Refine
Year of publication
Document Type
- Article (143)
- Conference Proceeding (2)
Language
- English (145) (remove)
Has Fulltext
- yes (145)
Is part of the Bibliography
- no (145)
Keywords
- Cirrhosis (7)
- cirrhosis (7)
- Antiviral therapy (6)
- Hepatocellular carcinoma (6)
- Liver diseases (6)
- hepatitis C virus (6)
- Hepatitis C virus (4)
- liver transplantation (4)
- ACLF (3)
- Chronic hepatitis C (3)
- HCC (3)
- acute-on-chronic liver failure (3)
- direct-acting antivirals (3)
- hepatitis C (3)
- liver cirrhosis (3)
- portal hypertension (3)
- Cancer treatment (2)
- Cytoskeletal proteins (2)
- DAA (2)
- Diabetes mellitus (2)
- Directly acting antiviral agent (2)
- Endoscopy (2)
- HBV (2)
- HIV (2)
- Hepatitis (2)
- Immunology (2)
- Inflammation (2)
- Liver cirrhosis (2)
- Liver fibrosis (2)
- Liver transplantation (2)
- Mortality (2)
- NASH (2)
- Ribavirin (2)
- SPTAN1 (2)
- Viral load (2)
- ascites (2)
- biliary stricture (2)
- chemotherapy (2)
- co-infection (2)
- fatigue (2)
- inflammation (2)
- insulin resistance (2)
- molecular dynamics (2)
- multidrug resistance (2)
- overall survival (2)
- resistance mutation (2)
- serine protease (NS3-4A) (2)
- transient elastography (2)
- 8 weeks (1)
- AGC kinase (1)
- APRI (1)
- ARA (1)
- Adeno associated virus (1)
- Adenylyl cyclase (1)
- Alcoholic liver disease (1)
- All oral (1)
- All-oral therapy (1)
- Antibiotic steward-ship (1)
- Antibiotics (1)
- Ascites (1)
- Aurora (1)
- B-cell (1)
- BNT162b2 (1)
- Bacterial abundance (1)
- Biliary physiology (1)
- Biochemistry (1)
- Blood (1)
- Blood plasma (1)
- Breast tumors (1)
- Burden of disease (1)
- CLIF-C ACLF score (1)
- CLIF-C ACLF-R score (1)
- COVID-19 vaccination (1)
- CT (1)
- Caco-2 cells (1)
- Cancer (1)
- Cancer chemotherapy (1)
- Capnography (1)
- Cardiovascular disease (1)
- Case report (1)
- Cell binding (1)
- Cell motility (1)
- Cell staining (1)
- Cellular (1)
- Chronic Hepatitis C (1)
- Chronic hepatitis (1)
- Clinical efficacy (1)
- Colorectal cancer (1)
- Computed axial tomography (1)
- DNA methylation (1)
- DNA mismatch repair (1)
- Death rates (1)
- Digestive system (1)
- Digestive system procedures (1)
- Direct-acting antiviral agents (DAAs) (1)
- Direct-acting antivirals (1)
- Discovery (1)
- Drug (1)
- EQ-5D (1)
- ESBL (1)
- Early goal-directed therapy (1)
- Eicosanoids (1)
- Endocrine cancer (1)
- Enterobacteriaceae (1)
- Etiology (1)
- FIB-4 (1)
- FSS (1)
- Fatty acids (1)
- Fatty liver (1)
- Fibrosis (1)
- Fibrotest (1)
- Flow cytometry (1)
- GSK2334470 (1)
- GSK3α (1)
- GSK3β (1)
- Gastric cancer (1)
- Gastroenterology (1)
- Gastrointestinal tract (1)
- Gene therapy (1)
- Genetics (1)
- Genome-wide association study (1)
- Genomic medicine (1)
- HBV reactivation (1)
- HCV (1)
- HCV treatment (1)
- Health care resource utilization (1)
- Hepatitis B virus (1)
- Hepatitis C (1)
- Hepatotoxicity (1)
- Hispanic people (1)
- Host-targeting agents (HTAs) (1)
- Hypoxia (1)
- IgG4-related disease (1)
- Immune complex vasculitis (1)
- Immune suppression (1)
- Immunohistochemistry techniques (1)
- Indeterminate biliary stricture (1)
- Individualized therapy (1)
- Infection (1)
- Infections (1)
- Infectious disease (1)
- Infectious disease epidemiology (1)
- Integrated Pulmonary Index (1)
- Intensive care unit (1)
- Interferon (1)
- Interferon-free HCV treatment (1)
- Interferon-α (1)
- Interferon-λ, (1)
- Interleukin-22 (1)
- Interventional oncological treatment (1)
- Intestinal neoplasms (1)
- Kupffer cells (1)
- Laser interstitial thermal therapy (1)
- Liver (1)
- Liver cancer (1)
- Liver enzymes (1)
- Liver-related complications (1)
- Lymphoma (1)
- MELD (1)
- MLH1 (1)
- MRP4 (1)
- Macrophages (1)
- Medical education (1)
- Membrane staining (1)
- Metabolic syndrome (1)
- Metastasis (1)
- Metastatic tumors (1)
- Methicillin-resistant Staphylococcus aureus (1)
- Microwave ablation (1)
- Molecular biology (1)
- Monitoring (1)
- Mouse models (1)
- Multidrug resistance (1)
- Multidrug-resistance (1)
- Multidrug-resistant organisms (1)
- NAFLD (1)
- NS3-4A protease inhibitor (1)
- NS3/4A protease inhibitors (PI) (1)
- NS5A inhibitors (1)
- NS5B polymerase inhibitor (1)
- Negative staining (1)
- Neuroendocrine cancer (1)
- Next-generation sequencing (1)
- Non-Hodgkin lymphoma (1)
- Non-nucleoside polymerase inhibitors (NNI) (1)
- Null responder (1)
- Obesity (1)
- PCR (1)
- PDK1 (1)
- PIF pocket (1)
- PKA (1)
- PROMISE (1)
- Pathogenesis (1)
- Percutaneous endoscopic gastrostomy (1)
- Personal medicine (1)
- Platelets (1)
- Portal hypertension (1)
- Portal veins (1)
- Primary sclerosing cholangitis (1)
- Prostaglandin (1)
- Protease inhibitor therapy (1)
- Quinolones (1)
- Radiation exposure (1)
- Regression analysis (1)
- SKI II (1)
- SVR (1)
- SW480 cells (1)
- Safety (1)
- Salmonella choleraesuis (1)
- Sarcopenia (1)
- Self-expandable metal stents (1)
- Self-expandable metal stents complications (1)
- Sepsis-bundle (1)
- Single nucleotide polymorphism (1)
- Specimen preparation and treatment (1)
- Sphingolipids (1)
- Surgical and invasive medical procedures (1)
- Surgical oncology (1)
- Survival (1)
- Sustained virological response (1)
- TACE (1)
- TMC435 (1)
- Thrombosis (1)
- Thromboxane (1)
- Transarterial chemoembolization (1)
- Transferases (1)
- Transient elastography (1)
- Tumor obstruction (1)
- Type three hypersensitivity (1)
- VRE (1)
- Veins (1)
- Vitamin D (1)
- Vitamin D deficiency (1)
- acoustic radiation force impulse (1)
- acoustic radiation force impulse imaging (1)
- acute decompensation (1)
- adaptation (1)
- adenosine (1)
- adenosine receptors (1)
- alcoholic hepatitis (1)
- allosteric regulation (1)
- angiopoietin-like 3 (ANGPTL3) (1)
- anti-EGFR therapy (1)
- antibiotic therapy (1)
- antimicrobial stewardship (1)
- antiviral therapy (1)
- arachidonate 12/15-lipoxygenase (Alox12/15) (1)
- arachidonic acid (1)
- bacterial translocation (1)
- bevacizumab (1)
- bile duct stenosis (1)
- biomarker (1)
- cAMP (1)
- cART (1)
- carbapenem resistance (1)
- chemorefractory metastatic colorectal cancer (1)
- cholangiocarcinoma (1)
- chronic hepatitis C (1)
- chronic viral hepatitis (1)
- colorectal cancer (1)
- combination (1)
- computed tomography (1)
- core expression (1)
- critical care unit (1)
- critical ill patients (1)
- cytokines (1)
- cytoskeleton (1)
- death rates (1)
- decompensated liver cirrhosis (1)
- dihydroceramide (1)
- direct antiviral (1)
- direct antiviral agents (1)
- direct-acting antiviral (DAA) treatment (1)
- direct-acting antivirals (DAAs) (1)
- directly acting antiviral agents (1)
- double-pigtail stents (1)
- drug interaction (1)
- drug resistance (1)
- eNPP2 (1)
- elderly (1)
- endoscopic retrograde cholangiography (1)
- endoscopic retrograde cholangiopancreatography (1)
- endoscopy (1)
- enterobacter infections; pseudomonas aeruginosa; epidemiology (1)
- eosinophilic cholangitis (1)
- epidemiology (1)
- evolution (1)
- exosomes (1)
- fibrosis (1)
- fibrotest (1)
- first-line chemotherapy (1)
- fumonisin B1 (1)
- genotype G (1)
- glecaprevir (1)
- graft rejection (1)
- health related quality of life (1)
- hemophilia (1)
- hepatic fibrosis (1)
- hepatitis (1)
- hepatitis B (1)
- hepatitis B virus (1)
- hepatitis C virus (HCV) (1)
- hepatitis E virus (1)
- hepatitis c (1)
- hepatocellular carcinoma (1)
- hospital admission (1)
- host-targeting antivirals (1)
- immune escape (1)
- immunity (1)
- immunohistochemistry (1)
- infection control (1)
- innate immunity (1)
- interferon (1)
- interferon-free (1)
- interferon-free antiviral treatment (1)
- interferons (1)
- intrahepatic cholangiocarcinoma (1)
- in vivo (1)
- ischemic type biliary lesions (1)
- lipoxin A4 (1)
- liver (1)
- liver fibrosis (1)
- liver immunology (1)
- long-term follow-up (1)
- macrophages (1)
- male (1)
- mechanical ventilation (1)
- medical risk factors (1)
- metastasis (1)
- metastatic colorectal cancer (1)
- miR-122 (1)
- microsatellite instability (1)
- mitochondrial antiviral signaling protein (MAVS) (1)
- molecular adaptation (1)
- molecular biology (1)
- mortality (1)
- non-invasive fibrosis assessment (1)
- omega-3 fatty acids (1)
- organ dysfunction (1)
- organ failure (1)
- orthopic liver transplantation (1)
- patient-reported outcomes (1)
- peg-interferon lambda (1)
- peginterferon (1)
- peginterferon-α (1)
- perioperative mortality (1)
- phylogenetic analysis (1)
- pibrentasvir (1)
- platelet count (1)
- point shear wave elastography (1)
- prevalence (1)
- primary sclerosing cholangitis (1)
- protease inhibitor (1)
- protein evolution (1)
- protein folding (1)
- protein kinase (1)
- pseudomonas aeruginosa (1)
- pulmonary failure (1)
- re-exposure (1)
- rechallenge (1)
- recurrent cholangitis (1)
- reintroduction (1)
- replicative fitness (1)
- resistance-associated substitutions (RAS) (1)
- resolution of inflammation (1)
- respiratory failure (1)
- ribavirin (1)
- screening routine (1)
- sepsis (1)
- short-course antibiotic therapy (1)
- signature (1)
- simeprevir (1)
- small compounds (1)
- sofosbuvir (1)
- sorafenib (1)
- specialized pro-resolving lipid mediators (SPMs) (1)
- spectrin (1)
- sphingolipid (1)
- sphingolipids (1)
- stent patency (1)
- structure constraints (1)
- thrombocytopenia (1)
- thrombocytosis (1)
- transmission (1)
- treatment (1)
- triple therapy (1)
- velpatasvir (1)
- viral fitness (1)
- voxilaprevir (1)
- whole-genome sequencing (1)
- work productivity (1)
Institute
- Medizin (145)
- Biowissenschaften (3)
- Georg-Speyer-Haus (3)
- Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit (ZAFES) (3)
- Institut für Ökologie, Evolution und Diversität (1)
- Interdisziplinäres Zentrum für Neurowissenschaften Frankfurt (IZNF) (1)
- Pharmazie (1)
- Senckenbergische Naturforschende Gesellschaft (1)
- Sonderforschungsbereiche / Forschungskollegs (1)
Background: MicroRNA-21 (miR-21) is up-regulated in tumor tissue of patients with malignant diseases, including hepatocellular carcinoma (HCC). Elevated concentrations of miR-21 have also been found in sera or plasma from patients with malignancies, rendering it an interesting candidate as serum/plasma marker for malignancies. Here we correlated serum miR-21 levels with clinical parameters in patients with different stages of chronic hepatitis C virus infection (CHC) and CHC-associated HCC.
Methodology/Principal Findings: 62 CHC patients, 29 patients with CHC and HCC and 19 healthy controls were prospectively enrolled. RNA was extracted from the sera and miR-21 as well as miR-16 levels were analyzed by quantitative real-time PCR; miR-21 levels (normalized by miR-16) were correlated with standard liver parameters, histological grading and staging of CHC. The data show that serum levels of miR-21 were elevated in patients with CHC compared to healthy controls (P<0.001); there was no difference between serum miR-21 in patients with CHC and CHC-associated HCC. Serum miR-21 levels correlated with histological activity index (HAI) in the liver (r = −0.494, P = 0.00002), alanine aminotransferase (ALT) (r = −0.309, P = 0.007), aspartate aminotransferase (r = −0.495, P = 0.000007), bilirubin (r = −0.362, P = 0.002), international normalized ratio (r = −0.338, P = 0.034) and γ-glutamyltransferase (r = −0.244, P = 0.034). Multivariate analysis revealed that ALT and miR-21 serum levels were independently associated with HAI. At a cut-off dCT of 1.96, miR-21 discriminated between minimal and mild-severe necroinflammation (AUC = 0.758) with a sensitivity of 53.3% and a specificity of 95.2%.
Conclusions/Significance: The serum miR-21 level is a marker for necroinflammatory activity, but does not differ between patients with HCV and HCV-induced HCC.
Background and aims: Expression of carbonic anhydrase IX (CA9), an enzyme expressed in response to hypoxia, acidosis and oncogenic alterations, is reported to be a prognostic factor in HCC patients. Here we evaluated serum CA9 levels in HCC and cirrhosis patients.
Methods: HCC and cirrhosis patients were prospectively recruited and CA9 levels were determined. CA9 levels were compared to stages of cirrhosis and HCC stages. The association of the CA9 levels and overall survival (OS) was assessed. Furthermore, immunohistochemical CA9 expression in HCC and cirrhosis was evaluated.
Results: 215 patients with HCC were included. The median serum CA9 concentration in patients with HCC was 370 pg/ml and significantly higher than in a healthy cohort. Patients with advanced cancer stages (BCLC and ALBI score) had hid significant higher levels of CA9 in the serum. HCC patients with high serum CA9 concentrations (>400 pg/ml) had an increased mortality risk (hazard ratio (HR) 1.690, 95% confidence interval (CI) 1.017–2.809, P = 0.043). Serum CA9 concentration in cirrhotic patients did not differ significantly from HCC patients. Higher CA9 levels in cirrhotic patients correlated with portal hypertension and esophageal varices. Patients with ethanol induced cirrhosis had the highest CA9 levels in both cohorts. Levels of CA9 did not correlate with immunohistochemical expression.
Conclusions: We conclude that a high CA9 level is a possible prognostic indicator for a poor outcome in HCC patients. The high CA9 levels are probably mainly associated with portal hypertension. Ductular reactions might be a possible source of serum CA9.
Enzymatic and antisense effects of a specific anti-Ki-ras ribozyme in vitro and in cell culture
(1999)
Due to their mode of action, ribozymes show antisense effects in addition to their specific cleavage activity. In the present study we investigated whether a hammerhead ribozyme is capable of cleaving mutated Ki-ras mRNA in a pancreatic carcinoma cell line and whether antisense effects contribute to the activity of the ribozyme. A 2[prime]-O-allyl modified hammerhead ribozyme was designed to cleave specifically the mutated form of the Ki-ras mRNA (GUU motif in codon 12). The activity was monitored by RT-PCR on Ki-ras RNA expression by determination of the relative amount of wild type to mutant Ki-ras mRNA, by 5-bromo-2[prime]-deoxy-uridine incorporation on cell proliferation and by colony formation in soft agar on malignancy in the human pancreatic adenocarcinoma cell line CFPAC-1, which is heterozygous for the Ki-ras mutation. A catalytically inactive ribozyme was used as control to differentiate between antisense and cleavage activity and a ribozyme with random guide sequences as negative control. The catalytically active anti-Ki-ras ribozyme was at least 2-fold more potent in decreasing cellular Ki-ras mRNA levels, inhibiting cell proliferation and colony formation in soft agar than the catalytically inactive ribozyme. The catalytically active anti-Ki-ras ribozyme, but not the catalytically inactive or random ribozyme, increased the ratio of wild type to mutated Ki-ras mRNA in CFPAC-1 cells. In conclusion, both cleavage activity and antisense effects contribute to the activity of the catalytically active anti-Ki-ras hammerhead ribozyme. Specific ribozymes might be useful in the treatment of pancreatic carcinomas containing an oncogenic GTT mutation in codon 12 of the Ki-ras gene.
Introduction. Balapiravir (R1626, RG1626) is the prodrug of a nucleoside analogue inhibitor of the hepatitis C virus (HCV) RNA-dependent RNA polymerase (R1479, RG1479). This phase 2, double-blind international trial evaluated the optimal treatment regimen of balapiravir plus peginterferon alfa-2a (40KD)/ribavirin.
Material and methods. Treatment-naive genotype 1 patients (N = 516) were randomized to one of seven treatment groups in which they received balapiravir 500, 1,000, or 1,500 mg twice daily, peginterferon alfa2a (40KD) 180 or 90 Mg/week and ribavirin 1,000/1,200 mg/day or peginterferon alfa-2a (40KD)/ribavirin. The planned treatment duration with balapiravir was reduced from 24 to 12 weeks due to safety concerns.
Results. The percentage of patients with undetectable HCV RNA was consistently higher in all balapiravir groups from week 2 to 12. However, high rates of dose modifications and discontinuations of one/all study drugs compromised the efficacy assessment and resulted in similar sustained virological response rates in the balapiravir groups (range 32-50%) and the peginterferon alfa-2a (40KD)/ribavirin group (43%). Balapiravir was discontinued for safety reasons in 28-36% of patients (most often for lymphopenia) and the percentage of patients with serious adverse events (especially hematological, infection, ocular events) was dose related. Serious hematological adverse events (particularly neutropenia, lymphopenia) were more common in balapiravir recipients. Two deaths in the balapiravir/peginterferon alfa-2a/ribavirin combination groups were considered possibly related to study medication.
Conclusion. Further development of balapiravir for the treatment of chronic hepatitis C has been halted because of the unacceptable benefit to risk ratio revealed in this study (www.ClinicalTrials.gov NCT 00517439).
The hepatitis C virus (HCV) was discovered in the late 1980s. Interferon (IFN)-α was proposed as an antiviral treatment for chronic hepatitis C at about the same time. Successive improvements in IFN-α-based therapy (dose finding, pegylation, addition of ribavirin) increased the rates of sustained virologic response, i.e. the rates of curing HCV infection. These rates were further improved by adding the first available direct-acting antiviral (DAA) drugs to the combination of pegylated IFN-α and ribavirin. An IFN-free era finally started in 2014, yielding rates of sustained virologic response over 90% in patients treated for 8 to 24 weeks with all-oral regimens. Major challenges however remain in implementation of these new treatment strategies, not only in low- to middle-income countries, but also in high-income countries where the price of these therapies is still prohibitive. Elimination of HCV infection through treatment in certain areas is possible but raises major public health issues.
While patients with chronic hepatitis C virus (HCV) infection are treated in order to prevent liver-related morbidity and mortality, we rely on sustained virological response (SVR) as a virological biomarker to evaluate treatment efficacy in both clinical practice as well as in drug development. However, conclusive evidence for the clinical benefit of antiviral therapy or validity of SVR as surrogate marker, as derived from trials randomizing patients to a treatment or control arm, is lacking. In fact, the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) trial recently showed an increased mortality rate among interferon-treated patients compared to untreated controls. Consequently, the recommendation to treat patients with chronic HCV infection was challenged.
Here, we argue that the possible harmful effect of long-term low-dose pegylated interferon mono therapy, as was observed in the HALT-C trial cohort, cannot be extrapolated to potentially curative short-term treatment regimens. Furthermore, we discuss SVR as a surrogate biomarker, based on numerous studies which indicated an association between SVR and improvements in health-related quality of life, hepatic inflammation and fibrosis, and portal pressure as well as a reduced risk for hepatocellular carcinoma (HCC), liver failure and mortality.
Recent data have clearly shown that a sustained virologic response can be achieved in different HCV infected patient populations with various interferon-free treatment regimens. Despite the successful implementation of telaprevir- and boceprevir-based triple therapies, all-oral regimens will certainly become a first choice for a number of HCV-infected patients in the very near future, as triple therapy approaches are burdened with significant side-effects and limited success in patients with advanced liver fibrosis and prior null-response to pegylated interferon-α (pegIFN-α)/ribavirin therapy. However, available data from phase I and II clinical trials evaluating interferon-free regimens have not yet revealed a clearly outstanding all-oral combination, and numerous challenges remain to be addressed by intensive ongoing and future research. In particular, thus far evaluated all-oral regimens did not cure a satisfactory percentage of patients with unfavorable baseline characteristics, namely patients infected with HCV genotype 1a, previous null-response to pegIFN-α/ribavirin, or liver cirrhosis. In this review, we summarize available data of interferon-free regimens for the treatment of chronic hepatitis C and assess implications for perspectives and challenges in the further development of all-oral therapies.
There is ample epidemiologic evidence for an association of chronic hepatitis C virus (HCV) infection with B-cell non-Hodgkin lymphoma (B-NHL). B-NHL subtypes most frequently associated with HCV are marginal zone lymphoma and diffuse large B-cell lymphoma. The most convincing evidence for a causal relationship between HCV infection and lymphoma development is the observation of B-NHL regression after HCV eradication by antiviral therapy (AVT). In fact, for indolent HCV-associated B-NHL, first-line AVT instead of standard immune-chemotherapy might be considered. Molecular mechanisms of HCV-NHL development are still poorly understood. Three general theories have emerged to understand the HCV-induced lymphomagenesis: (1) continuous external stimulation of lymphocyte receptors by viral antigens and consecutive proliferation; (2) HCV replication in B cells with oncogenic effect mediated by intracellular viral proteins; (3) permanent B-cell damage, e.g., mutation of tumor suppressor genes, caused by a transiently intracellular virus (“hit and run” theory). This review systematically summarizes the data on epidemiology, interventional studies, and molecular mechanisms of HCV-associated B-NHL.