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Volume: 14 Issue: 2 April 2016

FULL TEXT

ARTICLE
Lessons Learned From Review of a Single Center Experience With 500 Consecutive Liver Transplants in a Region With Insufficient Deceased-Donor Support

Objectives: We present here the outcomes of our first 500 liver transplants and discuss the lessons learned during this time.

Materials and Methods: We retrospectively analyzed the first 500 consecutive transplants within the listing criteria of the United Network for Organ Sharing, with recipients and donors with minimum 1-year follow-up. Patient survival and donor complications were analyzed for 31 liver transplant recipients with hepatocellular carcinoma beyond the Milan criteria who had transplant performed during the same time.

Results: Between August 2006 and March 2013, there were 519 liver transplants performed in 500 patients (365 adult, 135 pediatric). There were 394 living-donor and 125 deceased-donor liver transplants. In addition, 31 adult liver transplants were performed in patients with hepatocellular carcinoma beyond Milan criteria (22 living-donor and 9 deceased-donor transplants). The main cause of chronic liver failure was biliary atresia in pediatric patients (30.4%) and chronic hepatitis B infection in adults (35.6%). The complication rate for primary nonfunction was 3.8%, overall biliary complications 24.0% (significantly higher after adult living-donor liver transplant, 30.3%), hepatic artery thrombosis 1.6%, portal vein thrombosis 3.0%, retransplant 3.8%, acute cellular rejection 29.6%, and bacterial infection 39.4%. Overall 1-, 3-, and 5-year patient survival rates in the first 500 consecutive transplants performed on recipients within United Network for Organ Sharing listing criteria were 87.8%, 85.0%, and 78.6%; for hepatocellular carcinoma patients beyond the Milan criteria, survival rates were 71.9%, 52.5%, and 38.2%.

Conclusions: In regions without a sufficient number of deceased donors, living-donor liver transplant, with its associated problems, is the only alternative to deceased-donor liver transplant. Liver transplant requires teamwork, with all players working well together for a successful outcome. The important keys to success in liver transplant include decision-making, timing, surgical skills, experience, and close follow-up.


Key words : End-stage liver disease, Hepatocellular carcinoma, Living-donor transplant

Introduction

Currently, liver transplant (LT) is the only definitive treatment for acute liver failure, end stage chronic liver disease, and selected cases of malignancies and metabolic disorders. Following the first deceased-donor liver transplants performed by Dr. Thomas Starzl in the 1960s,1 many developments have been made in liver preservation,2 surgical procedures,3 and clinical and medical follow-up. Following the use of cyclosporine for clinical immunosuppression in transplant recipients in the early 1980s by Sir Roy Calne, LT, previously considered an experimental therapy, gained clinical therapeutic status.4 In the past 30 years, the number of LTs performed has increased annually, but due to increasing numbers of patients requiring LT and a shortage of deceased donors, a significant number of patients die on waiting lists worldwide.5,6 Living-donor liver transplant (LDLT) is a safe procedure and the only alternative to deceased-donor liver transplant (DDLT) in regions that do not have enough deceased donors to meet the needs of their waiting lists.

The current study consists of our center’s exper-ience with the first 500 consecutive LTs performed within United Network for Organ Sharing (UNOS) listing criteria and 31 consecutive LTs performed in recipients with the diagnosis of hepatocellular carcinoma (HCC) beyond the Milan criteria, including recipient survival and donor outcomes.

Methods and Patients

Patients
Between August 2006 and March 2014, there were 672 adult and pediatric LTs performed from deceased (n = 144) and living donors (n = 528) at the Organ Transplantation Center of Memorial Sisli Hospital, Istanbul, Turkey. The first 500 consecutive transplants were performed within UNOS listing criteria, and recipients and donors with minimum 1-year follow-up were analyzed retrospectively. In addition, patient survival in 31 consecutive LT recipients with HCC beyond Milan criteria and complications in their living donors during the same period were analyzed.

Organ procurement and preservation and surgical technique
The operations for both DDLT (whole, split) and LDLT (right, left, left lateral) were performed by the same surgical team. Deceased-donor operations were performed with en bloc removal of the liver. Living-donor and recipient operations were started simultaneously to minimize cold ischemia time. University of Wisconsin-Belzer solution was used as a preservation solution. Iliac vein graft from a deceased donor or polytetrafluoroethylene vascular graft (6 to 10-mm Gore-Tex vascular graft, [Gore & Associates, Inc., Newark, DE, USA]) was used during living-donor operations for back table reconstruction of the middle hepatic vein or branches of the middle hepatic vein. In all DDLT cases, the recipient surgical procedure was performed using a standard piggyback technique without venovenous bypass. Hepatic veins were anastomosed to the inferior vena cava using either a triangular or diagonal opening in LDLT cases. Arterial reconstruction was performed with magnification surgical loupes in DDLT cases and under a surgical microscope in most LDLT cases. Doppler ultrasonography was performed for examination of arterial, portal, and venous flow in the liver before biliary anastomosis and also before closing the abdomen. Bile duct reconstruction was performed with duct-to-duct or Roux-en Y anastomosis according to primary illness and bile duct number and structure. In some LDLT cases, a short transanastomotic silicone stent made from the tip of a catheter (4.2- or 6.6-French Broviac catheter, Bard Access Systems, Salk Lake City, UT, USA) was used during Roux-en Y hepaticojejunostomy, and a T-tube was used in a few cases.

Postsurgical care and medical treatment
In all LT recipients, extubation was attempted prior to leaving the operating room. All recipients and donors were taken to the intensive care unit (ICU) after surgery. After 1 day in the ICU, patients were transferred to the transplant unit depending upon clinical improvement. The LDLT recipients underwent Doppler ultrasonography examination of arterial, portal, and venous flow in the liver twice daily for the first 3 postoperative days and once daily on postoperative days 4 and 5. In DDLT recipients, Doppler ultrasonography was performed once daily for the first 5 postoperative days.

In all cases, immunosuppression consisted of tacrolimus, mycophenolate mofetil, and steroids. All patients with platelet count > 100 × 109/L and international normalized ratio < 2 received aspirin on postoperative day 1. For patients with liver failure due to hepatitis B virus (HBV), hepatitis immunoglobulin and antiviral treatment were administered. Antiviral treatment and prophylaxis against Pneumocystis were continued for 6 months posttransplant in children and 3 months in adults. In some cases, immunosuppressive treatment was changed due to adverse events or clinical reasons. All patients received follow-up by the same medical team.

Statistical analyses
Statistical evaluation included patient characteristics, source of transplanted organs, surgical details, postoperative complications, and 1-, 3-, and 5-year patient survival rates. Software was used for statistical analysis (SSPS for Windows, Version 13, SPSS Inc., Chicago, IL, USA). Survival rates were estimated by Kaplan-Meier method. The log-rank test was used for comparison of factors including age, Pediatric End-stage Liver Disease/Model for End stage Liver Disease (PELD/MELD) score, body weight, graft weight:body weight ratio (GWBWR), and within Milan criteria/beyond Milan criteria for HCC. Indications for transplant were analyzed in terms of patient survival. Values of P < .05 were considered significant.

Results

Between August 2006 and March 2013, there were 519 LTs performed in 500 patients within UNOS listing criteria, including 394 LDLT and 125 DDLT in 365 adult and 135 pediatric patients. There were more male than female patients (male, 63.8%). The mean age of adult recipients was 48.8 years (range, 18.3 to 71.5 y) and mean age of pediatric recipients was 4.7 years (range, 0.4 to 17.9 y). There were 46 pediatric recipients (34.1%) who were aged < 1 year and 34 adult recipients (9.3%) were older than 65 years. Mean adult body weight was 74.5 kg (range, 40 to 159 kg) and mean body mass index (BMI) was 26 kg/m² (range, 15.8 to 46.5 kg/m²). In pediatric recipients, mean body weight was 17.6 kg (range, 4.5 to 75 kg) and mean BMI was 17.6 kg/m² (range, 10.8 to 30.7 kg/m²). In the pediatric patients, 61 patients (45.2%) weighed < 10 kg. There were 54 patients (10.8%) who came to our center from other countries for LT. The mean physiologic PELD/MELD score was 16.1 in pediatric patients, and mean physiologic MELD score was 17.0 in adult patients. At transplant, 28.9% pediatric recipients (n = 39) had a physiologic high PELD/MELD score > 25, and 14.8% adult recipients (n = 54) had high physiologic MELD score (Table 1).

The main causes of chronic liver failure in pediatric recipients in our patient population included biliary atresia (30.4%) and progressive familial intrahepatic cholestasis (PFIC) (12.6%). The most common diagnoses in adults were chronic HBV infection (35.6%), chronic hepatitis C (HCV) infection (15.7%), alcoholic cirrhosis (10.4%), and cryptogenic cirrhosis (10.4%). The acute hepatic failure rate was 3.4% in all recipients and higher in pediatric patients (6.7%). The HCC was present in 20.6% adult recipients, and hepatoblastoma was present in 4.4% pediatric recipients. Mean waiting time to transplant after placement on the waiting list was 173.4 days for DDLT (range, 17 to 777 d) and 60.5 days for LDLT (range, 1 to 773 d). There were 10 simultaneous liver/kidney transplants (2.0%) performed in 6 pediatric and 4 adult patients from 9 living donors and 1 deceased donor in this series (Table 1). In 3 cases (1 adult and 2 pediatric), we performed the simultaneous liver/kidney transplant by using the same living donor’s kidney and liver graft (1 right lobe, 2 left lateral segment grafts). In 6 cases (4 pediatric and 2 adult), we used the kidney and liver grafts from different living donors. In 1 case (adult), transplant was performed from the same deceased donor. The only serious donor complication was early reoperation in the 1 kidney/left lateral segment living donor due to right donor nephrectomy fossa bleeding. Another 2 donors were treated because of wound infection. The etiology was primary oxaluria in 5 cases (4 pediatric and 1 adult), chronic HCV in 3 cases (adults), congenital hepatic fibrosis in 1 case (pediatric), and cryptogenic cirrhosis with chronic renal failure in 1 case (pediatric). There were 4 patients (2 adult and 2 pediatric) who died because of sepsis after simultaneous liver/kidney transplants. Overall survival was 60%. There were 5 split livers used, including 3 split right lobes for adults and 2 split left lateral segments for pediatric patients. In LDLT recipients, 271 right lobe grafts, 25 left lobe grafts, and 98 left lateral segment grafts were used. All left lateral segment grafts were used for pediatric patients (Table 2).

The mean age of deceased donors was 10.5 years (range, 0.4 to 32 y) for pediatric patients and 42.9 years (range, 7 to 80 y) for adults. There were 54 female deceased donors (43.2%) and 71 males (56.8%). Mean BMI of deceased donors was 24.5 kg/m² (range, 13.7 to 56.2 kg/m²). Mean age of living donors was 34.0 years (range, 18 to 61 y), mean BMI was 32.3 kg/m² (range, 17.5 to 40 kg/m²), and 177 living donors (44.9%) were female. Only 2.8% (n = 11) living donors were unrelated to the recipient. Mean cold ischemia time for DDLT was 6.7 hours (range, 3 to 17 h) and for LDLT was 1.3 hours (range, 0.3 to 7 h). Mean duration of operation was 7.9 hours (range, 3.5 to 17.3 h), and mean blood transfusion was 1.6 units (range, 0 to 22 units) during pediatric LT and 8.6 units (range, 0 to 81 units) during adult LT. Median ICU stay was 2 days (range, 1 to 125 d), and median hospital stay was 15 days (range, 7 to 207 d).

In this series, 84.6% (n = 423) patients were extubated by the end of the first postoperative day following LT (Table 1). Patient loss in the first 3 months after LT was significantly higher in patients who could not be extubated within the first 24 hours postoperatively (41.6% vs 3.8% in patients extubated within 24 hours).

The total retransplant (ReTx) rate in this series was 3.8% (n = 19). Early ReTx rate within the first month after transplant was 2.8% (n = 14). The acute cellular rejection rate was 29.6% (Table 3). The rate of primary nonfunction (PNF) was 3.8% (n = 19). The total biliary complication rate was 24.0% (n = 120), with a significantly higher rate after adult LDLT (30.3%). The hepatic artery thrombosis (HAT) rate was 1.6% (n = 8), and the rate of portal vein thrombosis (PVT) was 3.0% (n = 15). Ninety-seven patients (19.4%) underwent reoperation within the first month after transplant (Table 4).

Overall 1-, 3-, and 5-year patient survival rates in our first 500 consecutive LTs performed within UNOS listing criteria were 87.8%, 85.0%, and 78.6%. The 1-, 3-, and 5-year patient survival rates in adult recipients were 89.0%, 85.2%, and 78.0%, and in pediatric recipients were 84.4%, 84.4%, and 82.0%. The 1-, 3-, and 5- year patient survival rates after DDLT were 85.7%, 84.8%, and 75.4% and after LDLT were 88.0%, 84.9%, and 82.5 (Table 5 and Figure 2). In transplants performed for HCC within Milan criteria, the 1-, 3-, and 5-year patient survival rates were 92.4%, 87.3%, and 84.1%. With the diagnosis of HCC beyond Milan criteria, transplant was performed only after lengthy discussions with recipient and donor, and the survival rate was analyzed separately. Patient survival rates at 1, 3 and 5 years in this group were 71.9%, 52.5%, and 38.2%. Of the 31 patients beyond the Milan criteria, 22 were from living donors and 9 from deceased donors. Most deceased-donor transplants in this group were performed before 2009 and most were within University of California San Francisco criteria. All 9 deceased-donor liver grafts were with high donor risk index and they were highly risky grafts. Other centers in the country refused to use them, and these grafts were offered to our center. We offered these grafts to the HCC patients beyond Milan criteria who did not have any living donor candidate. Outcomes, benefits, and risks were discussed with the recipient and family.

There were 416 donors analyzed, including 22 donors who donated to a recipient with HCC beyond Milan criteria. The overall complication rate was 17.1% (n = 71). According to the Dindo-Clavien score, 36 donors (8.7%) had grade 1; 14 (3.4%) grade 2; 19 (4.6%) grade 3; and 2 (0.5%) grade 4a complications (Table 6).

Discussion

During the past 3 decades, LT has become the primary therapy for patients with end-stage liver disease, acute hepatic failure, HCC with cirrhosis, metabolic disease, and some specific malignancies. According to the Turkish Ministry of Health-National Organ and Tissue Transplantation System (TODBS), chronic HBV infection still is the main cause of adult chronic end-stage liver disease in Turkey, as observed in our center (Table 1). However, in the United States and Europe, chronic HCV infection and alcohol are the most common causes.5,7 The primary cause of liver failure in our pediatric recipients was biliary atresia (30.4%) (Table 1), which is similar to other regions in the world.5,7-10

In the early days of transplant, deceased donors were the only donor resource. With time, due to the growing gap between the number of available deceased donors and patients requiring LT, the transplant community developed new donor resources, resulting in use of split livers, expanded-criteria donors, donation after circulatory death (DCD), and living donors. In 2002, UNOS (United States) introduced a new liver allocation system using PELD/MELD scores with the principles of equity, justice, utility, and benefit. The UNOS also developed listing criteria with the same aims, which now are widely accepted worldwide.

Despite ongoing development of solutions to the donor liver shortage around the world, the gap between donor availability and patients in need of LT continues to increase. According to TODBS, the number of LTs performed in Turkey increased from 905 LTs in year 2011 to 1248 LTs in year 2013. However, the number of patients dying on the waiting list increased 40% during the same time in Turkey, similar to our center (20%) and around the world.5,6 The number of LDLTs increased, while the number of DDLTs did not change in Turkey during the same time as in our center (Figure 1). The number of brain death declarations increased to 1700 in year 2013, but only 379 brain deaths (22%) were approved for deceased donation according to the TODBS database. Countries and centers that do not have sufficient support from the deceased-donor pool have begun solving this problem with LDLT, with acceptable recipient and donor results.

Following the first successful LDLT performed in a pediatric patient in 1989 by Strong and coworkers11 from Australia and in an adult patient in 1992 by Haberal and associates12 from Turkey, living donors became a serious alternative resource for liver grafts. The LDLT also has many advantages compared with other technical variant grafts. Time to LT can be easily organized according to recipient status, markedly minimizing waiting time and post-operative mortality risk.13,14 Other advantages include the quality of the liver and shorter cold ischemia times. However, it is imperative to carefully balance donor and recipient risks. The LDLT presents a serious risk to the donor, but allows the donor to actively participate in saving the life of their loved one.13 In our living donors, 97.2% were related donors with mean age 33.9 years (range, 18 to 61 y).

The LDLT survival rates have been similar to survival rates in DDLT recipients, for both adult and pediatric populations,8,9,14-17 with similar 1-, 3-, and 5 year survival rates compared to United States data in both LDLT and DDLT (Table 5). The most important factor affecting recipient outcome is recipient PELD/MELD score at the time of LT. Worse outcomes are observed in patients with PELD/MELD scores > 25, and more so in patients with scores > 35.5,15,18 Studies have shown that patients on the waiting list with a high MELD score can develop pretransplant renal dysfunction, which increases the risk of renal failure after transplant.19-21 In addition, a correlation was noted between high PELD/MELD score and increased length of posttransplant hospitalization.18,22-25 Our experience was similar to the results reported in the literature. In our series, 93 (18.6%) patients (25%) had a high physiologic PELD/MELD score (≥ 25). In our pediatric recipient group, 39 patients (28.9%) had a high PELD/MELD score.

Patient death in the first 3 months after transplant in our high PELD/MELD pediatric recipient group was 25%, which was significantly higher than the 4.2% observed in the low PELD/MELD group (< 25). The 1- and 3-year survival rates are the same in our pediatric recipient group (84.4%) and 5 year survival is 82.0%, revealing that we are losing most of our physiologic high PELD/MELD pediatric recipients within the first 3 months after transplant. In our adult recipients, there was a lower frequency of patients with high MELD score (n = 60; 16.4%) than in the pediatric group. Early adult patient death in the high MELD group was 13.3%, which also was higher than in the low MELD group (8.5%); however, it is not as high as that observed in the pediatric group. The best survival rates we observed were the 1-, 3-, and 5-year survival rates in adults with HCC within Milan criteria whose physiologic MELD scores were low (92.4%, 87.3%, and 84.1%). These results suggest that in regions without a sufficient number of deceased donors such as our country, it is important to have these pretransplant patients followed at a transplant center so decisions regarding timing of liver transplant can be made prior to the development of complications that result in an increased risk of death after LT.

In 2 large, single-center reports, the requirement for ReTx due to long-term liver allograft failure occurred in 14% to 23% patients.26,27 Conversely, according to UNOS records in 49 288 recipients from January 1, 2002 through October 31, 2011, the ReTx rate was 5.5% (n = 2714), with a 2.1% (n = 1056) rate of ReTx in the first monthafter transplant; the main reasons within the first month posttransplant were HAT and PNF.28 The European Liver Transplant Registry (ELTR) reported a ReTx rate of 7% (n = 5596), according to records of 83 816 recipients from May 1968 through December 2009. The most common causes of ReTx in the ELTR group were vascular complications (27%) and PNF (25%).7 The overall ReTx rate in our series was 3.8% (n = 19), with 2.8% (n = 14) rate of early ReTx in the first month after transplant. The main cause in our series was PNF (n = 10) (Table 3).

The risk of not finding a suitable donor liver if ReTx is required is an added concern in a country with a low number of deceased donors, and precautions must be taken. There is no certainty that complications such as PNF can be avoided, and for that reason, when making the decision to perform LT, there must be serious discussion with the recipient about both living- and deceased-donor grafts. Liver quality, cold ischemia time, technical issues, GWBWR, and anatomic variations must be discussed for both living- and deceased-donor grafts. Earlier in our series, infection was the most common cause of death, and PNF was the second most common cause of death early after transplant. Our PNF rate was 3.8% (n = 19); we were not able to find a suitable organ from a deceased or living donor for 9 of these patients (47.4%), and these 9 patients died awaiting ReTx.

However, when posttransplant vascular complications occur, there are treatment options available. The HAT remains a major cause of graft loss after LT, especially in pediatric recipients with segmental grafts (4% to 15%).29-32 In our series, HAT occurred in 8 patients (1.6%), including 7 LDLT patients (5 adult, 2 pediatric) and 1 DDLT patient (pediatric). Microvascular surgery using a surgical microscope was introduced by the Kyoto group in LDLT.33 Emre and associates reported no instance of HAT in 48 consecutive segmental LTs using anastomosis with magnification loupes by a single surgeon.13 In our series, microsurgical technique with a surgical mic-roscope was used in most LDLTs, and magnification loupes were used in the most DDLTs, depending on the diameter of the graft hepatic arteries during hepatic arterial reconstruction. We believe that the delicate microsurgical technique and no-touch anas-tomosis are more important than the magnification tools for graft patency.

The PVT is another important vascular com-plication resulting in graft loss following LT. The PVT develops in 2% to 10% patients, usually early after transplant, and is more common in pediatric recipients and segmental liver recipients than adult recipients of whole liver grafts.13,14,29,34,35 Overall, the frequency of PVT in our series was 3.0% (n = 15). There was no PVT reported in our adult whole DDLT recipients, but the LDLT recipients had a PVT rate 1.9% (n = 5). The PVT was seen in 7.4% (n = 10) of our pediatric recipients, with a higher rate in pediatric DDLT. In pediatric recipients, the diameter of the portal vein decreases due to reduced flow in children with portal hypertension. In addition, the length and diameter of the portal vein is more important in left lateral segment LT due to a long gap and size discrepancy in infants. By achieving technical perfection in pediatric recipients, decreasing GWBWR, and avoiding redundancy, kinking, or stretching, the risk of PVT can be reduced. The PVT can be avoided by measuring mean airway, peak inspiratory, and intra-abdominal pressure prior to closing the abdomen in pediatric recipients with GWBWR > 3%. In patients with high intra-abdominal pressure at our center, only the skin is closed and the recipient is allowed to heal after hernia repair. Color Doppler ultrasonography examination of the hepatic vascular flow also is performed before and after closing the abdomen for early diagnosis and may minimize the risk of vascular thrombosis.

As previously stated, if vascular complications necessitate ReTx, it is difficult to locate a suitable donor liver for ReTx. For this reason, early diagnosis and treatment of vascular complications is very important to prevent graft loss. We are doing close follow-up with Doppler ultrasonography of liver arterial, portal, and venous flow. With timely diagnosis and early surgical reintervention, 73.3% (n = 11/15) grafts have been saved after early PVT and 75% (n = 6/8) grafts have been saved after early HAT in our series. Patient death occurred in 8.7% (n = 2/23) patients who developed early vascular complications.

Biliary complications remain the Achilles’ heel of LT, contributing to increased costs, posttransplant morbidity, graft loss, and patient loss. The overall incidence of biliary complications ranges from 5% to 40%. Biliary complications are the result of aberrant donor anatomy, biliary ischemia, and surgical technique. In addition, complication rates vary by graft type. Living-donor and DCD grafts are at significantly higher risk for biliary complications.36-41 In our series, the overall bile leak rate was 11.6% and the overall biliary stricture rate was 16.4%. When we evaluated the subgroups, the highest rates were observed in the adult LDLT group, with a bile leak rate 13.1% and a biliary stricture rate 23.6% (Table 4). In our series, 5 patients died due to biliary complications; 3 patients died because of sepsis due to abdominal infection which may have been exacerbated by the bile leak, and the other 2 patients underwent ReTx due to treatment-resistant biliary stricture but died from sepsis. We agree with the opinion previously described in the literature14,40,42 that careful surgical technique minimizing perivascular ductal tissue dissection, careful inspection and surgical repair of the bile ducts at the cut surface of the graft, and wide use of Roux-en-Y hepaticojejunostomy for bile duct anastomosis are key elements responsible for the reduction in biliary complications observed in our series of LDLT.

Another issue currently in discussion is HCC in liver transplant. From 60% to 90% HCC diagnoses are associated with underlying cirrhosis depending upon region, and the main risk factors in our recipients are chronic HBV and HCV infection with chronic alcohol abuse.43 In our series, 106 LTs were performed for HCC with cirrhosis and 82.1% recipients had chronic hepatitis due to HBV (66 patients) or HCV (21 patients). Policy discussion of LT in patients with HCC began in 1991.44,45 In 1996, Mazzaferro and associates46 described the Milan criteria for HCC recipients with cirrhosis. They demonstrated that patient survival was similar between Milan criteria HCC patients and patients with cirrhosis and no malignancy. Currently, the European Association for the Study of Liver (EASL) and the American Association for the Study of Liver Disease (AASLD) recommend liver transplant for HCC patients within Milan criteria.43 The HCC cases within Milan criteria had the best survival rates in our series at 1, 3, and 5 years (92.4%, 87.3% and 84.1%). On pathology review, we found 10 incidental HCC cases within Milan criteria; their current overall survival is 100%.

Some groups have argued that Milan criteria are too restrictive and exclude some patients who could benefit from LT. New expanded criteria have been des-cribed from multiple centers (University of California San Francisco, Bologna, Pittsburgh, Navarra, Alberta, Valencia, Shanghai, Metroticket study, UNOS Region 4, and Canadian Liver Transplant Study Group). Factors including microvascular invasion, alpha-fetoprotein level, and degree of differentiation appear to predict recurrence of HCC.43 Therefore, we decided to perform LT in cases beyond Milan criteria without macrovascular invasion and metastasis. The out-comes, benefits, and risks were discussed with the donor, recipient, and family. We performed LT in 31 HCC patients beyond Milan criteria. The survival rates at 1, 3, and 5 years in this group were 71.9%, 52.5%, and 38.2%. When patients who died within the first month after LT were excluded, these rates increased to 82.1%, 60.0%, and 43.7% in the patients followed. Discussions continue about the risk versus benefit of performing LT in this group of patients. We believe that with full disclosure of donor risks and recipient benefits and risks, LDLT can be offered to patients beyond Milan criteria. The size and biological behavior of the tumor must have a major role in this discussion.

It is clear that the most important discussion in LDLT is donor risk. There are major risks to the living donor, including the risk of death and substantial morbidity, which must be taken into account before patients, physicians, and transplant programs embark on LDLT. A data review of more than 300 articles, including nearly 6000 living-donor liver operations, reported an overall donor mortality rate of 0.2%.47,48 In contrast, donor morbidity in the United States is 14.5% after right lobe donation, and the Adult to Adult Living Donor Liver Transplantation Cohort Study Group (A2ALL) has published a complication rate of 39%.34,49 The Japanese National Registry has published morbidity rates after right lobe, left lobe, and left lateral grafting of 19%, 12%, and 8.2%.50

Our series included 416 living liver donors with an overall complication rate of 17.1% (n = 71), of which only 3.4% (n = 14) donors required surgical rein-tervention. According to the Dindo/Clavien score, 21 donors (5.0%) developed a greater than grade 3 complication, and only 2 donors had a grade 4a complication (Table 6). In 1 donor, the vascular staff loosened the right hepatic vein during the procedure and emergency thoracotomy was needed to stop the bleeding; subsequently, a serious pulmonary infection developed, necessitating a 1-month ICU stay. The second grade 4a complication occurred in a donor who had no sign of primary liver disease during evaluation, but 1 month after the donor procedure, the donor developed symptoms, and the diagnosis of benign recurrent intrahepatic cholestasis without life-threatening symptoms was made. The donor underwent liver transplant 1 year later from a deceased donor. This donor’s LDLT recipient also developed the same symptoms and underwent ReTx from a deceased donor 1 year later.

In conclusion, it is important to solve the problems which limit attempts to increase the deceased-donor pool in our country. At this time, we must resort to LDLT to save patient lives. A benefit of LDLT is timing of evaluation and transplant. Co-operation between hepatology clinics and transplant centers is important for optimal LT survival rates. The results in low PELD/MELD (< 25) recipients are better than those in high PELD/MELD (≥ 25) recipients. Due to the difficulty in finding a graft for ReTx, careful decisions must be made about donor graft quality and donor/recipient matching, and surgical complications must be eliminated to decrease graft loss. Patients with HCC beyond Milan criteria should have an opportunity to discuss LDLT and the decision to proceed with LT made together with the donor, recipient, and family. Liver trans-plant requires teamwork for successful outcomes. Correct decision making, timing, surgical skill, experience, and close follow-up are the most important factors for a successful transplant program.


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Volume : 14
Issue : 2
Pages : 191 - 200
DOI : 10.6002/ect.2014.0170


PDF VIEW [266] KB.

From the Organ Transplantation Center, Memorial Sisli Hospital, Istanbul, Turkey
Acknowledgements: The authors have no conflicts of interest to declare. No funding was received for this study.
Corresponding author: Yucel Yankol, MD, Memorial Sisli Hospital, Organ Transplantation Center, Piyalepasa Bulvari, Okmeydani-Sisli, 34385, Istanbul, Turkey
Phone: +90 212 314 6666
Fax: +90 212 314 6664
E-mail: yyankol@yahoo.com