Search results for "cirrhosis"

Copper/MYC/CTR1 interplay: A dangerous relationship in hepatocellular carcinoma

2018

Free serum copper correlates with tumor incidence and progression of human cancers, including hepatocellular carcinoma (HCC). Copper extracellular uptake is provided by the transporter CTR1, whose expression is regulated to avoid excessive intracellular copper entry. Inadequate copper serum concentration is involved in the pathogenesis of Non Alcoholic Fatty Liver Disease (NAFLD), which is becoming a major cause of liver damage progression and HCC incidence. Finally, MYC is over-expressed in most of HCCs and is a critical regulator of cellular growth, tumor invasion and metastasis. The purpose of our study was to understand if higher serum copper concentrations might be involved in the prog…

Dual proteotoxic stress accelerates liver injury via activation of p62‐Nrf2

2021

Protein accumulation is the hallmark of various neuronal, muscular, and other human disorders. It is also often seen in the liver as a major protein-secretory organ. For example, aggregation of mutated alpha1-antitrypsin (AAT), referred to as PiZ, is a characteristic feature of AAT deficiency, whereas retention of hepatitis B surface protein (HBs) is found in chronic hepatitis B (CHB) infection. We investigated the interaction of both proteotoxic stresses in humans and mice. Animals overexpressing both PiZ and HBs (HBs-PiZ mice) had greater liver injury, steatosis, and fibrosis. Later they exhibited higher hepatocellular carcinoma load and a more aggressive tumor subtype. Although PiZ and H…

The Potential of Serum Exosomal hsa_circ_0028861 as the Novel Diagnostic Biomarker of HBV-Derived Hepatocellular Cancer

2021

Hepatitis B virus (HBV)-derived hepatocellular cancer (HCC) is a serious threat to human health, especially in China. There is no highly sensitive and specific HCC biomarker at present, which makes it difficult to detect HCC at the early stage. Serum exosomal circular RNAs (circRNAs) have been reported as novel diagnostic and prognostic biomarkers of cancers. In the present study, we aimed to explore the diagnostic performance of serum exosomal circRNAs for HBV-derived HCC screening. At first, many circRNAs were found to be differentially expressed in the serum exosomes of HCC individuals by microarray analysis. The validation of dysregulated circRNAs by qRT-PCR revealed that serum exosomal…

2018

Abstract Chronic hepatitis leads to liver fibrosis and cirrhosis. Cirrhosis is a major cause of worldwide morbidity and mortality. Macrophages play a key role in fibrosis progression and reversal. However, the signals that determine fibrogenic vs fibrolytic macrophage function remain ill defined. We studied the role of interleukin-4 receptor α (IL-4Rα), a potential central switch of macrophage polarization, in liver fibrosis progression and reversal. We demonstrate that inflammatory monocyte infiltration and liver fibrogenesis were suppressed in general IL-4Rα−/− as well as in macrophage-specific IL-4Rα−/− (IL-4RαΔLysM) mice. However, with deletion of IL-4RαΔLysM spontaneous fibrosis revers…

AISF position paper on nonalcoholic fatty liver disease (NAFLD): Updates and future directions

2017

Abstract This review summarizes our current understanding of nonalcoholic fatty liver disease (NAFLD), a multi-factorial systemic disease resulting from a complex interaction between a specific genetic background and multiple environmental/metabolic “hits”. The role of gut microbiota, lipotoxicity, inflammation and their molecular pathways is reviewed in-depth. We also discuss the epidemiology and natural history of NAFLD by pinpointing the remarkably high prevalence of NAFLD worldwide and its inherent systemic complications: hepatic (steatohepatitis, advanced fibrosis and cirrhosis), cardio-metabolic (cardiovascular disease, cardiomyopathy, arrhythmias and type 2 diabetes) and neoplastic (…

Diagnostic accuracy of elastography and magnetic resonance imaging in patients with NAFLD: A systematic review and meta-analysis

2021

[Background and Aims] Vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), 2-dimensional shear wave elastography (2DSWE), magnetic resonance elastography (MRE), and magnetic resonance imaging (MRI) have been proposed as non-invasive tests for patients with non-alcoholic fatty liver disease (NAFLD). This study evaluated their diagnostic accuracy for liver fibrosis and non-alcoholic steatohepatitis (NASH).

Cirrhosis risk score of the donor organ predicts early fibrosis progression after liver transplantation.

2019

Background & Aims: Fibrosis progression (FP) after liver transplantation (LT) increases morbidity and mortality. Biomarkers are needed for early prediction of FP. A recipient’s seven-gene cirrhosis risk score (CRS) has been associated with FP, especially in non-transplant cohorts. A broader validation of CRS, including the genotype of the donor-organ and HCV-negative patients is lacking. We therefore analyzed the impact of donor- and recipient-specific genotypes on FP after LT in a large cohort of HCV-positive and -negative patients.Method: Genotyping from liver biopsies (n=201 donors) and peripheral blood (n=442 recipients) was performed. Cirrhosis risk score was correlated with FP at …

Inducible knockdown of procollagen I protects mice from liver fibrosis and leads to dysregulated matrix genes and attenuated inflammation.

2017

Organ fibrosis is characterized by a chronic wound-healing response, with excess deposition of extracellular matrix components. Here, collagen type I represents the most abundant scar component and a primary target for antifibrotic therapies. Liver fibrosis can progress to cirrhosis and primary liver cancer, which are the major causes of liver related morbidity and mortality. However, a (pro-)collagen type I specific therapy remains difficult and its therapeutic abrogation may incur unwanted side effects. We therefore designed tetracycline-regulated procollagen alpha1(I) short hairpin (sh)RNA expressing mice that permit a highly efficient inducible knockdown of the procollagen alpha1(I) gen…

Molecular targets in inhibition of hepatitis C virus replication

1997

Hepatitis C virus (HCV) is the major cause of transfusion-associated hepatitis and accounts for a significant proportion of hepatitis cases worldwide. Most, if not all, infections become persistent and about 60% of cases develop chronic liver disease with various outcomes ranging from an asymptomatic carrier state to chronic active hepatitis and liver cirrhosis, which is strongly associated with the development of hepatocellular carcinoma. Since the initial cloning of the viral genome in 1989, our knowledge of the molecular biology of HCV has increased rapidly and led to the identification of several potential targets for antiviral intervention. In contrast, the low replication of the virus…

Investigating fibrosis and inflammation in an ex vivo NASH murine model.

2020

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease, characterized by excess fat accumulation (steatosis). Nonalcoholic steatohepatitis (NASH) develops in 15–20% of NAFLD patients and frequently progresses to liver fibrosis and cirrhosis. We aimed to develop an ex vivo model of inflammation and fibrosis in steatotic murine precision-cut liver slices (PCLS). NASH was induced in C57Bl/6 mice on an amylin and choline-deficient l-amino acid-defined (CDAA) diet. PCLS were prepared from steatohepatitic (sPCLS) and control (cPCLS) livers and cultured for 48 h with LPS, TGFβ1, or elafibranor. Additionally, C57Bl/6 mice were placed on CDAA diet for 12 wk to receive elafibranor…