American Journal of Transplantation 2015; 15: 1591–1597 Wiley Periodicals Inc.

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Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons doi: 10.1111/ajt.13203

Live Donor Liver Transplantation: A Valid Alternative for Critically Ill Patients Suffering From Acute Liver Failure N. Goldaracena1, V. N. Spetzler1, M. Marquez1, N. Selzner2, M. S. Cattral1, P. D. Greig1, L. Lilly2, I. D. McGilvray1, G. A. Levy2, A. Ghanekar1, E. L. Renner2, D. R. Grant1 and M. Selzner1,*

tion; LT, liver transplantation; MELD, model for endstage liver disease; WIT, warm ischemia time; WL, waiting list Received 09 July 2014, revised 19 September 2014 and accepted for publication 07 October 2014

1

Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, Toronto, ON, Canada 2 Department of Medicine, Toronto General Hospital, Toronto, ON, Canada  Corresponding author: Markus Selzner, [email protected]

We report the outcome of live donor liver transplantation (LDLT) for patients suffering from acute liver failure (ALF). From 2006 to 2013, all patients with ALF who received a LDLT (n ¼ 7) at our institution were compared to all ALF patients receiving a deceased donor liver transplantation (DDLT ¼ 26). Groups were comparable regarding pretransplant ICU stay (DDLT: 1 [0–7] vs. LDLT: 1 days [0–10]; p ¼ 0.38), mechanical ventilation support (DDLT: 69% vs. LDLT: 57%; p ¼ 0.66), inotropic drug requirement (DDLT: 27% vs. LDLT: 43%; p ¼ 0.64) and dialysis (DDLT: 2 vs. LDLT: 0 patients; p ¼ 1). Median evaluation time for live donors was 24 h (18–72 h). LDLT versus DDLT had similar incidence of overall postoperative complications (31% vs. 43%; p ¼ 0.66). No difference was detected between LDLT and DDLT patients regarding 1- (DDLT: 92% vs. LDLT: 86%), 3- (DDLT: 92% vs. LDLT: 86%), and 5- (DDLT: 92% vs. LDLT: 86%) year graft and patient survival (p ¼ 0.63). No severe donor complication (Dindo–Clavien 3 b) occurred after live liver donation. ALF is a severe disease with high mortality on liver transplant waiting lists worldwide. Therefore, LDLT is an attractive option since live donor work-up can be expedited and liver transplantation can be performed within 24 h with excellent short- and longterm outcomes.

Abbreviations: ALF, acute liver failure; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CIT, cold ischemia time; DDLT, deceased donor liver transplantation; EBL, estimated blood loss; ICU, intensive care unit; LDLT, live donor liver transplanta-

Introduction Acute liver failure (ALF) is a critical condition, which is characterized by rapid deterioration of liver function (1). If untreated, it results in coma and death in over 80% of cases (1). The only effective therapy is liver transplantation (LT), which offers a 1-year survival of 60–70% (2,3). The success of LT for patients with ALF is largely dependent on the availability of a life saving graft and proceeding with LT in time before the liver failure has resulted in irreversible secondary organ damage or brain death. In 2011, 394 patients with ALF were registered in the LT waiting list in the United States (4), of whom only 234 patients received a LT. It has been estimated that almost 17% of patients with ALF die on the waiting list before a liver graft becomes available (5). In addition, in many cases, the liver graft is only offered after the liver failure has progressed to an advanced stage, which is associated with decreased chances of successful LT and increased risk of permanent extrahepatic organ (in particular brain) damage. This indicates an important need for new strategies to increase the donor pool, in particular for patients with an urgent need for LT. Live donor liver transplantation (LDLT) is an attractive option to overcome this problem (2). LDLT can be performed with a short waiting time minimizing mortality for patients with ALF on the waiting list, and improving the survival chances with LT. However, considering the increased postoperative mortality rate for patients receiving a LT for ALF together with the ethical concerns for an urgent live donor work-up, it is unclear if LDLT should be used to treat patients with ALF (6). For example, the New York State Health Department Guidelines list ALF as a contraindication for LDLT (7). Unfortunately, this policy is not based on data, but rather on anecdotal cases and might not be in the best interest of our patients and their families. The lack of data in this field limits transplant

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physicians, our patients and their potential live donors to make an informed decision about LDLT as an option for treating ALF. To the best of our knowledge, evidence supporting the use of LDLT to treat ALF in adult patients is scarce in the Western Hemisphere (8), while few reports are available from Asian centers (1,9–14). Herein, we report a single center experience of adult patients suffering from ALF who were treated at our institution with LDLT. In addition, we analyzed whether the usage of LDLT in patients suffering from ALF is comparable to the outcome of patients receiving a deceased donor liver transplantation (DDLT).

Materials and Methods Study design Between April 2006 and December 2013, all adult patients treated with LT at our institution were retrospectively analyzed using a prospectively collected database. Patients suffering from ALF were identified. Prognosis assessment and therefore, indication of LT in each case of ALF was based in the Kings College Criteria (15). We compared all patients with ALF who received a LDLT (n ¼ 7) to all ALF patients receiving a DDLT (n ¼ 26) during the same period of time.

LDLT with multiple bile ducts a Roux-en-y biliary reconstruction was used. In all other cases, a duct-to-duct reconstruction was the preferred choice. We identified patients receiving antibody induction therapy, the type of agent used for the induction and the postoperative immunosuppressive regimen in each case. The baseline immunosuppression regimen was based either on Tacrolimus or Cyclosporine. In addition, we evaluated the live donor outcome, including perioperative morbidity, as well as short- and long-term complications.

Postoperative outcome Liver graft function was evaluated clinically and through biochemical markers measured daily after transplant and until discharge. Reperfusion injury was determined by peak values of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) within 48 h of transplantation. To assess graft function, we measured the decrease of INR and bilirubin posttransplantation. Patient’s postoperative ICU and hospital stay was registered in each case. All major complications within 30 days were identified in donor and recipients, and classified according to Dindo and Clavien (20). Postoperative major complications were defined as grades 3 b–5 (i.e. requiring surgical intervention under general anesthesia or ICU admission or causing death, respectively) according to this validated classification system (20). In addition, we recorded every episode of postoperative bacterial infection and pneumonia within 30 days after surgery. Incidences of biliary complications during the entire follow-up were identified for comparison between both groups. Rejection within the first year was recorded for comparison. Longterm outcome was analyzed by actuarial graft and patient survival at 1, 3, and 5-years.

Listing practices for live donation at the University of Toronto At our institution, the listing process for liver transplantation is independent from the availability of a live donor. Once listed for DDLT, all patients are encouraged to consider and discuss within their family/friends live donor liver transplantation, irrespectively of their model for end-stage liver disease (MELD) score, disease etiology, and disease severity. Being active on the waiting list for deceased donor transplantation is a requirement before any living donor discussion can be initiated. Potential donors and recipients are advised of the morbidity and mortality rate based on the program experience (16,17). Also, they are informed that, at our institution, recipients overall survival rate for LDLT and DDLT is similar (18). Of note, all recipients suffering from ALF remain active on the deceased donor liver transplant waiting list until start of the live donor surgery. The live donation work-up will be canceled if a deceased donor organ becomes available.

Statistical analysis The data was analyzed with the SPSS 22 statistical package (IBM, Chicago, IL). Data was presented as median (range) or mean  SD. Student’s t-test was used for the comparison of continuous variables when normally distributed and Mann–Whitney U-test for non-normally distributed variables. Differences between categorical variables were tested with Fishers exact test. All tests were two-tailed. Graft and patient survivals were calculated by the Kaplan–Meier method and compared with the log-rank test. Event for graft survival outcome was ‘‘graft failure’’ or ‘‘no graft failure.’’ Graft failure was defined as death or retransplantation. Outcome for patient survival was ‘‘death’’ or ‘‘alive.’’ A p value below 0.05 was considered as significant.

Results Recipient data The following recipient data were collected: age, gender, cause of ALF, time on WL, biochemical profile, MELD score, need prior to transplantation of: intensive care unit (ICU) management, mechanical ventilation support, inotropic drugs requirement to maintain adequate blood pressure, and need of dialysis because of renal failure.

Donor and perioperative data In the LDLT group, we analyzed the work-up time needed for the urgent evaluation of each donor. Work-up time was defined as the duration of time between the initiation of the first donor evaluation and the start of donor surgery. Organ procurement for deceased donation and live donor hepatectomies were performed as previously described (17,19). The following data corresponding to donor, graft, and perioperative characteristics were identified: age, gender, cold ischemia time (CIT), and warm ischemia time (WIT). We also documented the estimated blood loss and type of biliary anastomosis for each recipient procedure. In patients receiving

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From April 2006 to December 2013, 1123 adult patients received a LT at the Multi Organ Transplant Program of the Toronto General Hospital, University of Toronto. Within this group, 33 patients were transplanted because of ALF. Of note, during the same study period, 13 patients were also listed with diagnosis of ALF but did not receive a liver transplant. Of these 13 patients, three recovered without the need of transplantation and 11 patients died while waiting for a donor organ. Among the transplanted patients, seven patients received a LDLT constituting our study group (LDLT group). The LDLT group (n ¼ 7) was compared to a control group of the 26 ALF patients that were treated with a DDLT (DDLT group) during the same period of time. Median follow-up time was of 35 versus 50 months for the DDLT and LDLT patients, respectively (p ¼ 0.6). American Journal of Transplantation 2015; 15: 1591–1597

Live Donor Transplant for Acute Liver Failure Table 1: Preoperative characteristics of patients suffering from ALF that received either DDLT or LDLT DDLT n ¼ 26 1

Age (years) Male sex (%) Unknown etiology of ALF (%) INR1 Creatinine (mg/dL)1 Bilirrubin (mg/dL)1 MELD1 Pretransplant ICU admission (%) Pretransplant ICU stay (days)2 Pretransplant mechanical ventilation need (%) Pretransplant mechanical ventilation (days)2 Pretransplant inotropic drugs (%) Pretransplant dialysis (%) Time on waiting list (days)2

44 7 18 4.72 1.57 24.44 37 18 1 18 1 7 2 1

( 13) (27%) (69) ( 2.25) ( 1.23) ( 10.64) ( 6) (69) (0–7) (69) (0–7) (27) (8%) (0–10)

LDLT n ¼ 7

p

47 ( 18) 2 (28%) 3 (42) 5.93 ( 3.31) 1.01 ( 0.44) 20.35 ( 3.39) 37 ( 4) 6 (86) 1 (0–10) 4 (57) 1 (0–2) 3 (43) 0 1 (0–12)

0.59 1 0.37 0.21 0.68 0.32 0.94 0.64 0.38 0.66 0.34 0.64 1 0.6

DDLT, deceased donor liver transplantation; LDLT, live donor liver transplantation; ALF, acute liver failure; INR, international normalized ratio; MELD, model for end-stage liver disease; ICU, intensive care unit. 1 Mean and standard deviation. 2 Median and range.

Recipient’s demographics and preoperative status Both groups were comparable in terms of age and gender (Table 1). Moreover, there was no difference between the DDLT and LDLT groups regarding disease severity as measured by the biochemical profile and MELD. Prior to transplantation, ICU admission, days in ICU, mechanical ventilation support, inotropic drug requirement, and need for dialysis were similar in both groups (Table 1). Of note, in the LDLT group, four patients out of seven had Grade IV encephalopathy, requiring intubation and mechanical ventilation for airway protection. The rest of the LDLT patients were suffering of an encephalopathy Grade III at the time of transplantation. Brain edema was managed by fluid restriction and positioning of the head at 308. It is not our practice to place intracranial catheters for pressure measurements in ALF patients. In 69% (18 patients) of the DDLT group the cause of ALF was not determined, while in eight patients the etiology for ALF was identified (one case each of: Hepatitis B infection, acute Budd Chiari syndrome and Wilson’s disease; two cases of acetaminophen overdose and three cases related to drug toxicity). In the LDLT group, the cause of ALF was unknown in three patients (42%) and four patients developed ALF due to drug toxicity. Median time on waiting list was similar in the DDLT and LDLT groups (DDLT: 1 [0–10] day vs. LDLT: 1 [0–12] day; p ¼ 0.6). Donor characteristics and perioperative data Median work-up time needed for live donor evaluations was 24 (18–72) h. In five patients out of seven, the work-up was completed within 24 h. In the other two patients, the donor work-up time was 46 and 72 h. Five out of seven donors were blood related to the recipient. From them, three were parents that donated to their sons. Although evaluations of the potential live donors were done in an American Journal of Transplantation 2015; 15: 1591–1597

urgent manner, the donor evaluation processes used the same protocol established for regular live donor evaluations done at our institution for nonurgent cases. In particular, imaging studies, evaluation by a transplant psychiatrist, assessment by two surgeons and two internal medicine physicians were identical between urgent and nonurgent live donor evaluations. Of note, all psychological assessments were done in the psychiatrist’s office, away from the recipient bedside. The confidential psychiatry evaluation was done without the presence of any relative or friends. During the psychological evaluation, special emphasis was taken on the assessment of potential coercion. In addition, to reduce the potential for coercion, all donors were offered in a confidential discussion the opportunity to withdraw from the live donation process. Moreover, to avoid any indirect pressure on the donor’s decision, the clinical assessment was done by two internal medicine physicians (one hepatologist) who were not involved in the care of the potential recipient. As shown in Table 2, donor characteristics were similar between the DDLT and LDLT groups. As expected, mean CIT was significantly lower in the LDLT (DDLT: 399 min vs. LDLT: 59 min; p ¼ 0.0001), while the mean WIT was equivalent in the DDLT and LDLT groups (50 vs. 45 min, respectively; p ¼ 0.66). All of the LDLT recipients received a right lobe graft without the middle hepatic vein. As expected, bile duct reconstruction using a Roux-en-y reconstruction was significantly higher in the LDLT group (DDLT: 4% vs. LDLT: 43%; p ¼ 0.023). The use of thymoglobulin and basiliximab as induction agents was not different (p ¼ 0.39 and p ¼ 0.42, respectively) (Table 2). Tracrolimus-based immunosuppression was most commonly used in the long-term (DDLT 100% vs. LDLT 86%; p ¼ 0.21). 1593

Goldaracena et al Table 2: Donor and perioperative characteristics of ALF patients receiving a LT DDLT n ¼ 26 1

Donor age (years) Donor male sex (%) Cold ischemia time (min)1 Warm ischemia time (min)1 Estimated blood loss (mL)1 Hepaticoyeyunostomy (%) Antibody induction (%)

45 15 399 50 1229 1 23

LDLT n ¼ 7

( 17) (58) ( 171) ( 10) ( 1328) (4) (88)

40 3 59 45 1416 3 7

( 10) (43) ( 15) ( 26) ( 832) (43) (100)

p 0.46 0.41 0.0001 0.66 0.34 0.023 1

DDLT, deceased donor liver transplantation; LDLT, live donor liver transplantation. Mean and standard deviation.

1

Short-term outcome after transplantation Maximum AST and ALT levels within 48 h as markers of preservation/reperfusion injury were similar in LDLT and DDLT patients (Table 3). Liver function was determined by the INR and bilirubin decrease within the first week after transplantation (pretransplant and day 7 difference). Pretransplant INR and bilirubin levels were equally distributed in both groups (Table 1). On day 7, the INR of DDLT and LDLT recipients had normalized (DDLT: 1.29  0.25 vs. LDLT: 1.10  0.10; p ¼ 0.06). The INR decrease in DDLT (3.28  2.26) and LDLT patients (4.83  3.26) was similar during this time (p ¼ 0.14). Similarly, mean bilirubin levels by day 7 were comparable (DDLT: 6.14  7.13 mg/dL vs. LDLT: 4.73  2.57 mg/dL; p ¼ 0.63) with a comparable decrease in DDLT (18.18  10.05 mg/dL) and LDLT (3.85  3.15 mg/dL) patients within the first week (p ¼ 0.13) (Table 3).

Incidence of bacterial infections and pneumonia within the first 30 days of transplant were the same in both groups (Table 3). The Incidence of major complications (Dindo– Clavien 3 b, 4, or 5) was similar in the LDLT and DDLT groups (DDLT: 31% vs. LDLT: 43%; p ¼ 0.66). The 30-day mortality after transplantation was comparable between the DDLT and LDLT groups (DDLT: 2 patients vs. LDLT: 1 patient; p ¼ 0.52). In the DDLT group the two patients that died, suffered their death in the 2nd and 3rd day after transplantation because of progressive cerebral edema resulting in brain death. Of note, both patients were in deep coma before LT. In the LDLT group, the only death occurred on the 5th postoperative day. This patient was a 22-year-old female with ALF of unknown etiology. At admission, she was severely encephalopathic and required intubation and mechanical ventilation support, as well as high doses of inotropic drugs to maintain an adequate blood pressure.

Table 3: Postoperative outcome following LT in ALF patients

1

AST peak (U/L) ALT peak (U/L)1 INR peak1 Bilirrubin peak (mg/dL)1 INR decrease (preTx-day 7)1 Bilirrubin decrease (preTx-day 7) (mg/dL)1 Dindo–Clavien 3 b, 4, 5 within 30 days (%) Bacterial infections within 30 days (%) Bacterial pneumonia within 30 days (%) 30-day mortality (%) ICU stay (days)2 Hospital stay (days)2 Biliary complications within 1 year (%) Biliary strictures within 1 year (%) Biliary leaks within 1 year (%) Graft rejection within first year (%) Re-tx (%) 1-/3-/5-year graft survival (%) 1-/3-/5-year patient survival (%)

DDLT n ¼ 26

LDLT n ¼ 7

p

1701 ( 1733) 1098 ( 1100) 2.92 ( 1.56) 11.98 ( 11.69) 3.28 ( 2.26) 18.18 ( 10.05) 8 (31) 5 (19) 3 (12) 2 (8) 3 (1–52) 13 (2–164) 2 (8) 2 (8) 0 9 (35) 0 92 (all time points)

579 ( 368) 499 ( 323) 2.69 ( 1.03) 13.91 ( 8.65) 4.83 ( 3.26) 15.55 ( 3.15) 3 (43) 3 (43) 1 (14) 1 (14) 4 (2–6) 21 (4–43) 3 (43) 1 (14) 2 (29) 2 (29) 0 86 (all time points)

0.086 0.064 0.792 0.509 0.14 0.13 0.66 0.32 1 0.52 0.28 0.23 0.052 0.52 0.042 1 – 0.63

DDLT, deceased donor liver transplantation; LDLT, live donor liver transplantation; AST, aspartate aminotransferase; ALT, alanine aminotransferase; INR, international normalized ratio; ICU, intensive care unit. 1 Mean and standard deviation. 2 Median and range.

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Following an uneventful LDLT, she developed a severe systemic inflammatory response syndrome and multiorgan failure. DDLT and LDLT recipients had the same ICU (DDLT: 3 [1–52] vs. LDLT: 4 [2–6] days; p ¼ 0.28) and hospital stay (DDLT: 13 [2–164] vs. LDLT: 21 [4–43] days; p ¼ 0.23) after transplantation. We compared the incidence of biliary complications occurring at any time point after transplantation. A higher incidence of biliary complications was observed in the LDLT versus DDLT group (DDLT: 2 vs. LDLT: 3; p ¼ 0.052). Of note, in the LDLT group, two patients developed a bile leak while one patient had an anastomotic stricture. The bile leaks were managed by drainage alone and subsequently stopped. The only biliary stricture in the LDLT group occurred 9 months after transplantation and was corrected by surgical revision of the biliary anastomosis. In the DDLT group, both biliary complications were strictures, occurring, one within the first 30 days and the other 9 months after transplantation. The first case was successfully managed with an endoscopically placed stent, while in the other case the stricture was corrected surgically 1 year after LT.

Long-term outcome The incidence of graft rejection occurring within the first year was similar between both groups (DDLT: 35% vs. LDLT: 29%; p ¼ 1). None of the patients in either group needed a retransplantation. The actuarial 1-, 3-, and 5-year graft and patient survival was similar for DDLT (92%, 92%, 92%) and LDLT (86%, 86%, 86%) patients (p ¼ 0.63) (Figure 1).

Live donor outcomes With a median follow-up time of 58 months, all donors are enjoying good health and returned to their baseline activities. None of them has required psychological support at any time point after the donation. Median hospital stay for live donors was of 6 (1–9) days. None of the donors were admitted to ICU during their postoperative course. No major complication occurred within 30 days after donor surgery (Dindo–Clavien 3 b). Only one patient presented a minor complication during the first 30 days after transplantation. He developed a urinary tract infection that was managed as an outpatient with oral antibiotics. During the entire follow-up period, only one

Figure 1: Graft and patient survival for ALF patients following either DDLT or LDLT (p ¼ 0.63).

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live donor developed an incisional hernia 1 year after his surgery. This was corrected surgically without complications and he is nowadays fully reincorporated to his normal activities.

Discussion This is the largest single center series reporting on the use of LDLT for the treatment of ALF in adult patients in the Western Hemisphere. We demonstrate that LDLT can be performed with excellent outcomes in patients with ALF and with minimal donor morbidity. Organ shortage has resulted in a waiting list mortality of 10–40%, triggering the interest of increasing the donor pool by live liver donation. Patients suffering from ALF have a dismal prognosis without LT (21). In addition, the need for liver transplant is particular urgent in this patient group since the disease can progress within hours to coma and brain death. Therefore, LDLT is an attractive option since live donor work-up can be expedited and liver transplantation can be performed within 24 h or less if needed. In our series, the median time between start of donor workup and transplant was 24 h, and the shortest donor workup was performed within 18 h. Reports on LDLT for the treatment of ALF in adult patients come mainly from Asia (1,9–14). Data regarding LDLT for the treatment of ALF form Western centers is scarce. In 2008, Campsen et al (8) published a multicenter experience of living liver donation for the treatment of ALF in the United States. Data were extracted from the Adult-to-Adult Living Donor Liver Transplantation Cohort study. The authors reported 10 adult patients with ALF who were treated with LDLT at nine different centers over a period of 9 years. Unfortunately, detailed information about patient characteristics and treatment regimen were not available from this series. The overall recipient survival was 70% with a 1-year mortality of 30%. In addition, the authors reported a living donor overall complication rate of 50%. A comparison to a DDLT control group was not performed. In 2012, Yamashiki et al (13) published the largest series of LDLT for the treatment of ALF. The authors reported the long-term outcome of 209 patients with ALF who received LDLT. The data was extracted from a Japanese National Survey of 1090 ALF patients over a period of 11 years. The authors reported a 1- and 5-year survival rate of 79 and 74%, respectively. Unfortunately, the authors did not report postoperative recipient complications and donor outcomes and no comparison to DDLT was available. In the present study, we demonstrated that LDLT can be performed in ALF patients with excellent short- and longterm outcomes. Moreover, postoperative graft function, major complication rates, 30-day mortality and survival were similar after LDLT when compared to patients receiving a DDLT (Table 3). The availability of deceased 1596

donor grafts for patients with ALF varies widely in the Western world. Depending on the clinical status of the ALF patient, the donor work-up can be performed at an early stage, and LDLT can be delayed under close observation if a deceased donor liver offer is likely to occur within 24 h. In contrast, rapid progressing ALF might warrant immediate LDLT to avoid permanent neurologic damage or death. Despite the urgency of the disease, the donor workup cannot be compromised and the timing of the donor evaluation has to be adjusted to the donor. In the present study, we did not observe a decreased waiting time in the LDLT group. We believe this is due to families opting for LDLT after they observe a clinical deterioration of the recipient. However, our results indicate, that if needed, live donor work-up time can be performed in less than 18 h. The limited time for the live donor workup in the setting of ALF raises the question of possible coercion of potential live donor candidates. In our series, we performed a complete donor work-up in a shorter period of time. The transplant psychiatrist as well as two independent internal medicine physicians and two surgeons evaluated the live donor candidate in single person interviews for signs of coercion. Despite all efforts, coercion cannot be excluded in the setting of living liver donation for ALF. The short time period for the donor evaluation and the severity of the liver disease with possible death within days places the live donor candidate under considerable pressure. In our series, five out of seven donors were blood related to the recipients making the decision a much easier one. However, we believe that is important to offer the potential live donor a confidential way to opt out of the donation process by providing a medical reason to the recipient and the family. In addition, all donor interviews should be performed on a private setting away from the recipient treatment side. As previously published (22), it is our policy to offer LDLT to every patient on the liver transplant waiting list, independently of their disease severity or etiology. However, donor and recipients are properly advised of the morbidity and mortality rates as well as of the long-term outcomes at our program so that they can make an informed decision about whether they opt for live donation or wait for a deceased donor. Based on the present and previous analysis (16,22), we believe that is appropriate to continue to offer LDLT to ALF patients, since the survival achieved is similar to the one obtained with DDLT (1, 3–5 year survival for DDLT: 92% vs. LDLT: 86%; p ¼ 0.63) and donor morbidity can be kept to the minimum. Our study has several limitations. It consists of a small sample size and a retrospective data analysis. In addition, the study was performed in a large LDLT program performing more than 40 adult-to-adult LDLT per year, and the outcome might not be generalizable to all centers. We compensated for these shortcomings by having a single center patient population, who was treated with a uniform pre and posttransplant regimen. In addition, we provide a DDLT American Journal of Transplantation 2015; 15: 1591–1597

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control group for comparison and all transplants were performed in a modern era. We believe that, despite being a small sample size, comparing live versus deceased donors provides of important information that determines risks and benefits of the procedure. The need for LDLT for patients with ALF varies from the transplant region and the availability of deceased donor grafts. The aim of our study was to determine that LDLT can be performed safely with good donor recipient outcome. The decision to offer live donation for patients with ALF has to be based on local deceased donor availability and center experience. In conclusion, our data suggest that LDLT is an excellent treatment option for ALF. The high mortality of ALF patients on the LT waiting list and the rapid disease progression makes LDLT an ideal option for this patient population. Patients with ALF and their families should be offered the opportunity to proceed with LDLT.

Disclosure The authors of this manuscript have no conflict of interest to disclose as described by the American Journal of Transplantation.

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7. Novello A. New York State Committee on quality improvement in liver living donation. Troy, NY: New York State Health Department; 2002. 8. Campsen J, Blei AT, Emond JC, et al. Outcomes of living donor liver transplantation for acute liver failure: The adult-to-adult living donor liver transplantation cohort study. Liver Transplant 2008; 14: 1273–1280. 9. Akamatsu N, Sugawara Y. Acute liver failure and living donor liver transplantation. Hepatol Res 2008; 38: S60–S71. 10. Hashikura Y. Living donor liver transplantation for patients with fulminant hepatic failure. Hepatol Res 2008; 38: S56–S59. 11. Ikegami T, Taketomi A, Soejima Y, et al. Living donor liver transplantation for acute liver failure: A 10-year experience in a single center. J Am Coll Surg 2008; 206: 412–418. 12. Park SJ, Lim YS, Hwang S, et al. Emergency adult-to-adult livingdonor liver transplantation for acute liver failure in a hepatitis B virus endemic area. Hepatology 2010; 51: 903–911. 13. Yamashiki N, Sugawara Y, Tamura S, et al. Outcomes after living donor liver transplantation for acute liver failure in Japan: Results of a nationwide survey. Liver Transplant 2012; 18: 1069–1077. 14. Yuan D, Liu F, Wei YG, et al. Adult-to-adult living donor liver transplantation for acute liver failure in China. World J Gastroenterol 2012; 18: 7234–7241. 15. O’Grady JG, Alexander GJ, Hayllar KM, Williams R. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology 1989; 97: 439–445. 16. Adcock L, Macleod C, Dubay D, et al. Adult living liver donors have excellent long-term medical outcomes: The University of Toronto liver transplant experience. Am J Transplant 2010; 10: 364–371. 17. Cattral MS, Molinari M, Vollmer CM Jr, et al. Living-donor right hepatectomy with or without inclusion of middle hepatic vein: Comparison of morbidity and outcome in 56 patients. Am J Transplant 2004; 4: 751–757. 18. Reichman TW, Katchman H, Tanaka T, et al. Living donor versus deceased donor liver transplantation: A surgeon-matched comparison of recipient morbidity and outcomes. Transplant Int 2013; 26: 780–787. 19. McCormack L, Selzner M, Clavien P-A. The transplant operation. In: Killenberg P, Clavien P-A, editors. Critical care of liver transplantation. Malden, MA: Blackwell Publishing Ltd., 2006; p. 229–241. 20. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: A new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004; 240: 205–213. 21. Kilic M, Aydin U, Noyan A, et al. Live donor liver transplantation for acute liver failure. Transplantation 2007; 84: 475–479. 22. Selzner M, Kashfi A, Cattral MS, et al. Live donor liver transplantation in high MELD score recipients. Ann Surg 2010; 251: 153–157.

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Live donor liver transplantation: a valid alternative for critically ill patients suffering from acute liver failure.

We report the outcome of live donor liver transplantation (LDLT) for patients suffering from acute liver failure (ALF). From 2006 to 2013, all patient...
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