Letter: PCSK9 inhibitor for liver transplant patients during the post‐statin era? Authors' reply

Editors, We thank Dr. Wang et al for their interest in our paper.1,2 They suggested that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors could be a promising option for the treatment of dyslipidaemia in liver transplant (LT) recipients since they may be better tolerated. Serious adverse drug reactions, unstable immunosuppression level and immunological reactions have been reported only rarely with PCSK9 inhibitors, supporting that they may have an acceptable safety profile in solid organ transplant (SOT) recipients.3 Although certainly true, this consideration falls outside the initial assumptions of our study, which did not focus primarily on the hypolipidaemic properties of statins, but rather on their pleiotropic effects. Indeed, part of the benefits attributed to statins in cardiovascular disease is due to their pleiotropic properties influencing vascular remodelling and protecting the liver sinusoidal endothelium, among others.4 These may explain the beneficial effects of statins in other conditions, and particularly the effect on decreasing fibrogenesis that may translate into preventing disease progression and facilitating its regression.4 Although recent studies have advocated pleiotropic effects for PCSK9 inhibitors,5 there are still no data on special populations such as SOT recipients to suggest a survival benefit.3 In our cohort, even with the limitation of a retrospective study, we demonstrated that the use of statins in LT recipients was associated with lower mortality (hazard ratio = 0.35; 95% confidence interval 0.12– 0.98; p = 0.047) and lower retransplantation rate.2 This is consistent with the findings of a recent small, doubleblind randomised controlled trial.6 Lastly, but not an irrelevant issue, the current prescription status of these drugs and their cost make them difficult to integrate into the standard of care for patients who do tolerate statins the vast majority in our studies. In summary, we believe that the use of these antibodies could certainly be an interesting future direction of improving postLT care, particularly for patients intolerant to statins. However, further studies are needed, especially for proving a survival benefit. AUTHOR CONTRIBUTIONS Chiara Becchetti: Conceptualization (equal); writing – original draft (equal); writing – review and editing (equal). Melisa Dirchwolf: Supervision (equal); writing – review and editing (equal). Annalisa Berzigotti: Supervision (equal). Jaume Bosch: Conceptualization (equal); supervision (equal); writing – review and editing (equal).