Ischemia and reperfusion injury (IRI) is a common complication caused by inflammation and oxidative stress resulting from liver surgery. Current therapeutic strategies do not present the desirable efficacy, and severe side effects can occur. To overcome these drawbacks, new therapeutic alternatives are necessary. Drug delivery nanosystems have been explored due to their capacity to improve the therapeutic index of conventional drugs. Within nanocarriers, liposomes are one of the most successful, with several formulations currently in the market. As improved therapeutic outcomes have been demonstrated by using liposomes as drug carriers, this nanosystem was used to deliver quercetin, a flavonoid with anti-inflammatory and antioxidant properties, in hepatic IRI treatment. In the present work, a stable quercetin liposomal formulation was developed and characterized. Additionally, an in vitro model of ischemia and reperfusion was developed with a hypoxia chamber, where the anti-inflammatory potential of liposomal quercetin was evaluated, revealing the downregulation of pro-inflammatory markers. The anti-inflammatory effect of quercetin liposomes was also assessed in vivo in a rat model of hepatic IRI, in which a decrease in inflammation markers and enhanced recovery were observed. These results demonstrate that quercetin liposomes may provide a significant tool for addressing the current bottlenecks in hepatic IRI treatment.

Familial amyloidotic polyneuropathy (FAP) has a high prevalence in Portugal, and the most common form of hereditary amyloidosis is caused by an amyloidogenic variant of transthyretin (TTR) with a substitution of methionine for valine at position 30 (V30M). Until now, the available efficient therapy is liver transplantation, when performed in an early phase of the onset of the disease symptoms. However, transplanted FAP patients have a significantly higher incidence of early hepatic artery thrombosis compared with non-FAP transplanted patients. Because FAP was described as an independent risk factor for early hepatic artery thrombosis, more studies to understand the underlying mechanisms involved in this outcome are of the utmost importance. Knowing that the liver is the major site for TTR production, we investigated the biological effects of TTR proteins in the vasculature and on angiogenesis. In this study, we identified genes differentially expressed in endothelial cells exposed to the WT or V30M tetramer. We found that endothelial cells may acquire different molecular identities when exposed to these proteins, and consequently TTR could regulate angiogenesis. Moreover, we show that V30M decreases endothelial survival by inducing apoptosis, and it inhibits migration. These findings provide new knowledge that may have critical implications in the prevention of early hepatic artery thrombosis in FAP patients after liver transplantation.

Early thrombotic complications are critical causes of in-hospital morbidity after orthotopic liver transplantation (OLT), potentially culminating in graft loss. The aim of this study was to retrospectively analyse these complications, trying to identify associated independent risk factors. This retrospective analysis included 223 OLTs performed on 213 patients, in a 30-month period. Eighty-six OLTs were performed on familial amyloidotic polyneuropathy (FAP) patients. Preoperative details (primary diagnosis and Child-Turcotte-Pugh classification, when applicable), surgical features (including type of arterial reconstruction), postoperative variables and outcome were analysed. The observation period ended 30 days post-OLT, until discharge or in-hospital death. Early thrombotic complications were diagnosed in 16 cases (7.2%), affecting mainly FAP patients (n = 12). Hepatic artery thrombosis (HAT) was the most frequent early thrombotic event (n = 12): incidence in FAP patients 11.6% (n = 10) versus incidence in non FAP patients 1.5% (n = 2), P = 0.001. By logistic regression analysis, FAP turned out to be an independent risk factor for early thrombotic complications, and specifically for HAT. The type of arterial reconstruction and other analysed surgical and medical factors did not influence early HAT occurrence. In conclusion, FAP was identified in this study as an independent risk factor for early HAT, a new datum not yet described in the literature.