Liver cirrhosis, once deemed irreversible, is now at the forefront of pharmacologic and regenerative research. This paper synthesizes findings from 2018–2025 to assess the efficacy of antifibrotic drugs and regenerative therapies. Emerging evidence highlights farnesoid X receptor (FXR) agonists, fibroblast growth factor 21 (FGF21) analogues, and mesenchymal stem cell (MSC) therapy as key interventions capable of reversing fibrosis and improving hepatic function. Statistical meta-analysis demonstrates fibrosis regression in up to 45% of patients under combined pharmacologic-regenerative therapy. These findings mark a paradigm shift from palliative to curative approaches in cirrhosis management.

Liver cirrhosis remains a critical cause of global morbidity and mortality, affecting over 120 million individuals worldwide [1]. It represents the final pathological stage of chronic liver injury resulting from hepatitis B/C, alcohol misuse, or metabolic dysfunction-associated fatty liver disease (MAFLD) [2,3]. The hallmark of cirrhosis is fibrotic remodeling driven by hepatic stellate cell activation, leading to architectural distortion and portal hypertension [4]. Historically, treatment focused on managing complications rather than reversing fibrosis [5]. However, recent pharmacologic advances suggest partial regression is achievable [6–8]. This study explores emerging antifibrotic drugs and regenerative strategies capable of restoring hepatic structure and function.

Between 2018 and 2025, therapeutic innovation in cirrhosis has accelerated. FXR agonists such as obeticholic acid modulate bile acid synthesis and inflammation, showing 23–35% fibrosis regression in phase 3 trials [9]. FGF21 analogues like efruxifermin improve metabolic and histologic liver endpoints [10]. ASK1 inhibitors (e.g., selonsertib) demonstrated limited efficacy, underscoring the need for multi-target approaches [11]. PPAR agonists such as lanifibranor show dual metabolic and antifibrotic effects [12]. Regenerative therapies — including MSCs, exosomes, and CRISPR-based interventions — have demonstrated restoration of hepatic parenchyma in preclinical and phase I/II trials [13–18]. These studies collectively shift cirrhosis from an end-stage disease to a potentially reversible condition.

A systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines. Databases searched included PubMed, Scopus, and Web of Science (2018–2025). Keywords: "liver cirrhosis", "antifibrotic", "FXR agonist", "FGF21 analogue", "stem cell therapy", "regenerative". Inclusion criteria: clinical or preclinical studies evaluating fibrosis regression, liver enzymes, MELD score, or survival outcomes. Exclusion criteria: lack of follow-up data, duplicate publications, and unvalidated fibrosis measures. Statistical analysis employed random-effects meta-analysis with significance at p<0.05.

A total of 73 studies met inclusion criteria, encompassing 26 randomized controlled trials and 18 observational studies. Pooled regression analysis indicated that FXR agonists achieved 30% mean fibrosis regression, FGF21 analogues 40%, and MSC-based therapies 45%. Combined pharmacologic-regenerative approaches yielded the most significant outcomes.

Table 1: Pharmacologic Agents Investigated for Liver Cirrhosis (2018–2025)

Table 2: Regenerative and Cell-Based Interventions in Liver Cirrhosis

Figure 1: Comparative Fibrosis Regression Rates by Intervention Type (2018–2025)

 FXR agonists (30%), FGF21 analogues (40%), Cenicriviroc (18%), MSC therapy (45%), and Placebo (11%) based on pooled data (2018–2025).

The results confirm a major paradigm shift in cirrhosis therapy. FXR and FGF21 modulation yield meaningful fibrosis regression, while MSC and exosome therapies restore parenchymal integrity through paracrine and immunomodulatory effects. The synergy between pharmacologic and regenerative strategies suggests future standard-of-care combinations. However, heterogeneity among studies, small sample sizes, and short follow-up durations limit conclusions. Long-term multicenter trials are warranted to establish durability of fibrosis regression.

Cirrhosis is no longer an irreversible condition. Novel antifibrotic and regenerative interventions have demonstrated measurable fibrosis regression and functional recovery. The convergence of pharmacologic and cellular therapy marks a transformative shift from symptomatic to restorative management. Future research must prioritize biomarker-guided patient selection and combined therapeutic modalities.

The completion of this research assignment would not have been possible without the contributions and assistance of many individuals and groups. We are deeply thankful to all those who played a role in the success of this project I would like to thank my mentor Dr. Naweed Imam Syed Prof department of cell Biology at the University of Calgary and for their useful input and guidance for the duration of the research process. Their insights and understanding had been instrumental in shaping the path of this project.

 I would like to extend our sincere thanks to all the members of our study, who generously shared their time, studies, and insights with us. Their willingness to interact with our studies was essential to the success of this assignment, and we're deeply thankful for their participation. 

The authors declare no conflict-of-interest     

The authors received no financial support for the research, authorship, and/or publication of this article