Pleiotropic effects of statins in hepatology and venous thromboembolism: real-world evidence analysis (2016–2025)

Abstract

Statins, as inhibitors of HMG-CoA reductase, exert pleiotropic effects beyond lipid lowering, including endothelialprotective, anti-inflammatory, and antifibrotic properties relevant to liver diseases and venous thromboembolism (VTE). Objective. To summarize real-world evidence on the pleiotropic effects of statins in hepatology, define the “therapeutic window” in cirrhosis, and evaluate their role in VTE prevention. Materials and Methods. A structured literature search was performed in PubMed for the period 2016–2025 using predefined keywords related to statins, cirrhosis, hepatocellular carcinoma, portal hypertension, and VTE. A total of 261 publications were identified, of which 35 met the inclusion criteria. To minimize bias, studies employing modern pharmacoepidemiological approaches were prioritized, including propensity score matching, time-lag analysis, and sensitivity analyses. Results. Statin therapy is associated with improved intrahepatic hemodynamics through KLF2 signaling and nitric oxide pathways, as well as antifibrotic effects mediated by Rho-kinase inhibition. In real-world cohort studies, statin use has been linked to reduced risks of cirrhosis decompensation, hepatocellular carcinoma, and mortality, particularly in patients with compensated disease. The concept of a “therapeutic window” suggests the most favorable benefit-risk balance in patients with Child–Pugh class A cirrhosis. In the context of VTE, statins demonstrate modest effects in primary prevention but a more consistent reduction in recurrence risk. Observational data support a favorable safety profile and challenge the concept of “statin phobia.” Conclusions. Statins may be considered as adjunctive therapy in selected patients with chronic liver disease and increased thrombotic risk. The greatest benefit appears to be observed in compensated stages of disease, while further randomized controlled trials are needed to establish causality and refine clinical indications.

У статті представлено аналіз плейотропних ефектів статинів у гепатології та за наявності венозних тромбоемболій (ВТЕ), що базується на даних PubMed за період 2016–2025 рр. Розглянуто молекулярні механізми гепатопротекції. Наведено докази ефективності статинів у зниженні ризику декомпенсації цирозу печінки та профілактиці гепатоцелюлярної карциноми у пацієнтів із вірусними гепатитами. Окрему увагу приділено зниженню частоти первинних та рецидивуючих ВТЕ в умовах реальної практики.