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Volume: 12 Issue: 5 October 2014

FULL TEXT

ARTICLE
Risk Factors for Abdominal Bleeding After Living-Donor Liver Transplant

Objectives: The purpose of this study was to identify the incidence, outcomes, and risk factors of postoperative abdominal bleeding after living-donor liver transplant.

Materials and Methods: Adult patients who had living-donor liver transplant between 2001 and 2013 were evaluated. Preoperative and intraoperative variables of transplant recipients were analyzed retrospectively with univariate analysis. Cox proportional hazards regression model was used to identify independent factors for postoperative bleeding.

Results: There were 241 living-donor liver transplant recipients included in the study. Postoperative abdominal bleeding was observed in 12 recipients (5%). The 3-month cumulative survival was sig-nificantly lower in recipients who had postoperative bleeding (survival, 8 patients [67%]) than recipients who did not have postoperative bleeding (survival, 204 patients [89%]; P = .009). Univariate analysis showed that preoperative albumin level, Child-Pugh class, and intraoperative blood loss were risk factors for postoperative bleeding. In multivariate analysis, intraoperative blood loss and Child-Pugh status were significant risk factors for postoperative bleeding.

Conclusions: Living-donor liver transplant recipients who had postoperative bleeding had a poor outcome. Postoperative bleeding was associated with higher intraoperative blood loss and Child-Pugh class.


Key words : Complications, Hepatic failure, Outcomes, Transfusion, Treatment

Liver transplant may be curative treatment for patients who have end-stage liver disease. However, this treatment is limited by the worldwide scarcity of deceased-donor liver grafts. Living-donor liver transplant is an alternative option to deceased-donor liver transplant.1 Liver transplant is a highly invasive procedure, and many factors may cause graft loss or death after living-donor liver transplant. Despite major advances in immunosuppressive regimens, perioperative treatment, surgical technique, and medical care, postoperative complications are common after liver transplant including infection, bleeding, rejection, and biliary tract problems.2

Postoperative abdominal bleeding is a potentially life-threatening complication after liver transplant and often requires surgical treatment.3 Delay in the diagnosis and treatment of postoperative abdominal bleeding may cause death. Identifying the cause of postoperative bleeding is necessary to decrease the incidence of this complication. However, most previous studies about postoperative bleeding were performed with deceased-donor liver transplant, and few studies are available in patients after living-donor liver transplant.4,5 It is unknown whether risk factors for bleeding after deceased-donor liver transplant are applicable to living-donor liver transplant. Therefore, we evaluated the incidence, outcomes, and risk factors for postoperative abdominal bleeding after living-donor liver transplant.

Materials and Methods

Study group
All patients who had adult-to-adult living-donor liver transplant using the right hepatic lobe without the middle hepatic vein from 2001 to 2013 at our center were reviewed retrospectively. Transplant recipients were divided into 2 groups: (1) recipients who had postoperative abdominal bleeding and (2) recipients who did not have postoperative abdominal bleeding. All transplants were approved by the ethics committee of West China Hospital, Sichuan University. All protocols conformed with the ethical guidelines of the 1975 Helsinki Declaration, and informed consent was obtained from all subjects.

Donor selection and surgical procedure
Donors were healthy relatives of recipients, within the third degree of consanguinity, who had compatible ABO blood type and negative results of serologic testing for viral hepatitis, human immunodeficiency virus antibodies, and any other acute or chronic disease. Volumetric computed tomography with contrast was performed to evaluate vascular anatomy and graft volume. Subjects who were accepted as donors had a right hepatic lobe without middle hepatic vein that was ≥ 0.8% body weight of the recipient, and the liver volume was ≥ 40% for the donor. Magnetic resonance cholangiopancreatography was performed to assess the anatomy of the biliary tree.6,7

The decision for transfusion of blood products was based on the results of laboratory tests during donor and recipient operations. Packed red blood cells were transfused to maintain a hemoglobin level ≥ 7.0 g/L. Platelets were given to patients when platelet levels were < 50 ×109/L. Fresh frozen plasma was given when the international normalized ratio was > 1.5. Intraoperative autologous blood transfusion was used for donors and recipients who had benign liver disease.7

Definitions
Early postoperative abdominal bleeding after living-donor liver transplant was suspected when there was substantial bloody drainage from the abdominal drainage tube, rapid decrease of hemoglobin level, or instability of blood pressure that was not corrected by transfusion of blood products.4,8 Repeat laparotomy was performed in recipients who had active postoperative bleeding and hemodynamic instability.8 Model for End-Stage Liver Disease score was calculated with the formula: Model for End-Stage Liver Disease score = (9.57 × ln creatinine [mg/dL]) + (11.2 × ln international normalized ratio) + (3.78 × ln bilirubin [mg/dL]) + 6.43.9

Statistical analyses
Continuous variables were reported as mean ± SD and analyzed with 1-way analysis of variance. Categorical variables were analyzed with the chi-square test or the Fisher exact test. Independent risk factors were identified with Cox proportional hazards regression model. Factors significant at P < .10 in the univariate analyses were evaluated with multivariate analysis. The Kaplan-Meier method with log-rank test was performed to compare the short-term survival of the 2 groups. Statistical significance was defined by P ≤ .05.

Results

A total of 241 living-donor liver transplant recipients were included in the present study. The most common indications for living-donor liver transplant were hepatitis B virus cirrhosis and hepatocellular carcinoma (Table 1). Mean age was greater for recipients than donors, and recipients most frequently had Child-Pugh class B (Table 2). Most recipients did not have postoperative bleeding (Table 3). The mean graft-to-recipient–weight ratio, intraoperative transfusion volumes, and surgical duration were similar between recipients who had or did not have postoperative bleeding (Table 3). Mean intraoperative blood loss was greater for recipients who had postoperative bleeding than recipients who did not have postoperative bleeding (Table 3).

In the 12 recipients who had early postoperative abdominal bleeding, 9 patients had reoperation, 1 patient had interventional embolization, and 2 patients died of bleeding. The postoperative bleeding occurred from the cut surface of the graft (4 patients), retrohepatic region (2 patients), subhepatic region (2 patients), diffuse surface exudation (2 patients), adrenal gland (1 patient), and subdiaphragmatic region (1 patient).

There were 29 recipients who died within 3 months after surgery, including 4 patients who had postoperative bleeding (33%) and 25 patients who had no postoperative bleeding (11%) (Table 3). Survival at 3 months was significantly greater in recipients who did not have postoperative bleeding (Table 3 and Figure 1). The causes of death included multiple organ failure (14 patients), infection (9 patients), renal failure (3 patients), bleeding (2 patients), and graft rejection (1 patients).

Univariate analyses showed that risk factors for postoperative abdominal bleeding in recipients included preoperative albumin level, Child-Pugh class, and intraoperative blood loss (Table 3). Multivariate analysis showed that intraoperative blood loss and Child-Pugh class were independent risk factors for postoperative abdominal bleeding in recipients (Table 4).

Discussion

Postoperative bleeding is a potentially fatal complication and often requires urgent surgical treatment. The current study showed that living-donor liver transplant recipients who had postoperative abdominal bleeding had low short-term survival (Table 3 and Figure 1). Preoperative intraoperative blood loss and Child-Pugh class were independent risk factors associated with postoperative abdominal bleeding after living-donor liver transplant (Table 4).

The frequency of postoperative bleeding observed in recipients in the present study (5%) was lower than previously reported (8.4% to 14.4%).3-5 A possible reason for this difference may be the different amount of intraoperative blood loss at different centers. The mean intraoperative blood loss observed in this study (Table 2) was lower than previously reported.3-5 In addition, intraoperative blood loss was an independent risk factor for postoperative abdominal bleeding after living-donor liver transplant (Table 4).

Living-donor liver transplant includes an additional cut surface on the graft than deceased-donor liver transplant. In the present study, the cut surface on the graft was the most common intra-abdominal bleeding site. In a previous study, the hepatic artery was the most frequent site of bleeding that necessitated laparotomy after liver transplant.3 In the present study, hepatic artery reconstruction was performed by a vascular surgeon, and a low incidence of hepatic artery complications was observed.10 During liver transplant, the graft may develop an ischemia-reperfusion injury that may cause graft loss or primary failure to function.11,12 In addition, recipients may have a hypocoagulable state after liver transplant. Early postoperative thrombocytopenia is common after liver transplant because of platelet activation and consumption after graft reperfusion.13,14 These factors may increase the incidence of postoperative bleeding.

Living-donor liver transplant is a complex procedure that is associated with potential massive intraoperative blood loss that may prompt massive transfusion of blood products. Massive blood loss during liver transplant may be associated with poor preoperative coagulation status, varicose collateral vessels, technical difficulties, or low preoperative platelet count.15 Intraoperative massive blood loss may cause consumption of clotting factors, further compromising coagulation function in recipients. This may explain the finding that massive intraoperative blood loss was a risk factor for postoperative bleeding after living-donor liver transplant (Table 4).

A similar conclusion was noted with thyroid and pancreas surgeries.18,19 Intraoperative blood loss may be a risk factor for early reoperation because of varied complications after living-donor liver transplant.8 In contrast with other studies, red blood cell transfusion was not an independent risk factor in multivariate analysis.4,20 In the present study, intraoperative autologous blood transfusion was used for patients with benign liver disease, and intraoperative allogeneic red blood cell transfusion did not parallel the intraoperative blood loss after living-donor liver transplant. In addition, other studies have shown that massive intraoperative blood loss and blood product transfusion may be associated with high postoperative morbidity and mortality after liver transplant and other operations.21-24 The mean volume of intraoperative blood loss was greater in recipients who had postoperative bleeding than recipients who did not have postoperative bleeding (Table 3). Reoperation, which may further compromise the patient’s condition, also may cause higher morbidity and mortality in patients who had postoperative bleeding after the primary transplant procedure.

Child-Pugh class was another independent risk factor associated with postoperative bleeding, and the frequency of postoperative bleeding increased with increased Child-Pugh class (Tables 3 and 4). Patients who have high Child-Pugh class may have severe varicose collateral vessels, poor preoperative condition, severely enlarged spleen, and coagulation dysfunction, and these factors may cause massive intraoperative blood loss and necessitate blood product transfusion.15 Other studies have shown that higher preoperative Child-Pugh class is an independent risk factor associated with massive intraoperative transfusion, and that Child-Pugh class A may be a protective factor for massive intraoperative bleeding after liver transplant.25-27 In addition, preoperative international normalized ratio and presence of ascites may correlate independently with the amount of blood transfusion after liver transplant.28 Patients who have advanced Child-Pugh class have poor preoperative coagulation status and massive ascites.

In conclusion, postoperative bleeding is associated with poor short-term outcome after living-donor liver transplant and is independently associated with massive intraoperative blood loss and advanced preoperative Child-Pugh class.


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Volume : 12
Issue : 5
Pages : 424 - 428
DOI : 10.6002/ect.2013.0223


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From the Division of Liver Transplantation, West China Hospital, Sichuan University, Chengdu, China
Acknowledgements: Chuan Li and Tian-Fu Wen proposed this study; Chuan Li collected and analyzed the data; and Lu-Nan Yan and Bo Li contributed to the discussion. This work was supported by a grant from the National Science and Technology Major Project of China (2012ZX10002-016 and 2012ZX10002017-006). The authors have no conflicts of interest to disclose.
Corresponding author: Tian-Fu Wen, Division of Liver Transplantation, West China Hospital, Sichuan University, Chengdu 610041, China
Phone: +86 18 980601471
E-mail: aderwe@163.com