2026-04-29T23:04:18Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/171902024-09-27T20:53:20Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud
author
Sepulveda-Crespo, Daniel
author
Resino, Salvador
author
Martinez, Isidoro
funder
Instituto de Salud Carlos III
funder
Plan Nacional de I+D+i (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Fundación Seimc-Gesida
funder
Fundación ONCE
funder
Unión Europea. Fondo Social Europeo (ESF/FSE)
2024-01-17T10:54:40Z
2024-01-17T10:54:40Z
2021-03
Drugs. 2021 Mar;81(4):419-443.
10.1007/s40265-020-01458-x
1179-1950
Drugs
33400242
http://hdl.handle.net/20.500.12105/17190
Direct-acting antivirals eliminate hepatitis C virus (HCV) in more than 95% of treated individuals and may abolish liver injury, arrest fibrogenesis, and reverse fibrosis and cirrhosis. However, liver regeneration is usually a slow process that is less effective in the late stages of fibrosis. What is more, fibrogenesis may prevail in patients with advanced cirrhosis, where it can progress to liver failure and hepatocellular carcinoma. Therefore, the development of antifibrotic drugs that halt and reverse fibrosis progression is urgently needed. Fibrosis occurs due to the repair process of damaged hepatic tissue, which eventually leads to scarring. The innate immune response against HCV is essential in the initiation and progression of liver fibrosis. HCV-infected hepatocytes and liver macrophages secrete proinflammatory cytokines and chemokines that promote the activation and differentiation of hepatic stellate cells (HSCs) to myofibroblasts that produce extracellular matrix (ECM) components. Prolonged ECM production by myofibroblasts due to chronic inflammation is essential to the development of fibrosis. While no antifibrotic therapy is approved to date, several drugs are being tested in phase 2 and phase 3 trials with promising results. This review discusses current state-of-the-art knowledge on treatments targeting the innate immune system to revert chronic hepatitis C-associated liver fibrosis. Agents that cause liver damage may vary (alcohol, virus infection, etc.), but fibrosis progression shows common patterns among them, including chronic inflammation and immune dysregulation, hepatocyte injury, HSC activation, and excessive ECM deposition. Therefore, mechanisms underlying these processes are promising targets for general antifibrotic therapies.
eng
Strategies Targeting the Innate Immune Response for the Treatment of Hepatitis C Virus-Associated Liver Fibrosis
review article
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URL
https://repisalud.isciii.es/bitstreams/db16ecfb-e339-4782-aa28-c6277c2a8053/download
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StrategiesTargetingInnateImmune_2021.pdf
URL
https://repisalud.isciii.es/bitstreams/512bd212-9aaf-4739-8c61-c1d18dc0548c/download
File
MD5
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text/plain
StrategiesTargetingInnateImmune_2021.pdf.txt