Liver transplantation is an imperative procedure for treatment of hepatic failure and early stages of hepatocellular carcinoma. The suitability of donors has been decided by the surgeons on the basis of prerequisite investigation data and liver biopsy results . The livers of LLDs are investigated for the existence of steatosis or fibrosis, which excludes transplant candidacy and results in poor post-operative outcome . Despite liver biopsy is traditionally considered as a diagnostic criterion standard, it is not carried out in all centres and has many limitations. It is costly, painful, and invasive procedure associated with sampling errors and potential complications. Also, it only examines a very small portion, which does not exceed 1/50,000 of the volume of the examined organ with intra- and inter-observer variability. These limitations reduce the relevance of liver biopsy and yield an urge for a non-invasive efficient tool [10, 18].
Recently, MRE technique, which estimates hepatic stiffness even in absence of fibrosis, is successfully employed as a non-invasive diagnostic tool. It is an optimal procedure for evaluation of liver parenchyma in adults LLDs prior to donation surgery [16, 19].
The study in hand was conducted on 37 consecutive eligible healthy LLDs candidates, whose suitability for liver donation was assessed on the basis of their livers’ stiffness measurements estimated by MRE. They were 28 (75.68%) males and 9 (24.32%) females with their ages ranged from 24 to 45 years (34.55 ± 9.45 years) and their BMI ranged from 17.55 to 50.60 kg/m2 (34.05 ± 8.14 kg/m2).
Based on the hepatic MRE findings, which were confirmed by the results of liver biopsy that obtained from the same area evaluated by the MRE, we found that most of the study participants were candidates with absolutely normal hepatic tissue (26/37; 70.27%); most of them were males (19/26; 73.08%), aged less than 35 years (23/26; 88.46%) and had BMI less than 25 kg/m2 (24/26; 92.31%). Additionally, we found 11 (29.73%) candidates with abnormal hepatic tissues; most of them were males (9/11; 81.82%) and aged ≥ 35 years (7/11), while near all of them (10/11; 90.91%) had body BMI ≥ 25 kg/m2. Moreover, our results revealed significant statistical differences between LLDs with normal and abnormal hepatic tissues regarding age, gender, and BMI (P < 0.003, P < 0.02, and P < 0.001, respectively). In a parallel manner, Gallegos-Orozco et al.  reported that 10 out of 11 (90.91%) LLDs with abnormal liver biopsy results were males with significantly higher BMI > 25 kg/m2 than that of candidates with normal liver biopsy results (P = 0.02). On the other hand, Yoon et al.  found that the BMI did not significantly differ between LLDs with normal hepatic biopsy results and those with simple steatosis. However, they observed that LLDs with normal hepatic biopsy results had significantly lower BMI than those with abnormal liver biopsy due to fibrosis or steatosis with inflammatory activity (P = 0.013 and P = 0.0001, respectively).
Noteworthy, we observed that the liver stiffness values were not significantly affected by age nor gender of the studied candidates (P = 0.0687 and P = 0.60; respectively). This is in agreement with Lee et al.  who found a non-significant difference in the values of liver stiffness neither between genders nor among different age groups (P > 0.001).
In harmony with the results obtained by Gallegos-Orozco et al. , we observed that the liver stiffness in candidates with BMI ≥ 25 kg/m2 was significantly higher than those with BMI < 25 kg/m2 (P < 0.001). On the contrary, Yoon et al.  observed a non-significant difference in BMI between donors with normal hepatic tissue and those with simple steatosis (P > 0.05), while they concluded that LLDs with normal hepatic tissue and average measurements of liver stiffness had BMI significantly lower than that in candidates with abnormal hepatic tissue of non-alcoholic fatty liver diseases including steatosis with inflammatory activity.
Quantitative evaluation of the potential LLDs for coexistence of hepatic steatosis, which influences the hepatic functional recovery, is crucial . Moreover, hepatic fibrosis is not a homogenous process; generating the potential for sampling error in biopsy-based diagnosis. Noteworthy, the presence of liver fibrosis is usually associated with elevated hepatic parenchymal stiffness. However, increased liver stiffness is not necessarily indicating the presence of fibrosis .
In the current study, we correlated the liver stiffness values and the histopathological results of liver biopsy. A highly significant correlation was observed between the MRE values and liver biopsy results (P < 0.0003). The previous studies recorded the average values of liver stiffness in normal LLDs candidates to be ranged from 1.54 to 2.87 kPa with the mean liver stiffness measurements to be ranged from 2.052 to 2.44 kPa [12, 15, 16, 19], while, in the current study, the LLDs candidates with absolutely normal hepatic tissue yielded liver stiffness values ranged from 0.74 to 2.20 with the mean stiffness value of 1.72 ± 0.30 kPa [15, 21]. Furthermore, we compared the liver stiffness values between normal and abnormal hepatic tissues, the grades of steatosis to each other, METAVIR stages of fibrosis to each other, as well as steatosis with fibrosis. Intriguingly, our results revealed statistically significant differences in all comparisons (P < 0.05). Moreover, our results demonstrated that the MRE liver stiffness measurements in LLDs with absolutely normal hepatic parenchyma was significantly lower than those with abnormal hepatic tissue (P = 0.0001). Additionally, we noted that the increase in liver stiffness is highly significant between S1a and F2 (P < 0.001), S1b and F1 (P < 0.002), as well as S1b and F2 (with P < 0.001) much more than between S1a and S1b (P = 0.045), F1 and F2 (P = 0.016), as well as S1a and F1 (P = 0.026).
In accordance with our results, Gallegos-Orozco et al.  reported a significant increase in the liver stiffness in LLDs with hepatic steatosis ≥ 20% more than in candidates with hepatic steatosis < 20% (P < 0.0001). Additionally, Yoon et al.  concluded that liver stiffness measurements in LLDs with normal hepatic tissue was significantly lower than those with abnormal hepatic tissue due to existence of fibrosis (P = 0.0001). Also, they observed that the liver stiffness value in candidates with liver fibrosis was significantly higher than liver stiffness in candidates with simple steatosis (P = 0.001). However, they found non-significant difference in the values of liver stiffness between donors with hepatic fibrosis, as well as those with non-alcoholic steato-hepatitis and steatosis with inflammatory activity (P = 0.812 and P = 0.204, respectively). On the other hand, Yin et al.  reported non-significant differences in the liver stiffness values on comparing between F0 and F1, between F1 and F2, as well as between F0 and F2 stages of fibrosis.
The study in hand proposed a cut-off value of ≥ 2.24 kPa with 0.992 AUC to distinguish between absolutely normal hepatic tissue and abnormal hepatic tissue with steatosis and/or fibrosis with highest specificity, sensitivity and accuracy (100%, 98.65%, and 99.24%, respectively). On the other hand, Gallegos-Orozco et al.  proposed 2.6 kPa as an optimal cut-off value for discrimination between normal and abnormal hepatic tissues in LLDs candidates with AUC of 0.81, 0.72% sensitivity, and 0.85% specificity.
Interestingly, by using liver stiffness measurements estimated by means of MRE in the studied LLDs candidates, we accurately discriminated completely normal hepatic tissue from mild steatosis with detection of mild steatosis of grade ≥ S1 (with fat contents ≥ 5%) via using a cut-off value of ≥ 2.35 kPa with 0.981 AUC (100% specificity, 98.10% accuracy, and 96.83% sensitivity), while by utilizing a cut-off value ≥ 2.38 kPa with 0.984 AUC, we accurately discriminated non-substantial hepatic steatosis with fat contents < 20% from substantial steatosis with fat contents ≥ 20% with 100% specificity, 98.44% accuracy, and 96.90% sensitivity. On contrary, Gallegos-Orozco et al.  reported 2.82 kPa as an optimal cut-off value for identification of substantial hepatic steatosis of ≥ 20% with 88% sensitivity and 100% specificity.
Relied upon the liver stiffness measurements, the previous studies [11, 15, 23] reported cut-off values ranged between 2.4 and 2.93 kPa with sensitivity 98% and specificity 99% for detection of hepatic fibrosis. In the present study, to detect mild hepatic fibrosis, we suggested a cut-off value ≥ 2.42 kPa, with 0.990 AUC, 100% specificity, 99% accuracy, and 97.51% sensitivity, for discrimination between completely normal hepatic tissue and mild fibrosis of ≥ F1 stage METAVIR score of fibrosis. Additionally, we proposed a cut-off value ≥ 2.57 kPa for discrimination between normal and non-significant hepatic fibrosis of F1 stage of METAVIR score and significant substantial hepatic fibrosis ≥ F2 stages of fibrosis with 0.988 AUC, 100% specificity, 98.80% accuracy, and 97.22% sensitivity. In contrast, Kim et al. , distinguished significant substantial liver fibrosis (≥ F2) from normal or mild fibrosis (F0–1) by using 3.05 kPa as an optimal cut-off value with 89.7% sensitivity and 87.1% specificity, while by using the same cut-off value (3.05 kPa), the results of Yin et al.  yielded 86% sensitivity and 85% specificity.
These variations in the cut-off values of liver stiffness measurements in LLDs candidates among different studies, including the current study, might be attributed to differences in the study design, selection criteria, and technical variations including dissimilarities between MRI systems, the used scanning parameters, and methods of interpretation, in addition to differences in the used statistical methods.
To the best of our knowledge, in our area, this is the first study to highlight the diagnostic performance of MRE as a pre-transplant non-invasive screening imaging modality for selection and validation of LLDs who can participate in the donation surgery. Furthermore, very limited researches emphasized the diagnostic utility of using liver stiffness values estimated by means of MRE technique with most of them were limited by their retrospective design and errors in the liver biopsy as a result of heterogeneity of the hepatic fibrosis process. We did our best to overcome the limitations of the previous studies, so the study in hand was designed to be a prospective observational study and in each study participant, we used the confidence image to measure liver stiffness and to obtain liver biopsy. Moreover, we tried to assume optimal cut-off values for detection of hepatic steatosis, in addition to differentiation between normal or non-significant steatosis (with fat contents < 20%) and substantial steatosis (with fat contents ≥ 20%). Also, we proposed optimal cut-off values for detection of non-significant mild hepatic fibrosis of stage ≥ F1 and for discrimination between normal or non-significant fibrosis and significant advanced stage of fibrosis (≥ F2).