SciCombinator

Discover the most talked about and latest scientific content & concepts.

Concept: Cirrhosis

0

Metabolic syndrome (MetS) is a disease composed of different risk factors such as obesity, type 2 diabetes or dyslipidemia. The prevalence of this syndrome is increasing worldwide in parallel with the rise in obesity. Nonalcoholic fatty liver disease (NAFLD) is now the most frequent chronic liver disease in western countries, affecting more than 30% of the general population. NAFLD encompasses a spectrum of liver manifestations ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis, which may ultimately progress to hepatocellular carcinoma. There is accumulating evidence supporting an association between NAFLD and MetS. Indeed, NAFLD is recognized as the liver manifestation of MetS. Insulin resistance is increasingly recognized as a key factor linking MetS and NAFLD. Insulin resistance is associated with excessive fat accumulation in ectopic tissues, such as the liver, and increased circulating free fatty acids, which can further promote inflammation and endoplasmic reticulum stress. This in turn aggravates and maintains the insulin resistant state, constituting a vicious cycle. Importantly, evidence shows that most of the patients developing NAFLD present at least one of the MetS traits. This review will define MetS and NAFLD, provide an overview of the common pathophysiological mechanisms linking MetS and NAFLD, and give a perspective regarding treatment of these ever growing metabolic diseases.

Concepts: Insulin, Diabetes mellitus, Obesity, Cirrhosis, Metabolic syndrome, Non-alcoholic fatty liver disease, Fatty liver, Steatosis

0

Harmful use of alcohol is one of the top five risks for burden of disease globally and in Europe; in 2012, 3.3 million net deaths (approximately 6% of all global deaths) were attributable to this risk factor. It is also linked to the development of a wide spectrum of alcohol use disorders, ranging from mild manifestations to a severe disease known as alcohol dependence. Alcohol dependence is a progressive, chronic, and relapsing brain disease resulting from the prolonged effects of alcohol on the brain. Alcohol dependence imposes a significant societal burden, with indirect societal costs reaching up to 0.64% of European countries׳ annual gross domestic product. With these facts in mind, it is important to recognize and manage alcohol dependence. Although the biological mechanisms behind the development of alcohol dependence are not fully known, factors that have been shown to influence its development include genetic predisposition, psychological problems, and social interactions. Alcohol use has also been linked to the development of hypertension, liver cirrhosis, chronic pancreatitis, multiple types of cancer, and psychiatric comorbidities such as depression and anxiety disorders. With such severe effects on both individuals and society, it is important to recognize the characteristic signs and symptoms of alcohol dependence and explore new ways to better manage patients with this brain disease. Effective treatment approaches for alcohol dependence include biological, behavioral, and social components addressing the multiple aspects of this disease. Comprehensive, educational platforms in which to explore the many facets of this disease such as the Progress in Mind: Focus on Alcohol Use Disorders Resource Centre, will provide clinicians with the tools necessary for recognizing patients with alcohol dependence and managing their disease along with related comorbidities. Online Access: http://progressinmind.elsevierresource.com.

Concepts: Psychology, Medicine, Brain, Cirrhosis, Alcoholism, Cognition, Mind, Alcohol abuse

0

Sustained liver injury causes liver fibrosis and eventually cirrhosis. Understanding the pathophysiological mechanisms of liver fibrosis and interventions in the fibrotic process is crucial for improving the prognosis of patients with chronic liver diseases. Although studies have shown that splenectomy suppresses liver fibrosis, the mechanism by which this occurs is poorly understood. The present study focuses on the immunological functions of the spleen to investigate its role in liver fibrosis.

Concepts: Immune system, White blood cell, Scar, Fibrosis, Cirrhosis, Hepatitis, Liver, Splenomegaly

0

Hepatitis B (HepB) vaccination is the most effective measure to prevent HBV infection and its consequences. In the United States, routine HepB vaccination was recommended for infants in 1991 and catch-up vaccination has been recommended for adolescents since in 1995. The purpose of this study is to assess HepB vaccination among adolescents 13-17 years in the United States.

Concepts: United States, Cirrhosis, Hepatitis, Poverty in the United States, U.S. state, Infant mortality, Hepatitis B, Hepatitis B virus

0

Liver fibrosis is a relatively common consequence of chronic liver diseases, especially chronic viral hepatitis B and C. Biopsy still remains the gold standard in the assessment of liver fibrosis. However, due to its invasiveness and possible complications, less or even non-invasive methods are being developed, e.g. using biochemical parameters (Fibrotest) or elastography. Elastography is a new diagnostic tool that aims to evaluate stiffness of the tissues. Elastography techniques that are used in the assessment of liver fibrosis are transient elastography (TE), acoustic radiation force impulse (ARFI) and shear-wave elastography (SWE). SWE is a novel real-time two-dimensional elastography technique, which allows one to estimate stiffness quantitatively in kilopascals (kPa). Moreover, lapping elastography over regular B-mode allows precise choice of the region of interest. Therefore SWE creates the opportunity for accurate assessment of liver fibrosis. In this paper we describe processes leading to liver fibrosis as well as methods of liver fibrosis assessment, e.g. liver biopsy, biochemical tests or elastography. The main goal of this paper is to present the SWE technique, its role in liver fibrosis assessment and a short review of the most important clinical studies on SWE. We also present several examples of SWE examinations performed on patients with different stages of liver fibrosis - F0 to F4 on the METAVIR scale.

Concepts: Cirrhosis, Hepatitis, Liver, Hepatitis C, Hepatitis B, Hepatitis A, Viral hepatitis, Alcoholic liver disease

0

Liver inflammation plays a critical role in hepatocellular carcinoma (HCC) etiology. Damage associated molecular patterns (DAMPs), such as high mobility group box-1 (HMGB1), and dysregulated microRNAs (miRNAs) involved in inflammatory disease states, such as miR-21, may participate in the link between inflammation and cancer. We sought to determine the role of HMGB1 signaling in HCC tumor progression. We first document the concordant expression increase of HMGB1 and miR-21 in HCC cell lines and primary HCC tumor samples and subsequently show that HMGB1 stimulation results in over-expression of miR-21. These changes were found to be dependent on the IL-6/Stat3 signaling axis. Invasion and migration of HCC cells in vitro was inhibited by both Stat3 and miR-21 antagonists, suggesting a role for this pathway in HCC tumor progression. We verified that HMGB1-induced expression of miR-21 in HCC provides a post-transcriptional repression of the matrix metalloproteinase (MMP) inhibitors RECK and TIMP3, which are known to impact HCC progression and metastases. Finally, we found that inhibition of miR-21 in murine HMGB1-overexpressing HCC xenografts led to reduced tumor MMP activity through released repression of the miR-21 targets RECK and TIMP3, which ultimately impeded tumor progression. The prototypical DAMP, HMGB1, is released during liver inflammation and provides a favorable environment for HCC growth. HMGB1 signaling increases miR-21 expression to mediate the enhanced activity of MMPs through RECK and TIMP3. These findings provide a novel mechanism for HMGB1-mediated HCC progression through the IL-6/Stat3-miR-21 axis.

Concepts: Inflammation, Gene expression, Cancer, Extracellular matrix, Cirrhosis, Anti-inflammatory, Matrix metalloproteinase, Tissue inhibitor of metalloproteinases

0

To investigate the outcomes of living donor liver transplantation for advanced hepatocellular carcinoma in Child-Pugh A/B patients and the usefulness of our expanded selection criteria, the Kyoto criteria.

Concepts: Cancer, Cirrhosis, Liver, Liver transplantation

0

Greenland remains a highly endemic area for hepatitis B virus (HBV) infection. This is in sharp contrast to other modern societies, such as Denmark. To address this discrepancy, we investigated the natural history of HBV infection in Greenland by estimating the age-specific incidence of HBV infection, the proportion of chronic carriers, and the rates of hepatitis B surface antigen seroclearance. In total, 8,879 Greenlanders (16% of the population) from population-based surveys conducted in 1987 and 1998 were followed through March 2010. Data on HBV status were supplemented by HBV test results from all available HBV registries in Greenland to determine changes in HBV status over time. Incidence rates of HBV infection and hepatitis B surface antigen seroclearance were estimated after taking into account interval censoring. The incidence of HBV infection in 5-14-year-old subjects was less than 1 per 100 person-years and peaked at 5 per 100 person-years in persons 15-24 years of age. Overall, 17.5% of persons infected in adulthood were estimated to become chronic carriers. HBV is primarily transmitted in adolescence and adulthood in Greenland. In contrast to what is observed in most other populations, HBV-infected adults in Greenland have a high risk of progressing to chronic HBV carriage. This phenomenon might explain how the high rate of infection is maintained in Greenland.

Concepts: Cohort study, Epidemiology, Cirrhosis, Hepatitis, Hepatitis B, Hepatitis B virus, Denmark, Greenland

0

Daclatasvir (Daklinza(®)) is an inhibitor of hepatitis C virus (HCV) NS5A protein. It is a new, oral, direct-acting antiviral with potent pangenotypic activity. This article provides a narrative review of the efficacy and tolerability of daclatasvir in combination with other agents in the treatment of patients with chronic HCV infection and summarizes its pharmacological properties. Since daclatasvir has a different mechanism of action to other current direct-acting antivirals, it provides additive or synergistic antiviral activity when used in combination. It produces high sustained virological response rates when used in combination with peginterferon-α plus ribavirin in patients chronically infected with HCV genotypes 1-4, and provides even higher response rates when used in an interferon-free, all-oral combination with sofosbuvir, with or without ribavirin. Daclatasvir has a moderately high genetic barrier to resistance, is effective during short-term treatment over 12 weeks and has a tolerability profile similar to that of placebo. In conclusion, daclatasvir is a highly effective and well tolerated, oral, once-daily, direct-acting antiviral for use in combination therapy in adult patients chronically infected with HCV.

Concepts: Genetics, Virus, Cirrhosis, Hepatitis, Antiviral drug, Hepatitis C, Hepatitis B, Hepatitis C virus

0

Adefovir dipivoxil (ADV) is recommended for patients infected with lamivudine-refractory hepatitis B virus (HBV). We report a case of low-dose ADV-induced hypophosphatemic osteomalacia that initially presented as diffuse musculoskeletal pain.

Concepts: Cirrhosis, Hepatitis, Hepatitis B, Viruses, Hepatitis B virus, Hepadnaviridae, Adefovir, Fanconi syndrome