. (15) provided the impetus tostudy our own outcomes with RLLD’s for LDLT. Their studyis arguably the most careful and timely analysis of the topiccurrently available and is the most objective assessmentof morbidity by the treatment based 5-tier Clavien system(30). The results of our study are in accordance with theirresults to a large extent, especially as regards the nonimprovement in the overall donor morbidity with time.

In the most comprehensive review on donor mortality af-ter LDLT, Trotter et al (6) reported that there were 9 RLLDdeaths worldwide ‘definitely related’ to donor hepatec-tomy, and 2 other ‘possibly related’ to donor surgery. Theestimated rate of donor death ‘definitely’ related to donorsugery was 0.15% and ‘definitely or possibly’ related todonor sugery was 0.2%.

In our QOL study, in spite of the high level of satisfactionand well being in the long-term expressed by the donors, asigificant proportion felt that their surgery prevented themfrom practicing vigorous activity, expressed increased anx-

iety and nervousness post surgery and suffered from al-tered bowel habits and fluid retention. Hence when as-sessed objectively, the effects of the donation are indeedconsiderable. Our QOL evaluation does have a potentiallimitation because 40 donors (44%) did not reply to thequestionnaire. Donors are not ‘patients’ in true sense ofthe term, so are not always ready to respond in the longterm (22).

Among studies regarding post RLLDLT QOL (31–37),Beavers et al. (31) found that despite complications (64%in their study), postoperative functional status of 27 RLLD’swas equal to or better than population norms. Parolin et al.(33) concluded, that most of the donors felt that the experi-ence of donating their liver changed their lives for the betterand that they would donate again if feasible and required.In a larger study of 68 Japanese donors (36), two donorsindicated that they would not donate again. In both thesecases, the recipients had died. Two studies expressed con-trary opinions as regards the long-term persistence of postdonation psychological disturbances (37,38). In the A2ALLstudy cohort (39), 16 of the 392 donors (4.1%) had psy-chiatric consequences including one suicide, one suicideattempt and one accidental drug overdose. Thus, there is adefinite underestimation of the consequences of RLLDLTon the long-term QOL and there might be a place for in-corporation of QOL indices into grading systems to assesslong-term morbidity.

In addition, aborted donor surgeries (intraoperative no-gohepatectomies) (40), and donor hepatectomies cancelledafter preparation (due to extrahepatic disease recognizedin a cancer recipient, as seen in our series); are a greatamount of stress for the donor and will probably never finda place in any grading system.

In conclusion, our study from a high volume hepatobil-iary centre found an overall morbidity rate of 47.3% inRLLD’s, with no significant improvement with time. Thereis no provision for including intra operative complications(which may have a bearing on the immediate and long-term outcome) in the otherwise optimal 5-tier Clavien grad-ing. Also, some disfiguring complications graded as mi-nor may in fact have a significant impact on donor QOL.Though most of the donors are satisfied with their long-term QOL, their responses must be interpreted with cau-tion. Absence of reduction in overall morbidity rate withtime, and a high proportion of major complications, warn usagainst lackadaisical vigilance once the operation becomesroutine.

Acknowledgments

The authors thank Prof. Thomas Starzl for a very indepth and thoughtfuldiscussion on the topic during the course of writing this article and theLiver Transplant Coordination Staff of Centre Hepatobiliaire, Paul Brousse

108 American Journal of Transplantation 2011; 11: 101–110

Donor Morbidity in Right Lobe Living Donors

Hospital, Villejuif, France for their dedication and contribution to patientfollow up and data collection.

Funding: None.

Disclosure

The authors of this manuscript have no conflicts of inter-est to disclose as described by the American Journal ofTransplantation.

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