Hepatic stellate cell activation and liver fibrosis are associated with necroinflammatory injury and Th1-like response in chronic hepatitis C

Gianluca Svegliati Baroni, Alfredo Pastorelli, Aldo Manzin, Antonio Benedetti, Luca Marucci, Laura Solforosi, Antonio Di Sario, Eugenio Brunelli, Francesco Orlandi, Massimo Clementi, Giampiero Macarri

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Background/Aims: The involvement of a direct viral cytopathic effect or an immune-mediated mechanism in the progression of hepatic damage in chronic hepatitis C is controversial. The type of immune response is itself a matter of controversy, and histological data are lacking. The aim of this study was to identify the factors associated with the progression of liver injury in 30 HCV/RNA-positive untreated patients with chronic hepatitis. Methods: Necroinflammatory and architectural damage were evaluated using Ishak's score. Activated hepatic stellate cells (HSC) were visualized by immunohistochemistry for α-smooth muscle actin (αSMA) and quantitated by morphometry. Plasma HCV/RNA was evaluated using a competitive RT-PCR method. To study the type of immune response involved in the progression of liver injury, interferonγ (IFNγ)-positive cells (as expression of a Th1-like response) were evaluated by immunohistochemistry and quantitated by morphometry. Results: HSC were mostly detected close to areas of lobular necroinflammation or lining fibrotic septa. The αSMA- and Sirius Red-positive parenchyma correlated significantly with necroinflammatory and architectural scores. IFNγ-positive cells were detected in periportal areas associated with the inflammatory infiltrates and significantly correlated with architectural damage. No relationship was found between the histological features of liver injury and viral load. Conclusions: HSC activation and progression of liver injury are unrelated to viral load but associated with a Th1-like response, a plausible target for the treatment of chronic hepatitis C.

Original languageEnglish
Pages (from-to)212-219
Number of pages8
JournalLiver
Volume19
Issue number3
DOIs
Publication statusPublished - 1999

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Hepatic Stellate Cells
Chronic Hepatitis C
Liver Cirrhosis
Liver
Wounds and Injuries
Viral Load
Interferons
Smooth Muscle
Actins
Viral Cytopathogenic Effect
Immunohistochemistry
RNA
Chronic Hepatitis
Polymerase Chain Reaction

Keywords

  • Fibrosis
  • HCV
  • Hepatic stellate cells
  • Interferon gamma
  • Viral load

ASJC Scopus subject areas

  • Hepatology

Cite this

Hepatic stellate cell activation and liver fibrosis are associated with necroinflammatory injury and Th1-like response in chronic hepatitis C. / Baroni, Gianluca Svegliati; Pastorelli, Alfredo; Manzin, Aldo; Benedetti, Antonio; Marucci, Luca; Solforosi, Laura; Di Sario, Antonio; Brunelli, Eugenio; Orlandi, Francesco; Clementi, Massimo; Macarri, Giampiero.

In: Liver, Vol. 19, No. 3, 1999, p. 212-219.

Research output: Contribution to journalArticle

Baroni, GS, Pastorelli, A, Manzin, A, Benedetti, A, Marucci, L, Solforosi, L, Di Sario, A, Brunelli, E, Orlandi, F, Clementi, M & Macarri, G 1999, 'Hepatic stellate cell activation and liver fibrosis are associated with necroinflammatory injury and Th1-like response in chronic hepatitis C', Liver, vol. 19, no. 3, pp. 212-219. https://doi.org/10.1111/j.1478-3231.1999.tb00038.x
Baroni, Gianluca Svegliati ; Pastorelli, Alfredo ; Manzin, Aldo ; Benedetti, Antonio ; Marucci, Luca ; Solforosi, Laura ; Di Sario, Antonio ; Brunelli, Eugenio ; Orlandi, Francesco ; Clementi, Massimo ; Macarri, Giampiero. / Hepatic stellate cell activation and liver fibrosis are associated with necroinflammatory injury and Th1-like response in chronic hepatitis C. In: Liver. 1999 ; Vol. 19, No. 3. pp. 212-219.
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AU - Baroni, Gianluca Svegliati

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AU - Manzin, Aldo

AU - Benedetti, Antonio

AU - Marucci, Luca

AU - Solforosi, Laura

AU - Di Sario, Antonio

AU - Brunelli, Eugenio

AU - Orlandi, Francesco

AU - Clementi, Massimo

AU - Macarri, Giampiero

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AB - Background/Aims: The involvement of a direct viral cytopathic effect or an immune-mediated mechanism in the progression of hepatic damage in chronic hepatitis C is controversial. The type of immune response is itself a matter of controversy, and histological data are lacking. The aim of this study was to identify the factors associated with the progression of liver injury in 30 HCV/RNA-positive untreated patients with chronic hepatitis. Methods: Necroinflammatory and architectural damage were evaluated using Ishak's score. Activated hepatic stellate cells (HSC) were visualized by immunohistochemistry for α-smooth muscle actin (αSMA) and quantitated by morphometry. Plasma HCV/RNA was evaluated using a competitive RT-PCR method. To study the type of immune response involved in the progression of liver injury, interferonγ (IFNγ)-positive cells (as expression of a Th1-like response) were evaluated by immunohistochemistry and quantitated by morphometry. Results: HSC were mostly detected close to areas of lobular necroinflammation or lining fibrotic septa. The αSMA- and Sirius Red-positive parenchyma correlated significantly with necroinflammatory and architectural scores. IFNγ-positive cells were detected in periportal areas associated with the inflammatory infiltrates and significantly correlated with architectural damage. No relationship was found between the histological features of liver injury and viral load. Conclusions: HSC activation and progression of liver injury are unrelated to viral load but associated with a Th1-like response, a plausible target for the treatment of chronic hepatitis C.

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