Treatment of liver fibrosis: Past, current, and future

Abstract

Liver fibrosis accompanies the progression of chronic liver diseases independent of etiologies, such as hepatitis viral infection, alcohol consumption, and metabolic-associated fatty liver disease. It is commonly associated with liver injury, inflammation, and cell death. Liver fibrosis is characterized by abnormal accumulation of extracellular matrix components that are expressed by liver myofibroblasts such as collagens and alpha-smooth actin proteins. Activated hepatic stellate cells contribute to the major population of myofibroblasts. Many treatments for liver fibrosis have been investigated in clinical trials, including dietary supplementation ( e.g. , vitamin C), biological treatment ( e.g. , simtuzumab), drug ( e.g. , pegbelfermin and natural herbs), genetic regulation ( e.g. , non-coding RNAs), and transplantation of stem cells ( e.g. , hematopoietic stem cells). However, none of these treatments has been approved by Food and Drug Administration. The treatment efficacy can be evaluated by histological staining methods, imaging methods, and serum biomarkers, as well as fibrosis scoring systems, such as fibrosis-4 index, aspartate aminotransferase to platelet ratio, and non-alcoholic fatty liver disease fibrosis score. Furthermore, the reverse of liver fibrosis is slowly and frequently impossible for advanced fibrosis or cirrhosis. To avoid the life-threatening stage of liver fibrosis, anti-fibrotic treatments, especially for combined behavior prevention, biological treatment, drugs or herb medicines, and dietary regulation are needed. This review summarizes the past studies and current and future treatments for liver fibrosis.

LP340, a novel histone deacetylase inhibitor, decreases liver injury and fibrosis in mice: role of oxidative stress and microRNA-23a

“…Many antifibrotic treatments targeting various fibrotic pathways have been assessed in liver fibrosis, such as angiotensinconverting enzyme inhibitors, angiotensin receptor blockers, interferon, pioglitazone, colchicine, farglitazar, simtuzumab, non-coding RNAs, pegbelfermin, natural herbs, and transplantation of stem cells (Friedman, 2015;Rockey et al, 2015;Trautwein et al, 2015). Unfortunately, only a very few of these treatments show modest effects in clinical trials, whereas most other treatments are ineffective (Friedman, 2015;Malaguarnera et al, 2015;Rockey et al, 2015;Trautwein et al, 2015;Zhang et al, 2023). The lack of broadly effective treatment for fibrosis continues to fuel the search for new molecular targets of fibrosis and effective drugs for prevention and therapy.…”

“…Liver fibrosis results from wound-healing responses to repeated injury during the progression of most chronic liver diseases (Bataller and Brenner, 2005;Zhang et al, 2023). Many cellular and molecular signals contribute to the initiation and progression of liver fibrosis, including cell death, oxidative stress, mitochondrial dysfunction, inflammatory processes, proinflammatory/profibrotic cytokines, vasoactive substances, adipokines, microRNAs, ductular reactions, and genetic factors (Gabele et al, 2003;Bataller and Brenner, 2005;Zhang et al, 2023).…”

“…Liver fibrosis results from wound-healing responses to repeated injury during the progression of most chronic liver diseases (Bataller and Brenner, 2005;Zhang et al, 2023). Many cellular and molecular signals contribute to the initiation and progression of liver fibrosis, including cell death, oxidative stress, mitochondrial dysfunction, inflammatory processes, proinflammatory/profibrotic cytokines, vasoactive substances, adipokines, microRNAs, ductular reactions, and genetic factors (Gabele et al, 2003;Bataller and Brenner, 2005;Zhang et al, 2023). Chronic liver injury stimulates a multicellular response involving many hepatic resident and infiltrating cells, which release a variety of mediators to stimulate inflammatory, proliferative, and profibrogenic responses (Guo et al, 2009;Brenner et al, 2012;Higashi et al, 2017).…”

NAFLD Fibrosis Progression and Type 2 Diabetes: The Hepatic–Metabolic Interplay

“…On the other hand, multiple drugs have been tested for their potential anti-inflammatory, cytoprotective, and antifibrotic effects in NAFLD patients [3,173,174]. Unfortunately, a great number of them have failed to demonstrate histologic improvement in fibrosis in clinical trials, but a few have shown some promising benefits [174][175][176]. However, there is no drug approved so far for NASH-associated fibrosis in patients with or without T2DM.…”

Can Nutraceuticals Support the Treatment of MASLD/MASH, and thus Affect the Process of Liver Fibrosis?

“…According to the authors, antifibrotic treatment should include behavioral therapy, medications, and nutritional factors. Introducing such a procedure may be helpful in reducing inflammation and oxidative stress and preventing the death of hepatocytes, which may significantly reduce the risk of fibrosis and organ failure [7].…”