Caspase Inhibitors for the Treatment of Hepatitis C

Howard Masuoka, Maria Eugenia Guicciardi, Gregory J. Gores

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Decreasing hepatocyte injury and death is an attractive therapeutic target in chronic hepatitis C and other liver diseases. Apoptotic cell death is a critical mechanism responsible for liver injury in hepatitis C, and contributes to hepatic fibrogenesis. At the cellular level, apoptosis is executed by a family of cysteine proteases termed caspases. Caspase inhibitors have been developed to inhibit these proteases and attenuate cellular apoptosis in vivo. By reducing hepatocyte apoptosis these agents have the potential to serve as hepatoprotective agents, minimizing liver injury and fibrosis. Studies on a variety of animal models, and time-limited studies in human patients with hepatitis C suggest these are promising therapeutic agents. However, although these agents hold promise, their usefulness requires further studies, especially longer duration studies using hepatic fibrogenesis as the end point before they can be considered further for the treatment of patients infected with the hepatitis C virus.

Original languageEnglish (US)
Pages (from-to)467-475
Number of pages9
JournalClinics in Liver Disease
Volume13
Issue number3
DOIs
StatePublished - Aug 2009
Externally publishedYes

Fingerprint

Caspase Inhibitors
Hepatitis C
Apoptosis
Hepatocytes
Liver
Wounds and Injuries
Cysteine Proteases
Chronic Hepatitis C
Caspases
Hepacivirus
Liver Cirrhosis
Liver Diseases
Peptide Hydrolases
Cell Death
Therapeutics
Animal Models

Keywords

  • Caspase inhibitors
  • Death receptors
  • Hepatic fibrogenesis
  • Hepatitis C
  • Nonalcoholic steatohepatitis

ASJC Scopus subject areas

  • Hepatology

Cite this

Caspase Inhibitors for the Treatment of Hepatitis C. / Masuoka, Howard; Guicciardi, Maria Eugenia; Gores, Gregory J.

In: Clinics in Liver Disease, Vol. 13, No. 3, 08.2009, p. 467-475.

Research output: Contribution to journalArticle

Masuoka, Howard ; Guicciardi, Maria Eugenia ; Gores, Gregory J. / Caspase Inhibitors for the Treatment of Hepatitis C. In: Clinics in Liver Disease. 2009 ; Vol. 13, No. 3. pp. 467-475.
@article{fc441ca140dd4d1f86c2f23f2cf20292,
title = "Caspase Inhibitors for the Treatment of Hepatitis C",
abstract = "Decreasing hepatocyte injury and death is an attractive therapeutic target in chronic hepatitis C and other liver diseases. Apoptotic cell death is a critical mechanism responsible for liver injury in hepatitis C, and contributes to hepatic fibrogenesis. At the cellular level, apoptosis is executed by a family of cysteine proteases termed caspases. Caspase inhibitors have been developed to inhibit these proteases and attenuate cellular apoptosis in vivo. By reducing hepatocyte apoptosis these agents have the potential to serve as hepatoprotective agents, minimizing liver injury and fibrosis. Studies on a variety of animal models, and time-limited studies in human patients with hepatitis C suggest these are promising therapeutic agents. However, although these agents hold promise, their usefulness requires further studies, especially longer duration studies using hepatic fibrogenesis as the end point before they can be considered further for the treatment of patients infected with the hepatitis C virus.",
keywords = "Caspase inhibitors, Death receptors, Hepatic fibrogenesis, Hepatitis C, Nonalcoholic steatohepatitis",
author = "Howard Masuoka and Guicciardi, {Maria Eugenia} and Gores, {Gregory J.}",
year = "2009",
month = "8",
doi = "10.1016/j.cld.2009.05.010",
language = "English (US)",
volume = "13",
pages = "467--475",
journal = "Clinics in Liver Disease",
issn = "1089-3261",
publisher = "W.B. Saunders Ltd",
number = "3",

}

TY - JOUR

T1 - Caspase Inhibitors for the Treatment of Hepatitis C

AU - Masuoka, Howard

AU - Guicciardi, Maria Eugenia

AU - Gores, Gregory J.

PY - 2009/8

Y1 - 2009/8

N2 - Decreasing hepatocyte injury and death is an attractive therapeutic target in chronic hepatitis C and other liver diseases. Apoptotic cell death is a critical mechanism responsible for liver injury in hepatitis C, and contributes to hepatic fibrogenesis. At the cellular level, apoptosis is executed by a family of cysteine proteases termed caspases. Caspase inhibitors have been developed to inhibit these proteases and attenuate cellular apoptosis in vivo. By reducing hepatocyte apoptosis these agents have the potential to serve as hepatoprotective agents, minimizing liver injury and fibrosis. Studies on a variety of animal models, and time-limited studies in human patients with hepatitis C suggest these are promising therapeutic agents. However, although these agents hold promise, their usefulness requires further studies, especially longer duration studies using hepatic fibrogenesis as the end point before they can be considered further for the treatment of patients infected with the hepatitis C virus.

AB - Decreasing hepatocyte injury and death is an attractive therapeutic target in chronic hepatitis C and other liver diseases. Apoptotic cell death is a critical mechanism responsible for liver injury in hepatitis C, and contributes to hepatic fibrogenesis. At the cellular level, apoptosis is executed by a family of cysteine proteases termed caspases. Caspase inhibitors have been developed to inhibit these proteases and attenuate cellular apoptosis in vivo. By reducing hepatocyte apoptosis these agents have the potential to serve as hepatoprotective agents, minimizing liver injury and fibrosis. Studies on a variety of animal models, and time-limited studies in human patients with hepatitis C suggest these are promising therapeutic agents. However, although these agents hold promise, their usefulness requires further studies, especially longer duration studies using hepatic fibrogenesis as the end point before they can be considered further for the treatment of patients infected with the hepatitis C virus.

KW - Caspase inhibitors

KW - Death receptors

KW - Hepatic fibrogenesis

KW - Hepatitis C

KW - Nonalcoholic steatohepatitis

UR - http://www.scopus.com/inward/record.url?scp=67650552582&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67650552582&partnerID=8YFLogxK

U2 - 10.1016/j.cld.2009.05.010

DO - 10.1016/j.cld.2009.05.010

M3 - Article

C2 - 19628162

AN - SCOPUS:67650552582

VL - 13

SP - 467

EP - 475

JO - Clinics in Liver Disease

JF - Clinics in Liver Disease

SN - 1089-3261

IS - 3

ER -