Development of an unbiased method for the estimation of liver steatosis

Fiorini, Ryan N.; Kirtz, Jeremy; Periyasamy, Basker; Evans, Zachary; Haines, Julia K.; Cheng, Gang; Polito, Carmen; Rodwell, David W.; Shafizadeh, Stephen; Zhou, Xin; Campbell, Crystal; Birsner, Jennifer; Schmidt, Michael G.; Lewin, David; Chavin, Kenneth D.

doi:10.1111/j.1399-0012.2004.00282.x

Cited by 60 publications

(59 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…27 According to our data, fatty infiltration of the pancreas may be suspected preoperatively in elderly and overweight patients; moreover, CT scan seems useful in detecting the presence of fatty infiltration of the pancreas. 28,29 Interestingly, the percentage of fatty infiltration of the pancreas was not associated with the pancreatic fibrosis or the presence of a pancreatic adenocarcinoma. The biological mechanisms at the origin of the fatty infiltration of the pancreas seem different from those inducing pancreatic fibrosis.…”

Section: Discussionmentioning

confidence: 93%

The Role of “Fatty Pancreas” and of BMI in the Occurrence of Pancreatic Fistula After Pancreaticoduodenectomy

Rosso

Casnedi

Pessaux

et al. 2009

Journal of Gastrointestinal Surgery

126

109

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 93%

The Role of “Fatty Pancreas” and of BMI in the Occurrence of Pancreatic Fistula After Pancreaticoduodenectomy

Rosso

Casnedi

Pessaux

et al. 2009

Journal of Gastrointestinal Surgery

126

109

View full text Add to dashboard Cite

show abstract

“…The score was used to compare the liver damage after I/R and/or PHx between different study groups. Steatosis was assessed by oil red O staining as previously described (52). C3 deposition in liver samples was determined by immunofluorescence using anti-mouse FITCconjugated C3d antibody (Dako Cytomation) as previously described (18).…”

Section: Methodsmentioning

confidence: 99%

A complement-dependent balance between hepatic ischemia/reperfusion injury and liver regeneration in mice

He¹,

Atkinson²,

Qiao³

et al. 2009

J. Clin. Invest.

125

View full text Add to dashboard Cite

Massive liver resection and small-for-size liver transplantation pose a therapeutic challenge, due to increased susceptibility of the remnant/graft to ischemia reperfusion injury (IRI) and impaired regeneration. We investigated the dual role of complement in IRI versus regeneration in mice. Complement component 3 (C3) deficiency and complement inhibition with complement receptor 2-complement receptor 1-related protein y (CR2-Crry, an inhibitor of C3 activation) provided protection from hepatic IRI, and while C3 deficiency also impaired liver regeneration following partial hepatectomy (PHx), the effect of CR2-Crry in this context was dose dependent. In a combined model of IRI and PHx, either C3 deficiency or high-dose CR2-Crry resulted in steatosis, severe hepatic injury, and high mortality, whereas low-dose CR2-Crry was protective and actually increased hepatic proliferative responses relative to control mice. Reconstitution experiments revealed an important role for the C3a degradation product acylation-stimulating protein (ASP) in the balance between inflammation/injury versus regeneration. Furthermore, liver regeneration was dependent on the putative ASP receptor, C5L2. Several potential mechanisms of hepatoprotection and recovery were identified in mice treated with low-dose CR2-Crry, including enhanced IL-6 expression and STAT3 activation, reduced hepatic ATP depletion, and attenuated oxidative stress. These data indicate that a threshold of complement activation, involving ASP and C5L2, promotes liver regeneration and suggest a balance between complement-dependent injury and regeneration.

show abstract

“…Oil Red O staining was performed as previously described (25) and the percentage of steatosis was calculated using computerized image analysis with the Leica Microsystems Qwin Image analysis software. Total liver triglyceride levels were measured using a triglyceride reagent kit according to the manufacturer's instructions (Pointe Scientific).…”

Section: Liver Steatosismentioning

confidence: 99%

A Role for Complement in the Enhanced Susceptibility of Steatotic Livers to Ischemia and Reperfusion Injury

Atkinson²,

Evans

et al. 2009

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Hepatic steatosis typically renders the donor organ unusable, as donor organs with >30% steatosis are more likely to develop graft failure. The mechanisms leading to failure are not well defined, but steatosis enhances hepatic susceptibility to ischemia reperfusion injury (IRI). We investigated the role of complement in hepatic IRI in lean and steatotic (diet-induced) mice. Steatotic mice were significantly more susceptible to total warm hepatic IRI than lean mice as determined by serum alanine aminotransferase, histopathologically assessed damage, and 24-h survival. C3 deficiency protected both lean and steatotic mice from IRI, as determined by all measured outcomes. Furthermore, treatment of wild-type mice with the complement inhibitor CR2-Crry provided protection equivalent to that seen in C3-deficient mice. Importantly, although steatotic livers were much more susceptible to IRI than lean livers, by most measures there was no statistical difference between the level of IRI to steatotic or lean livers when complement was inhibited. To investigate the clinical relevance of these findings in the context of transplantation, we treated recipients of lean or steatotic liver grafts with saline or CR2-Crry. There was a marked reduction in graft inflammation and injury and significantly improved 7-day survival in CR2-Crry-treated recipients of either lean or steatotic grafts. These data indicate that complement plays a key role in the enhanced susceptibility of steatotic livers to IRI and suggest that complement inhibition represents a potential strategy to reduce the donor shortage by allowing the more routine use of marginal steatotic donor livers.

show abstract

Development of an unbiased method for the estimation of liver steatosis

Cited by 60 publications

References 22 publications

The Role of “Fatty Pancreas” and of BMI in the Occurrence of Pancreatic Fistula After Pancreaticoduodenectomy

The Role of “Fatty Pancreas” and of BMI in the Occurrence of Pancreatic Fistula After Pancreaticoduodenectomy

A complement-dependent balance between hepatic ischemia/reperfusion injury and liver regeneration in mice

A Role for Complement in the Enhanced Susceptibility of Steatotic Livers to Ischemia and Reperfusion Injury

Contact Info

Product

Resources

About