An Update on Efficacy and Safety of Emerging Hepatic Antifibrotic Agents

Abstract

Liver fibrosis represents a response to chronic liver injury. Metabolic dysfunction-associated fatty liver disease and metabolic dysfunction-associated steatohepatitis are the most common chronic liver diseases, both with increasing incidence. Therefore, there is a great impetus for development of agents targeting these conditions. Accumulating data on possible treatment options for liver fibrosis are emerging in the literature. However, despite extensive research and much effort in the field, approved agents for liver fibrosis are still lacking. In this critical review, we have summarized the main data about specific treatment options for liver fibrosis gained from ongoing clinical trials, with an emphasis on efficacy and safety of these agents.

Unraveling the pathophysiologic role of galectin‐3 in chronically injured liver

“…These promising experimental findings led to the evaluation of GR‐MD‐02 in clinical studies. Galectin inhibitors are shown to be beneficial in liver disease patients (Al Attar et al, 2021) and therefore, Gal‐3 inhibitors are emerging as an important antifibrotic agent (Rupcic Rubin et al, 2021). In a phase 1 clinical trial, single and 3 weekly repeated doses (2, 4, and 8 mg/kg) of belapectin (GR‐MD‐02) were shown to be safe and well‐tolerated in patients with histologically confirmed NASH and advanced fibrosis (Harrison et al, 2016).…”

Salvianolic acid B attenuates liver fibrosis by targeting Ecm1 and inhibiting hepatocyte ferroptosis

“…However, despite the emergence of small-molecule targeted drugs in recent years, their efficacy in treating liver fibrosis remains uncertain. Currently, there are no FDA-approved biological or chemical drugs available for liver fibrosis [ 4 , 5 ]. The urgent and critical clinical needs necessitate the investigation of novel therapeutic targets and candidate drugs that can significantly contribute to the prevention and treatment of liver fibrosis.…”

Side effect profile of pharmacologic therapies for liver fibrosis in nonalcoholic fatty liver disease: a systematic review and network meta-analysis

“…Multiple clinical trials have been conducted in an effort to find a recognized medical remedy for NAFLD/NASH [16]. However, there is no approved drug for NAFLD-related liver fibrosis currently [17,18]. Recently, a systematic review and network meta-analysis (NMA) was conducted to evaluate the effect of different drug interventions on NASH so as to evaluate their relative ranking in improving fibrosis [19].…”