Risk of de novo Hepatocellular Carcinoma after HCV Treatment with Direct-Acting Antivirals.

Background And Aims: The aim of the study was to evaluate the risk of hepatocellular carcinoma (HCC) development after treatment with direct-acting antivirals (DAAs) and to compare HCC occurrence in these patients with that among patients treated with interferon (IFN)-based therapies.

Methods: We analyzed a large cohort with chronic hepatitis C virus patients for the onset of new HCC after DAA treatment. A historical IFN-treated cohort was investigated for comparison.

Hypoxia Causes Downregulation of Dicer in Hepatocellular Carcinoma, Which Is Required for Upregulation of Hypoxia-Inducible Factor 1α and Epithelial-Mesenchymal Transition.

A role of Dicer, which converts precursor miRNAs to mature miRNAs, in the tumor-promoting effect of hypoxia is currently emerging in some tumor entities. Its role in hepatocellular carcinoma (HCC) is unknown. HepG2 and Huh-7 cells were stably transfected with an inducible Dicer expression vector and were exposed to hypoxia/normoxia.

High levels of the soluble programmed death-ligand (sPD-L1) identify hepatocellular carcinoma patients with a poor prognosis.

Aim: Immunotherapy in cancer is a recent and very promising approach, namely the inhibition of the PD/programmed death-ligand 1 (PD-L1) axis. Here we aimed to investigate the prognostic value of a soluble form of PD-L1 in hepatocellular carcinoma (HCC) patients.

Methods: HCC patients were prospectively recruited and soluble programmed death-ligand 1 (sPD-L1) levels were determined.

Cytokeratin 18-based cell death markers indicate severity of liver disease and prognosis of cirrhotic patients.

Background & Aims: Hepatocyte death is an important factor in development and progression of cirrhosis. Cytokeratin 18-based serum markers reflecting apoptotic (M30) and overall epithelial cell death (M65 and M65EpiDeath) have been used as prognostic parameters for survival in patients with acute liver failure. However, there has been no trial investigating M30, M65 and M65EpiDeath as survival parameters in patients with cirrhosis and acute-on-chronic liver failure.

Serum sphingolipidomic analyses reveal an upregulation of C16-ceramide and sphingosine-1-phosphate in hepatocellular carcinoma.

We have recently shown that major alterations of serum sphingolipid metabolites in chronic liver disease associate significantly with the stage of liver fibrosis in corresponding patients. In the current study we assessed via mass spectrometry serum concentrations of sphingolipid metabolites in a series of 122 patients with hepatocellular carcinoma (HCC) compared to an age- and sex-matched series of 127 patients with cirrhosis. We observed a highly significant upregulation of long and very long chain ceramides (C16-C24) in the serum of patients with HCC as compared to patients with cirrhosis (P < 0.

Vesicle-associated microRNAs are released from blood cells on incubation of blood samples.

MicroRNAs (miRNAs) circulating extracellularly in the blood are currently intensively studied as novel disease markers. However, the preanalytical factors influencing the levels of the extracellular miRNAs are still incompletely explored. In particular, it is unknown, whether the incubation of blood samples as occurring in clinical routine can lead to a release of miRNAs from blood cells and thus alter the extracellular miRNA levels before the preparation of serum or plasma from the blood cells.

Serum Sphingolipid Variations Associate with Hepatic Decompensation and Survival in Patients with Cirrhosis.

Background: Sphingolipids constitute bioactive molecules with functional implications in liver homeostasis. Particularly, ablation of very long chain ceramides in a knockout mouse model has been shown to cause a severe hepatopathy.

Methods: We aimed to evaluate the serum sphingolipid profile of 244 patients with cirrhosis prospectively followed for a median period of 228±217 days via mass spectrometry.

Improving Drug Penetrability with iRGD Leverages the Therapeutic Response to Sorafenib and Doxorubicin in Hepatocellular Carcinoma.

iRGD is a derivative of the integrin-binding peptide RGD, which selectively increases the penetrability of tumor tissue to various coadministered substances in several preclinical models. In this study, we investigated the ability of iRGD to improve the delivery of sorafenib and doxorubicin therapy in hepatocellular carcinoma (HCC) using established mouse models of the disease. A contrast-enhanced MRI method was developed in parallel to assess the in vivo effects of iRGD in this setting.

Low 25-Hydroxyvitamin D Levels Are Associated with Infections and Mortality in Patients with Cirrhosis.

Background & Aims: Vitamin D, best known to regulate bone mineralization, has numerous additional roles including regulation inflammatory pathways. Recently, an increased incidence of 25-hydroxyvitamin D3 (25(OH)D3) deficiency has been found in subjects suffering from liver diseases. We here investigated if low vitamin D levels might be associated with prognosis, inflammation and infectious complications in patients with cirrhosis.

No Distal Migration in Unfixed Versus Fixed Cell Structure Covered Self-Expanding Metal Stents for Treatment of Benign Biliary Disease.

Background: Fully covered self-expandable metal stents (FCSEMS) are increasingly used for treatment of benign common bile duct (CBD) stricture or leakage, but dislodgement of FCSEMS is frequent.

Aims: To compare dislocation rate and clinical outcome of a standard fixed cell structure FCSEMS (S-FCSEMS) to a novel FCSEMS with an unfixed cell structure (N-FCSEMS).

Methods: We performed a retrospective analysis of all patients with FCSEMS insertion for benign biliary disease at our Hospital from 03/2008 to 03/2014.

A novel, stiff-shaft, flexible-tip guidewire for cannulation of biliary stricture during endoscopic retrograde cholangiopancreatography: a randomized trial.

Background And Study Aims: During endoscopic retrograde cholangiopancreatography (ERCP), a guidewire is used to cannulate biliary strictures and allow for therapeutic interventions. The aim of this study was to assess the success of stricture cannulation using a combination of a flexible guidewire and a stable nitinol wire vs. a novel, single, stiff-shaft, flexible-tip guidewire.

Serum autotaxin is a parameter for the severity of liver cirrhosis and overall survival in patients with liver cirrhosis--a prospective cohort study.

Background: Autotaxin (ATX) and its product lysophosphatidic acid (LPA) are considered to be involved in the development of liver fibrosis and elevated levels of serum ATX have been found in patients with hepatitis C virus associated liver fibrosis. However, the clinical role of systemic ATX in the stages of liver cirrhosis was unknown. Here we investigated the relation of ATX serum levels and severity of cirrhosis as well as prognosis of cirrhotic patients.

Telaprevir drug monitoring during antiviral therapy of hepatitis C graft infection after liver transplantation.

Background & Aims: Recurrence of hepatitis C virus (HCV) infection after orthotopical liver transplantation (OLT) is common and associated with reduced graft and patient survival. The protease inhibitor telaprevir may enhance virological response rates in patients after OLT in combination with pegylated interferon-alfa and ribavirin. Pharmacokinetic studies have shown significant drug-drug interactions between telaprevir and immunosuppression (IS), but telaprevir pharmacokinetics in OLT patients with IS are unknown.

Single measurement of hemoglobin predicts outcome of HCC patients.

Anemia is a common complication in several types of cancer including hepatocellular carcinoma (HCC). The prognostic potential of hemoglobin (Hb) levels has not yet been investigated in HCC patients. One hundred and ninety-nine patients were prospectively recruited and Hb levels were determined.

Differential stability of cell-free circulating microRNAs: implications for their utilization as biomarkers.

Background: MicroRNAs circulating in the blood, stabilized by complexation with proteins and/or additionally by encapsulation in lipid vesicles, are currently being evaluated as biomarkers. The consequences of their differential association with lipids/vesicles for their stability and use as biomarkers are largely unexplored and are subject of the present study.

Methods: The levels of a set of selected microRNAs were determined by quantitative reverse-transcription PCR after extraction from sera or vesicle- and non-vesicle fractions prepared from sera.

Baseline MELD score predicts hepatic decompensation during antiviral therapy in patients with chronic hepatitis C and advanced cirrhosis.

Background And Aims: In patients with advanced liver cirrhosis due to chronic hepatitis C virus (HCV) infection antiviral therapy with peginterferon and ribavirin is feasible in selected cases only due to potentially life-threatening side effects. However, predictive factors associated with hepatic decompensation during antiviral therapy are poorly defined.

Methods: In a retrospective cohort study, 68 patients with HCV-associated liver cirrhosis (mean MELD score 9.

Investigation of viral escape mutations within HCV p7 during treatment with amantadine in patients with chronic hepatitis C.

Background: Combination of several direct-acting antiviral agents will be necessary to overcome viral resistance in interferon-free treatment regimens for chronic HCV infection. HCV p7 inhibitors may be part of such combination regimens. Understanding why amantadine, despite showing inhibition of HCV p7 in vitro, appears ineffective in clinical trials, may help in the design of novel HCV p7 inhibitors.

Serum microRNA-1 and microRNA-122 are prognostic markers in patients with hepatocellular carcinoma.

Background: The identification of new biomarkers to predict the aggressiveness of hepatocellular carcinoma (HCC) and supplement the current set of prognosis and treatment algorithms is an important clinical need. Extracellular microRNAs (miRNAs) circulating in the blood are a new class of highly promising disease markers.

Aim: Here we investigated the prognostic potential of miR-1 and miR-122 in sera from patients with HCC.

Diagnostic and prognostic significance of cell death and macrophage activation markers in patients with hepatocellular carcinoma.

Background & Aims: The serum cell death parameters M30 and M65 and the macrophage activation marker sCD163 (soluble CD163) are elevated in patients with acute and chronic liver diseases. However, their diagnostic and prognostic potential in patients with hepatocellular carcinoma (HCC) has not yet been investigated.

Methods: Serum levels of M30, M65, and sCD163 were measured in two cohorts of HCC patients and a cohort of cirrhotic patients.

High Serum Levels of the Interleukin-33 Receptor Soluble ST2 as a Negative Prognostic Factor in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor, usually arises in the setting of liver cirrhosis (LC), and has a poor prognosis. The recently discovered Th2-cytokine interleukin-33 (IL-33) is a possible mediator in pancreatic and gastric carcinogeneses. IL-33 binds to its receptor and to soluble ST2 (sST2), which thereby acts as a regulator.

Low vitamin D serum concentration is associated with high levels of hepatitis B virus replication in chronically infected patients.

Unlabelled: Vitamin D is an important immune modulator that plays an emerging role in inflammatory and metabolic liver diseases, including infection with hepatitis C virus (HCV). In contrast, the relationship between vitamin D metabolism and chronic hepatitis B (CHB) is less well characterized. Therefore, we quantified 25(OH)D3 serum levels in a cohort of 203 treatment-naïve patients with chronic hepatitis B virus (HBV) infection and tested for their association with clinical parameters of CHB.