Felix Stickel

Inselspital, Universitätsspital Bern, Berna, Bern, Switzerland

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Publications (202)1282.19 Total impact

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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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    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; 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.
  • 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.
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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 01/2015; 16:7057-7076. DOI:10.3390/ijms16047057 · 2.34 Impact Factor
  • 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; DOI:10.1128/AAC.04383-14 · 4.45 Impact Factor
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    ABSTRACT: Background & AimsIn liver fibrosis, activated hepatic stellate cells (HSC) secrete excess extracellular matrix, thus, represent key targets for antifibrotic treatment strategies. Intermediate-conductance Ca2+-activated K+-channels (KCa3.1) are expressed in non-excitable tissues affecting proliferation, migration and vascular resistance rendering KCa3.1 potential targets in liver fibrosis. So far, no information about KCa3.1 expression and their role in HSC exists. Aim was to quantify the KCa3.1 expression in HSC depending on HSC activation and investigation of antifibrotic properties of the specific KCa3.1 inhibitor TRAM-34 in vitro and in vivo.MethodsKCa3.1 expression and functionality were studied in TGF-β1-activated HSC by quantitative real time PCR, western-blot and patch-clamp analysis, respectively. Effects of TRAM-34 on HSC proliferation, cell cycle and fibrosis-related gene expression were assessed by [3H]-thymidine incorporation, FACS-analysis and RT-PCR, respectively. In vivo, vascular resistance and KCa3.1 gene and protein expression were determined in bile duct ligated rats by in situ liver perfusion, Taqman PCR and immunohistochemistry, respectively.ResultsFibrotic tissues and TGF-β1-activated HSC exhibited higher KCa3.1-expressions than normal tissue and untreated cells. KCa3.1 inhibition with TRAM-34 reduced HSC proliferation by induction of cell cycle arrest and reduced TGF-β1-induced gene expression of collagen I, alpha-smooth muscle actin and TGF-β1 itself. Further, TRAM-34 blocked TGF-β1-induced activation of TGF-β signaling in HSC. In vivo, TRAM-34 reduced the thromboxane agonist-induced portal perfusion pressure.Conclusion Inhibition of KCa3.1 with TRAM-34 downregulates fibrosis-associated gene expression in vitro, and reduces portal perfusion pressure in vivo. Thus, KCa3.1 may represent novel targets for the treatment of liver fibrosis.This article is protected by copyright. All rights reserved.
    Liver international: official journal of the International Association for the Study of the Liver 09/2014; 35(4). DOI:10.1111/liv.12681 · 4.41 Impact Factor
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    ABSTRACT: Autoimmune hepatitis (AIH) is an uncommon autoimmune liver disease of unknown etiology. We used a genome-wide approach to identify genetic variants that predispose individuals to AIH. We performed a genome-wide association study of 649 adults in the Netherlands with AIH type-1 and 13,436 controls. Initial associations were further analyzed in an independent replication panel comprising 451 patients with AIH type-1 in Germany and 4103 controls. We also performed an association analysis in the discovery cohort using imputed genotypes of the MHC region. We associated AIH with a variant in the MHC region, at rs2187668 (P=1.5x10(-78)). Analysis of this variant in the discovery cohort identified HLA-DRB1*0301 (P = 5.3x10(-49)) as a primary susceptibility genotype and HLA-DRB1*0401 (P=2.8x10(-18)) as a secondary susceptibility genotype. We also associated AIH with variants of SH2B3 (rs3184504, 12q24; P=7.7x10(-8)) and CARD10 (rs6000782, 22q13.1; P=3.0x10(-6)). Furthermore, strong inflation of association signal was found with single-nucleotide polymorphisms (SNPs) associated with other immune-mediated diseases, including primary sclerosing cholangitis and primary biliary cirrhosis, but not with SNPs associated with other genetic traits. In a genome-wide association study, we associated AIH type-1with variants in the MHC region, and identified variants of SH2B3and CARD10 as likely risk factors. These findings support a complex genetic basis for AIH pathogenesis and indicate that part of the genetic susceptibility overlaps with that for other immune-mediated liver diseases.
    Gastroenterology 08/2014; 147(2):443-452. DOI:10.1053/j.gastro.2014.04.022 · 13.93 Impact Factor
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    ABSTRACT: Background Obesity and increased visceral fat deposits are significant risk factors for surgical site infection (SSI). Interestingly, a potential role of hepatic steatosis on complications after extrahepatic surgery remains unknown. The aim of the present study was to investigate the impact of hepatic steatosis on SSI in patients that underwent open abdominal surgery. Methods A total of 231 patients that underwent either liver (n = 116) or colorectal (n = 115) resection and received preoperative contrast-enhanced computer tomography (CT)-scans were retrospectively investigated. Signal attenuation of the liver parenchyma was measured on CT-scans to assess hepatic steatosis. Results Significantly more SSI (including types 1, 2, and 3) were found in the group with hepatic steatosis (56/118 [47.5%]) compared to the control group (30/113 [26.6%]; p = 0.001). Patients with hepatic steatosis showed significantly higher median BMI than patients without hepatic steatosis (26.6 kg/m2 [range 16.8-47.0 kg/m2] vs. 23.2 kg/m2 [15.9-32.7 kg/m2]; p < 0.001). Patients with hepatic steatosis experienced significantly longer median operation times (297 min. [52-708 min.] vs. 240 min. [80-600 min.]; p = 0.003). In a multivariate analysis, hepatic steatosis was identified as an independent risk factor for SSI in patients undergoing hepatic (Odds ratio 10.33 [95% CI 1.19-89.76]; p = 0.03) or colorectal (Odds ratio 6.67 [95% CI 1.12-39.33]; p = 0.04) surgery. Conclusion Hepatic steatosis is associated with SSI after hepatic and colorectal surgery.
    Surgery 07/2014; DOI:10.1016/j.surg.2014.02.020 · 3.11 Impact Factor
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    ABSTRACT: Background & Aims: The genetic background of alcoholic liver diseases and their complications are increasingly recognized. A common polymorphism in the neurocan (NCAN) gene, which is known to be expressed in neuronal tissue, has been identified as a risk factor for non-alcoholic fatty liver disease (NAFLD). We investigated if this polymorphism may also be related to alcoholic liver disease (ALD) and hepatocellular carcinoma (HCC). Methods: We analysed the distribution of the NCAN rs2228603 genotypes in 356 patients with alcoholic liver cirrhosis, 126 patients with alcoholic HCC, 382 persons with alcohol abuse without liver damage, 362 healthy controls and in 171 patients with hepatitis C virus (HCV) associated HCC. Furthermore, a validation cohort of 229 patients with alcoholic cirrhosis (83 with HCC) was analysed. The genotypes were determined by LightSNiP assays. The expression of NCAN was studied by RT-PCR and immunofluorescence microscopy. Results: The frequency of the NCAN rs2228603 T allele was significantly increased in patients with HCC due to ALD (15.1%) compared to alcoholic cirrhosis without HCC (9.3%), alcoholic controls (7.2%), healthy controls (7.9%), and HCV associated HCC (9.1%). This finding was confirmed in the validation cohort (15.7% vs. 6.8%, OR = 2.53; 95%CI: 1.36-4.68; p = 0.0025) and by multivariate analysis (OR = 1.840; 95%CI: 1.22-2.78; p = 0.004 for carriage of the rs2228603 T allele). In addition, we identified and localised NCAN expression in human liver. Conclusions: NCAN is not only expressed in neuronal tissue, but also in the liver. Its rs2228603 polymorphism is a risk factor for HCC in ALD, but not in HCV infection.
    Journal of Hepatology 06/2014; 61(5). DOI:10.1016/j.jhep.2014.06.006 · 10.40 Impact Factor
  • Journal of Hepatology 04/2014; 60(1):S87. DOI:10.1016/S0168-8278(14)60224-5 · 10.40 Impact Factor
  • Journal of Hepatology 04/2014; 60(1):S60. DOI:10.1016/S0168-8278(14)60146-X · 10.40 Impact Factor
  • Journal of Hepatology 04/2014; 60(1):S132. DOI:10.1016/S0168-8278(14)60359-7 · 10.40 Impact Factor
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    ABSTRACT: Liver regeneration is of crucial importance for patients undergoing living liver transplantations or extended liver resections and can be associated with elevated portal venous pressure, impaired hepatic regeneration, and postoperative morbidity. The aim of this study was to assess whether reduction of portal venous pressure by terlipressin improves postoperative liver regeneration in normal and steatotic livers after partial hepatectomy in a rodent model. Portal venous pressure was assessed after minor (30%), standard (60%), or extended (80%) partial hepatectomy (PH) in mice with and without liver steatosis. Liver regeneration was assessed by BrdU incorporation and Ki-67 immunostaining. Portal venous pressure was significantly elevated post-PH in mice with normal and steatotic livers compared to sham-operated mice. Reduction of elevated portal pressure after 80% PH by terlipressin was associated with an increase of hepatocellular proliferation. In steatotic livers, animals treated with terlipressin had an increase in liver regeneration after 30% PH and increased survival after 60% PH. Mechanistically, terlipressin alleviated IL-6 mRNA expression following PH and down-regulated p21 and GADD45 mRNA suggesting a reduction of cell cycle inhibition and cellular stress. Reduction of elevated portal pressure post-PH by the use of terlipressin improves liver regeneration after PH in lean and steatotic mouse livers.
    Transplantation 03/2014; DOI:10.1097/TP.0000000000000045 · 3.78 Impact Factor
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    ABSTRACT: Genome wide association studies (GWAS) have revealed genetic determinants of iron metabolism, but correlation of these with clinical phenotypes is pending. Homozygosity for HFE C282Y is the predominant genetic risk factor for hereditary hemochromatosis (HH) and may cause liver cirrhosis. However, this genotype has a low penetrance. Thus, detection of yet unknown genetic markers that identify patients at risk of developing severe liver disease is necessary for better prevention.Genetic loci associated with iron metabolism (TF, TMPRSS6, PCSK7, TFR2, Chr2p14) in recent GWAS, and liver fibrosis (PNPLA3) in recent meta-analysis were analyzed for association with either liver cirrhosis or advanced fibrosis in 148 German HFE C282Y homozygotes. Replication of associations was sought in additional 499 Austrian/Swiss and 112 HFE C282Y homozygotes from Sweden.Only variant rs236918 in the PCSK7 gene (proprotein convertase subtilisin/kexin type 7) was associated with cirrhosis or advanced fibrosis (p=1.02×10(-5)) in the German cohort with genotypic odds ratios of 3.56 [95% CI 1.29-9.77] for CG heterozygotes and 5.38 [2.39-12.10] for C allele carriers. Association between rs236918 and cirrhosis was confirmed in Austrian/Swiss HFE C282Y homozygotes (p=0.014; ORallelic=1.82 [1.12-2.95] but not in Swedish patients. Posthoc combined analyses of German/Swiss/Austrian patients with available liver histology (N=244, p=0.00014, ORallelic=2.84) and of males only (N=431, p=2.17×10(-5), ORallelic=2.54) were consistent with the premier finding. Association between rs236918 and cirrhosis was not confirmed in alcoholic cirrhotics, suggesting specificity of this genetic risk factor for HH.PCSK7 variant rs236918 is a risk factor for cirrhosis in HH patients homozygous for the HFE C282Y mutation.
    Human Molecular Genetics 02/2014; DOI:10.1093/hmg/ddu076 · 6.68 Impact Factor
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    ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in industrialized countries, yet it's pathophysiology is incompletely understood. Small molecule metabolite screens may offer new insights into disease mechanisms and reveal new treatment targets. Discovery (N=33) and replication (N=66) liver biopsies spanning the range from normal liver histology to non-alcoholic steatohepatitis (NASH) were ascertained ensuring rapid freezing in under 30 seconds in patients. 252 metabolites were assessed using GC/MS. Replicated metabolites were evaluated in a murine high-fat diet model of NAFLD. In a two-stage metabolic screening hydroquinone (HQ, pcombined =3.0×10(-4) ) and nicotinic acid (NA, pcombined =3.9×10(-9) ) were inversely correlated with histological NAFLD severity. A murine high-fat diet model of NAFLD demonstrated a protective effect of these two substances against NAFLD: Supplementation with 1% HQ reduced only liver steatosis, whereas 0.6% NA reduced both liver fat content and serum transaminase levels and induced a complex regulatory network of genes linked to NALFD pathogenesis in a global expression pathway analysis. Human nutritional intake of NA equivalent was also consistent with a protective effect of NA against NASH progression. This first small molecular screen of human liver tissue identified two replicated protective metabolites. Either the use of NA or targeting its regulatory pathways might be explored to treat or prevent human NAFLD. This article is protected by copyright. All rights reserved.
    Liver international: official journal of the International Association for the Study of the Liver 02/2014; 35(1). DOI:10.1111/liv.12476 · 4.41 Impact Factor

Publication Stats

4k Citations
1,282.19 Total Impact Points

Institutions

  • 2008–2014
    • Inselspital, Universitätsspital Bern
      • Department of Visceral Surgery and Medicine
      Berna, Bern, Switzerland
    • Beth Israel Deaconess Medical Center
      • Division of Gastroenterology
      Boston, MA, United States
  • 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
    • Charité Universitätsmedizin Berlin
      • Medical Department, Division of Hepatology and Gastroenterology
      Berlin, Land Berlin, 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
  • 2005–2007
    • Harvard University
      Cambridge, Massachusetts, United States
    • Huazhong University of Science and Technology
      • Department of Gastroenterology
      Wu-han-shih, Hubei, China
  • 2001–2005
    • Friedrich-Alexander Universität Erlangen-Nürnberg
      Erlangen, Bavaria, Germany
    • The University of Arizona
      • College of Medicine
      Tucson, Arizona, United States
  • 2004
    • University of Vienna
      Wien, Vienna, Austria
  • 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
  • 1995
    • Universität Heidelberg
      Heidelburg, Baden-Württemberg, Germany