Key words : Conversion formula, Graft volume, Left lateral liver, Liver transplantation, Liver volumetry

Introduction

Liver volumetry is a widely used imaging modality for estimation of liver volume before any liver resection. More importantly, liver volumetry is used for the preoperative evaluation of donors in living donor liver transplant (LDLT).¹ The major concern of LDLT is not just the graft quality but, more importantly, whether the graft volume (GV) is adequate to fully satisfy the recipient’s metabolic demands.² However, in the context of living liver donation, the weight of the graft seems to be much more important. Graft weight (GW) is used to calculate the most important prognostic factor: donor graft weight-to-recipient body weight ratio (GRBWR), which should ideally be between 2.0% and 4.0%.^3,4 A GRBWR that is too high (>6%-8%) or too low (<0.8%) may also become a contraindication to transplant, depending on the individual situation.^5,6 Therefore, the relationship between volume and weight is crucial.

Computed tomography volumetry (CTV) perfor-med by a radiologist is a gold standard method for estimating GV in LDLT.⁷ However, as mentioned before, to calculate a GRBWR, it is mandatory to have an accurate estimated weight of the graft, not just the volume. The 1-to-1 rule has been a widely adopted approach for many years. However, most recent analyses of right liver grafts have shown that this rule may lead to a significant errors in graft size estimation, resulting in poor outcomes for some patients.⁸

A recent systematic review addressed the absence of research to determine the proper ratio between the weight and volume of healthy livers.⁹ Therefore, we aimed to analyze the relationship between the left liver GV and actual GW (AGW). Using this relationship analysis, we also aimed to define a conversion formula between volume and weight for the left lateral liver.

Materials and Methods

For the period from December 2008 to September 2020, we retrospectively reviewed 94 (41 men; 53 women) consecutive donors who underwent left lateral hepatectomy for pediatric LDLT. Before data collection, approval was obtained from the University of Duisburg-Essen ethics committee (No. 20-9294-BO). All donors were healthy adults and underwent a preoperative contrast-enhanced computed tomog-raphy (CT) scan during donor candidacy selection for LDLT. The CT images included in the study had to show normal anatomic features of the liver, gallbladder, and vasculature. All individuals evaluated as candidates who did not meet the donor evaluation criteria for LDLT were excluded.

The CT examinations were performed on a 16-slice CT system (LightSpeed 16, General Electric Medical Systems) according to a standard internal protocol for the liver. The CT images used for CTV were reconstructed on 5 slices before segmentation. Currently, most centers for hepatobiliary surgery use this thickness of sections for liver volumetry based on CT images, because the maximum error is <5%.¹⁰ An experienced radiologist performed the segmentation. The ligamentum teris, the ligamentum venosum, and the bifurcation of the left portal vein were used as reference points to depict segments II and III as accurately as possible. These structures are also used intraoperatively to perform a left lateral hepatectomy during separation of segment IV from segments II-III. A venous phase of CT scans was used for this study. The segmentation is carried out by coloring the voxels in the above-mentioned segmentation program ITK-SNAP (https://www. itksnap.org).¹¹ After manual segmentation, the individual layers were joined 3-dimensionally by the software. After that, a 3-dimensional image of the organ was displayed. Furthermore, the volume is presented in cubic centimeters as the sum of all segmented areas on the axial CT slices (Figure 1).

An experienced hepatobiliary surgeon performed all surgeries. Before the liver resection, every patient underwent a standard evaluation of intra-abdominal organs for any possible pathology (including intra-abdominal tumors and chronic liver diseases). The typical surgical incision plane at our institution is approximately 0.5 to 1.0 cm to the right of the ligamentum falciforme. Therefore, in all the cases, the cutting plane was slightly lateral to the left lateral hepatic lobe. After retrieval of grafts and before the perfusion with preservation solution, the grafts were weighted intraoperatively on a precalibrated digital scale to determine the AGW. For each case, the GV estimation obtained by CTV was compared with the AGW.

The classification of postoperative complications is based on the Clavien-Dindo Classification of Surgical Complications.¹² For further statistical analysis, complications were divided into 2 groups. All complications from Clavien-Dindo grade IIIb were classified as major complications, and all complications below grade IIIb were classified as minor complications. For better comparability of recipient complications among centers and countries, surgical complications were converted to the Comprehensive Complication Index.¹³

Statistical analyses

Data are presented as mean values ± standard deviation. Categorical variables are reported as numbers and percentages. Statistical analyses were performed with SPSS software (version 27.0). P < .05 was considered significant. The relationship between estimated GV and AGW was determined by linear regression analysis. Furthermore, the linear correlation of Spearman and its 95% confidence interval were presented, and Bland-Altman analysis and an intraclass correlation coefficient were also applied to assess the reliability of the data. The quartile method was used to identify the outliers. The data points below Q1 – 3 × IQR or above Q3 + 3 × IQR are outliers.

Ethics declarations

The study was performed in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The ethics committee of the University of Duisburg-Essen approved the study and its protocol and waived the need of informed consent for the present study (No. 20-9294-BO).

Results

Our study included 94 living liver donors. Most donors were women (56.4%). The mean age of the donors at the time of transplant was 32.52 ± 6.69 years. The donor relationship to the recipient varied as follows: 49 (52.1%) were mothers, 41 (43.6%) were fathers, 2 (2.1%) were grandmothers, 1 (1.1%) was an aunt, and 1 (1.1%) was an adoptive mother. Among them, the youngest donor was 21 years old, and the oldest was 52 years old. The mean body mass index (calculated as weight in kilograms divided by height in meters squared) was 24.8 ± 3.78. The mean duration of surgery in the donor was 293.2 ± 68.77 minutes. Postoperative complications were observed in 9 donors (9.6%), of whom 1 donor (1.0%) had a biliary leak, which required surgical treatment and thus counted as a severe postoperative complication according to the Clavien-Dindo classification (grade IIIB). The follow-up examination was after an average of 25.95 ± 16.65 months (Table 1). Donor demographic and clinical data for the training and validation sets were compared. There were no statistically significant differences (P > .05).

The mean weight of a liver segment II-III was approximately 283.4 ± 68.5 g, and the mean volume was 244.9 ± 63.86 mL. There was a statistically significant difference between the volume and weight (P < .001). A strong correlation between the left lateral liver graft was observed (r = 0.804; P < .001) (Figure 2). For a more detailed and accurate analysis of the agreement between left lateral liver volumes and weights, as well as determination of the probability of error in each measurement, we performed a Bland-Altman analysis. The analysis revealed an interobserver agreement of 38.0 ± 97.25 (Figure 3). Moreover, an intraclass correlation coefficient between volume and AGW was calculated, which showed excellent agreement (0.840; P < .001).

After determining a high degree of agreement (intraclass correlation coefficient = 0.840; P < .001) between CTV and AGW, we performed a linear regression analysis based on the volume and weight of the left lateral liver. After removing a few outliers (n = 6; 6.4%), we determined the formula for calculation of the left lateral liver weight from CTV: liver segment II-III weight (in grams) = 0.88 × (segment II-III volume [in milliliters]) + 41.63.

By this formula, 77.2% of the variance in AGW could be explained. The regression coefficient of the variable size is 0.88, and it is statistically significant (t[88] = 17.275; P < .001). Statistical requirements for the regression analysis or Gauss-Markov assump-tions were met when the formula was created.

Discussion

Preoperative estimation of the donor liver volume is an essential factor that affects not just the surgical strategy but also recipient mortality and morbidity after LDLT. However, in the context of living liver donation, the weight of the organ or graft to be transplanted is much more important because GW (rather than GV) is used to calculate the most important prognostic factor: GRBWR.^5,6 Therefore, the relationship between volume and weight is crucial, especially in pediatric LDLT. Unfortunately, data on this relationship for the left lateral liver segment are sparse and inconclusive.

Most transplant centers still use an approach for conversion of liver volume to liver weight by interpreting a mean density of healthy liver tissue as 1.00 g/mL.^7,14 The current discussion points out that 1 mL in CTV may not correspond to 1 g of liver tissue. The recent systematic review and meta-analysis conducted by Buijk and colleagues showed that CT-based manual liver volumetry will overestimate right liver volume by 2.99% and left liver volume by 14.41%. Moreover, they discuss the importance of a correction factor to make more accurate calculations.⁹ Furthermore, many authors who have analyzed the density of the liver and its segments (mostly right liver grafts) have already presented many different conversion coefficients. Therefore, based on these data, the conversion factor should be somewhere between 0.8 and 0.95, depending on which part of the liver the weight is to be calculated from, whether the surgical section plane matches the plane used for segmentation, and whether the GV is calculated with or without intrahepatic vessels.^9,15-18

By not considering around 5% to, in some cases, 20% of conversion error by using a 1-to-1 rule, we risk that some LDLT recipients will receive smaller organs than expected. Therefore, such a miscal-culation may put some recipients at risk for small-for-size syndrome.³ On the other hand, big grafts may result in pressure necrosis to the graft because of the smaller intra-abdominal cavity, outflow occlusion, or possibly the need for delayed abdominal closure to prevent compartment syndrome.¹⁸ However, many authors have suggested that a good surgical strategy for bigger grafts leads to no inferior results. They have also dismissed major concerns regarding delayed abdominal closure, such as the increased possibility of a local wound and abdominal infections.¹⁹ In conclusion, underestimation of liver graft size and associated recipient risks should be considered whenever the 1-to-1 rule is applied.

In our study, we analyzed the left lateral liver lobe. To date, only 1 formula, a body surface area (BSA)-based formula for calculating the volume of the left lateral liver lobe, has been published (left lateral liver lobe = 139 × BSA).²⁰ However, it was recently demonstrated that no demographic or anthropometric data correlate with left lateral hepatic lobe volume.²¹ Therefore, we conclude that, to date, no reliable conversion formula offers a standardized calculation of the left lateral liver GW based on CTV. The collective average weight of the left lateral liver lobe in our patients (~283.4 g) did not differ from the published data. In our study, we demonstrated a strong correlation between AGW and measured volume, which was significantly stronger compared with the published data, where only a moderate correlation was demonstrated (r = 0.804 vs r = 0.49; P < .001).⁷ Moreover, intraclass correlation coefficients analysis revealed almost excellent agreement (r = 0.840; P < .001).

We could conclude that there is a strong and significant relation between the AGW and GV, and a conversion formula could be determined. In our study, we established for the first time to our knowledge the formula for calculation of the standard weight of the left lateral liver graft. We also found that volume is a significant predictor of weight, and the suggested formula explains 77.2% of the variance.

A main limitation of this study is the possible differences in GW depending on surgical techniques or dissection lines between the centers or even surgeons. In our institution, we used a standardized cutting line slightly lateral to the ligamentum falciforme. Surgeons tend to have the habit of making a cutting line. Moreover, we weighed the graft before the perfusion with preservation solution. Therefore, our suggested formula depends on the surgical technique and timing of GW measurement we used. The other important limitation is that we did not investigate the actual clinical benefit of the formula. The focus of this study was to investigate the specific GV and GW association for the left lateral liver and determine calculation-associated risks for the recipients. Our data showed that the 1-to-1 rule produced a statistically significant overestimation of GRBWR, as GV is bigger than AGW.

Further studies should focus on the donor selection process using our suggested formula because there may be cases for which the 1-to-1 rule would overestimate the GRBWR and lead to an erroneous decision to change or exclude the potential donor. Moreover, with a standardized collection of preoperative volumetric data (possibly without liver vessels) and intraoperative data, including a surgical procedure with a clear cutting plane, it would be possible to create an even more precise and better variance-explaining formula for calculating the standard weight. This could significantly improve the evaluation of possible donor organs in calculating the GRBWR, thereby eliminating the risk of underestimation of liver graft size.

Conclusions

Attempts to calculate the weight of the left liver graft using only the 1-to-1 rule are prone to measurable variability for GW and tend to underestimate the GW. Instead, a new, improved conversion formula should be implemented so that the GW is more accurately estimated. This approach would allow for a more precise determination of GRBWR and reduce the risk of underestimating the weight of the liver graft during the donor selection process before LDLT.

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