Mutual Antagonism between Circadian Protein Period 2 and Hepatitis C Virus Replication in Hepatocytes

BackgroundHepatitis C virus (HCV) infects approximately 3% of the world population and is the leading cause of liver disease, impacting hepatocyte metabolism, depending on virus genotype. Hepatic metabolic functions show rhythmic fluctuations with 24-h periodicity (circadian), driven by molecular clockworks ticking through translational-transcriptional feedback loops, operated by a set of genes, called clock genes, encoding circadian proteins. Disruption of biologic clocks is implicated in a variety of disorders including fatty liver disease, obesity and diabetes. The relation between HCV replication and the circadian clock is unknown.MethodsWe investigated the relationship between HCV core…

Multicentre Survey of the Prevalence of Intrahepatic Cholestasis in 2520 Consecutive Patients with Newly Diagnosed Chronic Liver Disease

In order to establish the prevalence of intrahepatic cholestasis (IHC) in chronic liver disease, we retrospectively evaluated the frequency of increased serum total bilirubin (STB), serum conjugated bilirubin (SCB) and serum alkaline phosphatase (SAP) levels in a cohort of 2520 patients with newly diagnosed chronic liver disease presenting over 2 years. 882 patients (35%) [mean age 52.2 years] had IHC involving abnormal levels of STB (mean 89.8 μmol/L), SCB (mean 52.5 μmol/L), and SAP (mean 5.7 μkat/L) together with a negative ultrasonic scan. Demographic data were not predictive of IHC. IHC was more frequent in patients with cirrhosis (43%), primary biliary cirrhosis (54%), and primary scl…

Impact of HBV, HCV and GBV-C/HGV on hepatocellular carcinomas in Europe: results of a European concerted action.

Abstract Background/Aims: To investigate the impact of hepatitis B (HBV) and C (HCV) infections on hepatocellular carcinoma (HCC) in Europe. Methods: Five hundred and three patients with HCC, from six liver centers, were included. All 503 sera and 80 liver samples were tested for HBV DNA and HCV RNA by polymerase chain reaction. GBV-C/HGV RNA was also tested in 57 sera. Results: HBsAg and anti-HCV were detected in 19% and 40.1% of the patients, respectively. Serum and liver HBV DNA were detected in 82% and 91% of the HBsAg positive subjects. HBV DNA was also detected in the serum and liver of 33% and 47% of HBsAg negative patients. In this group, serum HBV DNA was more prevalent in anti-HBs…

Hepatic transferrin receptors in hereditary hemochromatosis.

Immunopositivity for histone macroH2A1 isoforms marks steatosisassociated hepatocellular carcinoma.

BackgroundHepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Prevention and risk reduction are important and the identification of specific biomarkers for early diagnosis of HCC represents an active field of research. Increasing evidence indicates that fat accumulation in the liver, defined as hepatosteatosis, is an independent and strong risk factor for developing an HCC. MacroH2A1, a histone protein generally associated with the repressed regions of chromosomes, is involved in hepatic lipid metabolism and is present in two alternative spliced isoforms, macroH2A1.1 and macroH2A1.2. These isoforms have been shown to predict lung and colon cancer recurrence but to ou…

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1

Contains fulltext : 232759.pdf (Publisher’s version ) (Closed access) In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to…