Pathophysiology and Pharmacological Management of Chronic Liver Injury: Current Challenges and Future Directions

Chronic liver injury results from persistent hepatic injuries such as metabolic disorders, alcohol consumption, viral infections, drug toxicity, autoimmune conditions, and genetic factors. It is a major global health concern due to its progression to fibrosis, cirrhosis, and hepatocellular carcinoma. This review aims to summarize key pathophysiological mechanisms and evaluate current and emerging pharmacological strategies.

A narrative review of preclinical and clinical studies was conducted, focusing on inflammation, oxidative stress, immune dysfunction, fibrogenesis, and therapeutic approaches, including conventional drugs, antifibrotics, metabolic modulators, and advanced drug delivery systems. A total of 352 records were identified, of which 158 studies were included in the review.

Chronic liver injury is characterized by persistent inflammation, oxidative stress, hepatocyte death, impaired regeneration, and activation of hepatic stellate cells, leading to extracellular matrix accumulation and fibrosis. Current therapies are largely etiology-based and slow disease progression but rarely reverse fibrosis. Emerging therapies targeting nuclear receptors, metabolic pathways, gene-based interventions, microbiome modulation, and nanocarrier-based systems show promising potential.

These findings indicate that chronic liver injury is a complex, multifactorial process involving interconnected molecular pathways, limiting the effectiveness of single-target therapies. The gap between mechanistic insights and clinical translation remains a key challenge. Multi-targeted, combination, and precision-based therapeutic approaches, along with targeted drug delivery systems, may enhance treatment efficacy and overcome current limitations.

Despite advances in understanding disease mechanisms, effective diseasemodifying therapies remain limited. The development of combination and personalized treatment strategies is essential for improving outcomes and preventing disease progression.