General, Modular Access toward Immobilized Chiral Phosphoric Acid Catalysts and Their Application in Flow Chemistry.

Chiral phosphoric acids (CPAs) are among the most frequently used organocatalysts, with an ever-increasing number of applications. However, these catalysts are only obtained in a multistep synthesis and are poorly recyclable, which significantly deteriorates their environmental and economic performance. We herein report a conceptually different, general strategy for the direct immobilization of CPAs on a broad scope of solid supports including silica, polystyrene, and aluminum oxide. Solid-state catalysts were obtained in high yields and thoroughly characterized with elemental analysis by inductively coupled plasma-optical emission spectrometry (ICP-OES), nitrogen sorption measurements, thermogravimetric analysis, scanning transmission electron microscopy/energy-dispersive X-ray spectroscopy (STEM/EDX) images, and solid-state NMR spectroscopy. Further, the immobilized catalysts were applied to a variety of synthetically valuable, highly stereoselective transformations under batch and flow conditions including transfer hydrogenations, a Friedländer condensation/transfer hydrogenation sequence, and Mannich reactions under cryogenic flow conditions. Generally, high yields and stereoselectivities were observed along with robust catalyst stability and reusability. After being used for 10 runs under batch conditions, no loss of selectivity or catalytic activity was observed. Under continuous-flow conditions, the heterogeneous system was in operation for 19 h and the high enantioselectivity remained unchanged throughout the entire process. We expect our approach to extend the applicability of CPAs to a higher level, with a focus on flow chemistry and a more environmentally friendly and resource-efficient use of these powerful catalysts.

A mitotic chromatin phase transition prevents perforation by microtubules.

Dividing eukaryotic cells package extremely long chromosomal DNA molecules into discrete bodies to enable microtubule-mediated transport of one genome copy to each of the newly forming daughter cells1-3. Assembly of mitotic chromosomes involves DNA looping by condensin4-8 and chromatin compaction by global histone deacetylation9-13. Although condensin confers mechanical resistance to spindle pulling forces14-16, it is not known how histone deacetylation affects material properties and, as a consequence, segregation mechanics of mitotic chromosomes. Here we show how global histone deacetylation at the onset of mitosis induces a chromatin-intrinsic phase transition that endows chromosomes with the physical characteristics necessary for their precise movement during cell division. Deacetylation-mediated compaction of chromatin forms a structure dense in negative charge and allows mitotic chromosomes to resist perforation by microtubules as they are pushed to the metaphase plate. By contrast, hyperacetylated mitotic chromosomes lack a defined surface boundary, are frequently perforated by microtubules and are prone to missegregation. Our study highlights the different contributions of DNA loop formation and chromatin phase separation to genome segregation in dividing cells.

Telemetric capsule-based upper gastrointestinal tract - blood detection - first multicentric experience.

INTRODUCTION: Risk stratification in upper gastrointestinal bleeding (UGIB) currently relies on clinical parameters and risk scores. HemoPill® acute (Ovesco Endoscopy, Tuebingen, Germany) is a pill-shaped, orally administered sensor capsule for real-time blood detection. The aim of this study was to evaluate the system in clinical routine. MATERIAL AND METHODS: Sixty-one consecutive patients in whom the HemoPill® had been used at 12 international hospitals between July 2019 and March 2020 were retrospectively analysed. Indications for application were the clinical suspicion of UGIB, small bowel bleeding, of rebleeding after hemostasis. Primary endpoints were technical success and bleeding detection/exclusion. Secondary endpoints included adverse events and change of clinical course. RESULTS: The capsule was used in 45 (73%) patients with UGIB, in 12 (20%) patients with small bowel bleeding and in four (7%) patients for exclusion of rebleeding. Technical success was 98%. 35/60 (58%) cases were capsule-positive and among these, endoscopy showed bleeding in 20/35 (57%) cases. None of the 25 capsule-negative patients rebled. Emergency endoscopy could be avoided in 18/25 (72%) cases. Serious adverse events did not occur. CONCLUSION: HemoPill®-based blood detection is feasible and safe. Negative capsule results might 'downgrade' the need for urgent endoscopy.

Chromosome clustering by Ki-67 excludes cytoplasm during nuclear assembly.

Gene expression in eukaryotes requires the effective separation of nuclear transcription and RNA processing from cytosolic translation1. This separation is achieved by the nuclear envelope, which controls the exchange of macromolecules through nuclear pores2. During mitosis, however, the nuclear envelope in animal and plant cells disassembles, allowing cytoplasmic and nuclear components to intermix3. When the nuclear envelope is reformed, cytoplasmic components are removed from the nucleus by receptor-mediated transport through nuclear pores2. These pores have a size limit of 39 nanometres4-7, which raises the question of how larger cytoplasmic molecules are cleared from the nucleus. Here we show in HeLa cells that large cytoplasmic components are displaced before nuclear envelope assembly by the movement of chromosomes to a dense cluster. This clustering occurs when chromosomes approach the poles of anaphase spindles, and is mediated by a microtubule-independent mechanism that involves the surfactant-like protein Ki-67. Ki-67 forms repulsive molecular brushes during the early stages of mitosis8, but during mitotic exit the brushes collapse and Ki-67 promotes chromosome clustering. We show that the exclusion of mature ribosomes from the nucleus after mitosis depends on Ki-67-regulated chromosome clustering. Thus, our study reveals that chromosome mechanics help to re-establish the compartmentalization of eukaryotic cells after open mitosis.

Phosphoric Acid Catalyzed Formation of Hydrogen-Bonded o-Quinone Methides. Enantioselective Cycloaddition with ß-Dicarbonyl Compounds toward Benzannulated Oxygen Heterocycles.

A full account of the Brønsted acid catalyzed, enantioselective synthesis of 4H-chromenes and 1H-xanthen-1-ones from o-hydroxybenzyl alcohols and ß-dicarbonyl compounds is provided. The central step of our strategy is the BINOL-phosphoric acid catalyzed, enantioselective cycloaddition of ß-diketones, ß-keto nitriles, and ß-keto esters to in situ generated, hydrogen-bonded o-quinone methides. Upon acid-promoted dehydration, the desired products were obtained with generally excellent yields and enantioselectivity. Detailed mechanistic studies including online-NMR and ESI-MS measurements were conducted to identify relevant synthetic intermediates. A reversible formation of a dimer from the starting alcohol and the reactive o-quinone methide in an off-cycle equilibrium was observed, providing a reservoir from which the o-quinone methide can be regenerated and introduced into the catalytic cycle again. Reaction progress kinetic analysis was utilized to determine kinetic profiles and rate constants of the reaction uncovering o-quinone methide formation as the rate-limiting step. In combination with Hammett plots, these studies document the relationship between o-quinone methide stabilization by electronic effects provided by the substituents and the reaction rate of the described process. In addition, DFT calculations reveal a concerted yet highly asynchronous [4 + 2]-cycloaddition pathway and an attractive CH-π interaction between the catalyst's tBu group and the o-quinone methide as an important stereochemical control element.

The biological classification of mental disorders (BeCOME) study: a protocol for an observational deep-phenotyping study for the identification of biological subtypes.

BACKGROUND: A major research finding in the field of Biological Psychiatry is that symptom-based categories of mental disorders map poorly onto dysfunctions in brain circuits or neurobiological pathways. Many of the identified (neuro) biological dysfunctions are "transdiagnostic", meaning that they do not reflect diagnostic boundaries but are shared by different ICD/DSM diagnoses. The compromised biological validity of the current classification system for mental disorders impedes rather than supports the development of treatments that not only target symptoms but also the underlying pathophysiological mechanisms. The Biological Classification of Mental Disorders (BeCOME) study aims to identify biology-based classes of mental disorders that improve the translation of novel biomedical findings into tailored clinical applications. METHODS: BeCOME intends to include at least 1000 individuals with a broad spectrum of affective, anxiety and stress-related mental disorders as well as 500 individuals unaffected by mental disorders. After a screening visit, all participants undergo in-depth phenotyping procedures and omics assessments on two consecutive days. Several validated paradigms (e.g., fear conditioning, reward anticipation, imaging stress test, social reward learning task) are applied to stimulate a response in a basic system of human functioning (e.g., acute threat response, reward processing, stress response or social reward learning) that plays a key role in the development of affective, anxiety and stress-related mental disorders. The response to this stimulation is then read out across multiple levels. Assessments comprise genetic, molecular, cellular, physiological, neuroimaging, neurocognitive, psychophysiological and psychometric measurements. The multilevel information collected in BeCOME will be used to identify data-driven biologically-informed categories of mental disorders using cluster analytical techniques. DISCUSSION: The novelty of BeCOME lies in the dynamic in-depth phenotyping and omics characterization of individuals with mental disorders from the depression and anxiety spectrum of varying severity. We believe that such biology-based subclasses of mental disorders will serve as better treatment targets than purely symptom-based disease entities, and help in tailoring the right treatment to the individual patient suffering from a mental disorder. BeCOME has the potential to contribute to a novel taxonomy of mental disorders that integrates the underlying pathomechanisms into diagnoses. TRIAL REGISTRATION: Retrospectively registered on June 12, 2019 on ClinicalTrials.gov (TRN: NCT03984084).

Intravenous thrombolysis with tPA and cortical involvement increase the risk of early poststroke seizures: Results of a case-control study.

The aim of this study was to identify the risk factors for early poststroke seizures (PSS) in patients with acute ischemic stroke. We undertook a case-control study at a single stroke center. Patients with seizure occurring during the first 7 days following ischemic stroke admitted between 2010 and 2016 were retrospectively identified and matched with controls (patients with stroke without early PSS) for age and sex. We included 79 cases and 158 controls. Blood sugar levels on admission, stroke localization, National Institutes of Health Stroke Scale (NIHSS) and Rankin score, and intravenous (i.v.) thrombolysis with recombinant tissue plasminogen activator (rtPA) were statistically associated with early PSS in univariate analysis. Multiple logistic regression after forward and backward variable selection identified cortical stroke localization (odds ratio (OR): 2.49; 95% confidence intervals (CI): 1.35 to 4.59; p = 0.003) and i.v. thrombolysis (OR: 2.26; 95% CI: 1.16 to 4.43; p = 0.008) as variables independently associated with early PSS. Cortical involvement and i.v. thrombolysis are independent risk factors associated with the occurrence of early PSS. This association is not explained by age or sex, concomitant drugs, diabetes or alcoholism, sodium and cholesterol levels, blood pressure on admission, stroke etiology or severity, and hemorrhage following i.v. thrombolysis. Further studies are required to fully elucidate the association between different reperfusion therapies and early PSS. This article is part of the Special Issue "Seizures & Stroke".

Early poststroke seizures following thrombolysis and/or thrombectomy for acute stroke: Clinical and stroke characteristics.

In this retrospective study, we explored the clinical and stroke characteristics of patients treated with thrombolysis and/or mechanical thrombectomy for an acute stroke and experiencing early poststroke seizures within 7 days of the cerebrovascular accident. Patients with prior epilepsy, primary intracerebral hemorrhage or transient ischemic attacks, or taking antiepileptic drugs were excluded. We retrospectively identified 32 patients admitted between 2010 and 2016 (mean age 75 years; range: 49-90; 14 females and 18 males). A cortical stroke was found in more than 70% of patients. Most epileptic seizures were focal aware (46.7%) or generalized convulsive (43.3%). The median time between stroke onset and seizure occurrence was 2 days; in 75.9% of the cases, seizures occurred within the first 3 days. This retrospective case series is the largest published so far providing details on clinical features of patients with early poststroke seizures following different reperfusion therapies, not only restricted to intravenous (i.v.) thrombolysis. Early poststroke seizures following reperfusion therapies are associated with cortical stroke involvement, are usually focal without impairment of awareness or generalized convulsive, and occur mostly within the first 3 days. Further studies are needed to clarify whether the low prevalence of focal impaired awareness seizures (and nonconvulsive seizures/status) is real or reflects the failure to recognize and correctly diagnose this seizure type in the acute poststroke period (risk of underascertainment due to the lack of systematic video-electroencephalogram (EEG) recording in patients with stroke and difficulties in recognizing these seizures). This article is part of the Special Issue "Seizures & Stroke".

Facile Fabrication of Bio- and Dual-Functional Poly(2-oxazoline) Bottle-Brush Brush Surfaces.

Poly(2-oxazoline)s (POx) bottle-brush brushes have excellent biocompatible and lubricious properties, which are promising for the functionalization of surfaces for biomedical devices. Herein, a facile synthesis of POx is reported which is based bottle-brush brushes (BBBs) on solid substrates. Initially, backbone brushes of poly(2-isopropenyl-2-oxazoline) (PIPOx) were fabricated via surface initiated Cu0 plate-mediated controlled radical polymerization (SI-Cu0 CRP). Poly(2-methyl-2-oxazoline) (PMeOx) side chains were subsequently grafted from the PIPOx backbone via living cationic ring opening polymerization (LCROP), which result in ≈100 % increase in brush thickness (from 58 to 110 nm). The resultant BBBs shows tunable thickness up to 300 nm and high grafting density (σ) with 0.42 chains nm-2 . The synthetic procedure of POx BBBs can be further simplified by using SI-Cu0 CRP with POx molecular brush as macromonomer (Mn =536 g mol-1 , PDI=1.10), which results in BBBs surface up to 60 nm with well-defined molecular structure. Both procedures are significantly superior to the state-of-art approaches for the synthesis of POx BBBs, which are promising to design bio-functional surfaces.

Joining Microfluidics with Infrared Photodissociation: Online Monitoring of Isomeric Flow-Reaction Intermediates.

A cryogenic ion trap vibrational spectrometer is combined with a microfluidic chip reactor in a proof-of-principle experiment on the Hantzsch cyclization reaction forming 2-amino-4-phenyl thiazole from phenacyl bromide and thiourea. First, the composition of the reaction solution is characterized using electrospray-ionization mass spectrometry combined with two-color infrared photodissociation (IRPD) spectroscopy. The latter yields isomer-specific vibrational spectra of the reaction intermediates and products. A comparison to results from electronic structure calculations then allows for an unambiguous structural assignment and molecular-level insights into the reaction mechanism. Subsequently, we demonstrate that isomeric and isobaric ions can be selectively monitored online with low process time, i.e., using a single IRPD wavelength per isomer, as the chip reaction parameters are varied.

Acetylcholine Receptor Antibody Titers and Clinical Course after Influenza Vaccination in Patients with Myasthenia Gravis: A Double-Blind Randomized Controlled Trial (ProPATIent-Trial).

BACKGROUND: It is a continuous matter of discussion whether immune activation by vaccination in general and Influenza vaccination in particular increases the risk for clinical deterioration of autoimmune diseases. This prospective study investigated the serological and clinical course of autoimmune Myasthenia gravis (MG) after a seasonal influenza vaccination. METHODS: This randomized, placebo-controlled, double-blind study enrolled MG patients with antibodies against acetylcholine-receptors (AChR-ab). They were allocated to receive seasonal influenza vaccine or placebo. The primary endpoint was the relative change of AChR-ab-titer over 12weeks. A relative increase of 20% was set as non-inferiority margin. Secondary endpoints were clinical changes in the modified Quantitative Myasthenia Gravis Score (QMG), increase of anti-influenza-ELISA-antibodies, and changes of treatment. The study is registered with Clinicaltrialsregister.eu, EudraCT number 2006-004374-27. FINDINGS: 62 patients were included. Mean±standard deviation (median) in the vaccine and placebo group were AChR-ab-titer changes of -6.0%±23.3% (-4.0%) and -2.8%±22.0% (-0.5%) and QMG score changes of -0.08±0.27 (0.17) and 0.11±0.31 (0.00), respectively. The difference between groups (Hodges-Lehmann estimate with 95% CI) was - for the AChR-ab-titer change 4·0% [-13.3%, 4.5%] (p=0.28 for testing a difference, p<0.0001 for testing non-inferiority) and for the QMG change 0·00 [-0.17, 0.00] (p=0.79 for testing a difference). The occurrence of 74 adverse events (AE) was comparable between groups. The most common AE was flu-like symptoms. One serious AE (hospitalisation following gastrointestinal haemorrhage) in the verum group was not related to the vaccine. INTERPRETATION: Influenza vaccination in MG is safe. Uprating the potential risk of a severe course of MG exacerbation during influenza infection compared to the 95% CI differences for the endpoints, vaccination is principally indicated in this patient population.

DNA Cross-Bridging Shapes a Single Nucleus from a Set of Mitotic Chromosomes.

Eukaryotic cells store their chromosomes in a single nucleus. This is important to maintain genomic integrity, as chromosomes packaged into separate nuclei (micronuclei) are prone to massive DNA damage. During mitosis, higher eukaryotes disassemble their nucleus and release individualized chromosomes for segregation. How numerous chromosomes subsequently reform a single nucleus has remained unclear. Using image-based screening of human cells, we identified barrier-to-autointegration factor (BAF) as a key factor guiding membranes to form a single nucleus. Unexpectedly, nuclear assembly does not require BAF's association with inner nuclear membrane proteins but instead relies on BAF's ability to bridge distant DNA sites. Live-cell imaging and in vitro reconstitution showed that BAF enriches around the mitotic chromosome ensemble to induce a densely cross-bridged chromatin layer that is mechanically stiff and limits membranes to the surface. Our study reveals that BAF-mediated changes in chromosome mechanics underlie nuclear assembly with broad implications for proper genome function.

Management of HCV-Associated Liver Cirrhosis.

BACKGROUND: Treatment of chronic hepatitis C infection is most urgent in patients with severe liver fibrosis and cirrhosis because of the high risk of decompensation, hepatocellular carcinoma, and consecutively death. The development and approval of several direct-acting antiviral drugs (DAA) in the past years has revolutionized antiviral therapy especially for patients with liver cirrhosis. METHODS: This review will focus on recent data from clinical trials and recommendations for the therapy of hepatitis C-infected patients with compensated cirrhosis. RESULTS: Clinical data for cirrhotic patients mainly exist for a combination of the nucleotide analog sofosbuvir with either a protease inhibitor (simeprevir) or an NS5A inhibitor (daclatasvir, ledipasvir) or a three-DAA combination consisting of an NS3 protease inhibitor, an NS5A inhibitor, and a non-nucleoside NS5B inhibitor (paritaprevir/ritonavir, ombitasvir, and dasabuvir). Rates of sustained virologic response in patients with compensated cirrhosis are comparable to patients without cirrhosis; however, the addition of ribavirin and/or longer treatment durations are especially recommended when other negative predictors are present, such as prior treatment failure, features of advanced cirrhosis, or the presence of baseline resistance. CONCLUSION: Nowadays, a highly active, short, and safe interferon-free treatment regimen is available for almost all patients.

Patterned Polypeptoid Brushes.

Patterned polypeptoid brushes on gold and oxide substrates are synthesized by surface-initiated polymerization of N-substituted glycine N-carboxyanhydrides. Their biofouling resistance is shown by protein and cell adhesion experiments. The accessibility of the system to common patterning protocols is demonstrated by UV-lithography and a µCP approach. Moreover, the terminal secondary amine group of the polypeptoid brushes is functionalized with different fluorescent dyes to demonstrate their chemical accessibility.

Mussel-Inspired Polymer Carpets: Direct Photografting of Polymer Brushes on Polydopamine Nanosheets for Controlled Cell Adhesion.

2D mussel-inspired polydopamine (PDA) nanosheets are prepared and exploited as a functional surface for grafting various polymer brushes. The PDA nanosheet and its polymer-brush derivatives show lateral integrity and are robust; therefore, they can be detached from their substrates. Cell-adhesion tests show that the PDA nanosheet promotes cell growth and attachment, while a PDA-based poly(3-sulfopropyl methacrylate) carpet exhibits nonfouling behavior.

Antiviral therapy of hepatitis C in 2014: do we need resistance testing?

The treatment of chronic hepatitis C has fundamentally changed since the approval of the first direct-acting antivirals (DAA) in 2011. In addition to telaprevir and boceprevir, in 2014 two new NS3 protease inhibitors (simeprevir and faldaprevir), one non-nucleoside polymerase inhibitor (sofosbuvir) and one NS5a replication complex inhibitor (daclatasvir) have expanded the treatment options for chronic hepatitis C. Resistance-associated variants (RAV) are naturally produced during the HCV life cycle. The frequency of RAVs within HCV quasispecies mainly depends on their replicational fitness. Variants conferring resistance to nucleos(t)ide analogues have not been detected, and the majority of NS3 protease-resistant variants are present at low frequencies (0.1-3%) before initiation of DAA-based therapies. However, the Q80K variant conferring resistance to simeprevir has been observed in 9-48% of untreated HCV genotype 1a-infected patients, leading to reduced SVR rates. Resistant variants are detectable in the majority of patients with treatment failure to NS3 protease inhibitor- or NS5a inhibitor-based antiviral therapy. Long-term follow-up studies by population-based sequence analysis have shown the disappearance of resistant variants in the majority of patients, with median times to loss of mutations of 4-64weeks. For the nucleotide analogue sofosbuvir, the emergence of the S282T resistant variant has been observed only in single patients, with reversion to wild-type within several weeks. Data are sparse on retreatment of patients with the same DAA or the same class of DAAs. However, retreatment with a different class of DAAs after failure of NS3 protease inhibitor-based therapy has been successful in small studies. This article forms part of a symposium in Antiviral Research on "Hepatitis C: next steps toward global eradication."

Toward a "molecular thermometer" to estimate the charring temperature of wildland charcoals derived from different biomass sources.

The maximum temperature experienced by biomass during combustion has a strong effect on chemical properties of the resulting charcoal, such as sorption capacity (water and nonpolar materials) and microbial degradability. However, information about the formation temperature of natural charcoal can be difficult to obtain in ecosystems that are not instrumented prior to fires. Benzene polycarboxylic acids (BPCA) are molecular markers specific for pyrogenic carbon (PyC) which can provide information on the degree of aromatic condensation in charcoals. Here we apply the BPCA molecular marker method to a set of 10 charcoals produced during an experimental fire in a Pitch pine-scrub oak forest from litter and bark of pitch pine and inkberry plants in the Pinelands National Reserve in New Jersey, USA. We deployed temperature-sensitive crayons throughout the burn site, which recorded the maximum air temperature and made comparisons to the degree of thermal alteration recorded by BPCA molecular markers. Our results show an increase of the degree of aromatic condensation with monitored temperatures for bark biomass, while for needles no clear trend could be observed. For leaf-derived charcoals at increasing monitored fire temperatures, decreasing degree of aromatic condensation was obtained. This suggests that molecular markers can be used to roughly estimate the maximum fire temperatures experienced by bark and wood materials, but not based on leaf- and needle-derived materials. Possible applications include verifying declared pyrolysis temperatures of biochars and evaluating ecosystem fire temperature postburn.

Polypeptoid brushes by surface-initiated polymerization of N-substituted glycine N-carboxyanhydrides.

Polypeptoid brushes were synthesized by surface-initiated polymerization of N-substituted glycine N-carboxyanhydrides on self-assembled amine monolayers. Using the presented grafting-from approach, polypeptoid brush thicknesses of approximately 40 nm could be obtained as compared to previously reported brush thicknesses of 4 nm. Moreover, hydrophilic, hydrophobic and amphiphilic polymer brushes were realized which are expected to have valuable applications as nonfouling surfaces and as model or references systems for surface grafted polypeptides.

Contrast-Enhanced Ultrasound for the differentiation of benign and malignant focal liver lesions: a meta-analysis.

BACKGROUND: International guidelines of Ultrasound recommend the performance of contrast-enhanced ultrasound (CEUS) as the first method of choice after conventional ultrasound for the diagnostic work-up of focal liver lesions. However, these recommendations are based on the results of multiple single studies and only few large multicentre studies. AIMS: The rationale of the present systematic review and meta-analysis was to assess the overall sensitivity and specificity of CEUS for the diagnosis of malignant liver lesions. METHODS: Literature databases were searched up to March 2012. Inclusion criteria were evaluation of CEUS, assessment of sensitivity and specificity of CEUS for the diagnosis of malignant liver lesions. The meta-analysis was performed using the random-effects model based on the DerSimonian Laird method. Quality analyses were carried out to assess sources of heterogeneity. RESULTS: A total of 45 studies with 8147 focal liver lesions were included in the analysis. Overall sensitivity and specificity of CEUS for the diagnosis of malignant liver lesions was 93% (95%-CI: 91-95%) and 90% (95%-CI: 88-92%) respectively. Significant heterogeneity was found between studies. However, subanalysis revealed no significant difference when evaluating studies using histology for all liver lesions, when comparing high-quality and low-quality studies, and blinded vs non-blinded studies. CONCLUSION: The results of this meta-analysis support the international recommendations on CEUS for the diagnostic work-up of focal liver lesions selecting patients who need further diagnostics.

Acoustic radiation force impulse imaging for evaluation of antiviral treatment response in chronic hepatitis C.

BACKGROUND AND AIMS: Antiviral therapy can stop progression of liver fibrosis and partially reverse it. Non-invasive methods have shown good diagnostic accuracies for the assessment of liver fibrosis. First studies have shown that transient elastography (TE) can be used to monitor fibrosis after antiviral therapy. Acoustic-Radiation-Force-Impulse (ARFI)-Imaging is an elastography method integrated in a conventional ultrasound machine. The aim of the present study was to demonstrate a significant difference of ARFI-values in patients with sustained-virological-response (SVR) as compared to patients without. METHOD: Ninety-eight patients infected with chronic hepatitis C virus (HCV) who had completed antiviral treatment were prospectively included in the study and received ARFI-imaging, TE and laboratory evaluation. RESULTS: Significantly lower ARFI and TE values were observed for 47 patients with SVR as compared to 51 patients without SVR (1.37 m/s vs. 2.00,p=0.0021; 4.9 kPa vs. 11.1 kPa,p<0.001), respectively. CONCLUSIONS: Liver stiffness values and shear wave velocity using ultrasound-based elastography methods are different in patients with SVR as compared to patients without SVR after antiviral therapy for chronic hepatitis C. However, the causes of this difference (fibrosis regression, cytolysis, baseline fibrosis) remain unclear and require further evaluation in future studies.