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Letter to the editor: Is there a place for machine perfusion strategies in pediatric liver transplantation?

With interest, we read the letter by Lee et al. and their study evaluating the value of serum thrombospondin2 (TSP2) as a predictive biomarker of advanced liver fibrosis (F ≥ 3) (ALF) in diabetic patients with NAFLD.[1] This largescale cohort study demonstrates that serum TSP2 level is capable of identifying those with ALF at high accuracy (area under the receiver operating characteristic curve [AUROC]: 0.80). They also show that serum TSP2 level is independently associated with the presence of ALF. These findings are consistent with our study,[2] further strengthening the high reliability of TSP2 as a noninvasive biomarker of ALF in patients with NAFLD. Meanwhile, as Lee et al. showed, there is a difference in the performance of TSP2 in the diagnosis of ALF, which is comparable to Fibrosisi4 index (FIB4) and NAFLD fibrosis score (NFS) in our study, but significantly better than them in Lee et al.’s study. This may be attributed to the different clinical backgrounds of the patients in the two studies (diabetes mellitus complication rate was about 30% in our study and 100% in Lee et al.’s study), but it should be noted here that diagnostic accuracy of FIB4 and NFS greatly differs between the two studies. Our data show relatively high accuracy of these tests (FIB4 AUROC: 0.78; NFS AUROC: 0.81), which is consistent with the result of a recent metaanalysis of noninvasive tests for histologically defined ALF (F ≥ 3) in patients with NAFLD (FIB4 AUROC: 0.76 [n = 5393]; NFS AUROC: 0.73 [n = 3248]).[3] In sharp contrast, their accuracy in Lee et al.’s study is surprisingly poor (FIB4 AUROC: 0.60; NFS AUROC: 0.58).[1] This result raises a concern of the accuracy of ALF diagnosis in Lee et al.’s study, which was done solely based on vibration controlled transient elastography value without histological evidence. Taken together, it is unclear whether discrepancy of diagnostic accuracy of FIB4 and NFS for ALF between two studies is due to the suboptimal performance of these noninvasive tests in diabetic patients or to the difference of methodology used for ALF diagnosis. Therefore, it is desired for further careful comparison of the performance of TSP2 and other noninvasive tests as a biomarker of ALF in diabetic patients with biopsyproven NAFLD. Nevertheless, these two studies complementary support the usefulness of serum TSP2 in patients with NAFLD as a diagnostic biomarker of ALF and NASH as well as a predictive biomarker of future disease progression including fibrosis progression, shown by Lee et al., and occurrence of hepatic complications (liver cancer and decompensative events) shown by us.