Author Affiliations: Liver Transplantation Center, Florence Nightingale Hospital, Istanbul, Turkey (Guler N, Yaprak O, Gunay Y, Dayangac M, Akyildiz M, Yuzer F, Yuzer Y and Tokat Y)

Corresponding Author: Necdet Guler, MD, Florence Nightingale Hastanesi Organ Nakli Birimi, 164 Abidei Hurriyet Cad, Sisli, Istanbul 34381, Turkey (Tel: +90-212-2128811; Fax: +90-212-2127708; Email: necdetguler1907@hotmail.com)

 

© 2015, Hepatobiliary Pancreat Dis Int. All rights reserved.

doi: 10.1016/S1499-3872(15)60346-0

Published online March 4, 2015.

 

Contributors: GN proposed the study. GN and YO performed research and wrote the first draft. GY, DM, AM, YF, YY and TY collected and analyzed the data. All authors contributed to the design and interpretation of the study and to further drafts. GN is the guarantor.

Funding: None.

Ethical approval: Not needed.

Competing interest: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

 

BACKGROUND: The right lobe of the liver is generally preferred for living donor liver transplantation in adult patients with end-stage liver disease. It is important to know the preoperative factors relating to the major postoperative complications. We therefore evaluated the possible risk factors for predicting postoperative complications in right lobe liver donors.

 

METHODS: Data from 378 donors who had undergone right lobe hepatectomy at our center were evaluated retrospectively. The factors we evaluated included donor age, gender, body mass index (BMI), remnant liver volume, operation time, history of previous abdominal surgery, inclusion of the middle hepatic vein and variations in the portal and bile systems.

 

RESULTS: Of the 378 donors, 219 were male and 159 female. None of the donors died, but 124 (32.8%) donors experienced complications including major complications (Clavien scores III and IV) in 27 (7.1%). Univariate analysis showed that complications were significantly associated with male gender and higher BMI (P<0.05), but not with donor age, remnant liver volume, operation time, graft with middle hepatic vein, variations in the portal and bile systems and previous abdominal surgery (P>0.05). Multivariate logistic regression analysis showed that major complications were significantly associated with male gender (P=0.005) and higher BMI (P=0.029). Moreover, the Chi-square test showed that there were significant relationships between major complications and male gender (P=0.010, χ²=6.614, df=1) and BMI >25 kg/m² (P=0.031, χ²=8.562, df=1). Of the 96 male donors with BMI >25 kg/m², 14 (14.6%) with major complications had significantly smaller mean remnant liver volume than those (82, 85.4%) without major complications (32.50%±4.45% vs 34.63%±3.11%, P=0.029).

 

CONCLUSION: Male donors with BMI >25 kg/m² and a remnant liver volume ≤32.50% had a significantly increased risk for major complications.

 

(Hepatobiliary Pancreat Dis Int 2015;14:150-156)

 

KEY WORDS: living donor; right lobe liver donor; major complications; risk factors

Living donor liver transplantation (LDLT) has been widely accepted for the treatment of end-stage liver disease and the outcomes have been improving with greater surgical experience and advances in surgical techniques.^[1-3] The right lobe is generally preferred for LDLT in adults because it provides sufficient liver volume for adult recipients, but this lobe has more variations in the vascular and bile systems than left lobe liver grafts.^[4-6] The most important concern in right lobe LDLT is donor safety. Morbidity rates in donors undergoing right hepatectomy varied because of different standards of morbidity.^[7-11]

 

The modified Clavien classification was to assess morbidity and outcomes in living liver donors.^{[12, 13]} This classification was based on the criteria including risks to the donor and a treatment model for complications, and it has been shown to be applicable in several multicenter studies.^{[14, 15]} We retrospectively evaluated major complications occurring in right lobe living liver donors and identified preoperative factors associated with postoperative complications.

 

 

Between January 2004 and June 2012, a total of 560 liver transplantations were performed at the Liver Transplantation Center of Istanbul Florence Nightingale Hospital (FNH). These included 378 right lobe LDLTs, 32 left lobe LDLTs, and 150 deceased donor liver transplantations (DDLTs). The 378 donors who had undergone right donor hepatectomy were included in this study; data were retrieved from their charts at our center. The factors we evaluated included donor age, gender, body mass index (BMI), remnant liver volume, operation time, history of previous abdominal surgery, inclusion of the middle hepatic vein (MHV) in the graft and variations in the anatomy of the portal vein and bile system. Liver volume was calculated by computed tomography (CT) (16-detector, Sensation 16-Siemens, Erlangen, Germany). Donor complications were scored based on the modified Clavien classification.^[16] Complications scored as Clavien III and IV were defined as major complications. The portal vein and bile system of donors were classified according to Cheng^[17] and Huang classifications.^[18] We compared the outcomes of donors with no complication versus those with major complications.

 

Donor candidates were ≥18 years old, in good health with no comorbidities, and up to fourth degree relatives of recipients. All prospective donors underwent extensive preoperative work-up including blood typing, extensive biochemistry analysis, urine analysis, coagulation tests, and tests for hepatitis B and C, human immunodeficiency virus, cytomegalovirus and Epstein-Barr virus. Microbiological analysis of blood and urine, venereal disease research laboratory tests, and tests for the prothrombin gene and factor 5 Leiden mutation were also performed. All donor candidates underwent chest X-rays, electrocardiography, and echocardiography. They were examined by a hepatologist, a transplant surgeon, a psychiatrist, a chest physician, and a cardiologist, female donors also by a gynecologist. Liver volume, parenchyma and vascular structure were assessed by CT, and the bile system was evaluated by magnetic resonance cholangiopancreaticography (MRCP; 1.5 T scanner, Magnetom Sonata, Siemens, Erlangen, Germany). Prior to 2008, remnant liver volume between 26%-30% was accepted in some selected donors such as younger (less than 30 years old) and with no liver steatosis. The donors were chosen only if the remnant liver was >30% and the graft weight to recipient weight ratio was >0.8% since 2008. Donors with hyperlipidemia, >10% liver steatosis as determined by ultrasound, BMI >30 kg/m², or positivity for HBcAb underwent percutaneous liver biopsy. Donors with no histological changes were accepted. Donors with >10% liver steatosis were prescribed a diet and an exercise program for weight loss, and they were subsequently reevaluated. If liver steatosis rate was still >10%, donors were rejected.

 

Informed consent was obtained from all donors prior to surgery. A median, J-shaped or reverse T incision was made^[19] and intraoperative ultrasound used to evaluate portal and hepatic vascular structures. After cholecystectomy, cholangiography through the cystic duct stump was performed to evaluate the biliary tree. No donor surgery was aborted due to abnormal findings. After completing right lobe mobilization, the hepatocaval ligament and all direct vein branches from the caudate to the inferior vena cava were ligated and divided. Accessory venous branches larger than 5 mm in diameter were temporarily clamped to test their drainage capacities; if congestion was observed, these branches were retained for anastomosis with the recipient vena cava. The right hepatic artery (RHA) and right portal vein (RPV) were temporarily clamped to mark the parenchymal border between the right and left lobes. A cavitron ultrasonic surgical aspirator (CUSA System 200 Macrodissector; Cavitron Surgical Systems, Stamford, CT, USA) was used for parenchymal division. Our approach to the MHV has been described.^[20] MHV was left with remnant liver if the remnant liver ≤30%, donors older than 50 years and with remnant liver volume ≤35%.

 

After completing parenchymal transection, the bile system was assessed by cholangiography. Heparin sodium 1500 units i.v. was administered before clamping the vessels after transection of the parenchyma. The graft was removed after transecting the right bile duct, RPV, RHA and right hepatic vein (RHV). The RHV remnant in the donor was closed using 4/0 prolene, the RPV was closed with 5/0 prolene and the bile duct was closed with 6/0 prolene. The bile system was checked for leakage using methylene blue. Cholangiography was performed if necessary. A silastic drainage tube was inserted into the subhepatic area.

 

Following extubation, all donors were taken to the intensive care unit and monitored for one day. The nasogastric tube was removed on postoperative day 1 and oral feeding was started. Controlled analgesia was continued for 48 hours after surgery. The central venous catheter was removed on postoperative day 4. The donors received prophylactic antibiotics. Liver function tests were performed every day for a week. An abdominal ultrasound was performed to ensure that there was no collection of intraabdominal fluid or bile leaks. If the drainage was less than 300 mL per day, the silastic drainage tube was removed on postoperative day 5 or 6. All of the donors were followed up by liver function tests after 1, 3 and 6 months. They were contacted every year and those with any problems were admitted to hospital for further evaluation.

 

SPSS 16 was used for analysis. Categorical variables were reported as numbers and percentages and continuous variables as mean±standard deviation. Categorical variables were compared using the Chi-square test; nonparametric continuous variables were compared using the Mann-Whitney U test; and parametric continuous variables were compared using Student's t test. Logistic regression and the Chi-square test with an automatic interaction detector (CHAID) were used to assess risk factors significantly related to major complications. P values less than 0.05 were considered statistically significant.

 

 

Of the 378 donors, 219 (57.9%) were male and 159 (42.1%) female. The mean follow-up time was 29.9±16.3 months (range 12-96). None of the donors died, but 124 (32.8%) experienced complications, including major complications in 27 (7.1%), described as Clavien scores III and IV (Table 1). Univariate analysis showed no significant relationships between complications and donor age, remnant liver volume, operation time, graft with MHV, variations in the portal and bile systems, and previous abdominal surgery (P>0.05, Table 2). Mean BMI was 25.103±0.231 kg/m² in 254 donors without complications, 25.525±0.307 kg/m² in 124 donors with complications, and 26.311±0.645 kg/m² in 27 donors with major complications. Univariate analysis revealed a significant relationship between BMI and major complications (P=0.046, Table 2). Of the 378 donors, 175 had a BMI of >25 kg/m² and 203 had a BMI of ≤25 kg/m². Donors with a BMI of >25 kg/m² had 62 (35.4%) complications including 18 (29.0%) major and 44 (71.0%) minor ones based on Clavien classifications. Donors with a BMI of ≤25 kg/m² had 62 (30.5%) complications including 9 (14.5%) major and 53 (85.5%) minor ones.

 

Of the 219 male donors, 147 (67.1%) had no complications, and 72 (32.9%) had complications. Of the male patients with complications, 22 (10.0%) had major complications. Of the 159 female donors, 107 (67.3%) had no complications, 52 (32.7%) had complications and 5 (3.1%) had major complications. Univariate analysis showed a significant relationship between male gender and major complications (P=0.010, Table 2). Multivariate logistic regression analysis showed that male gender (P=0.005) and higher BMI (P=0.029) were factors significantly associated with major complications (Table 3). CHAID analysis also showed a significant relationship between major complications and male gender (P=0.010, χ²=6.614, df=1) and BMI >25 kg/m² (P= 0.031, χ²=8.562, df=1).

 

Of the 123 male donors with a BMI of ≤25 kg/m², 8 (6.6%) had major complications, compared with 14 (14.6%) of the 96 male donors with a BMI of >25 kg/m² (P=0.050). Of the 96 male donors with a BMI of >25 kg/m², 14 (14.6%) donors with major complications had a significantly smaller mean remnant liver volume than 82 (85.4%) donors without major complications (32.50%±4.45% vs 34.63%±3.11%, P=0.029). Since the number of the patients were not sufficient and confidence interval was too large, multivariable logistic regression analysis was not possible. Unfortunately, the cutoff value for remnant liver volume could not be calculated since the area under the curve was too low.

 

There were no significant relationships between major complications and other factors except the remnant liver volume (Table 4). The distribution and treatment of major complications are described in detail in Table 5. Pulmonary embolism occurred in three donors and the three donors had a BMI greater than 25 kg/m². Pulmonary embolism occured in postoperative days 2, 3 and 5, respectively. Donors did not receive any prophylaxis of deep venous thrombosis postoperatively. Donors with pulmonary embolism were treated with low-molecular-weight heparins. Neither of these donors had previous lung diseases. We did not find a different rate of pulmonary embolism between donors with different liver remnant volume.

 

 

LDLT has been reported to reduce the mortality rate in patients with end-stage liver disease on the transplant waiting list, as well as to increase the survival rate in transplant recipients.^[21,22] The most important ethical issue in LDLT is thought to place a healthy living donor at risk for complications after hepatectomy. Multicenter studies have shown that 38% of living liver donors developed complications, with a mortality rate of about 0.2% and almost all donors resumed normal life 3 to 6 months after surgery.^[23,24] Complication rates were higher in right lobe liver donors, as the mortality rates of 0.3%-0.5%. And the complications had negative effects for a longer period of time.^{[25, 26]}

 

Since right lobe hepatectomy is a major procedure and carries a high morbidity risk, donors should be healthy to reduce the risk of complications. The selection criteria for donors must therefore be superior to those for recipients.^{[19, 27]} Although no ideal criteria are available for living liver donors, it is agreed that they must be at age of 20-50 years and ABO compatible with recipients, have a BMI of <30 kg/m², have no evidence of liver steatosis or other chronic diseases, and have a remnant liver volume of >35%. But most transplant centers accept donors who do not meet all of these criteria.^{[27, 28]}

 

In right lobe LDLT, using a graft with the MHV provides a better venous drainage in recipients but may increase risk to donors. A previous study^[20] showed that when a remnant liver volume was >30%, the donor complication rate not different no matter whether the MHV removed or not during donor hepatectomy; however, when the remnant liver volume was <30%, the removal of the MHV with the graft increased significantly the donor complication rate. Thus, we have not accepted the donors with a remnant liver volume of <30% at present. In this study, the MHV was removed from 109 (28.8%) donors, but the removal of the MHV did not show a significant effect on the donor complication rate.

 

The most crucial factor for donor safety is the retention of a sufficient and functional remnant liver volume of ≥30%.^[29] Our previous study^[30] on 262 donors found that the postoperative complication rate was significantly higher in patients with a remnant liver volume of <30% than in those with a volume of ≥30%. In this study, the major complication rate in male donors especially those with a BMI of >25 kg/m² was higher if the remnant liver volume was ≤32.50%.

 

The effect of donor age on donor and recipient outcomes after LDLT remains unclear.^{[31, 32]} Liver regeneration capacity decreases in older patients.^[33] Our previous study^[27] involving 150 donors showed that the complication rate was similar in donors of >50 years and ≤50 years old. However, major complication rate was higher in old than in young donors who underwent extensive right hepatectomy or if the MHV was removed. Moreover, mortality and morbidity rates were higher in recipients who received grafts from elderly donors who underwent extensive right hepatectomy or if the MHV was removed. These findings suggested that, for donor safety, the MHV should not be removed and the remnant liver volume should be >35% in aged donors, because congestion in the remnant liver may decrease the regeneration capacity and increase the risk of morbidity.^[27] Therefore, we still have strict rules for the selection of aged donors, although age has no effect on major complications.

 

Portal vein variations can make surgery technically challenging and increases donor risk. The rate of portal vein thrombosis in donors is dependent on the technique used to close the remnant portal vein.^[6] The rate of bile system variations is higher in donors with portal vein variations. It is therefore crucial to identify portal vein and biliary variations prior to surgery. However, MRCP can only identify 70% of bile system variations.^[34] In the present study, we found that 37.6% of our donors had bile system variations, including 12.9% of donors with portal vein variations. However, only one donor experienced complications of the portal vein but none of the recipients had any portal complications. Although the complication rate was higher in donors with bile variations than in those without bile variations, the difference was not significant (33.3% vs 29.8%, P=0.56). The lack of effect of bile and portal variation on major complications showed that it was possible to reconstruct these variations without putting donors and recipients at risk.

 

Longer operation time increases complication risk. Because the right lobe liver has more vascular and biliary system variations than the left lobe, removing the MHV makes surgery more challenging in these donors.^[4-6] In addition, as previous abdominal surgery causes dense adhesions in the abdomen, operation time may be longer and associated with a higher risk of complications. Our study showed that the complication rate was higher in donors with longer operation time, but there was no significant relationship between major complication rate and operation time.

 

The effect of gender on donor complications remains unclear, although clinical and experimental studies have shown that hormonally active females can tolerate traumatic shock better than males.^[35] Of the 27 patients who experienced major complications, 22 were males and 5 females. Male gender was a statistically significant risk factor for major complications in both univariate and multivariate analyses.

 

Immobilization increases the risk of postoperative complications such as pulmonary embolism, wound infections and lung diseases in obese donors compared with non-obese ones. However, selected obese individuals can be LDLT donors without risk of complications.^[36] In only one-fourth of 146 obese patients who underwent bariatric surgery and liver biopsy at the same time had steatosis,^[37] higher BMI was considered as a predictive factor for liver steatosis.^[38] Clinicians^[39-41] should keep in mind that CT volumetric measurements can make a mistake between 13%-20%. Liver steatosis may further reduce liver function in donors, even if the remnant liver volume is >30%. Thus, in our center, prospective donors who are hyperlipidemic, have >10% fat on ultrasound, or have a BMI of >30 kg/m² undergo routine liver biopsy. If their steatosis rate is >10%, these donors are rejected. As a previous study showed that if donors are carefully selected, the morbidity could be very low and acceptable.^[42] We observed a significant relationship between major complication and higher BMI, with CHAID analysis showing that male donors with a BMI of >25 kg/m² were at a higher risk for major complications. Although pulmonary embolism occurred in the 3 donors with a BMI greater than 25 kg/m², our management was not changed in the postoperative period. The percentage of pulmonary embolism was too low so we did not take the risk of bleeding by postoperatively deep venous thrombosis prophylaxis.

 

In conclusion, although LDLT is an accepted treatment for patients with end-stage liver disease in countries lacking sufficient deceased donors, donor safety remains a major concern. By analyzing the donor risk factors for major complications, we found that the risk of major complications is associated with a BMI of >25 kg/m² in male donors with a remnant liver volume of ≤32.50%. 

 

 

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