Objectives: Biochemical abnormalities after living-donor hepatectomy are attributed to the loss of liver volume and steatosis or fibrosis. In this study, we evaluated the intraoperative biochemical changes caused by the separation of the hepatic lobes before removal and the impact of those changes on postoperative biochemical abnormalities in patients who underwent adult-to-adult living-donor liver transplantation (LDLT).

Materials and Methods: The extent and postoperative impact of the biochemical changes that occur during hepatic parenchymal transection in adult-to-adult LDLT were studied in 38 patients who underwent that procedure (14 men and 24 women; mean age, 39.6 years; age range, 19.5-58.9 years). Preoperative, intraoperative, and postoperative biochemical values for the first 8 postoperative days were compared.

Results: The mean total hepatic volume was 1703.0 mL, the mean weight of the resected mass was 887.0 g (52.6%), and the mean weight of the residual mass was 816.0 g (47.4%). The mean total bilirubin, aspartate amino transferase (AST), and amino alanine transferase (ALT) values were 8.6 U/L, 21.4 U/L, and 27.6 U/L, respectively, before surgery, compared with 27.4 U/L (an increase of 3.2 times), 257.9.2 U/L (an increase of 12.0 times), and 224.64 U/L (an increase of 8.1 times), respectively, after separation of the hepatic lobes. Patients (n = 21) with an intraoperative ALT value of >= 200 had a significantly higher peak postoperative ALT (P = .001) than did those (n = 17) with an ALT value of < 200.

Conclusions: A significant increase in hepatic biochemical parameters occurs at the completion of hepatic parenchymal transection and before the removal of the right hepatic lobe from the donor. This has an impact on postoperative peak enzyme levels in the donor.

Key words : Living-donor, Intraoperative, Liver injury

The indications and demand for liver transplantation have increased over the last decade owing to improved outcomes. However, the deceased-donor pool has remained relatively stable. To overcome the demand for this life-saving procedure, increasing numbers of living-donor partial hepatic allografts are being used for transplantation [1-4]. The safety of the living liver donor, during and after the surgical procedure, is of paramount importance because the procedure is performed on a healthy individual who does not otherwise require an operation. Also, the size and quality of the donor liver are important for both donor and recipient outcomes. Donors who are overweight may have fatty infiltrates in their liver, and older donors may have a degree of hepatic fibrosis. A routine percutaneous liver biopsy is performed on all potential donors at our center and at many other centers. Potential donors with significant findings in the results of their liver biopsy may not be considered suitable candidates for partial liver donation [5-9].

Despite careful selection, hepatic dysfunction in the donor after the loss of hepatic mass often occurs [10] and is usually attributed to that loss [8, 11, 12]. However, the biochemical changes indicative of hepatic dysfunction are thought to occur before the loss of hepatic mass and purely as a result of the division of the hepatic lobes. To our knowledge, that degree of damage and its impact on overall postoperative hepatic biochemical abnormalities have never been studied. In this study, we examined 2 factors: the intraoperative biochemical changes caused by the separation of the hepatic lobes before removal and the impact of those changes on postoperative biochemical abnormalities in patients who underwent adult-to-adult living-donor liver transplantation (LDLT).

Materials and Methods

Thirty-eight LDLT donors (14 men and 24 women; mean age, 39.6 ± 9.9 years) were examined for intraoperative biochemical changes caused by the separation of the hepatic lobes. The mean total hepatic volume was 1703.0 ± 363.3 mL, as calculated by the volumetric mapping of abdominal computer tomographic (CT) scans [13-15]. The same surgical team performed all donor operations. The hepatic lobes were separated after the right hepatic vein, right hepatic artery, and right portal vein had been identified and dissected. Intraoperative cholangiography was performed through the cystic duct. The division line was determined by the transient obliteration of inflow from the right-sided hepatic arterial and right-sided portal venous flow.

All hepatic resections were performed with a Cavitronic Ultrasound Surgical Aspirator (CUSA) (Valleylab Inc, Boulder, Colo), unipolar electrocautery, Liga clips, Prolene sutures, and silk ties and the use of a low central venous pressure (1-5 cm of water) but without the Pringle maneuver. All donors had undergone liver function tests before surgery and after separation of the hepatic lobes. Biochemical changes were measured daily before discharge. Intraoperative biochemical changes were compared with preoperative values, postoperative values, and the remaining hepatic mass (estimated by CT volumetric analysis minus the weight of the hepatic mass removed) in relation to body weight.

All values are presented as the mean ± standard deviation. The mean intraoperative values and postoperative values were compared with the results of a t test. A P value of less than .05 was considered significant. SPSS software (Statistical Package for the Social Sciences, version 13.0, SSPS Inc, Chicago, Ill, USA) was used for all statistical analyses.

Results

All donors experienced a smooth operative procedure. The estimated average blood loss was < 300 mL, and none of the patients required a blood transfusion or a return to the operative room for the treatment of complications. The mean weight of liver mass removed was 887.0 ± 200.4 g (52.6%), and the mean weight of residual liver mass was 816.0 ± 247.2 g (47.4%). The mean remnant hepatic mass-weight ratio was 1.0% ± 0.3%.

Intraoperative biochemical changes
All donors demonstrated changes in their biochemical parameters to varying extents. The mean total bilirubin value before surgery was 8.6 ± 3.4 µmol/L, which increased to 27.4 ± 12.0 µmol/L (an increase of 3.2 times) after separation of the hepatic lobes and had normalized by postoperative day 8. The mean preoperative aspartate amino transferase (AST) value was 21.4 ± 5.1 U/L, which increased to 257.9 ± 90.2 U/L (an increase of 12.0 times) after separation of the lobes. The mean preoperative amino alanine transferase (ALT) value was 27.6 ± 11.0 U/L, which increased to 224.6 ± 90.4 U/L (an increase of 8.1 times) after separation of the lobes (Figure A, B, C).

Impact of intraoperative biochemical changes on postoperative parameters in donors
To examine the impact of an increase in intraoperative biochemical parameters on postoperative changes, the donors were grouped into categories based on their intraoperative bilirubin, AST, and ALT values and residual hepatic mass. These changes were correlated with peak postoperative values as shown in the Table. There were no differences in peak postoperative values between donors who had an intraoperative total bilirubin value of < 25.7 µmol/L and those with a value of >= 25.7 µmol/L, or between those who had more than a 3-fold rise or less in the bilirubin value. Similarly, when donors who had an AST level of < 200 U/L were compared with those who had an AST level of >= 200 U/L, no significant effect was found on the postoperative peak AST value (P = .188). However, donors with an intraoperative ALT level of >= 200 had a significantly higher postoperative peak ALT level than did those with an intraoperative ALT level of < 200 U/L (mean, 232.2 ± 79.0 U/L vs 385.9 ± 132.0 U/L, respectively; P = .001) (Table).

Impact of residual hepatic mass and hepatic mass donor-weight ratio
The mean total bilirubin, AST, and ALT values were higher in patients (n = 17) with a residual hepatic mass of < 750 g than in those (n = 21) with a residual mass of >= 750 g. However, that difference was not significant. When the residual hepatic mass was < 1% of the patient’s body weight (n = 18), the mean total bilirubin, AST, and ALT values were higher than those in the patients (n = 20) with a residual hepatic mass of >= 1%, although that difference also did not reach statistical significance (Table).

Impact of intraoperative biochemical changes on postoperative parameters in recipients
Similar changes in the biochemical profiles of the recipients were examined with respect to intraoperative changes in the donors. Unfortunately, the pretransplant biochemical profiles of the recipients varied greatly; hence, no meaningful comparison could be made.

Discussion

Knowledge of the surgical anatomy of the hepatic lobes, its segments, and the segmental nature of the portal venous supply makes the division of the hepatic segments and lobes possible without major crossing between the segments [16-18].

Hepatic resection has been performed successfully over last 3 decades in patients with a primary hepatic malignancy, metastatic disease, or a symptomatic benign lesion [16]. Various modifications have been made in techniques for hepatic lobe resection to reduce blood loss and operative time. The intraoperative use of ultrasonography to identify hepatic veins and portal structures enables surgeons to define the plane of dissection. Electrocautery (both unipolar and bipolar) and ultrasonic harmonic scalpels are useful in controlling the bleeding from small vessels. The use of a CUSA and a water jet increases the safety of hepatic resection [19-22].

The shortage of deceased-donor liver allografts and an increasing demand for LDLT has led to an increase in the number of living-donor hepatic resections that are performed. Strict guidelines, which are in place to ensure donor safety, include the performance of liver resection by skilled surgical teams experienced in hepatobiliary surgery and liver transplantation in addition to an institutional infrastructure that ensures the adequate postoperative care of donors [23-30]. At present, however, standardized information on postoperative donor morbidity is lacking [31].

There is a constant need to develop new strategies, plans, and techniques to improve the safety of liver donors. The unique ability of remnant liver to regenerate allows postoperative biochemical hepatic abnormalities to correct with time. Biochemical hepatic dysfunction after resection is usually attributed to a loss of hepatic mass. A lower residual liver mass may require a longer time to regenerate and may be the cause of a greater postoperative increase in the levels of total bilirubin and hepatic enzymes [32, 33]. We observed (as did other investigators) a correlation between the residual mass, the body-weight ratio, and the degree of postresection hepatic dysfunction. We found that the actual residual mass per se did not affect the degree of hepatic dysfunction.

Schemmer and colleagues reported that gentle in situ manipulation with the destruction of Kupffer cells produced a significant effect on hepatic injury in a rat model [34]. AST and ALT are hepatic cytoplasmic enzymes. During parenchymal handling and division, cell wall damage leads to the release of those enzymes in circulation and a subsequent elevation in the levels of hepatic enzymes. Removal of the transected hepatic mass further increases liver enzyme levels. However, the extent of that increase in liver enzymes has not been reported in human hepatic resection. The intraoperative increase in the bilirubin level that resulted from hepatic parenchymal division was a somewhat surprising and novel finding of this study.

We have shown that the postoperative biochemical abnormalities that occur after the resection of a hepatic lobe in patients who have undergone LDLT develop intraoperatively during the hepatic parenchymal division and that there is a further increase in those abnormalities during the first few days after the removal of the hepatic lobe. A mean increase in the levels of bilirubin of up to 3.2 times, ALT of up to 8.1 times, and AST of up to 12.0 times greater than preoperative values has been observed during the hepatic parenchymal division. In addition, we found that the ALT value after hepatic parenchymal division correlates with the peak postoperative ALT value, independent of the residual hepatic mass or the residual mass donor-weight ratio in the donors. Further investigation is necessary to determine whether factors such as tissue injury and inflammation along the margin of the parenchymal division or simply the handling and manipulation of hepatic tissue during that division are responsible for this finding.

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