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Hepatitis: HELP
Articles by Kai-Henrik Peiffer
Based on 12 articles published since 2009
(Why 12 articles?)
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Between 2009 and 2019, K-H Peiffer wrote the following 12 articles about Hepatitis.
 
+ Citations + Abstracts
1 Editorial Editorial: HBsAg serum levels in HBeAg-negative chronic HBV infection-is it a matter of genotype? Authors' reply. 2018

Kuhnhenn, L / Jiang, B / Kubesch, A / Zeuzem, S / Sarrazin, C / Hildt, E / Peiffer, K-H. ·Department of Gastroenterology and Hepatology, University Hospital Frankfurt, Frankfurt, Germany. · Division of Virology, Paul Ehrlich Institute, Langen, Germany. · Department of Gastroenterology, St. Josefs Hospital, Wiesbaden, Germany. · German Center for Infection Research (DZIF), Gießen-Marburg-Langen, Germany. ·Aliment Pharmacol Ther · Pubmed #29882986.

ABSTRACT: -- No abstract --

2 Review The importance of HCV RNA measurement for tailoring treatment duration. 2013

Peiffer, Kai-Henrik / Sarrazin, Christoph. ·Klinikum der J. W. Goethe-Universität, Medizinische Klinik 1, Theodor-Stern-Kai 7, Frankfurt am Main, Germany. ·Dig Liver Dis · Pubmed #24091111.

ABSTRACT: The introduction of telaprevir and boceprevir in the treatment of chronically HCV genotype 1 infected patients has led to substantially improved sustained virologic response rates and shorter treatment duration for a growing group of patients. Management and monitoring of patients receiving protease inhibitor-based triple therapy is of major importance and has become more complicated. Close monitoring of HCV RNA levels for patients on protease inhibitor-based therapy to identify subjects who are eligible for shortening of treatment duration, are virological non-responders or are in danger of experiencing a viral breakthrough is strongly recommended. Several virological tools including qualitative and quantitative HCV RNA assays for detection and quantification of HCV RNA are commercially available. We review these methods and their implications for HCV therapy as well as current sustained virologic response definition, stopping rules and recommendations for protease inhibitor-based treatment durations.

3 Clinical Trial Serum sphingolipid levels associate with upcoming virologic events and HBV genotype D in a cohort of patients with HBeAg-negative HBV infection. 2018

Mücke, Victoria Therese / Jakobi, Katja / Knop, Viola / Thomas, Dominique / Mücke, Marcus Maximilian / Peiffer, Kai-Henrik / Zeuzem, Stefan / Sarrazin, Christoph / Pfeilschifter, Josef / Grammatikos, Georgios. ·Universitätsklinikum Frankfurt, Frankfurt am Main, Germany. · Pharmazentrum Frankfurt, Institut für Allgemeine Pharmakologie, Frankfurt am Main, Germany. · Institut für Klinische Pharmakologie und Toxikologie, Frankfurt am Main, Deutschland. · St. Josefs-Hospital, Wiesbaden, Germany. ·PLoS One · Pubmed #30439997.

ABSTRACT: OBJECTIVES: Sphingolipids (SLs) have been implicated as potent regulators of the hepatitis B virus (HBV) life cycle. We investigated the SL biomarker potential regarding virologic endpoints in a prospective subgroup of patients with HBeAg-negative chronic HBV infection. METHODS: From 2009-2016 98 patients with HBeAg-negative HBV infection were prospectively followed over four years. Clinical, laboratory and imaging data were evaluated annually. SLs were assessed in available serum probes via liquid chromatography coupled to tandem mass spectrometry. RESULTS: Of those 98 patients, 10 (10.2%) showed HBV reactivation, 13 (13.2%) lost HBsAg and 9 (9.1%) gained status of HBsAg-/HBsAb-coexistence, whereas 66 (67.3%) had no events. Within the four-year analysis sphingosine (p = 0.020), sphinganine (p<0.001), dhS1P (p<0.001), C16DHC (p<0.01) and C20Cer (p<0.001) showed a significant upregulation in patients without virologic events, C18Cer significantly decreased (p<0.001). At baseline decreased S1P-, dhS1P- and C16Cer-levels were observed in patients with upcoming status of HBsAg-/HBsAb-coexistence. S1P and dhS1P levels were elevated HBV genotype D infected patients. CONCLUSIONS: In a prospective cohort of patients with a HBeAg-negative HBV infection, serum SLs associated with the virologic course and HBV genotype D. Further studies are required to elucidate SLs as potential novel predictors of the course of HBeAg-negative HBV infection.

4 Clinical Trial Improved pharmacodynamics and pharmacokinetics after i.v. application of peginterferon alfa-2a in hepatitis C null responders. 2015

Fülöp, Balazs / Biermer, Michael / Cornberg, Markus / Wedemeyer, Heiner / Port, Kerstin / Heyne, Renate / Zeuzem, Stefan / Peiffer, Kai-Henrik / Welzel, Tania / Herber, Adam / Buggisch, Peter / Moser, Christoph / Stoll, Sabine / Alshuth, Ulrich / Berg, Thomas. ·Section of Hepatology, Department of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany. · Jannsen-Cilag GmbH, Neuss, Germany. · Department of Gastroenterology, Hepatology & Endocrinology, Hannover Medical School, Hannover, Germany. · Liver Center Checkpoint, Berlin, Germany. · J.W. Goethe University Hospital, Frankfurt/M, Germany. · Institute for Interdisciplinary Medicine, Hamburg, Germany. · AMS Advanced Medical Services GmbH, Munich, Germany. · Roche Pharma AG, Grenzach-Wyhlen, Germany. ·Liver Int · Pubmed #25801095.

ABSTRACT: BACKGROUND & AIM: Mechanisms of non-responsiveness to peginterferon alfa-2a are not completely understood. Inadequate plasma levels may contribute to reduced response. The aim of this prospective, multicentre, crossover, Phase 1 study was to evaluate the pharmacokinetics and viral kinetics of intravenous vs. subcutaneous peginterferon alfa-2a in patients with genotype 1 chronic hepatitis C infection who showed null response to previous peginterferon/ribavirin. METHODS: Patients were randomized in four treatment arms to subcutaneous or intravenous peginterferon alfa-2a 180 μg, once or twice weekly for 2 weeks. After a washout phase of 6 weeks, patients first receiving intravenous administration switched to subcutaneous or vice versa for additional 2 weeks. RESULTS: Intravenous administration of pegylated interferon resulted in a stronger and faster decline in HCV RNA than subcutaneous administration with a maximum decline of 1.17 log10 vs. 0.41 log10 or 1.32 log10 vs. 0.54 log10 after a once or twice weekly application, respectively. Pharmacokinetic studies revealed significantly higher maximum concentration (C(max))(0-12) h and C(max 0-7) d following intravenous administration, irrespective of dosing frequency A rapid rebound in HCV RNA was observed in all treatment arms. Adverse events occurred more frequently following intravenous administration. CONCLUSION: Intravenous administration of peginterferon alfa-2a results in considerably higher plasma concentration and a stronger decline in HCV RNA and offers an interesting approach in order to overcome interferon non-responsive state in patients with full null response to previous peginterferon/ribavirin combination therapy.

5 Article Interferon-free treatment choice according to baseline RASs leads to high SVR rates in HCV genotype 1 infected patients. 2018

Peiffer, Kai-Henrik / Vermehren, Johannes / Kuhnhenn, Lisa / Susser, Simone / Dietz, Julia / Finkelmeier, Fabian / Weiler, Nina / Welzel, Tania / Grammatikos, Georgios / Zeuzem, Stefan / Sarrazin, Christoph. ·University Hospital Frankfurt, Department of Gastroenterology and Hepatology, 60590 Frankfurt, Germany. Electronic address: kai-henrik.peiffer@kgu.de. · University Hospital Frankfurt, Department of Gastroenterology and Hepatology, 60590 Frankfurt, Germany. · University Hospital Frankfurt, Department of Gastroenterology and Hepatology, 60590 Frankfurt, Germany; St. Josefs Hospital, Department of Gastroenterology, 65189 Wiesbaden, Germany. ·J Infect Chemother · Pubmed #29628383.

ABSTRACT: AIM: Different combinations of direct antiviral agents (DAA) lead to high SVR rates in HCV genotype 1 infected patients. However, presence of baseline resistance-associated substitutions (RASs) represents a major risk factor for treatment failure. It is unknown whether choice of treatment based on RASs has the potential to decrease virologic failure rates. METHODS: Population-based sequencing of NS3 and NS5A genes was performed in HCV genotype 1 infected patients at a German university hospital. Treatment was individually selected based on resistance analyses. RESULTS: In total, 319 patients (50% treatment-experienced and 30% with cirrhosis) were included. With the treatment choice based on the baseline NS3 and NS5A resistance profile SVR rates between 96 and 100% were observed in all subgroups, including treatment-experienced patients with cirrhosis and HCV genotype 1a infected cirrhotic patients. CONCLUSIONS: The choice of treatment based on the RASs status at baseline may be beneficial for optimizing treatment efficacy in patients with HCV genotype 1 infection and risk factors for treatment failure.

6 Article Patterns of Resistance-Associated Substitutions in Patients With Chronic HCV Infection Following Treatment With Direct-Acting Antivirals. 2018

Dietz, Julia / Susser, Simone / Vermehren, Johannes / Peiffer, Kai-Henrik / Grammatikos, Georgios / Berger, Annemarie / Ferenci, Peter / Buti, Maria / Müllhaupt, Beat / Hunyady, Bela / Hinrichsen, Holger / Mauss, Stefan / Petersen, Jörg / Buggisch, Peter / Felten, Gisela / Hüppe, Dietrich / Knecht, Gaby / Lutz, Thomas / Schott, Eckart / Berg, Christoph / Spengler, Ulrich / von Hahn, Thomas / Berg, Thomas / Zeuzem, Stefan / Sarrazin, Christoph / Anonymous5030927. ·Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt, Germany, German Center for Infection Research (DZIF), External Partner Site Frankfurt, Germany. · Institute for Medical Virology, University Hospital Frankfurt, Frankfurt, Germany. · Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. · Hospital Universitario Valle Hebron and Ciberehd del Instituto Carlos III, Barcelona, Spain. · Swiss Hepato-Pancreato-Biliary Center and Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland. · Somogy County Kaposi Mór Teaching Hospital, Kaposvár, Hungary. · Practice of Gastroenterology, Kiel, Germany. · Practice of Gastroenterology, Düsseldorf, Germany. · Institute for Interdisciplinary Medicine IFI, Hamburg, Germany. · Practice of Hepatology, Herne, Germany. · Infektiologikum, Frankfurt, Germany. · Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany. · Department of Internal Medicine I, University of Tübingen, Tübingen, Germany. · Department of Internal Medicine I, University of Bonn, Bonn, Germany. · Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany; German Center for Infection Research (DZIF), Hannover-Braunschweig Site, Germany. · Department of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany. · Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt, Germany, German Center for Infection Research (DZIF), External Partner Site Frankfurt, Germany; Medizinische Klinik II, St. Josefs-Hospital, Wiesbaden, Germany. Electronic address: sarrazin@em.uni-frankfurt.de. ·Gastroenterology · Pubmed #29146520.

ABSTRACT: BACKGROUND & AIMS: Little is known about substitutions that mediate resistance of hepatitis C virus (HCV) to direct-acting antivirals (DAAs), due to the small number of patients with treatment failure in approval studies. It is important to identify resistance patterns to select effective salvage treatments. METHODS: We performed a comprehensive analysis for resistance-associated substitutions (RASs) in HCV genes (nonstructural protein [NS]3, NS5A, NS5B) targeted by DAAs. We compared NS3, NS5A, and NS5B sequences from 626 patients in Europe with DAA failure with sequences from 2322 DAA-naïve patients, infected with HCV genotypes 1 to 4. We considered RASs to be relevant if they were associated with DAA failure in patients or conferred a greater than twofold change in susceptibility compared with a reference strain in in vitro replicon assays. Data were collected on pretreatment status, DAA regimen, the treatment initiation date and duration, and virologic response. Patients who received at least 4 weeks of antiviral treatment were included in the analysis. RESULTS: RASs in NS3 associated with simeprevir or paritaprevir failure include R155K and D168E/V. In addition, several RASs were specifically associated with failure of simeprevir (Q80K/R in patients with genotype 1a or 4) or paritaprevir (Y56H in combination with D168V in patients with genotype 1b). Y93H in NS5A was the RAS most frequently associated with failure of daclatasvir, ledipasvir, or ombitasvir in patients with genotype 1b infection, and L31M was associated with failure of daclatasvir or ledipasvir, but not ombitasvir. RASs in NS5A were heterogeneous among patients with HCV genotype 1a or genotype 4 infections. In patients with HCV genotype 3, Y93H was associated with resistance to daclatasvir, but no RASs were associated with ledipasvir failure, pointing to a limited efficacy of ledipasvir in patients with genotype 3. Among patients failed by sofosbuvir-containing regimens, L159F was enriched in patients with genotype 1b (together with C316N) or genotype 3 infection, whereas the RAS S282T was rarely observed. CONCLUSIONS: We compared RASs in NS3, NS5A, and NS5B among patients failed by DAA therapy. Theses varied with the HCV genotype and subtype, and the different drug classes. These findings might be used to select salvage therapies.

7 Article No evidence of hepatitis B virus reactivation in patients with resolved infection treated with direct-acting antivirals for hepatitis C in a large real-world cohort. 2017

Mücke, V T / Mücke, M M / Peiffer, K-H / Weiler, N / Welzel, T M / Sarrazin, C / Zeuzem, S / Berger, A / Vermehren, J. ·Medizinische Klinik 1, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany. · Institut für Klinische Virologie, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany. ·Aliment Pharmacol Ther · Pubmed #28627791.

ABSTRACT: BACKGROUND: Hepatitis B virus (HBV) reactivation has been observed following interferon (IFN)-based treatment in HBV/hepatitis C virus (HCV) co-infected patients. Recent reports suggest that reactivation may also occur in both hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative patients during HCV treatment with direct-acting antivirals (DAAs). AIM: To investigate the rate of patients with HBV reactivation during IFN-based and IFN-free HCV treatment in a large real-world cohort. METHODS: A total of 848 patients with chronic hepatitis C were treated with different combinations of DAAs. Among patients with available outcome and HBV data, there were 272 patients hepatitis B core antibody (HBcAb)-positive (HBsAg-positive, n=9; HBsAg-negative, n=263), and 536 were HBcAb-negative. All HBcAb-positive patients were tested for HBV DNA at the end of DAA therapy and alanine transaminase (ALT) levels were frequently measured during therapy and follow-up. RESULTS: Seventy-three percent (n=192/263) of HBsAg-negative/HBcAb-positive patients had elevated ALT levels at baseline, which declined to normal values in all but 18 patients, and no HBV reactivation was observed. Eight patients had detectable but not quantifiable HBV DNA (<20 IU/mL) at end of treatment, but none were associated with elevated ALT. Five of nine HBsAg-positive/HBcAb-positive patients experienced transient or permanent HBV reactivation, three of whom required nucleos(t)ide treatment during (n=1) or after (n=2) DAA therapy. CONCLUSIONS: HBV reactivation was not observed in HBsAg-negative/HBcAb-positive patients but common in HBsAg-positive/HBcAb-positive patients treated with different combinations of DAAs for HCV.

8 Article Comparative characterization of hepatitis B virus surface antigen derived from different hepatitis B virus genotypes. 2017

Hassemer, Matthias / Finkernagel, Malin / Peiffer, Kai-Henrik / Glebe, Dieter / Akhras, Sami / Reuter, Andreas / Scheiblauer, Heinrich / Sommer, Lisa / Chudy, Michael / Nübling, C Micha / Hildt, Eberhard. ·Paul-Ehrlich-Institut, Department of Virology, Langen, Germany. · University Hospital Frankfurt, Frankfurt/Main, Germany; Goethe University Frankfurt, Frankfurt/Main, Germany. · Justus Liebig University, Institute of Medical Virology, Gießen, Germany; German Center for Infection Research (DZIF), Gießen-Marburg-Langen, Germany. · Paul-Ehrlich-Institut, Department of Allergology, Langen, Germany. · Paul-Ehrlich-Institut, in-vitro-diagnostics, Langen, Germany. · Paul-Ehrlich-Institut, Department of Virology, Langen, Germany; German Center for Infection Research (DZIF), Gießen-Marburg-Langen, Germany. Electronic address: eberhard.hildt@pei.de. ·Virology · Pubmed #27951436.

ABSTRACT: For human hepatitis B virus eight distinct and two candidate genotypes are described. These genotypes differ with respect to geographic distribution, molecular virology and virus-associated pathogenesis. Comparative analysis of HBV genotypes revealed, with exception of HBV/G that shows impaired HBsAg release, that no fundamental disparities between genotypes exist regarding glycosylation, subcellular distribution, release of HBsAg and formation of subviral particles. However, there are distinctions regarding the proportion of L to M to S HBs proteins detected intra- and extracellularly for different genotypes. 2D electrophoresis revealed different posttranslational modification patterns for LHBs. In light of the relevance of HBsAg as diagnostic marker, detectability of purified recombinant HBsAg of various genotypes by HBsAg-specific detection systems licensed in Europe was investigated, showing similar sensitivities for genotypes included in this analysis. These data indicate that recombinant HBsAg reproducibly purified following a defined protocol might be used as an alternative to reference materials currently established.

9 Article The efficacy and safety of direct acting antiviral treatment and clinical significance of drug-drug interactions in elderly patients with chronic hepatitis C virus infection. 2016

Vermehren, J / Peiffer, K-H / Welsch, C / Grammatikos, G / Welker, M-W / Weiler, N / Zeuzem, S / Welzel, T M / Sarrazin, C. ·Medizinische Klinik 1, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany. Johannes.Vermehren@kgu.de. · Medizinische Klinik 1, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany. ·Aliment Pharmacol Ther · Pubmed #27549000.

ABSTRACT: BACKGROUND: Direct antiviral therapies for chronic hepatitis C virus (HCV) infection have expanded treatment options for neglected patient populations, including elderly patients who are ineligible/intolerant to receive interferon (IFN)-based therapy. AIM: To investigate the efficacy, tolerability and potential for drug-drug interactions (DDIs) of IFN-free treatment in patients aged ≥65 years in a large real-world cohort. METHODS: A total of 541 patients were treated with different combinations of direct antiviral agents (DAAs: ledipasvir/sofosbuvir ±ribavirin; daclatasvir/sofosbuvir ±ribavirin; paritaprevir/ombitasvir ±dasabuvir ±ribavirin or simeprevir/sofosbuvir ±ribavirin in genotype 1/4, and daclatasvir/sofosbuvir ±ribavirin or sofosbuvir/ribavirin in genotype 2/3). Efficacy, safety and potential DDIs were analysed and compared between patients aged <65 years (n = 404) and patients aged ≥65 years (n = 137) of whom 41 patients were ≥75 years. RESULTS: Sustained virological response rates were 98% and 91% in patients aged ≥65 years and <65 years, respectively. Elderly patients took significantly more concomitant medications (79% vs. 51%; P < 0.0001). The number of concomitant drugs per patient was highest in patients ≥65 years with cirrhosis (median, three per patient; range, 0-10). Based on the hep-druginteractions database, the proportion of predicted clinically significant DDIs was significantly higher in elderly patients (54% vs. 28%; P < 0.0001). The number of patients who experienced treatment-associated adverse events was similar between the two age groups (63% vs. 65%; P = n.s.). CONCLUSIONS: Elderly patients are at increased risk for significant DDIs when treated with DAAs for chronic HCV infection. However, with careful pre-treatment assessment of concomitant medications, on-treatment monitoring or dose-modifications, significant DDIs and associated adverse events can be avoided.

10 Article Investigation of NS3 Protease Resistance-Associated Variants and Phenotypes for the Prediction of Treatment Response to HCV Triple Therapy. 2016

Dietz, Julia / Rupp, Daniel / Susser, Simone / Vermehren, Johannes / Peiffer, Kai-Henrik / Filmann, Natalie / Bon, Dimitra / Kuntzen, Thomas / Mauss, Stefan / Grammatikos, Georgios / Perner, Dany / Berkowski, Caterina / Herrmann, Eva / Zeuzem, Stefan / Bartenschlager, Ralf / Sarrazin, Christoph. ·Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany. · Department of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany. · Institute of Biostatistics and Mathematical Modeling, Goethe University Frankfurt, Frankfurt am Main, Germany. · Klinik für Gastroenterologie und Hepatologie, Universitätsspital Zürich, Zürich, Switzerland. · Zentrum für HIV und Hepatogastroenterologie, Düsseldorf, Germany. · German Center for Infection Research, Heidelberg University, Heidelberg, Germany. ·PLoS One · Pubmed #27281344.

ABSTRACT: Triple therapy of chronic hepatitis C virus (HCV) infection with boceprevir (BOC) or telaprevir (TVR) leads to virologic failure in many patients which is often associated with the selection of resistance-associated variants (RAVs). These resistance profiles are of importance for the selection of potential rescue treatment options. In this study, we sequenced baseline NS3 RAVs population-based and investigated the sensitivity of NS3 phenotypes in an HCV replicon assay together with clinical factors for a prediction of treatment response in a cohort of 165 German and Swiss patients treated with a BOC or TVR-based triple therapy. Overall, the prevalence of baseline RAVs was low, although the frequency of RAVs was higher in patients with virologic failure compared to those who achieved a sustained virologic response (SVR) (7% versus 1%, P = 0.06). The occurrence of RAVs was associated with a resistant NS3 quasispecies phenotype (P<0.001), but the sensitivity of phenotypes was not associated with treatment outcome (P = 0.2). The majority of single viral and host predictors of SVR was only weakly associated with treatment response. In multivariate analyses, low AST levels, female sex and an IFNL4 CC genotype were independently associated with SVR. However, a combined analysis of negative predictors revealed a significantly lower overall number of negative predictors in patients with SVR in comparison to individuals with virologic failure (P<0.0001) and the presence of 2 or less negative predictors was indicative for SVR. These results demonstrate that most single baseline viral and host parameters have a weak influence on the response to triple therapy, whereas the overall number of negative predictors has a high predictive value for SVR.

11 Article Intracellular accumulation of subviral HBsAg particles and diminished Nrf2 activation in HBV genotype G expressing cells lead to an increased ROI level. 2015

Peiffer, Kai-Henrik / Akhras, Sami / Himmelsbach, Kiyoshi / Hassemer, Matthias / Finkernagel, Malin / Carra, Gert / Nuebling, Michael / Chudy, Michael / Niekamp, Hauke / Glebe, Dieter / Sarrazin, Christoph / Zeuzem, Stefan / Hildt, Eberhard. ·Goethe-University Hospital Frankfurt, Department of Gastroenterology and Hepatology, D-60590 Frankfurt am Main, Germany; Paul Ehrlich Institut, Division of Virology, D-63325 Langen, Germany. Electronic address: kai-henrik.peiffer@kgu.de. · Paul Ehrlich Institut, Division of Virology, D-63325 Langen, Germany. · Justus-Liebig University, Institute of Medical Virology, National Reference Centre for Hepatitis B and D Viruses, D-35392 Giessen, Germany; DZIF, German Center for Infection Research, Germany. · Goethe-University Hospital Frankfurt, Department of Gastroenterology and Hepatology, D-60590 Frankfurt am Main, Germany. · Paul Ehrlich Institut, Division of Virology, D-63325 Langen, Germany; DZIF, German Center for Infection Research, Germany. Electronic address: eberhard.hildt@pei.de. ·J Hepatol · Pubmed #25445396.

ABSTRACT: BACKGROUND & AIMS: Hepatitis B virus genotype G (HBV/G) is characterized by a lack of HBeAg secretion and very low HBsAg secretion. This study aimed at (1) comparing HBV genotype G and A2 with respect to morphogenesis and release of HBV-derived particles, (2) characterizing factors contributing to HBV/G-associated pathogenesis. METHODS: HBV/G- and HBV/A-expressing hepatoma cells and infected HepaRG cells were analyzed by confocal laser scanning microscopy, Western blot, real-time PCR, density gradient centrifugation, and electron microscopy. Modulation of the transcription factors Nrf2 and AP-1 was analyzed. RESULTS: While the release of viral particles is not affected in HBV/G replicating cells, the secretion of subviral particles is impaired, although they are produced in high amounts. These subviral particles, which display an increased density and a predominantly filamentous morphology, accumulate at the endoplasmic reticulum. The PreS1PreS2 domain of genotype G, which forms aggregates, causes the block of HBsAg-secretion at the ER and leads to decreased transcriptional activator function of LHBs. Intracellular accumulation of HBsAg and impaired induction of the cytoprotective transcription factor Nrf2 lead to an elevated level of ROIs. This results in activation of JNK and as a consequence in Ser-phosphorylation of IRS-1, which is known to impair insulin signaling, a key factor for liver regeneration. CONCLUSIONS: Although competent for release of viral particles, secretion of subviral particles is impaired in HBV/G expressing cells leading to ER-stress. In parallel, HBV-induced Nrf2 activation diminishes, which causes a decrease of the capacity to inactivate ROIs. This might be related to genotype-specific pathogenesis.

12 Article Clinical utility of the ARCHITECT HCV Ag assay for early treatment monitoring in patients with chronic hepatitis C genotype 1 infection. 2012

Vermehren, Johannes / Susser, Simone / Berger, Annemarie / Perner, Dany / Peiffer, Kai-Henrik / Allwinn, Regina / Zeuzem, Stefan / Sarrazin, Christoph. ·Medizinische Klinik 1, Klinikum der JW Goethe-Universität, Frankfurt am Main, Germany. ·J Clin Virol · Pubmed #22698697.

ABSTRACT: BACKGROUND: Virologic response-monitoring is essential for determining therapy duration in patients with chronic hepatitis C virus (HCV) infection. This is usually performed using highly sensitive HCV-RNA assays. However, HCV-RNA assays are time-consuming, expensive and require highly trained personnel. Quantitative determination of HCV core-antigen (HCVAg) levels may be used to supplement treatment monitoring. OBJECTIVES: The clinical utility of the ARCHITECT HCV Ag assay (Abbott Diagnostics) for response-guided therapy was investigated. STUDY DESIGN: We analyzed serum from 160 patients with HCV genotype 1 infection who had been treated with peg-interferon alfa-2b/ribavirin. HCVAg levels were determined at baseline, weeks 1, 2, 4 and 12. HCVAg levels were compared to those obtained with HCV-RNA assays: VERSANT HCV Quantitative 3.0 (bDNA) and Qualitative (TMA, both Siemens Healthcare) assay and the Abbott RealTime HCV assay (ART; Abbott Diagnostics). RESULTS: Baseline HCVAg levels correlated well with HCV-RNA as assessed by bDNA (r=0.91; p<0.0001) and ART (r=0.92; p<0.0001), respectively. Patients with undetectable HCVAg levels at week 1 had a 90.9% probability (positive predictive value) to achieve a rapid virologic response (HCV-RNA undetectable at week 4) based on TMA and 86.4% based on ART, respectively. Patients with less than 1 log(10) reduction in HCVAg between baseline and week 12 had a 90% probability (negative predictive value) to achieve a nonresponse (<2 log(10) decline in HCV-RNA between baseline and week 12) based on bDNA and 100% based on ART, respectively. CONCLUSIONS: Determination of HCVAg may be useful for antiviral response-monitoring in patients with HCV genotype 1 infection.