Felix Stickel

Inselspital, Universitätsspital Bern, Berna, Bern, Switzerland

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Publications (175)1083.34 Total impact

  • 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. · 2.01 Impact Factor
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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; · 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; · 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. · 12.82 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; · 3.11 Impact Factor
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    ABSTRACT: The genetic background of alcoholic liver diseases and its complications is increasingly recognized. A common polymorphism in the neurocan (NCAN) gene, which is known to be expressed in neuronal tissue, has been identified as 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).
    Journal of Hepatology 06/2014; · 10.40 Impact Factor
  • Journal of Hepatology 04/2014; 60(1):S60. · 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; · 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; · 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; · 4.41 Impact Factor
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    ABSTRACT: CXCL1 (CXC chemokine-ligand-1) is a ligand for CXC chemokine receptor 2 expressed on hepatic stellate cells (HSC). Thus, CXCL1 might contribute to HSC activation and fibrogenesis. In the present study, we investigated the influence of the CXCL1 rs4074 polymorphism on the occurrence of alcohol induced liver cirrhosis and hepatocellular carcinoma (HCC). The study involved 458 patients with alcoholic cirrhosis (170 with HCC), 115 alcoholics without liver disease and 342 healthy controls. All subjects were genotyped for the CXCL1 rs4074 polymorphism and CXCL1 serum levels of 132 patients were measured. In vitro CXCL1 secretion in TLR-transfected cell lines were studied by ELISA. Distribution of the CXCL1 genotypes (GG/GA/AA) was 159/219/80 in patients with alcoholic cirrhosis, 52/44/19 in alcoholic controls and 158/140/44 in healthy controls. Patients with alcohol-induced cirrhosis were significantly more often carriers of the CXCL1 rs4074 A allele (65.3%) than alcoholics without liver disease (54.8%, OR=1.55; 95%CI=1.025-2.350; p=0.04) and healthy controls (53.8%, OR=1.62; 95%CI=1.212-2.151; p=0.001). Accordingly, the frequency of the CXCL1 rs4074 A allele was significantly higher in the cirrhotic patients than in the subjects without cirrhosis (41.4% vs. 33.9%, OR=1.38, 95% CI:1.14-1.66, p=0.001). Furthermore cirrhotic carriers of the CXCL1 rs4074 A allele had significantly higher CXCL1 serum levels than carriers of the GG genotype. In contrast to sera from healthy controls, sera from patients with alcoholic cirrhosis induced CXCL1 secretion in TLR2- (p=0.016) and TLR4- (p=0.008) transfected HEK293 cells. This finding indicates that sera from patients with alcoholic cirrhosis contain soluble ligands that can induce CXCL1 production via stimulation of TLRs. The enhanced CXCL1 serum levels in carriers of the rs4074 A allele together with their increased frequency in patients with alcohol induced cirrhosis suggest the CXCL1 rs4074 A allele as a genetic risk factor for alcoholic cirrhosis.
    PLoS ONE 11/2013; 8(11):e80848. · 3.53 Impact Factor
  • H K Seitz, F Stickel
    DMW - Deutsche Medizinische Wochenschrift 10/2013; 138(40):2041-4. · 0.65 Impact Factor
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    ABSTRACT: We investigated changes in biomarkers of liver disease in HIV/HCV- coinfected individuals during successful combination antiretroviral therapy (cART) compared to changes in biomarker levels during untreated HIV-infection and to HIV-monoinfected individuals. Non-invasive biomarkers of liver disease [hyaluronic acid (HYA), APRI, FIB-4 and cytokeratin-18 (CK-18)] were correlated with liver histology in 49 HIV/HCV-coinfected patients. Changes in biomarkers over time were then assessed longitudinally in HIV/HCV-coinfected patients during successful cART (n=58), during untreated HIV-infection (n=59), and in HIV-monoinfected individuals (n=17). The median follow-up time was 3.4 years on-cART. All analyses were before starting HCV treatment. Non-invasive biomarkers of liver disease correlated significantly with the histological METAVIR-stage (P<0.002 for all comparisons). The AUROC values for advanced fibrosis (≥F3-METAVIR) for HYA, APRI, FIB-4 and CK-18 were 0.86±0.05, 0.84±0.08, 0.80±0.09 and 0.81±0.07, respectively. HYA, APRI and CK-18 levels were higher in HIV/HCV-coinfected compared to HIV-monoinfected patients (P<0.01). In the first year on cART, APRI and FIB-4 scores decreased (-35% and -33%, P=0.1), mainly due to the reversion of HIV-induced thrombocytopenia, while HYA and CK-18 levels remained unchanged. During long-term cART, there were only small changes (<5%) in median biomarker levels. Median biomarker levels changed less than 3% during untreated HIV-infection. Three patients died from end-stage liver disease, and 10 from other causes. Biomarkers of liver disease highly correlated with fibrosis in HIV/HCV-coinfected individuals and did not change significantly during successful cART. These findings suggest a slower than expected liver disease progression in many HIV/HCV-coinfected individuals, at least during successful cART.
    Antiviral therapy 09/2013; · 3.14 Impact Factor
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    ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in industrialized countries. Liver samples from morbidly obese patients (n = 45) with all stages of NAFLD and controls (n = 18) were analyzed by array-based DNA methylation and mRNA expression profiling. NAFLD-specific expression and methylation differences were seen for nine genes coding for key enzymes in intermediate metabolism (including PC, ACLY, and PLCG1) and insulin/insulin-like signaling (including IGF1, IGFBP2, and PRKCE) and replicated by bisulfite pyrosequening (independent n = 39). Transcription factor binding sites at NAFLD-specific CpG sites were >1,000-fold enriched for ZNF274, PGC1A, and SREBP2. Intraindividual comparison of liver biopsies before and after bariatric surgery showed NAFLD-associated methylation changes to be partially reversible. Postbariatric and NAFLD-specific methylation signatures were clearly distinct both in gene ontology and transcription factor binding site analyses, with >400-fold enrichment of NRF1, HSF1, and ESRRA sites. Our findings provide an example of treatment-induced epigenetic organ remodeling in humans.
    Cell metabolism 08/2013; 18(2):296-302. · 17.35 Impact Factor
  • The American Journal of Gastroenterology 07/2013; 108(7):1176-1178. · 9.21 Impact Factor
  • Felix Stickel, Helmut K Seitz
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    ABSTRACT: Among heavy drinkers with liver disease, the development of severe alcoholic hepatitis (AH) is a serious complication. Prognosis is grave and associated with a high mortality due to liver failure, hepatorenal syndrome or intractable sepsis. Clinically, AH presents as a syndrome of progressive inflammatory liver injury in patients with recent or ongoing heavy alcohol consumption. Although approximately 20% of alcoholics undergoing liver biopsy reveal histological features of AH, only a minority progress to severe AH with markedly elevated serum liver enzymes, jaundice and impaired liver function. To establish the diagnosis of AH, histology is recommended but not mandatory. Prognostic scores include the Maddrey's discriminant function, the model of end-stage liver disease, the Glasgow Alcoholic Hepatitis score, and the ABIC score. While the former scores identify patients at risk of death or the need for corticosteroids, the response to corticosteroid therapy can be assessed using the Lille model. Treatments include abstinence and enteral nutrition, while pharmacotherapy using corticosteroids either with or without N-acetylcysteine may be indicated for patients with severe AH. Pentoxifylline was found to reduce the risk of hepatorenal syndrome, but data on mortality are limited. Although considered a contraindication in most transplant centers, recent evidence indicates that carefully selected patients with AH could be good candidates for liver transplantation with a prognosis comparable to other indications.
    Journal of gastrointestinal and liver diseases: JGLD 06/2013; 22(2):189-197. · 1.85 Impact Factor
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    ABSTRACT: Introduction: Herbal and dietary supplements are widely used as measures to improve and preserve health and well-being. Among the bestselling preparations are dietary supplement containing glucosamine and chondroitine sulfate taken to improve symptoms of osteoarthritis. Methods and results: We here present a case of a male patient with biopsy-proven acute and severe autoimmune hepatitis subsequent to intake of a preparation containing glucosamine and chondroitine sulfate. Response to steroids was favorable and resulted in complete remission of the patient. Diagnostic work-up of the case revealed no other possible cause of liver injury, and causality assessment using the Roussel Uclaf Causality Assessment Method (RUCAM) resulted in a possible causal relationship between intake of glucosamine and chondroitine sulfate and the adverse hepatic reaction. Conclusion: The present case recalls that products containing glucosamine and chondroitine sulfate can occasionally cause acute liver injury mimicking autoimmune hepatitis, and reminds of the potential dangers of compounds with poor efficacy and ill-defined safety records.
    International journal of clinical pharmacology and therapeutics 02/2013; 51(03). · 1.04 Impact Factor
  • Liver international: official journal of the International Association for the Study of the Liver 01/2013; · 4.41 Impact Factor
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    ABSTRACT: High frequency electrosurgery has a key role in the broadening application of liver surgery. Its molecular signature, i.e. the metabolites evolving from electrocauterization which may inhibit hepatic wound healing, have not been systematically studied. Human liver samples were thus obtained during surgery before and after electrosurgical dissection and subjected to a two-stage metabolomic screening experiment (discovery sample: N = 18, replication sample: N = 20) using gas chromatography/mass spectrometry. In a set of 208 chemically defined metabolites, electrosurgical dissection lead to a distinct metabolic signature resulting in a separation in the first two dimensions of a principal components analysis. Six metabolites including glycolic acid, azelaic acid, 2-n-pentylfuran, dihydroactinidiolide, 2-butenal and n-pentanal were consistently increased after electrosurgery meeting the discovery (p<2.0×10(-4)) and the replication thresholds (p<3.5×10(-3)). Azelaic acid, a lipid peroxidation product from the fragmentation of abundant sn-2 linoleoyl residues, was most abundant and increased 8.1-fold after electrosurgical liver dissection (preplication = 1.6×10(-4)). The corresponding phospholipid hexadecyl azelaoyl glycerophosphocholine inhibited wound healing and tissue remodelling in scratch- and proliferation assays of hepatic stellate cells and cholangiocytes, and caused apoptosis dose-dependently in vitro, which may explain in part the tissue damage due to electrosurgery. Hepatic electrosurgery generates a metabolic signature with characteristic lipid peroxidation products. Among these, azelaic acid shows a dose-dependent toxicity in liver cells and inhibits wound healing. These observations potentially pave the way for pharmacological intervention prior liver surgery to modify the metabolic response and prevent postoperative complications.
    PLoS ONE 01/2013; 8(9):e72022. · 3.53 Impact Factor
  • M Soyka, F Stickel
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    ABSTRACT: Liver disorders are the most frequent somatic complications of alcoholism. As 10‑20% of alcoholic patients will develop liver cirrhosis, this is the most frequent reason for premature death in alcoholic patients. Liver transplantation is now an accepted therapy for alcoholic liver cirrhosis but psychiatric assessment is usually required for patients entering a waiting list for transplantation. Prognostic criteria are controversially discussed, especially the so-called 6-month rule. Numerous studies and recent meta-analyses have indicated that duration of alcoholism, family history, age, sex, comorbid substance use and psychiatric disorders, noncompliance and social instability are outcome predictors. The 6-month criterion is not well proven but some studies are indicative. Possible therapeutic interventions for alcoholic patients on a waiting list are discussed.
    Der Nervenarzt 12/2012; · 0.86 Impact Factor

Publication Stats

3k Citations
1,083.34 Total Impact Points


  • 2008–2014
    • Inselspital, Universitätsspital Bern
      • Department of Visceral Surgery and Medicine
      Berna, Bern, Switzerland
    • Venetian Institute of Molecular Medicine
      Padua, Veneto, Italy
  • 2013
    • Christian-Albrechts-Universität zu Kiel
      Kiel, Schleswig-Holstein, Germany
  • 2007–2013
    • Universität Bern
      • • Institute of Pharmacology
      • • Department of Clinical Pharmacology and Visceral Research
      • • Institute of Classical Philology
      Bern, BE, Switzerland
  • 1994–2013
    • Universität Heidelberg
      • • Center for Alcohol Research
      • • Medical Research Center
      • • University Hospital of Internal Medicine
      Heidelberg, Baden-Wuerttemberg, Germany
  • 2011
    • University Medical Center Schleswig-Holstein
      Kiel, Schleswig-Holstein, Germany
    • Charité Universitätsmedizin Berlin
      • Medical Department, Division of Hepatology and Gastroenterology
      Berlin, Land Berlin, Germany
  • 2010–2011
    • University Hospital Regensburg
      • Klinik und Poliklinik für Innere Medizin I
      Ratisbon, Bavaria, Germany
  • 2009
    • Universität zu Lübeck
      Lübeck Hansestadt, Schleswig-Holstein, Germany
  • 2006–2009
    • Beth Israel Deaconess Medical Center
      • Division of Gastroenterology
      Boston, MA, United States
  • 2001–2005
    • Friedrich-Alexander Universität Erlangen-Nürnberg
      Erlangen, Bavaria, Germany
  • 2000
    • Technische Universität München
      München, Bavaria, Germany
  • 1997
    • Tufts University
      • Department of Medicine
      Medford, MA, United States