The impact of emricasan on chronic liver diseases: current data

Immoderate caspase-mediated apoptosis in chronic liver injury is a crucial driver of sustained HSC activation and worsening hepatic inflammation as well as fibrosis, with the ultimate outcome of liver cirrhosis and its consequences. Therefore, the inhibition of hepatocyte apoptosis by caspase cascad...

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Bibliographic Details
Published in:Clinical journal of gastroenterology 2022-04, Vol.15 (2), p.271-285
Main Authors: Lekakis, Vasileios, Cholongitas, Evangelos
Format: Article
Language:English
Subjects:
Abdominal Surgery
Animals
Clinical Review
Colorectal Surgery
Gastroenterology
Hepatology
Humans
Hypertension, Portal - drug therapy
Liver - pathology
Liver Cirrhosis - drug therapy
Medicine
Medicine & Public Health
Pentanoic Acids - pharmacology
Pentanoic Acids - therapeutic use
Surgical Oncology
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Summary:Immoderate caspase-mediated apoptosis in chronic liver injury is a crucial driver of sustained HSC activation and worsening hepatic inflammation as well as fibrosis, with the ultimate outcome of liver cirrhosis and its consequences. Therefore, the inhibition of hepatocyte apoptosis by caspase cascade blockage may be a promising therapeutic strategy to achieve fibrosis regression in chronic liver diseases. Emricasan is a broad-spectrum, liver-targeted caspase inhibitor with a favorable pharmacokinetic profile, characterized by prolonged retention in the liver and low systemic exposure after oral administration. In animal models, emricasan had a clear intrahepatic anti-apoptotic effect with consequent elimination of circulating pro-inflammatory cytokines and favorable impact in liver fibrogenesis and portal pressure. Even though, this intrahepatic drug effect confirmed in human clinical trials, no clear linkage was emerged with portal hypertension, liver function or liver histology in both non-cirrhotic and cirrhotic patients except from a subgroup of patients with high MELD score (> 15) or severe HVPG (> 16 mmHg). As emricasan treatment appeared safe and well-tolerated, irrespective the severity of liver disease, more studies are required to clarify better these subgroups of patients who may benefit most from this drug.
ISSN:1865-7257
1865-7265
DOI:10.1007/s12328-021-01585-2