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Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis.

https://arctichealth.org/en/permalink/ahliterature117805
Source
JAMA. 2012 Dec 26;308(24):2584-93
Publication Type
Article
Date
Dec-26-2012
Author
Adriaan J van der Meer
Bart J Veldt
Jordan J Feld
Heiner Wedemeyer
Jean-François Dufour
Frank Lammert
Andres Duarte-Rojo
E Jenny Heathcote
Michael P Manns
Lorenz Kuske
Stefan Zeuzem
W Peter Hofmann
Robert J de Knegt
Bettina E Hansen
Harry L A Janssen
Author Affiliation
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Source
JAMA. 2012 Dec 26;308(24):2584-93
Date
Dec-26-2012
Language
English
Publication Type
Article
Keywords
Adult
Antiviral agents - therapeutic use
Canada - epidemiology
Cause of Death
Europe - epidemiology
Female
Follow-Up Studies
Hepatitis C, Chronic - complications - drug therapy - mortality - virology
Humans
Interferons - therapeutic use
Liver Cirrhosis - complications - virology
Liver Failure - complications - virology
Male
Middle Aged
Viremia
Abstract
Chronic hepatitis C virus (HCV) infection outcomes include liver failure, hepatocellular carcinoma (HCC), and liver-related death.
To assess the association between sustained virological response (SVR) and all-cause mortality in patients with chronic HCV infection and advanced hepatic fibrosis.
An international, multicenter, long-term follow-up study from 5 large tertiary care hospitals in Europe and Canada of 530 patients with chronic HCV infection who started an interferon-based treatment regimen between 1990 and 2003, following histological proof of advanced hepatic fibrosis or cirrhosis (Ishak score 4-6). Complete follow-up ranged between January 2010 and October 2011.
All-cause mortality. Secondary outcomes were liver failure, HCC, and liver-related mortality or liver transplantation.
The 530 study patients were followed up for a median (interquartile range [IQR]) of 8.4 (6.4-11.4) years. The baseline median (IQR) age was 48 (42-56) years and 369 patients (70%) were men. The Ishak fibrosis score was 4 in 143 patients (27%), 5 in 101 patients (19%), and 6 in 286 patients (54%). There were 192 patients (36%) who achieved SVR; 13 patients with SVR and 100 without SVR died (10-year cumulative all-cause mortality rate, 8.9% [95% CI, 3.3%-14.5%] with SVR and 26.0% [95% CI, 20.2%-28.4%] without SVR; P
Notes
Comment In: JAMA. 2013 Apr 10;309(14):145723571571
Comment In: JAMA. 2013 Apr 10;309(14):145723571570
Comment In: Hepatology. 2013 Oct;58(4):1508-1023703903
Comment In: Ann Hepatol. 2013 Mar-Apr;12(2):341-223538670
PubMed ID
23268517 View in PubMed
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Autoimmune hepatitis in the Alaska Native population: autoantibody profile and HLA associations.

https://arctichealth.org/en/permalink/ahliterature262772
Source
Liver Int. 2014 Sep;34(8):1241-9
Publication Type
Article
Date
Sep-2014
Author
Elizabeth D Ferucci
Tammy L Choromanski
Kathy J Hurlburt
Stephen Livingston
Julia Plotnik
Michael P Manns
Brian J McMahon
Judith A James
Source
Liver Int. 2014 Sep;34(8):1241-9
Date
Sep-2014
Language
English
Publication Type
Article
Keywords
Alaska - epidemiology
Antibodies, Antineutrophil Cytoplasmic - blood
Antibodies, Antinuclear - blood
Autoantibodies - blood
Cohort Studies
Enzyme-Linked Immunosorbent Assay
Fluorescent Antibody Technique
HLA-DR3 Antigen - blood
Hepatitis, Autoimmune - epidemiology - immunology
Humans
Indians, North American
Prevalence
Abstract
The Alaska Native population is one of few populations in the world with a high prevalence of autoimmune hepatitis. The objective of this study was to determine the frequency and HLA and clinical associations of autoantibodies in Alaska Native people with autoimmune hepatitis.
Alaska Native individuals with autoimmune hepatitis were recruited in clinics conducted statewide. Sera were tested for the presence of autoantibodies described in either autoimmune hepatitis or rheumatic disease. Associations between autoantibodies and HLA alleles and clinical features were assessed.
Seventy-one patients were included. At the study visit, 34 patients (47.9%) had antibodies to double-stranded DNA by immunofluorescence; 27 (38.0%) had anti-neutrophil cytoplasmic antibodies; and 11 (15.5%) had anti-Ro antibodies. Only one person had antibodies against soluble liver antigen, and in that person, anti-Ro was absent. Associations were found between autoantibodies and HLA alleles, including positive associations between HLA DR3 and anti-double-stranded DNA antibodies and between HLA DR14 and antineutrophil cytoplasmic antibodies. There was no association between autoantibodies and clinical outcomes.
As in other populations, the prevalence of anti-double-stranded DNA antibodies and antineutrophil cytoplasmic antibodies is high in Alaska Native people with autoimmune hepatitis. In contrast to data from other populations, there is a lower prevalence of anti-soluble liver antigen and a lack of association between anti-Ro and anti-soluble liver antigen. In addition, the HLA profile and associations with autoantibodies are unique. No clear prognostic implications of autoantibodies have emerged in this population.
PubMed ID
24939565 View in PubMed
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Epidemiological trends in incidence and mortality of hepatobiliary cancers in Germany.

https://arctichealth.org/en/permalink/ahliterature101653
Source
Scand J Gastroenterol. 2011 Sep;46(9):1092-8
Publication Type
Article
Date
Sep-2011
Author
Thomas von Hahn
Sandra Ciesek
Gerd Wegener
Ruben R Plentz
Tobias J Weismüller
Heiner Wedemeyer
Michael P Manns
Tim F Greten
Nisar P Malek
Author Affiliation
Department of Gastroenterology, Hepatology and Endocrinology , Medizinische Hochschule, Hannover Medical School, Hannover , Germany.
Source
Scand J Gastroenterol. 2011 Sep;46(9):1092-8
Date
Sep-2011
Language
English
Publication Type
Article
Abstract
Abstract Objective. While marked changes in the frequency of hepatobiliary malignancies, most notably hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), have been observed in different populations, no such data have been reported for Germany. We aimed to provide epidemiological data on recent trends in liver-related mortality, specifically mortality from hepatobiliary malignancies, in Germany. Material and methods. We used incidence and mortality data to determine changes in the frequency of malignant and non-malignant liver disease in Germany over the past 30 years. Results. While overall liver disease mortality has slightly declined in Germany, deaths from hepatobiliary malignancies have declined in women, but remained constant in men. Among hepatobiliary malignancies, ICC stands out, because mortality has more than tripled both in men and women between 1998 and 2008. This is mirrored by a marked increase in new cases reported to local cancer registries, that is, incidence. Over the same time period, HCC and extrahepatic cholangiocarcinoma (ECC) have remained largely constant while gall bladder cancers (GBC) have declined twofold. The rapid rise in ICC is in line with finding from different regions worldwide, but in contrast to recent data from Denmark and France, two of Germany's direct neighbors. Conclusions. The incidence of and mortality from ICC are rising markedly in Germany. The risk factors underlying this trend are as yet unclear.
PubMed ID
21692710 View in PubMed
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Genome-wide association analysis in primary sclerosing cholangitis and ulcerative colitis identifies risk loci at GPR35 and TCF4.

https://arctichealth.org/en/permalink/ahliterature122406
Source
Hepatology. 2013 Sep;58(3):1074-83
Publication Type
Article
Date
Sep-2013
Author
David Ellinghaus
Trine Folseraas
Kristian Holm
Eva Ellinghaus
Espen Melum
Tobias Balschun
Jon K Laerdahl
Alexey Shiryaev
Daniel N Gotthardt
Tobias J Weismüller
Christoph Schramm
Michael Wittig
Annika Bergquist
Einar Björnsson
Hanns-Ulrich Marschall
Morten Vatn
Andreas Teufel
Christian Rust
Christian Gieger
H-Erich Wichmann
Heiko Runz
Martina Sterneck
Christian Rupp
Felix Braun
Rinse K Weersma
Cisca Wijmenga
Cyriel Y Ponsioen
Christopher G Mathew
Paul Rutgeerts
Séverine Vermeire
Erik Schrumpf
Johannes R Hov
Michael P Manns
Kirsten M Boberg
Stefan Schreiber
Andre Franke
Tom H Karlsen
Author Affiliation
Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany.
Source
Hepatology. 2013 Sep;58(3):1074-83
Date
Sep-2013
Language
English
Publication Type
Article
Keywords
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics
Belgium
Case-Control Studies
Cholangitis, Sclerosing - epidemiology - ethnology - genetics
Colitis, Ulcerative - epidemiology - ethnology - genetics
Comorbidity
Genetic Loci - genetics
Genetic Predisposition to Disease - ethnology - genetics
Genome-Wide Association Study
Genotype
Germany
Great Britain
Humans
Netherlands
Norway
Polymorphism, Single Nucleotide - genetics
Receptors, G-Protein-Coupled - genetics
Risk factors
Transcription Factors - genetics
Abstract
Approximately 60%-80% of patients with primary sclerosing cholangitis (PSC) have concurrent ulcerative colitis (UC). Previous genome-wide association studies (GWAS) in PSC have detected a number of susceptibility loci that also show associations in UC and other immune-mediated diseases. We aimed to systematically compare genetic associations in PSC with genotype data in UC patients with the aim of detecting new susceptibility loci for PSC. We performed combined analyses of GWAS for PSC and UC comprising 392 PSC cases, 987 UC cases, and 2,977 controls and followed up top association signals in an additional 1,012 PSC cases, 4,444 UC cases, and 11,659 controls. We discovered novel genome-wide significant associations with PSC at 2q37 [rs3749171 at G-protein-coupled receptor 35 (GPR35); P = 3.0 × 10(-9) in the overall study population, combined odds ratio [OR] and 95% confidence interval [CI] of 1.39 (1.24-1.55)] and at 18q21 [rs1452787 at transcription factor 4 (TCF4); P = 2.61 × 10(-8) , OR (95% CI) = 0.75 (0.68-0.83)]. In addition, several suggestive PSC associations were detected. The GPR35 rs3749171 is a missense single nucleotide polymorphism resulting in a shift from threonine to methionine. Structural modeling showed that rs3749171 is located in the third transmembrane helix of GPR35 and could possibly alter efficiency of signaling through the GPR35 receptor.
By refining the analysis of a PSC GWAS by parallel assessments in a UC GWAS, we were able to detect two novel risk loci at genome-wide significance levels. GPR35 shows associations in both UC and PSC, whereas TCF4 represents a PSC risk locus not associated with UC. Both loci may represent previously unexplored aspects of PSC pathogenesis.
PubMed ID
22821403 View in PubMed
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No Evidence That Azathioprine Increases Risk of Cholangiocarcinoma in Patients With Primary Sclerosing Cholangitis.

https://arctichealth.org/en/permalink/ahliterature284952
Source
Clin Gastroenterol Hepatol. 2016 Dec;14(12):1806-1812
Publication Type
Article
Date
Dec-2016
Author
Roman Zenouzi
Tobias J Weismüller
Kristin K Jørgensen
Michael Bubenheim
Henrike Lenzen
Peter Hübener
Kornelius Schulze
Christina Weiler-Normann
Marcial Sebode
Hanno Ehlken
Nadine Pannicke
Johannes Hartl
Moritz Peiseler
Sina Hübener
Tom H Karlsen
Kirsten M Boberg
Michael P Manns
Ansgar W Lohse
Christoph Schramm
Source
Clin Gastroenterol Hepatol. 2016 Dec;14(12):1806-1812
Date
Dec-2016
Language
English
Publication Type
Article
Keywords
Adult
Azathioprine - adverse effects - therapeutic use
Cholangiocarcinoma - chemically induced - epidemiology
Cholangitis, Sclerosing - complications - drug therapy
Female
Germany - epidemiology
Humans
Immunosuppressive Agents - adverse effects - therapeutic use
Male
Middle Aged
Norway - epidemiology
Retrospective Studies
Risk assessment
Tertiary Care Centers
Young Adult
Abstract
Patients with primary sclerosing cholangitis (PSC) are at increased risk for developing cholangiocarcinoma (CCA). Patients with PSC also can have inflammatory bowel diseases (IBDs) or features of autoimmune hepatitis (AIH), and therefore are treated with azathioprine. Azathioprine has been associated with an increased risk for malignancy, therefore we investigated whether azathioprine use affects the risk of CCA in persons with PSC.
We performed a retrospective study of well-defined patients with PSC using data collected from 3 large-volume, tertiary care centers in Germany and Norway. We analyzed data from 638 patients (70% men; 5900 patient-years of follow-up evaluation); 91 patients had received azathioprine therapy (considered to be effective at 90 days after first intake). Risk analysis was performed using the Cox proportional hazard model when risks competing with study end points were present.
Of patients who received azathioprine treatment, 3.3% developed CCA, compared with 6.8% of patients without azathioprine treatment. However, azathioprine did not significantly affect the risk for CCA (hazard ratio, 0.96; 95% confidence interval, 0.29-3.13; P = .94). The only factor associated with an increased risk of CCA was age 35 years or older at PSC diagnosis (hazard ratio, 3.87; 95% confidence interval, 1.96-7.67; P
PubMed ID
27521513 View in PubMed
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