Felix Stickel

University of Zurich, Zürich, Zurich, Switzerland

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Publications (216)1355.62 Total impact

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    ABSTRACT: Liver biopsy (LB) is performed if non-invasive work-up of liver disease is inconclusive. The examination of liver tissue occasionally reveals normal histology. Long term follow-up of such patients has not been performed. We identified a total 70 subjects from our LB database with elevated liver tests and normal liver histology after a mean of 90.5±52.3 (range 15-216) months and conducted reassessment of medical history, physical examination, laboratory testing, ultrasound, transient elastography and LB if indicated. At follow-up examination, fifteen (7 females (f)/8 males (m); 21.4%) subjects had normal liver tests and no further evidence of liver disease. A subset of thirty-seven (29f/8m; 52.9%) subjects had persistently elevated liver tests without evidence indicating progressive liver disease but the cause thereof remained unexplained also at the follow-up visit. Three (0f/3m; 4.3%) subjects had consumed excessive alcohol with indicators of alcoholic liver disease. Eleven subjects (4f/7m; 15.7%) had developed steatosis on ultrasound examination along with weight gain and/or biochemical features of the metabolic syndrome. Additionally, three (2f/1m) patients developed autoimmune hepatitis, 1 female presented with primary biliary cirrhosis. One male was diagnosed with cholangiocellular carcinoma 3 months after the initial evaluation. The clinical course of most patients was benign but in approximately 20% of subjects a liver disease developed. Particular attention should be given to autoimmune liver diseases in subjects with positive autoantibodies. Additionally, lifestyle factors such as weight gain and alcohol consumption were associated with the manifestation of liver diseases. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Liver International 09/2015; DOI:10.1111/liv.12935
  • Zeitschrift für Gastroenterologie 08/2015; 41(08). DOI:10.1055/s-0035-1555425 · 1.67 Impact Factor
  • Zeitschrift für Gastroenterologie 08/2015; 41(08). DOI:10.1055/s-0035-1555400 · 1.67 Impact Factor
  • Zeitschrift für Gastroenterologie 08/2015; 41(08). DOI:10.1055/s-0035-1555478 · 1.67 Impact Factor
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    ABSTRACT: Molecular and clinical observations provide evidence for a potential role of parathyroid hormone (PTH) in colorectal cancer development. We therefore aimed to assess the association of PTH with regard to colorectal cancer precursor lesions. A cohort of 1432 participants, 777 men, 58.4 ± 9.6 years and 701 women, 59.1 ± 10.6 years, undergoing screening colonoscopy were allocated to PTH serum concentrations either above or below 55 ng/L. The number, localization, size, and histology of the polypoid lesions detected during screening colonoscopy were recorded according to PTH serum concentrations. Serum PTH concentrations were not different between men and women. Women with PTH serum concentrations above the cut-off had significantly more adenomas (13/40; 32.5 %) of the distal colon compared to women below the cut-off (91/659; 13.8 %; P = 0.001). Additionally, the rate of dysplasia in adenomas of the distal colon was higher in women with high compared to low PTH concentrations (P = 0.001). These findings remained robust after adjustments for serum vitamin D, age, plasma creatinine, BMI, diabetes, and liver steatosis. No associations were observed between serum PTH concentrations and colorectal lesions in men. These data suggest that elevated PTH serum concentrations might have a role in colorectal cancer development as indicated by higher rates of adenomas, specifically with dysplasia, in women. The role of PTH in colon carcinogenesis and its sex specificity deserve further study.
    Hormones and Cancer 05/2015; 6(4). DOI:10.1007/s12672-015-0227-0 · 2.15 Impact Factor
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    ABSTRACT: Background The risk of alcohol-related liver cirrhosis increases with increasing alcohol consumption, but many people with very high intake escape from liver disease. We postulate that susceptibility to alcoholic cirrhosis has a complex genetic component and propose that this can be dissected through a large and sufficiently powered genomewide association study (GWAS).Methods The GenomALC Consortium comprises researchers from Australia, France, Germany, Switzerland, United Kingdom, and United States, with a joint aim of exploring the genetic and genomic basis of alcoholic cirrhosis. For this National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism funded study, we are recruiting high-risk drinkers who are either cases (with alcoholic cirrhosis) or controls (drinking comparable amounts over similar time, but free of significant liver disease). Extensive phenotypic data are obtained using semistructured interviews and patient records, and blood samples are collected.ResultsWe have successfully recruited 859 participants including 538 matched case–control samples as of September 2014, using study-specific inclusion–exclusion criteria and data collection protocols. Of these, 580 are cases (442 men and 138 women) and 279 are controls (205 men and 74 women). Duration of excessive drinking was slightly greater in cases than controls and was significantly less in women than men. Cases had significantly lower lifetime alcohol intake than controls. Both cases and controls had a high prevalence of reported parental alcohol problems, but cases were significantly more likely to report that a father with alcohol problems had died from liver disease (odds ratio 2.53, 95% confidence interval 1.31 to 4.87, p = 0.0055).Conclusions Recruitment of participants for a GWAS of alcoholic cirrhosis has proved feasible across countries with multiple sites. Affected patients often consume less alcohol than unaffected ones, emphasizing the existence of individual vulnerability factors. Cases are more likely to report liver disease in a father with alcohol problems than controls, consistent with a potential genetic component to the risk of alcoholic cirrhosis.
    Alcoholism Clinical and Experimental Research 05/2015; 39(5). DOI:10.1111/acer.12693 · 3.31 Impact Factor
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    Hepatology 05/2015; DOI:10.1002/hep.27901 · 11.19 Impact Factor
  • Journal of Hepatology 04/2015; 62:S696. DOI:10.1016/S0168-8278(15)31138-7 · 10.40 Impact Factor
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    ABSTRACT: The endocannabinoid (EC) system is implicated in many chronic liver diseases, including hepatitis C viral (HCV) infection. Cannabis consumption is associated with fibrosis progression in patients with chronic hepatitis C (CHC), however, the role of ECs in the development of CHC has never been explored. To study this question, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) were quantified in samples of HCV patients and healthy controls by gas and liquid chromatography mass spectrometry. Fatty acid amide hydrolase (FAAH) and monoaclyglycerol lipase (MAGL) activity was assessed by [ 3 H]AEA and [ 3 H]2-AG hydrolysis, respectively. Gene expression and cytokine release were assayed by TaqMan PCR and ELISpot, respectively. AEA and 2-AG levels were increased in plasma of HCV patients, but not in liver tissues. Hepatic FAAH and MAGL activity was not changed. In peripheral blood mononuclear cells (PBMC), ECs inhibited IFN-γ, TNF-α, and IL-2 secretion. Inhibition of IL-2 by endogenous AEA was stronger in PBMC from HCV patients. In hepatocytes, 2-AG induced the expression of IL-6,-17A,-32 and COX-2, and enhanced activation of hepatic stellate cells (HSC) co-cultivated with PBMC from subjects with CHC. In conclusion, ECs are increased in plasma of patients with CHC and might reveal immunosuppressive and profibrogenic effects.
    International Journal of Molecular Sciences 04/2015; 16(4):7057-7076. DOI:10.3390/ijms16047057 · 2.86 Impact Factor
  • Journal of Hepatology 04/2015; 62:S763. DOI:10.1016/S0168-8278(15)31298-8 · 10.40 Impact Factor
  • Journal of Hepatology 04/2015; 62:S772. DOI:10.1016/S0168-8278(15)31321-0 · 10.40 Impact Factor
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    ABSTRACT: Steatosis and inherited host factors influence liver damage progression in chronic hepatitis C. The TM6SF2 gene E167K variant increases liver fat and the risk of progressive steatohepatitis by interfering with lipoproteins secretion. Aim was to determine whether the E167K variant affects the histological severity of steatosis, necroinflammation, and fibrosis in a cross-sectional cohort of 815 Italian therapy naïve chronic hepatitis C patients. The association with clinically significant fibrosis was replicated in 645 Swiss/German patients. The TM6SF2 E167K variant was genotyped by Taqman assays, steatosis graded according to the nonalcoholic fatty liver disease activity score, and necroinflammation and fibrosis graded and staged according to Ishak in Italian, and to METAVIR in Swiss/German patients. The E167K variant was detected in 69 (9%) of Italian patients and associated with more severe steatosis, independently of confounders (p=0.038). The association between E167K and steatosis severity was present in patients not infected by genotype-3 HCV (p=0.031), but not in those infected by genotype-3 HCV (p=0.58). Furthermore, the E167K variant was associated with more severe necroinflammation (Ishak grade; adjusted p=0.037), and nearly associated with more severe fibrosis (Ishak stage; adjusted p=0.058). At multivariate logistic regression analysis, the E167K variant was independently associated with histologically probable or definite cirrhosis (Ishak stage S6; OR 2.19, 95% c.i. 1.18-3.93, p=0.010). After further conditioning for steatosis and necroinflammation, the E167K variant remained associated with cirrhosis (OR 3.15, 95% c.i. 1.60-5.99, p<0.001). In Swiss/German patients, the E167K variant was independently associated with clinically significant fibrosis METAVIR stage F2-F4 (OR 1.81, 95% c.i 1.12-3.02; p=0.016). TM6SF2 E167K variant impacts on steatosis severity and is associated with liver damage and fibrosis in patients with chronic hepatitis C. This article is protected by copyright. All rights reserved. © 2015 by the American Association for the Study of Liver Diseases.
    Hepatology 03/2015; 62(1). DOI:10.1002/hep.27811 · 11.19 Impact Factor
  • Nora Renz · Michael Baur · Felix Stickel
    Journal of gastrointestinal and liver diseases: JGLD 03/2015; 24(1):10. · 1.85 Impact Factor
  • Felix Stickel · Daniel Shouval
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    ABSTRACT: Herbal and dietary supplements (HDS) have been used for health-related purposes since more than 5000 years, and their application is firmly anchored in all societies worldwide. Over last decades, a remarkable renaissance in the use of HDS can be noticed in affluent societies for manifold reasons. HDS are forms of complementary and alternative medicines commonly used to prevent or treat diseases, or simply as a health tonic. Another growing indication for HDS is their alleged benefit for weight loss or to increase physical fitness. Access is easy via internet and mail-order pharmacies, and their turnover reaches billions of dollars in the USA and Europe alone. However, HDS are generally not categorized as drugs and thus less strictly regulated in most countries. As a result, scientific evidence proving their beneficial effects is mostly lacking, although some HDS may have purported benefits. However, the majority lacks such proof of value, and their use is predominantly based on belief and hope. In addition to missing scientific evidence supporting their use, HDS are typically prone to batch-to-batch variability in composition and concentration, contamination, and purposeful adulteration. Moreover, numerous examples of preparations emerged which have been linked to significant liver injury. These include single ingredients, such as kava, germander, and several Chinese herbals. Other HDS products associated with liver toxicity consist of multiple, often ill-defined ingredients, such as Hydroxycut and Herbalife. Affirmative diagnostic tests are not available, and the assessment of liver injury ascribed to HDS depends on a thorough and proactive medical history, careful exclusion of other causes, and a search for available reports on similar events linked to the intake of the suspected preparation or ingredients contained therein.
    Archive für Toxikologie 02/2015; 89(6). DOI:10.1007/s00204-015-1471-3 · 5.08 Impact Factor
  • Felix Stickel
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    ABSTRACT: Patients with liver disease may require pharmacotherapy either for the underlying liver abnormality or for coexisting nonliver diseases. Prescribing medications to such individuals often raises concerns over drug safety, particularly if these have a record to occasionally cause drug-induced liver injury (DILI) in subjects without pre-existing liver disease. However, evidence demonstrating an increased risk of DILI in patients with liver diseases compared to those without is limited to only a few drugs. For most drugs, the same precautions are valid in individuals with liver disease as for patients without, and a potential risk of DILI should not deter to use such drugs outright. As a rule of thumb, benefits of potential hepatotoxins must outweigh their dangers, and particular consideration has to be given to patients with advanced liver disease who may tolerate a DILI event poorly.Exceptions for this permissive attitude in patients with compensated liver disease include several antimicrobial and antiviral drugs, and drugs with an intrinsic and, thus, predictable hepatotoxic potential.
    Cirrhosis: A practical guide to management, 01/2015: pages 261-273; , ISBN: 9781118274828
  • Zeitschrift für Gastroenterologie 01/2015; 53(01). DOI:10.1055/s-0034-1397146 · 1.67 Impact Factor
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    ABSTRACT: Alcoholic liver disease (ALD) accounts for the majority of chronic liver diseases in Western countries, and alcoholic cirrhosis is among the premier causes of liver failure, hepatocellular carcinoma (HCC) and liver-related mortality causes. Studies in different genders and ethnic groups, as well as in twins provide strong evidence for a significant contribution of host genetic factors to liver disease development in drinkers. The intense quest for genetic modifiers of alcohol-induced fibrosis progression have identified and repeatedly confirmed a genetic polymorphism in the gene coding for patatin-like phospholipase domaincontaining 3 (PNPLA3; adiponutrin; rs738409 C/G, M148I) as a risk factor for alcoholic cirrhosis and its related complication, HCC, in different populations. Although carriership of one or both mutated PNPLA3 alleles does not explain the entire liver phenotypic variability in drinkers, it clearly represents one of the strongest single genetic modulators in a complex trait such as ALD. As more genetic data supporting its important role aggregates, novel insight as to PNPLA3’s function and that of its genetic variation in liver injury is unveiled pointing to an important novel pathway in alcohol-mediated hepatic lipid turnover with strong implications on inflammation, extra cellular matrix remodelling, and hepatocarcinogenesis. Future study shall decipher whether the gathered knowledge can be translated into therapeutic benefits of patients.
  • Felix Stickel
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    ABSTRACT: Hepatocellular carcinoma shows a rising incidence worldwide, and the largest burden of disease in Western countries derives from patients with alcoholic liver disease (ALD) and cirrhosis, the latter being the premier premalignant factor for HCC. The present chapter addresses key issues including the epidemiology of alcohol-associated HCC, and its link to other coexisting non-alcoholic liver diseases, and additional host and environmental risk factors including the underlying genetics. Also discussed are molecular mechanisms of alcohol-associated liver cancer evolution involving the mediators of alcohol toxicity and carcinogenicity, acetaldehyde and reactive oxygen species, as well as the recently described mutagenic adducts which these mediators form with DNA. Specifically, interference of alcohol with retinoids and cofactors of transmethylation processes are outlined. Information presented in this chapter illustrates that the development of HCC in the context of ALD is multifaceted and suggests several molecular targets for prevention and markers for the screening of risk groups.
    Advances in Experimental Medicine and Biology 01/2015; 815:113-30. DOI:10.1007/978-3-319-09614-8_7 · 2.01 Impact Factor
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    ABSTRACT: Abstract: Alcoholic liver disease (ALD) accounts for the majority of chronic liver diseases in Western countries, and alcoholic cirrhosis is among the premier causes of liver failure, hepatocellular carcinoma (HCC) and liver-related mortality causes. Studies in different genders and ethnic groups, as well as in twins provide strong evidence for a significant contribution of host genetic factors to liver disease development in drinkers. The intense quest for genetic modifiers of alcohol-induced fibrosis progression have identified and repeatedly confirmed a genetic polymorphism in the gene coding for patatin-like phospholipase domaincontaining 3 (PNPLA3; adiponutrin; rs738409 C/G, M148I) as a risk factor for alcoholic cirrhosis and its related complication, HCC, in different populations. Although carriership of one or both mutated PNPLA3 alleles does not explain the entire liver phenotypic variability in drinkers, it clearly represents one of the strongest single genetic modulators in a complex trait such as ALD. As more genetic data supporting its important role aggregates, novel insight as to PNPLA3’s function and that of its genetic variation in liver injury is unveiled pointing to an important novel pathway in alcohol-mediated hepatic lipid turnover with strong implications on inflammation, extra cellular matrix remodelling, and hepatocarcinogenesis. Future study shall decipher whether the gathered knowledge can be translated into therapeutic benefits of patients.
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    ABSTRACT: Patients with advanced hepatic fibrosis or cirrhosis with chronic hepatitis C virus (HCV) infection represent an unmet need. The HCV NS3/4A inhibitor, faldaprevir, was evaluated in combination with the non-nucleoside NS5B inhibitor, deleobuvir, with or without ribavirin in treatment-naïve patients with HCV genotype-1 infection in the SOUND-C2 study. Here, the efficacy and safety of this interferon-free regimen in a subset of patients with advanced liver fibrosis, including those with compensated cirrhosis, were assessed. Patients (N=362) were randomized to once-daily faldaprevir with either twice-daily (BID) or three-times daily (TID) deleobuvir for 16 (TID16W), 28 (TID28W; BID28W), or 40 (TID40W) weeks with or without ribavirin (TID28W-NR). Patients were classified according to fibrosis stage (F0-F2 vs F3-F4) and the presence of cirrhosis (yes/no). In total, 85 (24%) patients had advanced fibrosis/cirrhosis (F3-F4) and 33 (9%) had cirrhosis. Within each treatment arm, differences in SVR12 rates between patients with mild to moderate fibrosis (F0-F2) vs F3-F4 did not show a consistent pattern and were not statistically significant (63% vs 47% for TID16W; 53% vs 76% for TID28W; 48% vs 67% for TID40W; 70% vs 67% for BID28W; and 40% vs 36% for TID28W-NR, respectively; p>0.05 for each arm). The most frequent adverse events in patients with/without cirrhosis were gastrointestinal and skin events, which were mostly mild or moderate in intensity. Conclusion: The degree of liver fibrosis did not appear to affect the probability of achieving SVR12 following treatment with the interferon-free regimen of faldaprevir, deleobuvir, and ribavirin. (ClinicalTrials.gov NCT01132313). Copyright © 2014, American Society for Microbiology. All Rights Reserved.
    Antimicrobial Agents and Chemotherapy 12/2014; 59(2). DOI:10.1128/AAC.04383-14 · 4.45 Impact Factor

Publication Stats

4k Citations
1,355.62 Total Impact Points

Institutions

  • 2015
    • University of Zurich
      Zürich, Zurich, Switzerland
  • 2008–2014
    • Inselspital, Universitätsspital Bern
      • Department of Visceral Surgery and Medicine
      Berna, Bern, Switzerland
  • 2006–2014
    • Universität Bern
      • • Department of Clinical Pharmacology and Visceral Research
      • • Institute of Classical Philology
      • • Institute of Pharmacology
      Berna, Bern, Switzerland
  • 2013
    • Institut für klinische Pharmakologie
      Stuttgart, Baden-Württemberg, Germany
  • 2012
    • Medical University of Vienna
      • Institute of Pharmacology
      Wien, Vienna, Austria
  • 2011
    • University Hospital Regensburg
      • Klinik und Poliklinik für Innere Medizin I
      Ratisbon, Bavaria, Germany
    • University Medical Center Schleswig-Holstein
      Kiel, Schleswig-Holstein, Germany
  • 2009
    • Universität zu Lübeck
      Lübeck Hansestadt, Schleswig-Holstein, Germany
  • 2007
    • Humboldt-Universität zu Berlin
      Berlín, Berlin, Germany
    • Columbia University
      • Division of Digestive and Liver Disease
      New York, New York, United States
  • 2006–2007
    • Harvard University
      Cambridge, Massachusetts, United States
  • 1995–2005
    • Universität Heidelberg
      • Center of Sleep Medicine
      Heidelburg, Baden-Württemberg, Germany
  • 2004
    • University of Vienna
      Wien, Vienna, Austria
  • 2001–2004
    • Friedrich-Alexander Universität Erlangen-Nürnberg
      Erlangen, Bavaria, Germany
    • The University of Arizona
      • College of Medicine
      Tucson, Arizona, United States
  • 1998–2004
    • Universitätsklinikum Erlangen
      Erlangen, Bavaria, Germany
  • 1994–2004
    • Tufts University
      Бостон, Georgia, United States
  • 2003
    • University of Freiburg
      Freiburg, Baden-Württemberg, Germany
    • Cracow University of Economics
      Cracovia, Lesser Poland Voivodeship, Poland
  • 2000
    • Technische Universität München
      München, Bavaria, Germany