Tamer A. Addissouky
1,2,3,4* 
1 Medical Laboratories Techniques Department, College of Technology and Health Sciences, AL-Mustaqbal University, 51001, Hillah, Babylon, Iraq
2 Department of Biochemistry, Science Faculty, Menoufia University, Menoufia, Egypt
3 New burg El-Arab Hospital, Ministry of Health, Alexandria, Egypt
4 American Society for Clinical Pathology (ASCP), Chicago, USA
Abstract
Liver fibrosis, characterized by excessive accumulation of extracellular matrix (ECM), is a critical precursor to cirrhosis and hepatocellular carcinoma. While the liver itself lacks pain fibers, fibrosis progression can induce pain through various mechanisms, significantly impacting patient quality of life and potentially influencing disease outcomes. This review aims to elucidate the complex relationship between liver fibrosis and pain, exploring recent advances in pain assessment, management strategies, and emerging therapies. The pathophysiology of liver fibrosis involves intricate cellular and molecular mechanisms, with hepatic stellate cell (HSC) activation playing a central role. Pain in liver fibrosis arises from capsular distension, inflammation-induced nociception, and neuropathic pain. Recent advances in pain assessment include the exploration of biomarkers, advanced imaging techniques, and liver-specific patient-reported outcome measures. Current management strategies encompass pharmacological approaches with liver-specific considerations, non-pharmacological interventions, and complementary medicine. Emerging therapies, including novel antifibrotic agents, targeted pain therapies, and regenerative medicine approaches, offer promising avenues for addressing both fibrosis and associated pain. However, challenges persist in balancing pain relief with the preservation of liver function and managing altered drug metabolism in liver disease. The future of pain management in liver fibrosis lies in personalized approaches, integrating pain management into comprehensive liver care and exploring the potential of fibrosis reversal for pain relief. As our understanding of the molecular mechanisms underlying both liver fibrosis and pain deepens, targeted therapies addressing patient-specific pain pathways while simultaneously targeting fibrosis progression may become a reality.