PARP‑1 in liver diseases: Molecular mechanisms, therapeutic potential and emerging clinical applications (Review).

Abstract

The liver, despite its capacity for self‑repair, faces major challenges when excessive damage leads to fibrosis and impaired function, potentially progressing to severe liver diseases, including cirrhosis, hepatocellular carcinoma (HCC) and non‑alcoholic fatty liver disease (NAFLD). Although advancements in understanding the molecular landscapes of these conditions have been made, clinical outcomes remain suboptimal. Therefore, novel therapeutic targets are necessary. Poly(ADP‑ribose) polymerase‑1 (PARP‑1), a pivotal enzyme in DNA damage response and repair, has emerged as a critical contributor to liver pathophysiology. The present review explores the expression, regulation and mechanism of action of PARP‑1 in various liver diseases, including viral hepatitis, alcoholic liver disease, NAFLD, hepatic fibrosis, HCC, drug‑induced liver injury and autoimmune liver diseases. The involvement of PARP‑1 in key cellular signaling pathways, particularly those associated with inflammation, apoptosis and immune regulation, highlights its clinical relevance as a biomarker and therapeutic target. The potential of PARP inhibitors to improve outcomes in patients with liver disease is discussed, both as stand‑alone treatments and in combination with modalities such as immune checkpoint inhibitors and DNA damage repair inhibitors. Leveraging recent advancements in PARP imaging and rare genetic biomarker research, this review underscores the potential of PARP‑1‑based diagnostics and therapies while advocating for future studies to overcome resistance mechanisms and expand therapeutic applications.