Orthotopic liver transplantation (OLT) was the first treatment able to modify the natural course of hereditary transthyretin (ATTRv) amyloidosis, which is a rare and fatal disorder caused by the accumulation of misfolded transthyretin (TTR) variants in different organs and tissues and which leads to a progressive and multisystem dysfunction. Because the liver is the main source of TTR, OLT dramatically reduces the production of the pathogenic TTR variant, which should prevent amyloid formation and halt disease progression. However, amyloidosis progression may occur after OLT due to wild-type TTR deposition, especially in the nerves and heart. In this review, we discuss the disease features influencing OLT outcomes and the clinical manifestations of ATTRv amyloidosis progression post-OLT to improve our understanding of disease worsening after OLT and optimize the follow-up and clinical management of these patients. By conducting a literature review on the PubMed database, we identified patient characteristics that have been associated with worse post-OLT outcomes, including late-onset V50M and non-V50M variants, age >40 years, long disease duration, advanced neuropathy and autonomic dysfunction, and malnutrition. Regarding post-OLT mortality, deaths occurring within the first year after OLT were mainly associated with fatal graft complications and infectious diseases, whereas cardiovascular-related deaths usually occurred later. Considering the diverse clinical manifestations of ATTRv amyloidosis progression post-OLT, including worsening neuropathy and/or cardiomyopathy, autonomic dysfunction, and oculoleptomeningeal involvement, we present advice on the most relevant tests for assessing disease progression post-OLT. Finally, we discuss the use of new therapies based on TTR stabilizers and TTR mRNA silencers for the treatment of ATTRv amyloidosis patients post-OLT.

Real-world evidence from published observational studies of adherence to Novel Oral Anticoagulants (NOACs) medications and associated clinical outcome events in Atrial Fibrillation (AF) patients, was reviewed systematically.
Observational studies assessing patient adherence to NOACs conducted on AF patients between September 2010 and June 2016 were identified by systematic searching keywords to locate eligible studies, in accordance with Cochrane guidelines. PubMed, Scopus and Google Scholar databases were searched to identify the studies. Meta-analysis was performed using a random effects model with DerSimonian-Laird weighting to obtain pooled effect sizes.
From 185 potentially relevant citations, 6 studies, comprising 1.6 million AF patients, were included. Among these, successful adherence to NOACs occurred in 75.6%. Adherence levels were higher in patients treated with dabigatran (72.7%) compared with those treated with apixaban (59.9%) or rivaroxaban (59.3%). However, adherence was still suboptimal (relative to an expected 80% adherence rate). Bleeding events in non-adherent patients were found to be 7.5%.
Suboptimal adherence to NOACs among AF patients was highlighted as a significant risk factor that may affect clinical outcomes, with a higher percentage of non-adherent patients having bleeding events. There is an urgent need for research on the effects of specific interventions to improve patient adherence to NOACs and to assess the related outcome factors that may be associated with adherence.

Atrial fibrillation (AF), a common arrhythmia, increases the risk of ischemic stroke. Stroke and bleeding scores for patients with AF can help to stratify risk and determine the need for antithrombotic therapy, for which warfarin has been the gold standard. Although highly effective, warfarin has several limitations that can lead to its underuse. Data from randomized, Phase III clinical trials of the novel oral anticoagulants, dabigatran, a direct thrombin inhibitor, and rivaroxaban and apixaban, both factor Xa inhibitors, indicate these drugs are at least noninferior to warfarin for the prevention of stroke and systemic embolism. They are easier to administer, and have an equivalent or lower risk of bleeding versus warfarin. A better understanding of the risks and benefits of the novel oral anticoagulants, and their use in clinical practice, will prepare clinicians to anticipate and address educational and clinical needs of AF patients and their families, and promote evidence-based prescription of appropriate and safe anticoagulation therapy.