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.

Keywords: Liver fibrosis; Molecular mechanism; Therapeutic targets; Treatments; Clinical trials

Core Tip: Liver fibrosis accompanies the progression of chronic liver diseases independent of their etiologies. The initiation and progression of liver fibrosis are mainly driven by liver inflammation, cell death, and metabolic dysregulation, which cause the activation of hepatic stellate cells and excessive accumulation of extracellular matrix proteins. Without effective treatments, liver fibrosis can lead to cirrhosis and primary liver cancer. To date, current therapeutic options for liver fibrosis are limited to prevent the initial causing factors for liver inflammation, hepatocyte cell death, and oxidative stress. However, 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 including biological, medicines, dietary change, and behavior prevention are needed, especially for combined therapy.