Hepatocyte apoptosis and Fas expression are prominent features of human nonalcoholic steatohepatitis

Ariel E. Feldstein, Ali Canbay, Paul Angulo, Makiko Taniai, Lawrence J. Burgart, Keith Lindor, Gregory J. Gores

Research output: Contribution to journalArticle

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Abstract

Background & Aims: The pathogenesis of nonalcoholic steatohepatitis (NASH) remains poorly understood. Although apoptosis is a common mechanism of liver injury, the extent and clinical significance of apoptosis in NASH has not been examined. Thus, the aims of this study were to quantify hepatocyte apoptosis in NASH, correlate it with disease severity, and identify possible mechanisms of apoptosis induction. Methods: Hepatocyte apoptosis was assessed in NASH, simple steatosis, alcoholic hepatitis, and controls without liver disease using the TUNEL assay and immunohistochemistry for activated caspases 3 and 7. Liver specimens were also graded according to the magnitude of inflammation and fibrosis. Results: TUNEL-positive cells were significantly increased in liver biopsy specimens from patients with NASH compared with simple steatosis and controls. Unexpectedly, TUNEL-positive cells were also greater in NASH vs. alcoholic hepatitis. Immunohistochemistry demonstrated active caspases 3 and 7 in NASH specimens, confirming the occurrence of apoptosis in this disease. A positive correlation was observed between hepatocyte apoptosis and hepatic fibrosis and inflammatory activity, respectively. The Fas receptor was strongly expressed in hepatocytes in liver specimens from NASH patients as compared with controls. Conclusions: Hepatocyte apoptosis is significantly increased in patients with NASH and correlates with disease severity, suggesting that antiapoptotic therapy may be useful in this syndrome.

Original languageEnglish (US)
Pages (from-to)437-443
Number of pages7
JournalGastroenterology
Volume125
Issue number2
DOIs
StatePublished - Aug 1 2003
Externally publishedYes

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Hepatocytes
Apoptosis
In Situ Nick-End Labeling
Liver
Alcoholic Hepatitis
Caspase 7
Caspase 3
Fibrosis
Immunohistochemistry
CD95 Antigens
Non-alcoholic Fatty Liver Disease
Liver Diseases
Inflammation
Biopsy
Wounds and Injuries

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Hepatocyte apoptosis and Fas expression are prominent features of human nonalcoholic steatohepatitis. / Feldstein, Ariel E.; Canbay, Ali; Angulo, Paul; Taniai, Makiko; Burgart, Lawrence J.; Lindor, Keith; Gores, Gregory J.

In: Gastroenterology, Vol. 125, No. 2, 01.08.2003, p. 437-443.

Research output: Contribution to journalArticle

Feldstein, Ariel E. ; Canbay, Ali ; Angulo, Paul ; Taniai, Makiko ; Burgart, Lawrence J. ; Lindor, Keith ; Gores, Gregory J. / Hepatocyte apoptosis and Fas expression are prominent features of human nonalcoholic steatohepatitis. In: Gastroenterology. 2003 ; Vol. 125, No. 2. pp. 437-443.
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