No abstract

Ischemia reperfusion injury (IRI) is an adverse factor for hepatocellular carcinoma (HCC) recurrence after liver transplantation. Ischemic-free liver transplantation (IFLT) is a novel transplant procedure that can largely reduce or even prevent IRI, but the clinical relevance of IFLT and the recurrence of HCC after liver transplantation are still unknown. This retrospective study compared survival outcomes, HCC recurrence, perioperative data and IRI severity following liver transplantation (LT). 30 patients received IFLT and 196 patients received conventional liver transplantation (CLT) were chosen for the entire cohort between June 2017 and August 2020. A 1:3 propensity score matching was performed, 30 IFLT recipients and 85 matched CLT patients were enrolled in propensity-matched cohorts. An univariate and multivariate Cox regression analysis was performed, and showed surgical procedure (CLT vs IFLT) was an independent prognostic factor (HR 3.728, 95% CI 1.172-11.861, P=0.026) for recurrence free survival (RFS) in HCC patients following liver transplantation. In the Kaplan–Meier analysis, the RFS rates at 1 and 3 years after LT in recipients with HCC in the IFLT group were significantly higher than those in the CLT group both in the entire cohort and propensity-matched cohort (P=0.006 and P=0.048, respectively). In addition, patients in the IFLT group had a lower serum lactate level, lower serum ALT level and serum AST level on postoperative Day 1. LT recipients with HCC in the IFLT group had a lower incidence of early allograft dysfunction than LT recipients with HCC in the CLT group. Histological analysis showed no obvious hepatocyte necrosis or apoptosis in IFLT group. In conclusion, IFLT can significantly reduce IRI damage and has the potential to be a useful strategy to reduce HCC recurrence after liver transplantation.

Background As a critical metabolic substrate, glutamine is not only involved in the progression of many cancers but is also related to angiogenesis. Glutamate dehydrogenase (GLDH), a key enzyme in glutamine metabolism, has been reported to regulate tumor proliferation; however, its relationship with microvascular invasion (MVI) is unclear. This study evaluated the ability of preoperative serum GLDH levels to predict MVI and the long-term survival of hepatocellular carcinoma (HCC) patients after liver transplantation (LT). Methods HCC patients that underwent LT from January 2015 to May 2020 at the First Affiliated Hospital of Sun Yat-Sen University were enrolled in our retrospective analysis. Clinicopathological variables were extracted from medical records. A receiver operating characteristic curve was created to determine the optimal cut-off value of GLDH for MVI. Results Preoperative GLDH was significantly elevated in the MVI-positive group (U = 454.00, p = 0.000). The optimal cut-off value of GLDH for MVI was 7.45 U/L, with an area under the curve of 0.747 (95% CI [0.639–0.856], p = 0.000). The sensitivity was 79.3%, while the specificity was 64.5%. GLDH > 7.45 U/L (p = 0.023) and maximum diameter >5 cm (p = 0.001) were independent risk factors for the presence of MVI. Patients with GLDH > 7.45 U/L had significantly poorer overall survival (p = 0.001) and recurrence-free survival (p = 0.001) after LT than patients with GLDH ≤ 7.45 U/L. Similarly, patients with MVI were associated with poor survival (p = 0.000). Conclusions Preoperative elevated serum GLDH levels predict MVI and poorer long-term survival for HCC after LT.

Background: Atrial fibrosis is involved in non-paroxysmal atrial fibrillation (NPAF) and is mainly mediated by the calcium-binding protein S100A4. This study aimed to verify the role of circulating S100A4 in the diagnosis of atrial fibrosis and the prognosis of NPAF. Methods: Consecutive NPAF patients undergoing catheter ablation were selected. Patients with low voltage amplitudes (<0.40 mV) in the left atrium (LA), defined as low voltage zones (LVZs), were grouped in the scar group by electroanatomic mapping (EAM). Circulating S100A4 was detected by a human enzyme-linked immunosorbent assay (ELISA). The role of S100A4 in atrial fibrosis was further evaluated by Masson's trichrome staining and immunochemistry (IHC) in NPAF (atrial pacing) and control dogs. The prognostic value of the circulating S100A4 was evaluated by Cox regression analyses, the Kaplan-Meier (KM) method, and receiver operating characteristic (ROC) curves. Results: We enrolled a total of 101 NPAF patients (age 60±8 years) who underwent EAM, including 53 patients with scars and 48 patients without scars at 1-year follow-up. The scar group showed a higher serum level of S100A4 (3.4±1.7 vs. 2.5±1.4 ng/mL, P<0.001) than the non-scar group. In the canine model, scar size matched the larger location of interstitial fibrosis in the NPAF group determined by Masson's trichrome staining. The expression of α-SMA and S100A4 was elevated in the NPAF group as determined by IHC compared to the control group (P<0.001). The clinical recurrence rate was markedly elevated in the scar group (27.1% vs. 8.9%, P<0.001), and the area under the ROC curve was high (0.865, 95% CI: 0.750-0.981) in predicting clinical recurrence of NPAF with the circulating S100A4 model. Conclusions: Circulating S100A4 plays a role in atrial fibrosis in NPAF patients following ablation. The level of serum S100A4 can predict the clinical recurrence of NPAF.