Non-alcoholic steatohepatitis (NASH) has no approved therapy. The farnesoid X nuclear receptor (FXR) agonist obeticholic acid (OCA) has shown promise as a drug for NASH, but can adversely affect plasma lipid profiles. Therefore, the present study aimed to investigate the effects and underlying mechanisms of OCA in combination with simvastatin (SIM) in a high-fat diet (HFD)-induced model of NASH.
View Article and Find Full Text PDFHepatic fibrosis is a crucial pathological process involved in the development of chronic hepatitis C (CHC) and may progress to liver cirrhosis and hepatocellular carcinoma. Activated peripheral blood monocytes and intrahepatic macrophages further promote hepatic fibrogenesis by releasing proinflammatory and profibrogenic cytokines. The present study aimed to investigate the role of peripheral CD14 monocytes and intrahepatic CD163 macrophages in hepatitis C virus (HCV)-associated liver fibrosis and clarify whether serum soluble CD163 (sCD163) may serve as a fibrosis marker in patients with CHC.
View Article and Find Full Text PDFPrimary biliary cholangitis (PBC) is an autoimmune disease characterized by chronic destruction of the bile ducts. A major unanswered question regarding the pathogenesis of PBC is the precise mechanisms of small bile duct injury. Emperipolesis is one of cell-in-cell structures that is a potential histological hallmark associated with chronic hepatitis B.
View Article and Find Full Text PDFObjective(s): Long noncoding RNAs (lncRNAs)-activated by transforming growth factor beta (lncRNA-ATB) is known to be involved in the invasion of hepatocellular carcinoma by regulating target genes of miR-200a. However, the role and molecular mechanisms of lncRNA-ATB/miR-200a in HCV-related liver fibrosis remains unclear. In this study, we examined the expression of lncRNA-ATB/miR-200a, and their target gene β-Catenin in liver tissues of HCV patients and hepatic stellate cells (HSCs) to elucidate the possible role of lncRNA-ATB/miR-200a axis in HSC activation and development of liver fibrosis.
View Article and Find Full Text PDFObjective: To investigate the regulation mechanism of T cell immunoglobulin and mucin domain-3 (Tim-3) combined with toll-like receptor 3 (TLR3) or TLR4 on antiviral immune and inflammatory response in patients with chronic hepatitis C virus (HCV) infection.
Methods: Patients with chronic HCV infection and healthy control subjects were recruited. Patients received interferon (IFN)-α based therapy.
Introduction: Both primary biliary cirrhosis (PBC) and Wilson's disease (WD) can cause copper retention in the liver, which is an important factor for liver cellular damage. Copper chelation may preserve liver cell function. It is challenging to distinguish WD from copper accumulation in patients with PBC.
View Article and Find Full Text PDFObjective To evaluate whether gamma-glutamyl transpeptidase to platelet ratio index (GPRI) can diagnose the extent of liver fibrosis in Chinese patients with chronic hepatitis B (CHB) infection. Methods This prospective observational study used liver biopsy results as the gold standard to evaluate the ability of GPRI to predict hepatic fibrosis compared with two other markers, the aspartate aminotransferase (AST) to platelet ratio index (APRI) and fibrosis-4 score (FIB-4). The clinical and demographic factors that affected GPRI, independent of liver fibrosis, were assessed using multivariate linear regression analyses.
View Article and Find Full Text PDFCombination therapy comprising pegylated interferon-alpha (PegIFNα) and ribavirin (RBV) has been the standard of care for the chronic hepatitis C patients for more than a decade. Recently, direct antiviral agents show better efficacy, tolerance, and shorter treatment duration. However, the prohibitive costs of the regimens limit their use in developing countries where most of the HCV infection exists.
View Article and Find Full Text PDFIntroduction: Drug-induced liver injury is a frequent cause of hepatic dysfunction. Several drugs have been identified to cause autoimmune hepatitis (AIH). Environmental chemicals are capable of triggering a certain degree of liver injury.
View Article and Find Full Text PDFObjectives: Fuzheng Huayu recipe (FZHY) exerts significant protective effects against liver fibrosis by strengthening the body's resistance and removing blood stasis. However, the molecular mechanisms through which FZHY affects liver fibrosis are still unclear. In this study, we examined the expression levels of factors involved in the inhibitor κB kinase-β (IKK-β)/nuclear factor-κB (NF-κB) and transforming growth factor beta 1 (TGF-β1)/Smad signaling pathways to elucidate whether FZHY could attenuate nutritional steatohepatitis and fibrosis in mice.
View Article and Find Full Text PDFWorld J Gastroenterol
July 2014
Alcoholic liver injury represents a progressive process with a range of consequences including hepatic steatosis, steatohepatitis, liver fibrosis, cirrhosis, and hepatocellular carcinoma. Targeting key molecular regulators involved in the development of alcoholic liver injury may be of great value in the prevention of liver injury. Peroxisome proliferator-activated receptor α (PPARα) plays a pivotal role in modulation of hepatic lipid metabolism, oxidative stress, inflammatory response and fibrogenesis.
View Article and Find Full Text PDFBackground & Aims: The cellular immunity has a profound impact on the status of hepatitis C virus (HCV) infection. However, the response of cellular immunity on the virological response in patients with antiviral treatment remains largely unclear. We aimed to clarify the response of peripheral T cells and monocytes in chronic hepatitis C patients with antiviral treatment.
View Article and Find Full Text PDFObjective: To explore the role and mechanism of the Fas/Fas ligand (FasL) system and its downstream signaling pathway related to the progression of alcoholic steatohepatitis and liver fibrosis.
Methods: Eighteen C57BL/6J mice were randomly divided into three groups: controls; alcoholic steatohepatitis model, given four-weeks of a 4% ethanol-containing Lieber-DeCarli liquid diet; alcoholic steatohepatitis and liver fibrosis model, given the four-week alcohol diet followed by twice weekly intraperitoneal injections of carbon tetrachloride (5% olive oil solution; 2 mL/kg dose) during the fifth to eighth weeks. Mice in the model groups were sacrificed at the end of week 4 and 8, respectively, along with control mice for comparative analyses.
Background: Peroxisome proliferator activated receptor alpha (PPARα) ameliorates ethanol induced hepatic steatohepatitis. However, its role in alcoholic liver fibrosis has not been fully clarified. The aim of this study was to elucidate the effect and the molecular basis of PPARα in ethanol induced liver fibrosis in mice.
View Article and Find Full Text PDFBackground: Fuzheng Huayu recipe (FZHY), a compound of Chinese herbal medicine, was reported to improve liver function and fibrosis in patients with hepatitis B virus infection. However, its effect on nutritional fibrosing steatohepatitis is unclear. We aimed to elucidate the role and molecular mechanism of FZHY on this disorder in mice.
View Article and Find Full Text PDFZhonghua Gan Zang Bing Za Zhi
September 2011
Objective: Our previous study indicated that the death receptor Fas played a key role on hepatocyte apoptosis in nutritional steatohepatitis in mice. This study aimed to explore whether Fas mutation accelerated hepatic steatosis and inflammatory infiltration in methionine-choline deficient (MCD) diet feeding mice.
Methods: Mice homozygous for the lymphoproliferation spontaneous mutation (C57BL/6J-Faslpr) and wild type C57BL/6J mice were fed with MCD diet for three weeks to induce non-alcoholic steatohepatitis (NASH).
Objective: To elucidate the effect of targeted gene modulation of peroxisome proliferator activated receptor gamma (PPARg) on hepatocellular apoptosis in nutritional fibrotic steatohepatitis in mice. C57BL/6J mice were fed with high fat, methionine-choline deficient (MCD) diet for 8 weeks to induce fibrotic steatohepatitis. Mice fed the MCD diet were treated with adenovirus carrying PPARg (Ad-PPARg), adenovirus-beta-galactosidase (Ad-LacZ), Ad-PPARg plus PPARg agonist rosiglitazone, or PPARg antagonist 2-chloro-5-nitro- benzanilide (GW9662), respectively.
View Article and Find Full Text PDFBackground: Heme oxygenase-1 (HO-1), an antioxidant defense enzyme, has been shown to protect against oxidant-induced liver injury. However, its role on liver fibrosis remains unclear. This study aims to elucidate the effect and the mechanism of HO-1 in nutritional fibrosing steatohepatitis in mice.
View Article and Find Full Text PDFObjective: Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme catabolism, has been reported to have potential antioxidant properties. However, the role of HO-1 on hepatocyte apoptosis remains unclear. We aim to elucidate the effects of HO-1 on oxidative stress related hepatocellular apoptosis in nutritional steatohepatitis in mice.
View Article and Find Full Text PDFObjective: The pathogenesis of non-alcoholic steatohepatitis is still unclear. We have demonstrated previously that peroxisome proliferator activated receptor gamma (PPARγ) ligand protects against inflammation and fibrogenesis in experimental non-alcoholic steatohepatitis. We aim to elucidate the effect and the mechanism of PPARγ itself on nutritional fibrotic steatohepatitis in mice.
View Article and Find Full Text PDFZhonghua Gan Zang Bing Za Zhi
September 2010
Objective: To investigate the potential role of heme oxygenase-1 on preventing non-alcoholic steatohepatitis (NASH) in mice.
Methods: Experimental models of NASH were established by feeding male C57BL/6J mice with choline-methionine deficient diet (MCD) for four weeks. Control animals were fed with choline-methionine supplemented diet.
Scand J Gastroenterol
February 2010
Objective: Hepatic oxidative stress plays a key role in the development of non-alcoholic steatohepatitis (NASH). However, the protective effects of antioxidants on NASH are largely unknown. The aim of this study was to elucidate the effect and mechanism of antioxidants on NASH in mice.
View Article and Find Full Text PDFScand J Gastroenterol
May 2009
Objective: Currently, no agent has been confirmed as preventing the fibrosing progression of non-alcoholic steatohepatitis (NASH). In this study, rosiglitazone was used in the clinical treatment of insulin resistance in patients with type 2 diabetes mellitus. However, its protective effect on non-alcoholic fibrosing steatohepatitis is not clear.
View Article and Find Full Text PDFZhongguo Shi Yan Xue Ye Xue Za Zhi
June 2003
Unlabelled: To study the clinical significance of the expression of antiapoptosis gene, survivin and bcl-2, and proapoptosis gene, Fas and bax, in acute myeloid leukemia (AML), RT-PCR was used to examine the expression of survivin and flow cytometry (FCM) to detect the expression of Fas, bcl-2, bax and bcl-2/bax ratio in 68 cases of AML. The results demonstrated that: (1) The positivity of survivin mRNA expression was significantly higher in AML compared to control (70.6% vs 30%, P < 0.
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