560,528 research outputs found
Pediatric liver diseases: current challenges and future perspectives
Chronic liver diseases in children represent a rising problem with significant effects on public health. In fact, several pediatric liver diseases are precursors of adult chronic hepatopathies, cirrhosis and hepatocellular carcinoma. The prevalence of liver diseases in children is unknown. In the USA, every year, 15,000 children are hospitalized for liver diseases, but these disorders continue to be under-recognized or diagnosed late. The main reason is due to the frequent absence of symptoms in the vast majority of liver diseases, especially in the early stages. In the last few decades several advances have been made in understanding the pathogenesis of liver diseases, permitting the discovery of new therapeutic targets to treat liver diseases, thus improving the natural history of these disorders. In this article we discuss the most recent advances in the understanding of the pathogenesis, diagnosis and treatment of the most frequent pediatric liver diseases
Recommended from our members
Immunoglobulin A and liver diseases.
Immunoglobulin A (IgA) is a major immunoglobulin isotype in the gut and plays a role in maintenance of gut homeostasis. Secretory IgA (SIgA) has multiple functions in the gut, such as to regulate microbiota composition, to protect intestinal epithelium from pathogenic microorganisms, and to help for immune-system development. The liver is the front-line organ that receives gut-derived products through the portal vein, implying that the liver could be severely affected by a disrupted intestinal homeostasis. Indeed, some liver diseases like alcoholic liver disease are associated with an altered composition of gut microbiota and increased blood endotoxin levels. Therefore, deficiency of SIgA function appears as a significant factor for the pathogenesis of liver diseases associated with altered gut microbiome. In this review, we describe SIgA functions on the gut microbiome and discuss the role of IgA for liver diseases, especially alcoholic liver disease and non-alcoholic fatty liver disease/non-alcoholic steatohepatitis
Critical Role of microRNA-21 in the Pathogenesis of Liver Diseases
MicroRNAs are small non-coding RNAs that range in length from 18 to 24 nucleotides. As one of the most extensively studied microRNAs, microRNA-21 (miR-21) is highly expressed in many mammalian cell types. It regulates multiple biological functions such as proliferation, differentiation, migration, and apoptosis. In this review, we summarized the mechanism of miR-21 in the pathogenesis of various liver diseases. While it is clear that miR-21 plays an important role in different types of liver diseases, its use as a diagnostic marker for specific liver disease or its therapeutic implication are not ready for prime time due to significant variability and heterogeneity in the expression of miR-21 in different types of liver diseases depending on the studies. Additional studies to further define miR-21 functions and its mechanism in association with each type of chronic liver diseases are needed before we can translate the bedside observations into clinical settings
The Impact of Chronic Liver Diseases on the Level of Heart-Type Fatty Acid-Binding Protein (H-FABP) Concentrations
Objectives: Heart-type fatty acid binding-protein (H-FABP) has been reported to be a potential novel biochemical marker for the early diagnosis of acute myocardial infarction (AMI). The presence of H-FABP in the liver has not been reported. The aim of this study was to compare the effect of chronic liver diseases on the level of H-FABP concentrations. Methods: The effects of chronic liver diseases including infective hepatitis and cirrhosis on the concentration of H-FABP was studied in a small group of patients (n=10, mean age ±SD = 58.33 ± 7.19 years). The serum concentrations of the following markers were measured: H-FABP, alanine aminotransferase (ALT) and bilirubin and compared with a reference control group (20 healthy blood donors, mean age ±SD = 63.8 ±8.01). Results: The serum concentrations of these markers in the control group as compared to patients with chronic liver disease were as follows (mean ± SD): H-FABP = 6.86 ±2.21 µg/L versus 6.44 ±3.06 µg/L (p = NS); ALT = 29.8 ±14.7 U/L versus ALT = 198.67 ±122.89 U/L (p < 0.0005) and bilirubin = 9.6 ±4.0 µmol/L versus bilirubin = 100.89 ±87.85 µmol/L (p < 0.0001). Conclusion: These data illustrate clearly that there is no significant interference with the normal concentration of H-FABP in the presence of liver diseases, despite the significant elevation of liver enzymes and proteins. These data may support a useful role of H-FABP for the diagnosis of myocardial injury in patients with liver diseases
Cholangiocytes: Cell transplantation
Background:Due to significant limitations to the access to orthotropic liver transplantation, cell therapies forliver diseases have gained large interest worldwide.Scope of review:To revise current literature dealing with cell therapy for liver diseases. We discussed the ad-vantages and pitfalls of the different cell sources tested so far in clinical trials and the rationale underlying thepotential benefits of transplantation of human biliary tree stem cells (hBTSCs).Major conclusions:Transplantation of adult hepatocytes showed transient benefits but requires immune-sup-pression that is a major pitfall in patients with advanced liver diseases. Mesenchymal stem cells and hemato-poietic stem cells transplanted into patients with liver diseases are not able to replace resident hepatocytes butrather they target autoimmune or inflammatory processes into the liver. Stem cells isolated from fetal or adultliver have been recently proposed as alternative cell sources for advanced liver cirrhosis and metabolic liverdisease. We demonstrated the presence of multipotent cells expressing a variety of endodermal stem cell markersin (peri)-biliary glands of bile ducts in fetal or adult human tissues, and in crypts of gallbladder epithelium. Inthefirst cirrhotic patients treated in our center with biliary tree stem cell therapy, we registered no adverse eventbut significant benefits.General significance:The biliary tree stem cell could represent the ideal cell source for the cell therapy of liverdiseases. This article is part of a Special Issue entitled: Cholangiocytes in Health and Diseaseedited by JesusBanales, Marco Marzioni, Nicholas LaRusso and Peter Jansen
Hepatic stellate cells and parasite-induced liver fibrosis
ABSTRACT: Fibrogenesis is a common feature of many diseases where there is severe insult to the liver. The hepatic stellate cell trans-differentiation into a myofibroblast has been identified as an important event in liver fibrogenesis and has been well investigated over the last few years in a number of liver diseases. The trans-differentiation process can be monitored in vitro by evaluation of biomarkers that are characteristic of normal quiescent hepatic stellate cells or activated myofibroblasts. Two major parasitic diseases associated with liver injury and fibrosis are schistosomiasis and echinococcosis. Recent studies have highlighted a role for activated hepatic stellate cells in both murine and human schistosomiasis as well as demonstrating that schistosome antigens are able to regulate this trans-differentiation process. Study of the hepatic stellate cell and its interaction with parasite-derived antigens may be pivotal in our understanding of the pathology associated with schistosomiasis and other parasitic diseases, including echinococcosis, as well as revealing new information on the trans-differentiation process in this cell type
A note on the prothrombin time abnormality in the patients with amebic liver abscess
Amebic liver abscess is reported worldwide and can present with a a wide spectrum of clinical manifetations. Similar to the other liver diseases, the prothrombin time abnormality can be seen in the patients with amebic liver abscess. We retrospectively studied the prothrombin times among 30 Thai hospitalized patients with amebic liver abscesses and did not find any correlation between the prothrombin time and any other studied manifestatio
Liver resections: complications and survival outcome
none1noToday, liver resection represents one of the most effective therapies in the treatment of defined liver diseases, particularly for hepatocellular carcinomas, liver metastases and tumors originating from the bile ducts. There have been a number of improvements in the technique but the use of kellyclasia associated with meticulous control of hemostasis and biliostasis appears to be more effective and efficient. The procedure is still burdened with some postoperative complications, the more characteristic of which are liver insufficiency, biliary leakage and ascites. Several neoplastic diseases, both primitive and secondary, can benefit from this therapy with substantial improvement of long-term survival, and a
notable change in the natural history of the disease. For these situations, a consultation should always be performed by a surgeon experienced in hepatic surgery.mixedGrazi GLGrazi G
Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis
Background
A non-invasive method to grade the severity of steatohepatitis and liver fibrosis is magnetic resonance imaging (MRI) based corrected T1 (cT1). We aimed to identify genetic variants influencing liver cT1 and use genetics to understand mechanisms underlying liver fibroinflammatory disease and its link with other metabolic traits and diseases.
Methods
First, we performed a genome-wide association study (GWAS) in 14,440 Europeans in UK Biobank with liver cT1 measures. Second, we explored the effects of the cT1 variants on liver blood tests, and a range of metabolic traits and diseases. Third, we used Mendelian randomisation to test the causal effects of 24 predominantly metabolic traits on liver cT1 measures.
Results
We identified six independent genetic variants associated with liver cT1 that reached GWAS significance threshold (p<5x10-8). Four of the variants (rs75935921 in SLC30A10, rs13107325 in SLC39A8, rs58542926 in TM6SF2, rs738409 in PNPLA3) were also associated with elevated transaminases and had variable effects on liver fat and other metabolic traits. Insulin resistance, type 2 diabetes, non-alcoholic fatty liver and BMI were causally associated with elevated cT1 whilst favourable adiposity (instrumented by variants associated with higher adiposity but lower risk of cardiometabolic disease and lower liver fat) was found to be protective.
Conclusion
The association between two metal ion transporters and cT1 indicates an important new mechanism in steatohepatitis. Future studies are needed to determine whether interventions targeting the identified transporters might prevent liver disease in at risk individuals
- …