Non-invasive index of liver fibrosis induced by alcohol, thioacetamide and schistosomal infection in mice

Abstract

BackgroundNon invasive approaches will likely be increasing utilized to assess liver fibrosis. This work provides a new non invasive index to predict liver fibrosis induced in mice.MethodsFibrosis was generated by thioacetamide (TAA), chronic intake of ethanol, or infection with S. mansoni in 240 mice. Both progression and regression of fibrosis (after treatment with silymarin and/or praziquantel) were monitored. The following methods were employed: (i) The METAVIR system was utilized to grade and stage liver inflammation and fibosis; (ii) Determination of hepatic hydroxyproline and collagen; and (iii) Derivation of a new hepatic fibrosis index from the induced changes, and its prospective validation in a group of 70 mice.ResultsThe index is composed of 4 serum variable including total proteins, γ-GT, bilirubin and reduced glutathione (GSH), measured in diseased, treated and normal mice. These parameters were highly correlated with both the histological stage and the grade. They were combined in a logarithmic formula, which non-invasively scores the severity of liver fibrosis through a range (0 to 2), starting with healthy liver (corresponding to stage 0) to advanced fibrosis (corresponding stage 3).Receiver operating characteristic curves (ROC) for the accuracy of the index to predict the histological stages demonstrated that the areas under the curve (AUC) were 0.954, 0.979 and 0.99 for index values corresponding to histological stages 1, 2 and 3, respectively. Also, the index was correlated with stage and grade, (0.947 and 0.859, respectively). The cut off values that cover the range between stages 0-1, 1-2 and 2-3 are 0.4, 1.12 and 1.79, respectively. The results in the validation group confirmed the accuracy of the test. The AUROC was 0.869 and there was good correlation with the stage of fibrosis and grade of inflammation.ConclusionThe index fulfils the basic criteria of non-invasive marker of liver fibrosis since it is liver-specific, easy to implement, reliable, and inexpensive. It proved to be accurate in discriminating precirrhotic stages.

Prediction of fibrosis in hepatitis C patients: assessment using hydroxyproline and oxidative stress biomarkers

“…Together, using TAS cut-off values, the diagnostic accuracy of significant fibrosis and cirrhosis in accordance to liver biopsy were reported in 86.7 and 81.3 % of CHC patients respectively. The data obtained revealed like others, that oxidative stress markers, antioxidant enzymes and hydroxyproline have been documented to play a part in the pathogenesis of CHC [5,13,20,34].…”

Tranilast ameliorates impaired hepatic functions in Schistosoma mansoni-infected mice

“…S. mansoni infection resulted in egg deposition with formation of dense granulomatous mass surrounding the deposited egg and intense hepatic reaction. Hessien et al (2010) reported similar increase in hepatic hydroxyproline and collagen due to S. mansoni-induced Mice were infected by subcutaneous injection of 60 ± 10 cercariae/ mouse, left for 28 days, and then treatment started and persisted for another 4 weeks…”

“…The absorbance of the reddish purple complex was measured at 550 nm. Liver collagen content was calculated according to Hessien et al (2010). The collagen content was calculated by multiplying the hydroxyproline concentration by 7.46, where this imino acid represents 13.4% of collagen.…”

A Novel Hepatic Anti-Fibrotic Strategy Utilizing the Secretome Released from Etanercept-Synthesizing Adipose-Derived Stem Cells

“…To validate the in vivo effects of etanercept-secretome, we generated in vivo model of liver fibrosis by subcutaneous injection of TAA (200 mg/kg, three times a week for 8 weeks) into experimental mice [31][32][33][34][35][36]. Subsequently, control mice (n = 30) and TAA-treated mice (n = 30) received four injections (two times a week during 7th and 8th week of TAA treatment) of 0.1 mL normal saline (n = 10), 0.1mL control secretome (n = 10), and 0.1mL etanercept-secretome (n = 10), respectively.…”