Objectives: In this retrospective study, we aimed to determine the diagnostic value of unenhanced computed tomography in the assessment of macrovesicular steatosis in potential living liver transplant donors by using biopsy as a reference standard.
Materials and Methods: This retrospective study was approved by our institutional review board, and all included patients provided written informed consent. Our study group included 181 donor candidates (mean age of 35.9 ± 9.3 y) who underwent unenhanced computed tomography and subsequent needle biopsy (mean period after scan of 12.74 d) in the right hepatic lobe (at least 2 samples per patient). Histologic degree of macrovesicular steatosis was determined. A radiologist with 10 years of experience assessed steatosis of the right hepatic lobe by using 2 methods: (1) a 4-point visual grading system that used attenuation comparison between the liver and hepatic vessels and (2) the liver attenuation index, which was calculated with region of interest measurements of hepatic attenuation. We used statistical analyses to compare accuracy in the diagnosis of macrovesicular steatosis.
Results: Our study population was divided into 3 groups according to histologic steatosis grade. Group 1 consisted of 157 candidates with 0% to 5% steatosis, group 2 consisted of 11 candidates with 6% to 15% steatosis, and group 3 consisted of 13 candidates with 16% to 100% steatosis. Mean liver attenuation (in Hounsfield units ± standard deviation) was 58.93 ± 5.07 for group 1, 47.8 ± 4.17 for group 2, and 39.11 ± 6.5 for group 3. Significant differences in liver attenuation were observed between groups using one-way analyses of variance (F = 107 307; P < .01). For visual grading, correlation coefficient for computed tomography was 0.959.
Conclusions: Unenhanced computed tomography to assess liver attenuation represents an objective and noninvasive means for detection of hepatic steatosis. This method can prevent unnecessary biopsies.
Key words : Donor safety, Hepatic steatosis, Liver biopsy
Living-donor liver transplant can restore the health of the recipient; however, equally important is maintaining the health of the donor during the process. In liver transplant, graft failure is the most unwanted result and can negatively affect both sides, with macrovesicular steatosis being one of the most significant factors leading to graft failure.1 A standard evaluation of the donor candidate includes a physical examination, laboratory tests, imaging with computed tomography (CT) or magnetic resonance imaging, and liver biopsy. Although liver biopsy is considered to be the standard method for quantitative assessment of hepatic steatosis, it is invasive and may cause morbidity.2 Therefore, a noninvasive method is needed to diagnose steatosis for improving donor safety. In this study, our aim was to determine the diagnostic performance of unenhanced CT in the assessment of macrovesicular steatosis in potential living donors of liver transplant by using biopsy as a reference standard.
Materials and Methods
This retrospective study was approved by our institutional review board, and all study participants provided written informed consent.
Our study included 181 donor candidates (mean age of 35.9 ± 9.3 y), which included 94 men and 87 women. Potential donors underwent unenhanced CT and subsequent ultrasonographic-guided liver biopsy (mean of 12.74 d post-CT scan) from the right hepatic lobe (at least 2 samples per patient). Unenhanced CT examinations were routinely performed on a 16-detector row CT system (Siemens Somatom Sensation, Siemens AG, Erlangen, Germany). Imaging parameters were as follows: tube voltage 120 kVp/400 mA and section thickness of 3 mm. All CT data were reviewed on a picture-archiving and communication system.
A radiologist with 10 years of experience assessed steatosis of the right hepatic lobe by using 2 methods: (1) a 4-point visual grading system that compared attenuation between the liver and hepatic vessels (Figure 1) and (2) the liver attenuation value, which was calculated with region of interest (ROI) measurements. After scans were visually graded, donor candidates were classified into 3 groups. Group 1 included grade 0 and 1 (mild) steatosis, group 2 included grade 2 (moderate) steatosis, and group 3 included grade 3 (severe) steatosis. Liver attenuation values were derived using blood-free hepatic parenchymal attenuation and ROI measurements on liver parenchyma, avoiding large vessels. For liver attenuation measurements, 1 × 1 cm ROIs were placed on 4 different sites in the right hepatic lobe, with averages of the 4 sites calculated with Hounsfield units (HU).
The biopsy specimens were prepared with hematoxylin-eosin staining for histologic review. An experienced hepatic pathologist who was blinded to the radiologic findings defined the degree of macrovesicular steatosis semiquantatively as the percentage of fatty cells that replaced the liver parenchyma on the histologic specimen.
Accuracy of diagnosis of macrovesicular steatosis was compared by statistical analyses. Statistical analyses were performed with SPSS software (version 11.5; SPSS, Chicago, IL, USA). P < .05 was considered statistically significant.
The study population was divided into 3 groups according to histologic steatosis grade. Group 1 consisted of 157 candidates with 0% to 5% steatosis, group 2 consisted of 11 candidates with 5% to 30% steatosis, and group 3 consisted of 13 candidates with ≥ 30% steatosis.
For groups 1 and 2, there were no abnormal findings in liver function tests, including alanine aminotransferase (ALT; normal level of 0-55 U/L), aspartate aminotransferase (AST; normal level of 5-34 U/L), gamma-glutamyltransferase (normal level of 5-36 U/L), and alkaline phosphatase (normal range of 40-150 U/L). However, in group 3, 1 donor candidate with 80% steatosis had elevated AST and ALT (40 and 69 U/L, respectively), 2 donor candidates (with 70% and 40% steatosis, respectively) had elevated gamma-glutamyltransferase (77 and 83 U/L, respectively), 1 patient with 30% steatosis had elevated ALT (58 U/L), and 1 patient with 30% steatosis had elevated AST (38 U/L). We observed no significant correlation between liver function tests and liver steatosis. Computed tomography results showed mean (± standard deviation) liver attenuation of 58.93 ± 5.07 HU for group 1, 47.8 ± 4.17 HU for group 2, and 39.11 ± 6.5 HU for group 3 (Figure 2). One-way analyses of variance showed that the differences in liver attenuation between groups were significant (F = 107 307; P < .01). For visual grading, correlation coefficient for CT was 0.959. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated as 84.62%, 100%, 100%, 98.82%, and 98.89%, respectively.
In the moderate (grade 2) and high (grade 3) steatosis groups, 7 of 11 candidates and 0 of 13 candidates, respectively, were selected as donors. During transplant and follow-up, there were no serious complications thought to be secondary to steatosis for both recipients and donors in this study.
In this retrospective study, we evaluated the value of unenhanced CT as a noninvasive way to detect hepatic steatosis in living liver donor candidates. Our results showed that accuracy of both the visual grading technique and the liver attenuation value in the diagnosis of severe steatosis was similar to that shown previously.3,4
For the ROI measurement method, an optimal result requires the sample area to contain a large volume of parenchyma without large vessels, thus avoiding large vessels decreasing the sample area. Therefore, biopsies with limited sampling size may lead to inaccurate detection of steatosis because the fat distribution in the liver may not be equal at all points.5,6 However, this problem could be overcome by using multiple ROIs and averaging the measurements. In our study, the area under the receiver operating characteristic curve of liver attenuation measurement was 0.982 (95% confidence interval, 0.962-1) and the cutoff value of 49.3 HU showed 100% sensitivity and 91.8% specificity in donor candidates with ≤ 30% steatosis. Kodama and colleagues found that a liver attenuation value of 59.1 ± 7.3 HU represents 1% to 25% fat accumulation.7 Our results showed that liver attenuation results per unenhanced CT scans of 58.93 ± 5.07 HU and 47.8 ± 4.17 HU correlated with 0% to 5% and 5% to 30% steatosis, respectively.
We found that visual grading with CT for diagnosis of severe steatosis provided high sensitivity (11/13 donor candidates ≥ 30% steatosis) and high specificity (100%), as similarly previously shown.8 Radiologists can evaluate a large area of hepatic parenchyma in seconds with this technique. We believe that the high diagnostic performance of our results may have been based on the low prevalence of severe macrovesicular steatosis in our study population, as seen in other studies.4,8 Nevertheless, we believe that our results are encouraging and that use of the visual grading technique with CT for diagnosis of ≥ 30% steatosis is a fast and reliable method.
Although biopsy remains the only way to detect occult pathologic abnormalities, such as hepatitis, iron deposition, and fibrosis, it can adversely affect both the recipient allograft and the donor remnant after transplant. Liver biopsy is an invasive method and may cause morbidity.9 Today, its necessity in evaluation of living liver donors remains controversial.10 For our donor candidates who had ≥ 30% macrovesicular steatosis according to CT findings, there were no abnormal medical findings and further decision-making before donation would not be needed. Although further evaluation with biopsy can be expensive and risky and although the liver transplant donor pool remains low, a false exclusion for false-positive diagnosis using CT is unacceptable. Therefore, a biopsy is still needed to confirm the steatosis and rule out any hidden pathologies.
As shown previously, a macrovesicular steatosis of < 30% is considered suitable for transplant,11 which is in line with the outcomes of our study. We did not observe any complications in our study groups.
This study has some limitations. First, the effects of microvesicular steatosis on hepatic attenuation were not calculated. Microvesicular steatosis might also have an additional impact on the liver attenuation value.8 Second, in our study, there were only 13 donor candidates with severe steatosis (30%). Third, although biopsy is considered to be the reference standard for quantification of hepatic steatosis, sampling failure can occur due to limited sampling size.6 Fourth, hemosiderin deposits were not analyzed in pathologic specimens. Deposition of iron has an effect on liver attenuation, making liver parenchyma densities less reliable for detecting steatosis.12
Assessment of liver attenuation by use of unenhanced CT represents an objective and noninvasive method for detection of severe hepatic steatosis. Its use can prevent unnecessary biopsies in donor candidates who have ≥ 30% macrovesicular steatosis.
DOI : 10.6002/ect.2019.0326
From the 1Department of Radiology and the 2Department
of Pathology, Baskent University, Faculty of Medicine, Ankara, Turkey
Acknowledgements: The authors have no sources of funding for this study and have no conflicts of interest to declare.
Corresponding author: Kemal Murat Haberal, Department of Radiology, Baskent University, Faculty of Medicine, 06490, Bahcelievler, Ankara, Turkey
Phone: +90 312 203 6868/1165
Figure 1. Unenhanced Computed Tomography Scans Showing Visual Grading of Degree of Hepatic Steatosis
Figure 2. Simple Boxplot of Hounsfield Unit/Fat Accumulation