Search results for "inflammation"

Digital Pathology Enables Automated and Quantitative Assessment of Inflammatory Activity in Patients with Chronic Liver Disease

2021

Traditional histological evaluation for grading liver disease severity is based on subjective and semi-quantitative scores. We examined the relationship between digital pathology analysis and corresponding scoring systems for the assessment of hepatic necroinflammatory activity. A prospective, multicenter study including 156 patients with chronic liver disease (74% nonalcoholic fatty liver disease-NAFLD, 26% chronic hepatitis-CH etiologies) was performed. Inflammation was graded according to the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network system and METAVIR score. Whole-slide digital image analysis based on quantitative (I-score: inflammation ratio) and morphometric (C-sco…

Evolving therapies for liver fibrosis

2013

Fibrosis is an intrinsic response to chronic injury, maintaining organ integrity when extensive necrosis or apoptosis occurs. With protracted damage, fibrosis can progress toward excessive scarring and organ failure, as in liver cirrhosis. To date, antifibrotic treatment of fibrosis represents an unconquered area for drug development, with enormous potential but also high risks. Preclinical research has yielded numerous targets for antifibrotic agents, some of which have entered early-phase clinical studies, but progress has been hampered due to the relative lack of sensitive and specific biomarkers to measure fibrosis progression or reversal. Here we focus on antifibrotic approaches for li…

The lipid lowering drug lovastatin protects against doxorubicin-induced hepatotoxicity.

2012

Liver is the main detoxifying organ and therefore the target of high concentrations of genotoxic compounds, such as environmental carcinogens and anticancer drugs. Here, we investigated the usefulness of lovastatin, which is nowadays widely used for lipid lowering purpose, as a hepatoprotective drug following the administration of the anthracycline derivative doxorubicin in vivo. To this end, BALB/c mice were exposed to either a single high dose or three consecutive low doses of doxorubicin. Acute and subacute hepatotoxicities were analyzed with or without lovastatin co-treatment. Lovastatin protected the liver against doxorubicin-induced acute pro-inflammatory and pro-fibrotic stress respo…

Deletion of organic cation transporter Oct3 promotes hepatic fibrosis via upregulation of TGFβ

2019

Organic cation transporters (OCT) are responsible for the intracellular uptake and detoxification of a broad spectrum of endogenous and exogenous substrates. OCTs are downregulated in cholestasis, fibrosis, and hepatocellular carcinoma, but the underlying molecular mechanisms and downstream effects of OCT deletion are unknown. Oct3-knockout ( Oct3−/−; FVB.Slc22a3tm10pb) and wild-type (WT; FVB) mice were subject to escalating doses of carbon tetrachloride (CCl4) or thioacetamide (TAA) for 6 wk to induce advanced parenchymal liver fibrosis. Secondary biliary fibrosis was generated by bile duct ligation. Liver fibrosis was assessed by hydroxyproline determination, quantitative Sirius red morp…

Clinical states of cirrhosis and competing risks.

2018

The clinical course of cirrhosis is mostly determined by the progressive increase of portal hypertension, hyperdynamic circulation, bacterial translocation and activation of systemic inflammation. Different disease states, encompassing compensated and decompensated cirrhosis and a late decompensated state, are related to the progression of these mechanisms and may be recognised by haemodynamic or clinical characteristics. While these disease states do not follow a predictable sequence, they correspond to varying mortality risk. Acute-on-chronic liver failure may occur either in decompensated or in compensated cirrhosis and is always associated with a high short-term mortality. The increasin…

Traditional Chinese Medicine (TCM) for fibrotic liver disease: Hope and hype

2014

Definite and indeterminate nonalcoholic steatohepatitis share similar clinical features and prognosis : A longitudinal study of 1893 biopsy-proven no…

2021

[Background and Aim] Histological score systems may not fully capture the essential nonalcoholic steatohepatitis (NASH) features, which is one of the leading causes of screening failure in clinical trials. We assessed the NASH distribution and its components across the fibrosis stages and their impact on the prognosis and their relationship with the concept of metabolic-associated fatty liver disease (MAFLD).

PNPLA3 rs738409 C>G Variant Predicts Fibrosis Progression by Noninvasive Tools in Nonalcoholic Fatty Liver Disease

2020

Liver fibrosis is the main predictor of events in patients with nonalcoholic fatty liver disease (NAFLD),1 and its evolution is characterized by a nonlinear trend2,3 mostly affected by metabolic risk factors, severity of liver inflammation and steatosis, and weight loss.3 The rs738409 C>G common variant in PNPLA3 gene has been associated with severity of fibrosis and risk of liver-related events in NAFLD.4,5 Noninvasive tests as Fibrosis-4 (FIB-4) and liver stiffness measurement (LSM) are useful to rule-out advanced fibrosis and they could be reliable to predict fibrosis progression.2,6 We aimed to evaluate in patients with NAFLD whether PNPLA3 rs738409 C>G variant impacts on fibrosis…

Fibroblast Growth Factor 21 Limits Lipotoxicity by Promoting Hepatic Fatty Acid Activation in Mice on Methionine and Choline-Deficient Diets

2014

Background & Aims Nonalcoholic fatty liver disease is a common consequence of human and rodent obesity. Disruptions in lipid metabolism lead to accumulation of triglycerides and fatty acids, which can promote inflammation and fibrosis and lead to nonalcoholic steatohepatitis. Circulating levels of fibroblast growth factor (FGF)21 increase in patients with nonalcoholic fatty liver disease or nonalcoholic steatohepatitis; therefore, we assessed the role of FGF21 in the progression of murine fatty liver disease, independent of obesity, caused by methionine and choline deficiency. Methods C57BL/6 wild-type and FGF21-knockout (FGF21-KO) mice were placed on methionine- and choline-deficient (MCD)…

Phenolic Extract from Sonchus oleraceus L. Protects Diabetes-related Liver Injury in Rats through TLR4/NF-κB Signaling Pathway

2019

Sonchus oleraceus Linn. is of great interest in scientific platform because it exhibits significant biological activities. This study investigated the liver protective effects and mechanism of phenolic extract from S. oleraceus (SOL) on Streptozotocin (STZ)-induced diabetic rats. SOL significantly increased both superoxide dismutase activity and glutathione level, while causing a reduction of malondialdehyde level in the liver. Moreover, SOL ameliorates STZ-induced liver function and pathological damages. Diabetic rats fed with S. oleraceus daily for 6 weeks showed significantly decreased levels of tumor necrosis factor alpha and interleukin-1β in the liver. Sonchus oleraceus decreased the …