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1
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Bitzer M, Groß S, Albert J, Blödt S, Boda-Heggemann J, Borucki K, Brunner T, Caspari R, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, Gebert J, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Krug D, La Fougère C, Lang H, Langer T, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Nothacker M, Ockenga J, Oldhafer K, Ott J, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ringe K, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schütte K, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Trojan J, van Thiel I, Utzig M, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wenzel G, Wildner D, Wörns MA, Galle P, Malek N. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2025; 63:e159-e260. [PMID: 40064172 DOI: 10.1055/a-2460-6298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2025]
Affiliation(s)
- Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | - Susanne Blödt
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | | | - Katrin Borucki
- Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Institut für Klinische Chemie und Pathobiochemie
| | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | - Markus Follmann
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | | | - Cihan Gani
- Klinik für Radioonkologie, Universitätsklinikum Tübingen
| | - Jamila Gebert
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Thomas Langer
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Eberhard-Karls Universität, Tübingen
| | | | - Monika Nothacker
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Julia Ott
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Digestive Diseases and Nutrition, Gastroenterology, University of Kentucky
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | - Kristina Ringe
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | | | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Kerstin Schütte
- Klinik für Innere Medizin und Gastroenterologie, Niels-Stensen-Kliniken, Marienhospital Osnabrück
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Martin Utzig
- Abteilung Zertifizierung, Deutsche Krebsgesellschaft e.V., Berlin
| | - Arndt Vogel
- Institute of Medical Science, University of Toronto
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie, Infektiologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Gregor Wenzel
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
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Groß S, Bitzer M, Albert J, Blödt S, Boda-Heggemann J, Borucki K, Brunner T, Caspari R, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, Gebert J, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Krug D, Fougère CL, Lang H, Langer T, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Nothacker M, Ockenga J, Oldhafer K, Ott J, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ringe K, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schütte K, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Trojan J, van Thiel I, Utzig M, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wenzel G, Wildner D, Wörns MA, Galle P, Malek N. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2025; 63:e82-e158. [PMID: 39919781 DOI: 10.1055/a-2460-6347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/09/2025]
Affiliation(s)
- Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | - Susanne Blödt
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | | | - Katrin Borucki
- Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Institut für Klinische Chemie und Pathobiochemie
| | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | - Markus Follmann
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | | | - Cihan Gani
- Klinik für Radioonkologie, Universitätsklinikum Tübingen
| | - Jamila Gebert
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Thomas Langer
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Eberhard-Karls Universität, Tübingen
| | | | - Monika Nothacker
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Julia Ott
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Digestive Diseases and Nutrition, Gastroenterology, University of Kentucky
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | - Kristina Ringe
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | | | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Kerstin Schütte
- Klinik für Innere Medizin und Gastroenterologie, Niels-Stensen-Kliniken, Marienhospital Osnabrück
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Martin Utzig
- Abteilung Zertifizierung, Deutsche Krebsgesellschaft e.V., Berlin
| | - Arndt Vogel
- Institute of Medical Science, University of Toronto
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie, Infektiologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Gregor Wenzel
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
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Hříbek P, Vrtělka O, Králová K, Klasová J, Fousková M, Habartová L, Kubíčková K, Kupsa T, Tůma T, Setnička V, Urbánek P. Efficacy of blood plasma spectroscopy for early liver cancer diagnostics in obese patients. Ann Hepatol 2024; 29:101519. [PMID: 38866366 DOI: 10.1016/j.aohep.2024.101519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Revised: 04/12/2024] [Accepted: 05/16/2024] [Indexed: 06/14/2024]
Abstract
INTRODUCTION AND OBJECTIVES Hepatocellular carcinoma (HCC) represents one of the most common cancers worldwide. A considerable proportion of HCC is caused by cirrhosis related to metabolic dysfunction-associated steatohepatitis (MASH). Due to the increasing prevalence of metabolic syndrome, it is estimated that MASH-related HCC will become the most prevalent etiology of HCC. Currently, HCC screening is based on liver ultrasonography; however, the sensitivity of ultrasonography for early HCC stages in obese patients only reaches 23 %. To date, no studied biomarker shows sufficient efficacy for screening purposes. Nevertheless, the usage of spectroscopic methods offers a new perspective, as its potential use would provide cheap, fast analysis of samples such as blood plasma. MATERIAL AND METHODS We employed a combination of conventional and chiroptical spectroscopic methods to study differences between the blood plasma of obese cirrhotic patients with and without HCC. We included 20 subjects with HCC and 17 without evidence of liver cancer, all of them with body mass index ≥ 30. RESULTS Sensitivities and specificities reached values as follows: 0.780 and 0.905 for infrared spectroscopy, 0.700 and 0.767 for Raman spectroscopy, 0.840 and 0.743 for electronic circular dichroism, and 0.805 and 0.923 for Raman optical activity. The final combined classification model based on all spectroscopic methods reached a sensitivity of 0.810 and a specificity of 0.857, with the highest area under the receiver operating characteristic curve among all models (0.961). CONCLUSIONS We suggest that this approach can be used effectively as a diagnostic tool in patients who are not examinable by liver ultrasonography. CLINICAL TRIAL REGISTRATION NCT04221347.
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Affiliation(s)
- Petr Hříbek
- Military University Hospital Prague, Department of Medicine 1st Faculty of Medicine Charles University and Military University Hospital, U Vojenske nemocnice 1200, 16902 Prague, Czechia; Department of Internal Medicine, University of Defense, Faculty of Military Health Sciences, Trebesska 1575, 50001 Hradec Kralove, Czechia.
| | - Ondřej Vrtělka
- Department of Analytical Chemistry, University of Chemistry and Technology, Technicka 5, 16628 Prague, Czechia
| | - Kateřina Králová
- Department of Analytical Chemistry, University of Chemistry and Technology, Technicka 5, 16628 Prague, Czechia
| | - Johana Klasová
- Military University Hospital Prague, Department of Medicine 1st Faculty of Medicine Charles University and Military University Hospital, U Vojenske nemocnice 1200, 16902 Prague, Czechia
| | - Markéta Fousková
- Department of Analytical Chemistry, University of Chemistry and Technology, Technicka 5, 16628 Prague, Czechia
| | - Lucie Habartová
- Department of Analytical Chemistry, University of Chemistry and Technology, Technicka 5, 16628 Prague, Czechia
| | - Kristýna Kubíčková
- Military University Hospital Prague, Department of Medicine 1st Faculty of Medicine Charles University and Military University Hospital, U Vojenske nemocnice 1200, 16902 Prague, Czechia
| | - Tomáš Kupsa
- Department of Internal Medicine, University of Defense, Faculty of Military Health Sciences, Trebesska 1575, 50001 Hradec Kralove, Czechia
| | - Tomáš Tůma
- Department of Internal Medicine, University of Defense, Faculty of Military Health Sciences, Trebesska 1575, 50001 Hradec Kralove, Czechia
| | - Vladimír Setnička
- Department of Analytical Chemistry, University of Chemistry and Technology, Technicka 5, 16628 Prague, Czechia
| | - Petr Urbánek
- Military University Hospital Prague, Department of Medicine 1st Faculty of Medicine Charles University and Military University Hospital, U Vojenske nemocnice 1200, 16902 Prague, Czechia
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Clark PJ, Valery PC, Strasser SI, Weltman M, Thompson A, Levy MT, Leggett B, Zekry A, Rong J, Sinclair M, George J, Sievert W, MacQuillan G, Tse E, Nicoll A, Wade A, Cheng W, Roberts SK. Alcohol does not impact chronic hepatitis C treatment outcomes but increases risk for progressive liver disease: Findings from a prospective multicentre Australian study (OPERA-C). Drug Alcohol Rev 2024; 43:1559-1572. [PMID: 39091194 DOI: 10.1111/dar.13914] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Revised: 06/19/2024] [Accepted: 07/08/2024] [Indexed: 08/04/2024]
Abstract
INTRODUCTION Alcohol use is common in patients with chronic hepatitis C virus (HCV) infection. We examined the impact of alcohol use on direct-acting antiviral (DAA) therapy outcome and the clinical course of liver disease and 2-year survival for patients receiving HCV DAA therapy. METHODS Adults (n = 2624) recruited from 26 Australian hospital liver clinics during 2016-2021 were followed up for 2 years. Risky alcohol use was defined by a combination of self-report (≥40 g/day of ethanol), physician-reported history of problematic alcohol use, and anti-craving medication prescription via population-based database linkage. We examined factors associated with advanced liver fibrosis and survival using multivariable logistic and Cox regression. RESULTS Among 1634 patients (62.3%) with risky alcohol use, 24.6% reported consuming ≥40 g/day of alcohol, 98.3% physician-reported problematic alcohol use; only 4.1% were dispensed naltrexone/acamprosate. One hundred and forty-three patients with cirrhosis reported ≥40 g/day of alcohol, 6 (4.3%) were prescribed naltrexone/acamprosate. Risky alcohol use was associated with advanced fibrosis (adjusted-odds ratio 1.69, 95% confidence interval 1.32-2.17) and patients were over-represented for cirrhosis (45.1% vs. 25.6% in no-risky alcohol use [p < 0.001]) and hepatocellular carcinoma (5.7% vs. 2.5% [p < 0.001]). Sustained viral response (p = 0.319) and 2-year survival (adjusted-hazard ratio 1.98, 95% confidence interval 0.84-4.63) after DAA therapy were not associated with risky alcohol use. DISCUSSION AND CONCLUSIONS Risky alcohol use in HCV patients was prevalent, but did not reduce HCV cure. Treatment for alcohol dependence was low. Risky alcohol use may be under-recognised in liver clinics. Better integration of addiction medicine into liver services and increased resourcing and addiction medicine training opportunities for hepatologists may help address this.
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Grants
- Commonwealth Department of Health, the Gastroenterological Society of Australia (GESA)
- Gilead Sciences
- Merck
- Abbvie
- Robert W. Storr Bequest
- Sydney Medical Foundation, University of Sydney
- APP1053206 A National Health and Medical Research Council of Australia (NHMRC) Program
- APP2001692 Project, Ideas, and Investigator
- APP1107178 Project, Ideas, and Investigator
- APP1108422 Project, Ideas, and Investigator
- APP1196492 Project, Ideas, and Investigator
- 2021/ATRG2028 Cancer Institute, NSW
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Affiliation(s)
- Paul J Clark
- Department of Gastroenterology, Alcohol and Drug Assessment Unit, Princess Alexandra and Mater Hospitals, Brisbane, Australia
- Faculty of Medicine, The University of Queensland, Brisbane, Australia
| | - Patricia C Valery
- Faculty of Medicine, The University of Queensland, Brisbane, Australia
- QIMR Berghofer Medical Research Institute, Brisbane, Australia
| | - Simone I Strasser
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, Australia
| | | | - Alex Thompson
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia
| | - Miriam T Levy
- Department of Gastroenterology and Liver, Liverpool Hospital, Sydney, Australia
| | - Barbara Leggett
- Faculty of Medicine, The University of Queensland, Brisbane, Australia
- Department of Gastroenterology and Hepatology, Royal Brisbane and Women's Hospital, Brisbane, Australia
| | - Amany Zekry
- Department of Gastroenterology and Hepatology, St George Hospital, Sydney, Australia
| | - Julian Rong
- Gippsland Gastroenterology, Latrobe Regional Hospital, Traralgon, Australia
| | - Marie Sinclair
- Department of Gastroenterology and Hepatology, Austin Hospital, Melbourne, Australia
| | - Jacob George
- Faculty of Medicine, The University of Sydney, Sydney, Australia
- Storr Liver Centre, Westmead Hospital, Sydney, Australia
| | - William Sievert
- Gastrointestinal and Liver Unit, Monash Health and Monash University, Melbourne, Australia
| | - Gerry MacQuillan
- Department of Hepatology and Liver Transplant Unit, Sir Charles Gairdner Hospital, Perth, Australia
| | - Edmund Tse
- Hepatology, Royal Adelaide Hospital, Adelaide, Australia
| | | | - Amanda Wade
- Burnet Institute, Melbourne, Australia
- Barwon Health Liver Clinic University Hospital, Geelong, Australia
| | - Wendy Cheng
- Department of Gastroenterology & Hepatology, Royal Perth Hospital, Perth, Australia
| | - Stuart K Roberts
- The Alfred Hospital and Monash University CCS, Melbourne, Australia
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5
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Capasso M, Cossiga V, Guarino M, Ranieri L, Morisco F. The Role of Hepatitis Viruses as Drivers of Hepatocancerogenesis. Cancers (Basel) 2024; 16:1505. [PMID: 38672587 PMCID: PMC11048534 DOI: 10.3390/cancers16081505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 04/08/2024] [Accepted: 04/12/2024] [Indexed: 04/28/2024] Open
Abstract
Recently, metabolic associated steatotic liver disease (MASLD) became the leading cause of chronic liver disease worldwide and one of the most frequent causes of hepatocellular carcinoma (HCC). Nonetheless, in this epidemiological trend, viral hepatitis remains the major driver in hepatic carcinogenesis. Globally, hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma, with an overall attributable risk of approximately 40%, followed by hepatitis C virus (HCV), which accounts for 28-30% of cases, with significant geographic variations between the Eastern and Western world. Considering all the etiologies, HCC risk increases proportionally with the progression of liver disease, but the risk is consistently higher in patients with viral triggers. This evidence indicates that both direct (due to the oncogenic properties of the viruses) and indirect (through the mechanisms of chronic inflammation that lead to cirrhosis) mechanisms are involved, alongside the presence of co-factors contributing to liver damage (smoking, alcohol, and metabolic factors) that synergistically enhance the oncogenic process. The aim of this review is to analyze the oncogenic role of hepatitis viruses in the liver, evaluating epidemiological changes and direct and indirect viral mechanisms that lead to liver cancer.
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Affiliation(s)
| | - Valentina Cossiga
- Diseases of the Liver and Biliary System Unit, Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy; (M.C.); (M.G.); (L.R.); (F.M.)
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6
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Groß S, Bitzer M, Albert J, Blödt S, Boda-Heggemann J, Brunner T, Caspari R, De Toni E, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Krug D, La Fougère C, Lang H, Langer T, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Nothacker M, Ockenga J, Oldhafer K, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ritterbusch U, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Tholen R, Trojan J, van Thiel I, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wildner D, Wörns MA, Galle P, Malek N. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:e213-e282. [PMID: 38364849 DOI: 10.1055/a-2189-8567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/18/2024]
Affiliation(s)
- Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | - Susanne Blödt
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein, Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | | | - Markus Follmann
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e. V., Berlin
| | | | - Cihan Gani
- Klinik für Radioonkologie, Universitätsklinikum Tübingen
| | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Thomas Langer
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e. V., Berlin
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Eberhard-Karls Universität, Tübingen
| | | | - Monika Nothacker
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Klinik für Innere Medizin, Gesundheit Nord, Klinikverbund Bremen
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | | | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg
| | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Reina Tholen
- Deutscher Bundesverband für Physiotherapie (ZVK) e. V
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Arndt Vogel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
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7
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Bitzer M, Groß S, Albert J, Blödt S, Boda-Heggemann J, Brunner T, Caspari R, De Toni E, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Krug D, Fougère CL, Lang H, Langer T, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Nothacker M, Ockenga J, Oldhafer K, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ritterbusch U, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Tholen R, Trojan J, van Thiel I, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wildner D, Wörns MA, Galle P, Malek N. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:e67-e161. [PMID: 38195102 DOI: 10.1055/a-2189-6353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2024]
Affiliation(s)
- Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | - Susanne Blödt
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V.(AWMF), Berlin
| | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | | | - Markus Follmann
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e. V., Berlin
| | | | - Cihan Gani
- Klinik für Radioonkologie, Universitätsklinikum Tübingen
| | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Thomas Langer
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e. V., Berlin
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Eberhard-Karls Universität, Tübingen
| | | | - Monika Nothacker
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V.(AWMF), Berlin
| | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Klinik für Innere Medizin, Gesundheit Nord, Klinikverbund Bremen
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | | | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | | | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Reina Tholen
- Deutscher Bundesverband für Physiotherapie (ZVK) e. V
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Arndt Vogel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
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8
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Renu K, Myakala H, Chakraborty R, Bhattacharya S, Abuwani A, Lokhandwala M, Vellingiri B, Gopalakrishnan AV. Molecular mechanisms of alcohol's effects on the human body: A review and update. J Biochem Mol Toxicol 2023; 37:e23502. [PMID: 37578200 DOI: 10.1002/jbt.23502] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Revised: 07/18/2023] [Accepted: 07/31/2023] [Indexed: 08/15/2023]
Abstract
Alcohol consumption has been linked to numerous negative health outcomes although it has some beneficial effects on moderate dosages, the most severe of which being alcohol-induced hepatitis. The number of people dying from this liver illness has been shown to climb steadily over time, and its prevalence has been increasing. Researchers have found that alcohol consumption primarily affects the brain, leading to a wide range of neurological and psychological diseases. High-alcohol-consumption addicts not only experienced seizures, but also ataxia, aggression, social anxiety, and variceal hemorrhage that ultimately resulted in death, ascites, and schizophrenia. Drugs treating this liver condition are limited and can cause serious side effects like depression. Serine-threonine kinases, cAMP protein kinases, protein kinase C, ERK, RACK 1, Homer 2, and more have all been observed to have their signaling pathways disrupted by alcohol, and alcohol has also been linked to epigenetic changes. In addition, alcohol consumption induces dysbiosis by changing the composition of the microbiome found in the gastrointestinal tract. Although more studies are needed, those that have been done suggest that probiotics aid in keeping the various microbiota concentrations stable. It has been argued that reducing one's alcohol intake may seem less harmful because excessive drinking is a lifestyle disorder.
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Affiliation(s)
- Kaviyarasi Renu
- Department of Biochemistry, Centre of Molecular Medicine and Diagnostics (COMManD), Saveetha Dental College & Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu, India
| | - Haritha Myakala
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, India
| | - Rituraj Chakraborty
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, India
| | - Sharmishtha Bhattacharya
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, India
| | - Asmita Abuwani
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, India
| | - Mariyam Lokhandwala
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, India
| | - Balachandar Vellingiri
- Department of Zoology, Stem Cell and Regenerative Medicine/Translational Research, School of Basic Sciences, Central University of Punjab (CUPB), Bathinda, Punjab, India
| | - Abilash Valsala Gopalakrishnan
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, India
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9
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Stroffolini T, Stroffolini G. A Historical Overview on the Role of Hepatitis B and C Viruses as Aetiological Factors for Hepatocellular Carcinoma. Cancers (Basel) 2023; 15:cancers15082388. [PMID: 37190317 DOI: 10.3390/cancers15082388] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 04/14/2023] [Accepted: 04/19/2023] [Indexed: 05/17/2023] Open
Abstract
Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the leading cause of hepatocellular carcinoma (HCC) worldwide. Currently, HBV-related HCC predominates in Sub-Saharan Africa and South-East-Asia, while HCV-related HCC predominates in northern Africa and in the western world. Liver cirrhosis is the underlying condition in most HBV cases and in nearly all HCV cases. Several cofactors, viral and non-viral, play a role in the progression toward HCC: dual HBV/HCV infection, HDV, HIV, alcohol intake, smoking, diabetes mellitus, obesity, and NAFLD/NASH. HBV vaccine is effective in preventing both infection and HCC; antiviral drugs may suppress HBV replication and eradicate HCV infection, halting progression to HCC. Inequalities exist between high- and low-income countries with respect to vaccine availability and access to antivirals. These factors represent barriers to the control of HCC incidence. Lack of an effective vaccine against HCV is also a serious barrier to HCV elimination and HCC prevention. The most crucial steps and knowledge that have arisen over time on the association between the two major hepatotropic viruses and HCC are discussed in this historical review.
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Affiliation(s)
- Tommaso Stroffolini
- Department of Tropical and Infectious Diseases, Policlinico Umberto I, 00161 Rome, Italy
| | - Giacomo Stroffolini
- Department of Infectious-Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Via Don A. Sempreboni, 5, Negrar, 37024 Verona, Italy
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10
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Bitzer M, Groß S, Albert J, Boda-Heggemann J, Brunner T, Caspari R, De Toni E, Dombrowski F, Evert M, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Kautz A, Krug D, Fougère CL, Lang H, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Ockenga J, Oldhafer K, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ritterbusch U, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schuler A, Seehofer D, Sinn M, Stengel A, Stoll C, Tannapfel A, Taubert A, Tholen R, Trojan J, van Thiel I, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wildner D, Wörns MA, Galle P, Malek N. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:e92-e156. [PMID: 37040776 DOI: 10.1055/a-2026-1240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/13/2023]
Affiliation(s)
- Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | | | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | | | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschrirugie, Eberhard-Karls Universität, Tübingen
| | | | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Klinik für Innere Medizin, Gesundheit Nord, Klinikverbund Bremen
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | | | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | | | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Reina Tholen
- Deutscher Bundesverband für Physiotherapie (ZVK) e. V
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Arndt Vogel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
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11
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Deltenre P, Zanetto A, Saltini D, Moreno C, Schepis F. The role of transjugular intrahepatic portosystemic shunt in patients with cirrhosis and ascites: Recent evolution and open questions. Hepatology 2023; 77:640-658. [PMID: 35665949 DOI: 10.1002/hep.32596] [Citation(s) in RCA: 36] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 05/14/2022] [Accepted: 05/16/2022] [Indexed: 01/28/2023]
Abstract
In selected patients with cirrhosis and ascites, transjugular intrahepatic portosystemic shunt (TIPS) placement improves control of ascites and may reduce mortality. In this review, we summarize the current knowledge concerning the use of TIPS for the treatment of ascites in patients with cirrhosis, from pathophysiology of ascites formation to hemodynamic consequences, patient selection, and technical issues of TIPS insertion. The combination of these factors is important to guide clinical decision-making and identify the best strategy for each individual patient. There is still a need to identify the best timing for TIPS placement in the natural history of ascites (recurrent vs. refractory) as well as which type and level of renal dysfunction is acceptable when TIPS is proposed for the treatment of ascites in cirrhosis. Future studies are needed to define the optimal stent diameter according to patient characteristics and individual risk of shunt-related side effects, particularly hepatic encephalopathy and insufficient cardiac response to hemodynamic consequences of TIPS insertion.
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Affiliation(s)
- Pierre Deltenre
- Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology , CUB Hôpital Erasme, Université Libre de Bruxelles , Brussels , Belgium.,Department of Gastroenterology and Hepatology , CHU UCL Namur, Université Catholique de Louvain , Yvoir , Belgium.,Department of Gastroenterology and Hepatology , Clinique St Luc , Bouge , Belgium
| | - Alberto Zanetto
- Division of Gastroenterology, Hepatic Hemodynamic Laboratory , Azienda Ospedaliero-Universitaria di Modena, and University of Modena and Reggio Emilia , Modena , Italy.,Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology , Padova University Hospital , Padova , Italy
| | - Dario Saltini
- Division of Gastroenterology, Hepatic Hemodynamic Laboratory , Azienda Ospedaliero-Universitaria di Modena, and University of Modena and Reggio Emilia , Modena , Italy
| | - Christophe Moreno
- Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology , CUB Hôpital Erasme, Université Libre de Bruxelles , Brussels , Belgium.,Laboratory of Experimental Gastroenterology , Université Libre de Bruxelles , Brussels , Belgium
| | - Filippo Schepis
- Division of Gastroenterology, Hepatic Hemodynamic Laboratory , Azienda Ospedaliero-Universitaria di Modena, and University of Modena and Reggio Emilia , Modena , Italy
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12
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The Effect of Alcohol Consumption in Unresectable Hepatocellular Carcinoma with Transarterial Chemoembolization. JOURNAL OF ONCOLOGY 2022; 2022:7062105. [PMID: 36618073 PMCID: PMC9822749 DOI: 10.1155/2022/7062105] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Revised: 11/28/2022] [Accepted: 12/12/2022] [Indexed: 01/01/2023]
Abstract
Background Alcohol consumption can increase the risk of developing hepatocellular carcinoma (HCC). However, whether continuous alcohol consumption can influence outcomes in patients with HCC who undergo transarterial chemoembolization (TACE) remains unclear. This study aimed to explore the effect of alcohol consumption in patients with unresectable HCC who underwent TACE. Methods The data used in the study were obtained from two centers and were retrospectively reviewed between January, 2014, and December, 2021. 254 patients with TACE were included in this study. Among them, 101 patients were continuous alcohol consumers and 153 patients had alcohol abstinence. Propensity score matching (PSM) and competing risk analysis were used to reduce the selection bias. Results The median overall survival (mOS) and median progression-free survival (mPFS) in the alcohol consumers' group were longer than those in the alcohol abstinence group, before and after PSM. Multivariate regression analysis showed that alcohol consumption increased all-cause mortality risk (HR: 1.486, 95% CI: 1.074-2.055; P=0.016) and tumor progression risk (HR: 1.434, 95% CI: 1.091-1.886; P=0.01) more than that with alcohol abstinence. In the competing risk analysis, after excluding deaths caused by other reasons, alcohol consumption increased cancer-specific mortality risk more than alcohol abstinence did before and after PSM. Adverse event analysis showed that alcohol consumption increased the risk of all grades of nausea and vomiting and grade III or IV nausea more than alcohol abstinence did after patients underwent TACE. Conclusion Alcohol consumption may lead to a poor prognosis and increase adverse events in patients receiving TACE compared to those with alcohol abstinence.
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13
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Khanam A, Kottilil S. New Therapeutics for HCC: Does Tumor Immune Microenvironment Matter? Int J Mol Sci 2022; 24:ijms24010437. [PMID: 36613878 PMCID: PMC9820509 DOI: 10.3390/ijms24010437] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 12/21/2022] [Accepted: 12/22/2022] [Indexed: 12/28/2022] Open
Abstract
The incidence of liver cancer is continuously rising where hepatocellular carcinoma (HCC) remains the most common form of liver cancer accounting for approximately 80-90% of the cases. HCC is strongly prejudiced by the tumor microenvironment and being an inflammation-associated condition, the contribution of various immune mechanisms is critical in its development, progression, and metastasis. The tumor immune microenvironment is initially inflammatory which is subsequently replenished by the immunosuppressive cells contributing to tumor immune escape. Regardless of substantial advancement in systemic therapy, HCC has poor prognosis and outcomes attributed to the drug resistance, recurrence, and its metastatic behavior. Therefore, currently, new immunotherapeutic strategies are extensively targeted in preclinical and clinical settings in order to elicit robust HCC-specific immune responses and appear to be quite effective, extending current treatment alternatives. Understanding the complex interplay between the tumor and the immune cells and its microenvironment will provide new insights into designing novel immunotherapeutics to overcome existing treatment hurdles. In this review, we have provided a recent update on immunological mechanisms associated with HCC and discussed potential advancement in immunotherapies for HCC treatment.
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14
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Tümen D, Heumann P, Gülow K, Demirci CN, Cosma LS, Müller M, Kandulski A. Pathogenesis and Current Treatment Strategies of Hepatocellular Carcinoma. Biomedicines 2022; 10:3202. [PMID: 36551958 PMCID: PMC9775527 DOI: 10.3390/biomedicines10123202] [Citation(s) in RCA: 70] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 12/02/2022] [Accepted: 12/05/2022] [Indexed: 12/14/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most frequent liver cancer with high lethality and low five-year survival rates leading to a substantial worldwide burden for healthcare systems. HCC initiation and progression are favored by different etiological risk factors including hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, non-/and alcoholic fatty liver disease (N/AFLD), and tobacco smoking. In molecular pathogenesis, endogenous alteration in genetics (TP53, TERT, CTNNB1, etc.), epigenetics (DNA-methylation, miRNA, lncRNA, etc.), and dysregulation of key signaling pathways (Wnt/β-catenin, JAK/STAT, etc.) strongly contribute to the development of HCC. The multitude and complexity of different pathomechanisms also reflect the difficulties in tailored medical therapy of HCC. Treatment options for HCC are strictly dependent on tumor staging and liver function, which are structured by the updated Barcelona Clinic Liver Cancer classification system. Surgical resection, local ablative techniques, and liver transplantation are valid and curative therapeutic options for early tumor stages. For multifocal and metastatic diseases, systemic therapy is recommended. While Sorafenib had been the standalone HCC first-line therapy for decades, recent developments had led to the approval of new treatment options as first-line as well as second-line treatment. Anti-PD-L1 directed combination therapies either with anti-VEGF directed agents or with anti-CTLA-4 active substances have been implemented as the new treatment standard in the first-line setting. However, data from clinical trials indicate different responses on specific therapeutic regimens depending on the underlying pathogenesis of hepatocellular cancer. Therefore, histopathological examinations have been re-emphasized by current international clinical guidelines in addition to the standardized radiological diagnosis using contrast-enhanced cross-sectional imaging. In this review, we emphasize the current knowledge on molecular pathogenesis of hepatocellular carcinoma. On this occasion, the treatment sequences for early and advanced tumor stages according to the recently updated Barcelona Clinic Liver Cancer classification system and the current algorithm of systemic therapy (first-, second-, and third-line treatment) are summarized. Furthermore, we discuss novel precautional and pre-therapeutic approaches including therapeutic vaccination, adoptive cell transfer, locoregional therapy enhancement, and non-coding RNA-based therapy as promising treatment options. These novel treatments may prolong overall survival rates in regard with quality of life and liver function as mainstay of HCC therapy.
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Affiliation(s)
| | | | | | | | | | | | - Arne Kandulski
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases University Hospital Regensburg Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany
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15
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Gao Z, Wang D, Zhang H, Yang J, Li M, Lu H, Shen H, Tang Y. An iron-deficient diet prevents alcohol- or diethylnitrosamine-induced acute hepatotoxicity in mice by inhibiting ferroptosis. Curr Res Food Sci 2022; 5:2171-2177. [PMID: 36387594 PMCID: PMC9664348 DOI: 10.1016/j.crfs.2022.11.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 09/28/2022] [Accepted: 11/01/2022] [Indexed: 11/08/2022] Open
Abstract
The liver is easily injured by exogenous chemicals through reactive oxygen species (ROS), which lead to ferroptosis, a ROS-dependent programmed cell death characterized by iron accumulation and lipid peroxidation. However, whether iron restriction has a positive role in chemicals-induced liver injuries is unknown. The present study investigated the effects of an iron-deficient diet on liver injuries induced by alcohol or diethylnitrosamine (DEN). Mice were fed an iron-deficient diet for four weeks, then treated with three doses of alcohol (5 g/kg, 24 h interval, gavage) to mimic mild liver injury or five doses of DEN (50 mg/kg, 24 h interval, i. p.) to mimic severe liver failure. The results showed that mice were iron-deficient after four weeks of feeding. Interestingly, as evaluated by H&E staining of liver slices, liver/body weight ratio, serum ALT and AST, iron deficiency significantly alleviated liver injuries triggered by alcohol or DEN. The activities of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH), and the expression of CYP2E1 were increased by iron deficiency. Mechanistically, iron deficiency prevented the decrease of glutathione peroxidase 4 (GPX4), which eliminated malondialdehyde (MDA) by utilizing glutathione (GSH). In summary, alcohol- or DEN-induced liver injuries were mitigated by the iron-deficient diet by inhibiting ferroptosis, which might be a promising measure for preventing liver injuries induced by alcohol, DEN, or other exogenous chemicals.
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Affiliation(s)
- Zelong Gao
- Department of Nutrition, Second Military Medical University, Shanghai, China
| | - Dongyao Wang
- School of Pharmacy, Second Military Medical University, Shanghai, China
| | - Hongwei Zhang
- Department of Nutrition, Second Military Medical University, Shanghai, China
- Department of Clinical Nutrition, Zhumadian Second People's Hospital, Henan, China
| | - Jianxin Yang
- Department of Nutrition, Second Military Medical University, Shanghai, China
| | - Min Li
- Department of Nutrition, Second Military Medical University, Shanghai, China
| | - Hongtao Lu
- Department of Nutrition, Second Military Medical University, Shanghai, China
| | - Hui Shen
- Department of Nutrition, Second Military Medical University, Shanghai, China
| | - Yuxiao Tang
- Department of Nutrition, Second Military Medical University, Shanghai, China
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Bajaj JS, Nagy LE. Natural History of Alcohol-Associated Liver Disease: Understanding the Changing Landscape of Pathophysiology and Patient Care. Gastroenterology 2022; 163:840-851. [PMID: 35598629 PMCID: PMC9509416 DOI: 10.1053/j.gastro.2022.05.031] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 05/12/2022] [Accepted: 05/14/2022] [Indexed: 12/02/2022]
Abstract
Alcohol use and consequent liver disease are major burdens that have worsened during the COVID-19 pandemic. There are several facets to the pathophysiology and clinical consequences of alcohol-use disorder (AUD) and progression to alcohol-associated liver disease (ALD) that require a concerted effort by clinicians and translational and basic science investigators. Several recent advances from bedside to bench and bench to bedside have been made in ALD. We focused this review on a case-based approach that provides a human context to these important advances across the spectrum of ALD.
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Affiliation(s)
- Jasmohan S Bajaj
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, Virginia; Central Virginia Veterans Healthcare System, Richmond, Virginia.
| | - Laura E Nagy
- Center for Liver Disease Research, Departments of Inflammation and Immunity and Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio; Department of Molecular Medicine, Case Western Reserve University, Cleveland, Ohio
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The Hidden Epidemic: The Prevalence and Impact of Concurrent Liver Diseases in Patients Undergoing Liver Transplantation in Australia and New Zealand. Transplant Direct 2022; 8:e1345. [PMID: 37077731 PMCID: PMC10109460 DOI: 10.1097/txd.0000000000001345] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/31/2022] [Accepted: 04/18/2022] [Indexed: 11/26/2022] Open
Abstract
Prevalence of concurrent liver diseases among liver transplant recipients and impact on posttransplant outcomes are unknown. Methods This retrospective study included adult liver transplants between January 1' 1985' and December 31' 2019' from the Australian and New Zealand Liver and Intestinal Transplant Registry. Up to 4 liver disease causes were recorded for each transplant; concurrent liver diseases were defined as >1 liver disease indication for transplantation, excluding hepatocellular carcinoma. Impact on posttransplant survival was determined using Cox regression. Results A total of 840 (15%) of 5101 adult liver transplant recipients had concurrent liver diseases. Recipients with concurrent liver diseases were more likely male (78% versus 64%) and older (mean age 52 versus 50 y). A higher proportion of liver transplants for hepatitis B (12% versus 6%), hepatitis C (33% versus 20%), alcohol liver disease (23% versus 13%), and metabolic-associated fatty liver disease (11% versus 8%, all P < 0.001) were identified when all indications were included than with primary diagnosis only. The number and proportion of liver transplants performed for concurrent liver diseases have increased from 8 (6%) during Era 1 (1985-1989) to 302 (20%) during Era 7 (2015-2019; P < 0.001). Concurrent liver diseases were not associated with increased posttransplant mortality (adjusted hazard ratio, 0.98, 95% confidence interval, 0.84-1.14). Conclusions Concurrent liver diseases are increasing among adult liver transplant recipients in Australia and New Zealand; however, they do not appear to impact posttransplant survival. Reporting all liver disease causes in the transplant registry reports provides more accurate estimates of liver disease burden.
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Rattanasupar A, Chang A, Prateepchaiboon T, Pungpipattrakul N, Akarapatima K, Songjamrat A, Pakdeejit S, Prachayakul V, Piratvisuth T. Impact of alcohol consumption on treatment outcome of hepatocellular carcinoma patients with viral hepatitis who underwent transarterial chemoembolization. World J Hepatol 2022; 14:1162-1172. [PMID: 35978671 PMCID: PMC9258258 DOI: 10.4254/wjh.v14.i6.1162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 04/24/2022] [Accepted: 06/13/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Alcohol consumption increases the risk of hepatocellular carcinoma (HCC) in patients with pre-existing liver disease, including viral hepatitis. However, studies on the impact of alcohol consumption on the outcomes of HCC are limited. We hypothesized that alcohol had an additional effect with chronic viral hepatitis infection on treatment outcomes after transarterial chemoembolization (TACE) in patients with intermediate-stage HCC (Barcelona Clinical Liver Cancer [BCLC] -B). AIM To evaluate the additional effect of alcohol on treatment outcomes of TACE among HCC patients with viral hepatitis. METHODS This study, conducted at Hatyai Hospital in Thailand, included HCC patients over 18 years of age with chronic viral hepatitis. Records of HCC patients with viral hepatitis classified as BCLC-B who underwent TACE as the first treatment modality between 2014 and 2019 were retrospectively reviewed. Patients with chronic viral hepatitis only were categorized under group A, and those with chronic viral hepatitis and concurrent alcohol consumption were categorized under group B. Both groups were compared, and the Cox proportional-hazards model was used to identify the survival-influencing variables. RESULTS Of the 69 patients, 53 were categorized in group A and 16 in group B. There were no statistically significant differences in tumor characteristics between the two patient groups. However, Group A had a statistically significantly higher proportion of complete response (24.5% vs 0%, P = 0.030) and a higher median survival rate (26.2 mo vs 8.4 mo; log-rank P = 0.012) compared to group B. Factors associated with decreased survival in the proportional-hazards model included alcohol consumption (hazards ratio [HR], 2.377; 95% confidence interval [CI], 1.109-5.095; P = 0.026), presence of portal hypertension (HR, 2.578; 95%CI, 1.320-5.037; P = 0.006), largest tumor size > 5 cm (HR, 3.558; 95%CI, 1.824-6.939; P < 0.001), and serum alpha-fetoprotein level > 100 ng/mL (HR, 2.536; 95%CI, 1.377-4.670; P = 0.003). CONCLUSION In HCC BCLC B patients with chronic viral hepatitis, alcohol consumption is an independent risk factor for increased mortality and decreases the rate of complete response and survival after TACE.
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Affiliation(s)
- Attapon Rattanasupar
- Division of Gastroenterology, Department of Internal Medicine, Hatyai Hospital, Hatyai 90110, Songkhla, Thailand
| | - Arunchai Chang
- Division of Gastroenterology, Department of Internal Medicine, Hatyai Hospital, Hatyai 90110, Songkhla, Thailand.
| | | | | | - Keerati Akarapatima
- Division of Gastroenterology, Department of Internal Medicine, Hatyai Hospital, Hatyai 90110, Songkhla, Thailand
| | - Apiradee Songjamrat
- Division of Intervention Radiology, Department of Radiology, Hatyai Hospital, Hatyai 90110, Songkhla, Thailand
| | - Songklod Pakdeejit
- Division of Intervention Radiology, Department of Radiology, Hatyai Hospital, Hatyai 90110, Songkhla, Thailand
| | - Varayu Prachayakul
- Siriraj Gastrointestinal Endoscopy Center, Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkoknoi 10700, Bangkok, Thailand
| | - Teerha Piratvisuth
- NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Faculty of Medicine, Prince of Songkla University, Hatyai 90110, Songkhla, Thailand
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Immune-related biomarkers shared by inflammatory bowel disease and liver cancer. PLoS One 2022; 17:e0267358. [PMID: 35452485 PMCID: PMC9032416 DOI: 10.1371/journal.pone.0267358] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Accepted: 04/04/2022] [Indexed: 12/24/2022] Open
Abstract
It has been indicated that there is an association between inflammatory bowel disease (IBD) and hepatocellular carcinoma (HCC). However, the molecular mechanism underlying the risk of developing HCC among patients with IBD is not well understood. The current study aimed to identify shared genes and potential pathways and regulators between IBD and HCC using a system biology approach. By performing the different gene expression analyses, we identified 871 common differentially expressed genes (DEGs) between IBD and HCC. Of these, 112 genes overlapped with immune genes were subjected to subsequent bioinformatics analyses. The results revealed four hub genes (CXCL2, MMP9, SPP1 and SRC) and several other key regulators including six transcription factors (FOXC1, FOXL1, GATA2, YY1, ZNF354C and TP53) and five microRNAs (miR-124-3p, miR-34a-5p, miR-1-3p, miR-7-5p and miR-99b-5p) for these disease networks. Protein-drug interaction analysis discovered the interaction of the hub genes with 46 SRC-related and 11 MMP9- related drugs that may have a therapeutic effect on IBD and HCC. In conclusion, this study sheds light on the potential connecting mechanisms of HCC and IBD.
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20
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Semmler G, Meyer EL, Kozbial K, Schwabl P, Hametner-Schreil S, Zanetto A, Bauer D, Chromy D, Simbrunner B, Scheiner B, Stättermayer AF, Pinter M, Schöfl R, Russo FP, Greenfield H, Schwarz M, Schwarz C, Gschwantler M, Alonso López S, Manzano ML, Ahumada A, Bañares R, Pons M, Rodríguez-Tajes S, Genescà J, Lens S, Trauner M, Ferenci P, Reiberger T, Mandorfer M. HCC risk stratification after cure of hepatitis C in patients with compensated advanced chronic liver disease. J Hepatol 2022; 76:812-821. [PMID: 34871626 DOI: 10.1016/j.jhep.2021.11.025] [Citation(s) in RCA: 86] [Impact Index Per Article: 28.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 11/15/2021] [Accepted: 11/21/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality in patients with advanced chronic liver disease (ACLD) caused by chronic hepatitis C who have achieved sustained virologic response (SVR). We developed risk stratification algorithms for de novo HCC development after SVR and validated them in an independent cohort. METHODS We evaluated the occurrence of de novo HCC in a derivation cohort of 527 patients with pre-treatment ACLD and SVR to interferon-free therapy, in whom alpha-fetoprotein (AFP) and non-invasive surrogates of portal hypertension including liver stiffness measurement (LSM) were assessed pre-/post-treatment. We validated our results in 1,500 patients with compensated ACLD (cACLD) from other European centers. RESULTS During a median follow-up (FU) of 41 months, 22/475 patients with cACLD (4.6%, 1.45/100 patient-years) vs. 12/52 decompensated patients (23.1%, 7.00/100 patient-years, p <0.001) developed de novo HCC. Since decompensated patients were at substantial HCC risk, we focused on cACLD for all further analyses. In cACLD, post-treatment-values showed a higher discriminative ability for patients with/without de novo HCC development during FU than pre-treatment values or absolute/relative changes. Models based on post-treatment AFP, alcohol consumption (optional), age, LSM, and albumin, accurately predicted de novo HCC development (bootstrapped Harrel's C with/without considering alcohol: 0.893/0.836). Importantly, these parameters also provided independent prognostic information in competing risk analysis and accurately stratified patients into low- (~2/3 of patients) and high-risk (~1/3 of patients) groups in the derivation (algorithm with alcohol consumption; 4-year HCC-risk: 0% vs. 16.5%) and validation (3.3% vs. 17.5%) cohorts. An alternative approach based on alcohol consumption (optional), age, LSM, and albumin (i.e., without AFP) also showed a robust performance. CONCLUSIONS Simple algorithms based on post-treatment age/albumin/LSM, and optionally, AFP and alcohol consumption, accurately stratified patients with cACLD based on their risk of de novo HCC after SVR. Approximately two-thirds were identified as having an HCC risk <1%/year in both the derivation and validation cohort, thereby clearly falling below the cost-effectiveness threshold for HCC surveillance. LAY SUMMARY Simple algorithms based on age, alcohol consumption, results of blood tests (albumin and α-fetoprotein), as well as liver stiffness measurement after the end of hepatitis C treatment identify a large proportion (approximately two-thirds) of patients with advanced but still asymptomatic liver disease who are at very low risk (<1%/year) of liver cancer development, and thus, might not need to undergo 6-monthly liver ultrasound.
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Affiliation(s)
- Georg Semmler
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Elias Laurin Meyer
- Institute for Medical Statistics, Center for Medical Statistics, Informatics and Intelligent Systems, Medical University Vienna, Vienna, Austria
| | - Karin Kozbial
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Philipp Schwabl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | | | - Alberto Zanetto
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padua University Hospital, Padua, Italy
| | - David Bauer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - David Chromy
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Benedikt Simbrunner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Bernhard Scheiner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Albert F Stättermayer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Matthias Pinter
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Rainer Schöfl
- Internal Medicine IV, Ordensklinikum Linz Barmherzige Schwestern, Linz, Austria
| | - Francesco Paolo Russo
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Helena Greenfield
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Michael Schwarz
- Department of Gastroenterology and Hepatology, Klinikum Ottakring, Vienna, Austria
| | - Caroline Schwarz
- Department of Gastroenterology and Hepatology, Klinikum Ottakring, Vienna, Austria
| | - Michael Gschwantler
- Department of Gastroenterology and Hepatology, Klinikum Ottakring, Vienna, Austria
| | - Sonia Alonso López
- Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto De Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | | | - Adriana Ahumada
- Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Rafael Bañares
- Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto De Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; Universidad Complutense de Madrid, Madrid, Spain; Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Mònica Pons
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Sergio Rodríguez-Tajes
- Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Liver Unit, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Joan Genescà
- Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Sabela Lens
- Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Liver Unit, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Peter Ferenci
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
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21
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Yu J, Zhang W, Ding D, Hu Y, Guo G, Wang J, Han Y. Bioinformatics Analysis Combined With Experiments Predicts PUDP as a Potential Prognostic Biomarker for Hepatocellular Carcinoma Through Its Interaction With Tumor Microenvironment. Front Oncol 2022; 12:830174. [PMID: 35350563 PMCID: PMC8957838 DOI: 10.3389/fonc.2022.830174] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 02/15/2022] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the deadliest tumors in the world and is notorious for poor prognosis. There is mounting evidence that pseudouridine performs key functions in the initiation and progression of several cancers. A previous study demonstrated that Pseudouridine 5’-phosphatase (PUDP) may be a novel prognostic biomarker in colorectal cancer. However, in the past, we have paid little attention to PUDP and we are still not clear about its function and role in cancer. In this study, a pan-cancer analysis of PUDP expression and prognosis was performed firstly using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data and we found that PUDP may be a potential oncogene for HCC. Then the most potential upstream microRNA contributing to PUDP was identified as let-7c-5p through expression analysis, correlation analysis, and survival analysis. Subsequently, the result of single cell RNA sequencing (scRNA-seq) demonstrated that PUDP was significantly highly expressed on malignant cells. In addition, there are significantly positive correlations between PUDP and tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression, especially with tumor-promoting immune cells such as T cell regulatory (Treg), Myeloid-derived suppressor cell (MDSC), cancer-associated fibroblast (CAF). Moreover, we found the methylation level of three loci was positively correlated with PUDP expression and four loci were negatively correlated. 15 pairs of HCC and normal adjacent tissues from HCC patients who were treated at our center were used to verify the results of the bioinformatics analysis and the results of experiments are similar to the bioinformatics analysis. Our study demonstrated that HCC patients with high PUDP expression are less likely to benefit from immunotherapy, and in addition, we explored the relationship between PUDP and anticancer drugs. Finally, we explored the clinical relevance of PUDP, identified PUDP as an independent risk factor for HCC patients and constructed a prognostic model, used International Cancer Genome Consortium (ICGC) data to do external validation. Collectively, our study demonstrated that high expression of PUDP suggested a poor prognosis and low response to immunotherapy, providing new insight into the treatment and prognosis of HCC.
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Affiliation(s)
- Jiahao Yu
- State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, China
| | - Weirui Zhang
- Department of Biomedical Engineering, The Fourth Military Medical University, Xi'an, China
| | - Dawei Ding
- State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, China
| | - Yinan Hu
- State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, China
| | - Guanya Guo
- State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, China
| | - Jingbo Wang
- State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, China
| | - Ying Han
- State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, China
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22
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Song C, Lv J, Yu C, Zhu M, Yu C, Guo Y, Yang L, Chen Y, Chen Z, Jiang T, Ma H, Jin G, Shen H, Hu Z, Li L. Adherence to Healthy Lifestyle and Liver cancer in Chinese: a prospective cohort study of 0.5 million people. Br J Cancer 2022; 126:815-821. [PMID: 34853434 PMCID: PMC8888610 DOI: 10.1038/s41416-021-01645-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 09/02/2021] [Accepted: 11/17/2021] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Little prospective evidence exists about whether a combination of healthy lifestyle factors is related to a considerable reduction of liver cancer risk. METHODS Based on the prospective China Kadoorie Biobank (CKB) cohort with a total of 492,640 Chinese adults, we examined the associations of five lifestyle factors with risk of liver cancer. Low-risk lifestyle factors were defined as non-smoking, non-drinking, median or higher level of physical activity, a healthy diet, and waist-to-hip ratio (WHR) < 0.90 for men and <0.85 for women. RESULTS During a median of 10.12 years of follow-up, 2529 liver cancer events were observed. There was a significant decrease in liver cancer risk with the increasing of the healthy lifestyle index scores (P < 0.001). Participants with a favourable lifestyle (4 or 5 healthy lifestyle factors) had a 43% reduced liver cancer risk compared with those with an unfavourable lifestyle (0 or 1 healthy lifestyle factor) (HR, 0.57 [95% CI, 0.47-0.68]). The cumulative protective effect of a healthy lifestyle on liver cancer appeared to be more dramatic for patients with hepatitis B surface antigen (HBsAg) positive, the individuals at high risk of liver cancer. CONCLUSIONS Individuals adhering to a favourable lifestyle was associated with a considerable absolute risk reduction of liver cancer.
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Affiliation(s)
- Ci Song
- Department of Epidemiology, China International Cooperation Center on Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, China
| | - Jun Lv
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, 100191, China
- Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing, 100191, China
| | - Chengxiao Yu
- Department of Epidemiology, China International Cooperation Center on Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, China
- The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215008, China
| | - Meng Zhu
- Department of Epidemiology, China International Cooperation Center on Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, China
| | - Canqing Yu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, 100191, China
- Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing, 100191, China
| | - Yu Guo
- Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Ling Yang
- Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Yiping Chen
- Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Zhengming Chen
- Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Tao Jiang
- Department of Epidemiology, China International Cooperation Center on Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, China
| | - Hongxia Ma
- Department of Epidemiology, China International Cooperation Center on Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, China
| | - Guangfu Jin
- Department of Epidemiology, China International Cooperation Center on Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, China
| | - Hongbing Shen
- Department of Epidemiology, China International Cooperation Center on Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, China
| | - Zhibin Hu
- Department of Epidemiology, China International Cooperation Center on Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, China.
| | - Liming Li
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, 100191, China.
- Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing, 100191, China.
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23
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Chen F, Wang J, Wu Y, Gao Q, Zhang S. Potential Biomarkers for Liver Cancer Diagnosis Based on Multi-Omics Strategy. Front Oncol 2022; 12:822449. [PMID: 35186756 PMCID: PMC8851237 DOI: 10.3389/fonc.2022.822449] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 01/17/2022] [Indexed: 12/11/2022] Open
Abstract
Liver cancer is the fourth leading cause of cancer-related death worldwide. Hepatocellular carcinoma (HCC) accounts for about 85%-90% of all primary liver malignancies. However, only 20-30% of HCC patients are eligible for curative therapy mainly due to the lack of early-detection strategies, highlighting the significance of reliable and accurate biomarkers. The integration of multi-omics became an important tool for biomarker screening and unique alterations in tumor-associated genes, transcripts, proteins, post-translational modifications and metabolites have been observed. We here summarized the novel biomarkers for HCC diagnosis based on multi-omics technology as well as the clinical significance of these potential biomarkers in the early detection of HCC.
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Affiliation(s)
- Fanghua Chen
- Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China
| | - Junming Wang
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China
| | - Yingcheng Wu
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China
| | - Qiang Gao
- Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China
| | - Shu Zhang
- Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China
- *Correspondence: Shu Zhang,
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24
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Precision Medicine for Hepatocellular Carcinoma: Clinical Perspective. J Pers Med 2022; 12:jpm12020149. [PMID: 35207638 PMCID: PMC8879044 DOI: 10.3390/jpm12020149] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Revised: 01/19/2022] [Accepted: 01/20/2022] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the major malignant diseases worldwide, characterized by growing incidence and high mortality rates despite apparent improvements in surveillance programs, diagnostic and treatment procedures, molecular therapies, and numerous research initiatives. Most HCCs occur in patients with liver cirrhosis, and the competing mortality risks from the tumor and the cirrhosis should be considered. Presently, previously identified risk factors, such as hepatitis virus infection, hepatic inflammation and fibrosis, and metabolic syndrome, may be used as chemoprevention targets. The application of precision medicine for HCC management challenges the one-size-fits-all concept; moreover, patients should no longer be treated entirely according to the histology of their tumor but based on molecular targets specific to their tumor biology. Next-generation sequencing emphasizes HCC molecular heterogeneity and aids our comprehension of possible vulnerabilities that can be exploited. Moreover, genetic sequencing as part of a precision medicine concept may work as a promising tool for postoperative cancer monitoring. The use of genetic and epigenetic markers to identify therapeutic vulnerability could change the diagnosis and treatment of HCC, which so far was based on Barcelona clinic liver cancer (BCLC) staging. In daily clinical practice, the shift from a stage-oriented to a therapeutic-oriented approach is needed to direct the choice of HCC treatment toward the potentially most effective option on an individual basis. The important factor in precision medicine is the promotion of patient management based on the individual approach, knowing that the final decision must be approved by a multidisciplinary expert team.
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25
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Sabrina V, Michael B, Jörg A, Peter B, Wolf B, Susanne B, Thomas B, Frank D, Matthias E, Markus F, Christian LF, Paul F, Andreas G, Eleni G, Martin G, Elke H, Thomas H, Ralf-Thorsten H, Wolf-Peter H, Peter H, Achim K, Gabi K, Jürgen K, David K, Frank L, Hauke L, Thomas L, Philipp L, Andreas M, Alexander M, Oliver M, Silvio N, Huu Phuc N, Johann O, Karl-Jürgen O, Philipp P, Kerstin P, Philippe P, Thorsten P, Mathias P, Ruben P, Jürgen P, Jutta R, Peter R, Johanna R, Ulrike R, Elke R, Barbara S, Peter S, Irene S, Andreas S, Dietrich VS, Daniel S, Marianne S, Alexander S, Andreas S, Nadine S, Christian S, Andrea T, Anne T, Jörg T, Ingo VT, Reina T, Arndt V, Thomas V, Hilke V, Frank W, Oliver W, Heiner W, Henning W, Dane W, Christian W, Marcus-Alexander W, Peter G, Nisar M. S3-Leitlinie: Diagnostik und Therapie des hepatozellulären Karzinoms. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:e56-e130. [PMID: 35042248 DOI: 10.1055/a-1589-7568] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Voesch Sabrina
- Medizinische Klinik I, Universitätsklinikum Tübingen, Tübingen
| | - Bitzer Michael
- Medizinische Klinik I, Universitätsklinikum Tübingen, Tübingen
| | - Albert Jörg
- Abteilung für Gastroenterologie, Hepatologie und Endokrinologie, Stuttgart
| | | | - Bechstein Wolf
- Klinik für Allgemein-, Viszeral-, Transplantations- und Thoraxchirurgie, Universitätsklinikum Frankfurt, Frankfurt am Main
| | | | - Brunner Thomas
- Klinik für Strahlentherapie, Universitätsklinikum Magdeburg A. ö. R., Magdeburg
| | - Dombrowski Frank
- Institut für Pathologie, Universitätsmedizin Greifswald, Greifswald
| | | | - Follmann Markus
- Office des Leitlinienprogrammes Onkologie, c/o Deutsche Krebsgesellschaft e.V. Berlin
| | | | | | - Geier Andreas
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg
| | - Gkika Eleni
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg, Freiburg
| | | | - Hammes Elke
- Lebertransplantierte Deutschland e. V., Ansbach
| | - Helmberger Thomas
- Institut für Radiologie, Neuroradiologie und minimal-invasive Therapie, München Klinik Bogenhausen, München
| | | | - Hofmann Wolf-Peter
- Gastroenterologie am Bayerischen Platz, medizinisches Versorgungszentrum, Berlin
| | | | | | - Knötgen Gabi
- Konferenz onkologischer Kranken- und Kinderkrankenpflege, Hamburg
| | - Körber Jürgen
- Klinik Nahetal, Fachklinik für onkologische Rehabilitation und Anschlussrehabilitation, (AHB), Bad Kreuznach
| | - Krug David
- Klinik für Strahlentherapie, Universitätsklinikum Schleswig-Holstein, Kiel
| | | | - Lang Hauke
- Klinik für Allgemein-, Viszeral und Transplantationschirurgie, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz
| | - Langer Thomas
- Office des Leitlinienprogrammes Onkologie, c/o Deutsche Krebsgesellschaft e.V. Berlin
| | - Lenz Philipp
- Universitätsklinikum Münster, Zentrale Einrichtung Palliativmedizin, Münster
| | - Mahnken Andreas
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Gießen und Marburg GmbH, Marburg
| | - Meining Alexander
- Medizinische Klinik und Poliklinik II des Universitätsklinikums Würzburg, Würzburg
| | - Micke Oliver
- Klinik für Strahlentherapie und Radioonkologie, Franziskus Hospital Bielefeld, Bielefeld
| | - Nadalin Silvio
- Universitätsklinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Tübingen, Tübingen
| | | | | | - Oldhafer Karl-Jürgen
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Semmelweis Universität, Asklepios Campus Hamburg, Hamburg
| | - Paprottka Philipp
- Abteilung für interventionelle Radiologie, Klinikum rechts der Isar der Technischen Universität München, München
| | - Paradies Kerstin
- Konferenz onkologischer Kranken- und Kinderkrankenpflege, Hamburg
| | - Pereira Philippe
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, Klinikum am Gesundbrunnen, SLK-Kliniken Heilbronn GmbH, Heilbronn
| | - Persigehl Thorsten
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln, Köln
| | | | | | - Pohl Jürgen
- Interventionelles Endoskopiezentrum und Schwerpunkt Gastrointestinale Onkologie, Asklepios Klinik Altona, Hamburg
| | - Riemer Jutta
- Lebertransplantierte Deutschland e. V., Bretzfeld
| | - Reimer Peter
- Institut für diagnostische und interventionelle Radiologie, Städtisches Klinikum Karlsruhe gGmbH, Karlsruhe
| | - Ringwald Johanna
- Psychosomatische Medizin und Psychotherapie, Universitätsklinikum Tübingen, Tübingen
| | | | - Roeb Elke
- Medizinische Klinik II, Universitätsklinikum Gießen und Marburg GmbH, Gießen
| | - Schellhaas Barbara
- Medizinische Klinik I, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen
| | - Schirmacher Peter
- Pathologisches Institut, Universitätsklinikum Heidelberg, Heidelberg
| | - Schmid Irene
- Zentrum Pädiatrische Hämatologie und Onkologie, Dr. von Haunersches Kinderspital, Klinikum der Universität München, München
| | | | | | - Seehofer Daniel
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig
| | - Sinn Marianne
- Medizinische Klinik II, Universitätsklinikum Hamburg-Eppendorf, Hamburg
| | | | - Stengel Andreas
- Psychosomatische Medizin und Psychotherapie, Universitätsklinikum Tübingen, Tübingen
| | | | | | - Tannapfel Andrea
- Institut für Pathologie der Ruhr-Universität Bochum am Berufsgenossenschaftlichen Universitätsklinikum Bergmannsheil, Bochum
| | - Taubert Anne
- Kliniksozialdienst, Universitätsklinikum Heidelberg, Bochum
| | - Trojan Jörg
- Medizinische Klinik I, Universitätsklinikum Frankfurt, Frankfurt am Main
| | | | - Tholen Reina
- Deutscher Verband für Physiotherapie e. V., Köln
| | - Vogel Arndt
- Klinik für Gastroenterologie, Hepatologie, Endokrinologie der Medizinischen Hochschule Hannover, Hannover
| | - Vogl Thomas
- Universitätsklinikum Frankfurt, Institut für Diagnostische und Interventionelle Radiologie, Frankfurt
| | - Vorwerk Hilke
- Klinik für Strahlentherapie, Universitätsklinikum Gießen und Marburg GmbH, Marburg
| | - Wacker Frank
- Institut für Diagnostische und Interventionelle Radiologie der Medizinischen Hochschule Hannover, Hannover
| | - Waidmann Oliver
- Medizinische Klinik I, Universitätsklinikum Frankfurt, Frankfurt am Main
| | - Wedemeyer Heiner
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie Medizinische Hochschule Hannover, Hannover
| | - Wege Henning
- I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg
| | - Wildner Dane
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Lauf an der Pegnitz
| | | | | | - Galle Peter
- I. Medizinische Klinik und Poliklinik, Universitätsklinikum Mainz, Mainz
| | - Malek Nisar
- Medizinische Klinik I, Universitätsklinikum Tübingen, Tübingen
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Diao P, Jia F, Wang X, Hu X, Kimura T, Nakajima T, Aoyama T, Moriya K, Koike K, Tanaka N. Mechanisms of Steatosis-Derived Hepatocarcinogenesis: Lessons from HCV Core Gene Transgenic Mice. ENGINEERING 2021; 7:1797-1805. [DOI: 10.1016/j.eng.2021.08.019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/11/2025]
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Xu HQ, Wang CG, Zhou Q, Gao YH. Effects of alcohol consumption on viral hepatitis B and C. World J Clin Cases 2021; 9:10052-10063. [PMID: 34904075 PMCID: PMC8638036 DOI: 10.12998/wjcc.v9.i33.10052] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 04/15/2021] [Accepted: 08/25/2021] [Indexed: 02/06/2023] Open
Abstract
The liver is the main target organ for hepatitis viruses and the vital organ for alcohol metabolism. These two factors of viral hepatitis and alcohol abuse in combination can exert dual harmful actions, leading to enhanced damage to the liver. Epidemiological studies have revealed a higher prevalence of hepatitis C virus (HCV) infection among alcoholics than the general population. The interaction of alcohol with viral hepatitis [e.g., hepatitis B virus (HBV), HCV] and the underlying mechanisms are not fully understood. The effects of alcohol on viral hepatitis include promoted viral replication, weakened immune response, and increased oxidative stress. Clinically, alcohol abuse is correlated with an increased risk of developing end-stage liver cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis B and C, suggesting that the combination of alcohol and HBV/HCV lead to more severe liver damage. The influence of mild to moderate alcohol drinking on the HBV-induced liver fibrosis, cirrhosis, and hepatocellular carcinoma among patients infected with HBV remains unclear. Unlike HBV infected patients, no safe level of alcohol intake has been established for patients with HCV. Even light to moderate alcohol use can exert a synergistic effect with viral hepatitis, leading to the rapid progression of liver disease. Furthermore, interferon-based therapy is less effective in alcohol drinkers than in control patients, even after abstinence from alcohol for a period of time. Therefore, abstaining from alcohol is highly recommended to protect the liver, especially in individuals with HBV/HCV infection, to improve the clinical efficacy of antiviral treatment and prevent the rapid progression of chronic viral hepatitis.
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Affiliation(s)
- Hong-Qin Xu
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun 130021, Jilin Province, China
| | - Chun-Guang Wang
- Department of Surgery, The Second Hospital of Jilin University, Jilin University, Changchun 130041, Jilin Province, China
| | - Qiang Zhou
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun 130021, Jilin Province, China
| | - Yan-Hang Gao
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun 130021, Jilin Province, China
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Pearson MM, Kim NJ, Berry K, Moon AM, Su F, Vutien P, Green PK, Williams EC, Ioannou GN. Associations Between Alcohol Use and Liver-Related Outcomes in a Large National Cohort of Patients With Cirrhosis. Hepatol Commun 2021; 5:2080-2095. [PMID: 34601829 PMCID: PMC8631097 DOI: 10.1002/hep4.1776] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 05/10/2021] [Accepted: 06/13/2021] [Indexed: 11/11/2022] Open
Abstract
Alcohol use can cause hepatic necroinflammation and worsening portal hypertension in patients with cirrhosis. We aimed to evaluate the associations between degree of alcohol use and clinical liver‐related outcomes according to etiology of cirrhosis. In this retrospective cohort analysis, 44,349 U.S. veterans with cirrhosis from alcohol‐associated liver disease (ALD), chronic hepatitis C virus (HCV) infection, or nonalcoholic fatty liver disease were identified who completed the Alcohol Use Disorders Identification Test Consumption questionnaire in 2012. Based on this score, level of alcohol use was categorized as none, low level, or unhealthy. Multivariable Cox proportional hazards regression was used to assess for associations between alcohol use and mortality, cirrhosis decompensation (new ascites, encephalopathy, or variceal bleeding), and hepatocellular carcinoma (HCC). At baseline, 36.4% of patients endorsed alcohol use and 17.1% had unhealthy alcohol use. During a mean 4.9 years of follow‐up, 25,806 (57.9%) patients died, 9,409 (21.4%) developed a new decompensation, and 4,733 (11.1%) developed HCC. In patients with ALD‐cirrhosis and HCV‐cirrhosis, unhealthy alcohol use, compared with no alcohol use, was associated with higher risks of mortality (adjusted hazard ratio [aHR] = 1.13, 95% confidence interval [CI] = 1.07‐1.19 and aHR = 1.14, 95% CI = 1.08‐1.20, respectively) and decompensation (aHR = 1.18, 95% CI = 1.07‐1.30 and aHR = 1.08, 95% CI = 1.00‐1.16, respectively). Alcohol use was not associated with HCC, regardless of cirrhosis etiology. Conclusion: Unhealthy alcohol use was common in patients with cirrhosis and was associated with higher risks of mortality and cirrhosis decompensation in patients with HCV‐cirrhosis and ALD‐cirrhosis. Therefore, health care providers should make every effort to help patients achieve abstinence. The lack of association between alcohol use and HCC merits further investigation.
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Affiliation(s)
- Meredith M Pearson
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, WA, USA
| | - Nicole J Kim
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, WA, USA
| | - Kristin Berry
- Health Service Research and Development, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA
| | - Andrew M Moon
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
| | - Feng Su
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, WA, USA
| | - Philip Vutien
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, WA, USA
| | - Pamela K Green
- Health Service Research and Development, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA
| | - Emily C Williams
- Health Service Research and Development, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA.,Department of Health Services, University of Washington, Seattle, WA, USA
| | - George N Ioannou
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, WA, USA.,Division of Gastroenterology, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA
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Alcohol consumption increases the incidence of hepatocellular carcinoma in patients with hepatitis B cirrhosis but not in patients with hepatitis C cirrhosis. Eur J Gastroenterol Hepatol 2021; 33:1218-1221. [PMID: 32658012 DOI: 10.1097/meg.0000000000001837] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Liver cirrhosis and hepatocellular carcinoma (HCC) are common diseases in developing countries. HCC is a serious consequence of liver cirrhosis. METHODS A total of 1095 decompensated hepatic cirrhotic patients admitted to our hospital were enrolled from September 2014 to August 2019. We described the components of cirrhotic etiology. We evaluated the impact of alcohol consumption on the incidence of HCC in patients with hepatitis B cirrhosis and hepatitis C cirrhosis. RESULTS Among all cirrhotic patients admitted, the constituent ratios of hepatitis B cirrhosis and alcohol cirrhosis were 31.32% and 30.32%, respectively. The HCC incidence was higher in patients with hepatitis cirrhosis than in those with alcohol cirrhosis (24.2% in hepatitis B, 17.5% in hepatitis C and 3.92% in alcohol, P < 0.05). The HCC incidence in patients with concomitant hepatitis B virus (HBV) and alcohol consumption was higher than that in patients with HBV alone (33.70% vs. 20.72%, P < 0.05). CONCLUSION Hepatitis B and alcohol were major etiologies for cirrhotic patients. Alcohol consumption increased the incidence of HCC in patients with hepatitis B cirrhosis but not in patients with hepatitis C cirrhosis.
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Minami T, Tateishi R, Fujiwara N, Nakagomi R, Nakatsuka T, Sato M, Uchino K, Enooku K, Nakagawa H, Fujinaga H, Izumiya M, Hanajiri K, Asaoka Y, Kondo Y, Tanaka Y, Otsuka M, Ohki T, Arai M, Tanaka A, Yasuda K, Miura H, Ogata I, Kamoshida T, Inoue K, Koike Y, Akamatsu M, Mitsui H, Fujie H, Ogura K, Yoshida H, Wada T, Kurai K, Maekawa H, Obi S, Teratani T, Masaki N, Nagashima K, Ishikawa T, Kato N, Moriya K, Yotsuyanagi H, Koike K. Impact of Obesity and Heavy Alcohol Consumption on Hepatocellular Carcinoma Development after HCV Eradication with Antivirals. Liver Cancer 2021; 10:309-319. [PMID: 34414119 PMCID: PMC8339497 DOI: 10.1159/000513705] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 12/08/2020] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND AND AIMS It remains unclear whether obesity increases the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C who achieved a sustained virological response (SVR) with antiviral therapy. METHODS In this multicenter cohort study, we enrolled patients with chronic hepatitis C who achieved SVR with interferon (IFN)-based therapy (IFN group) or direct-acting antiviral (DAA) therapy (DAA group) between January 1, 1990, and December 31, 2018. The patients underwent regular surveillance for HCC. Cumulative incidence of and the risk factors for HCC development after SVR were assessed using the Kaplan-Meier method and Cox proportional hazard regression analysis, respectively. RESULTS Among 2,055 patients (840 in the IFN group and 1,215 in the DAA group), 75 developed HCC (41 in the IFN group and 34 in the DAA group) during the mean observation period of 4.1 years. The incidence rates of HCC at 1, 2, and 3 years were 1.2, 1.9, and 3.0%, respectively. Multivariate analysis revealed that in addition to older age, lower albumin level, lower platelet count, higher alpha-fetoprotein level, and absence of dyslipidemia, obesity (body mass index ≥25 kg/m2) and heavy alcohol consumption (≥60 g/day) were independent risk factors for HCC development, with adjusted hazard ratio (HR) of 2.53 (95% confidence interval [CI]: 1.51-4.25) and 2.56 (95% CI: 1.14-5.75), respectively. The adjusted HR was not significant between the 2 groups (DAA vs. IFN; HR 1.19, 95% CI: 0.61-2.33). CONCLUSIONS Obesity and heavy alcohol consumption increased the risk of HCC development after SVR.
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Affiliation(s)
- Tatsuya Minami
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ryosuke Tateishi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Naoto Fujiwara
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ryo Nakagomi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Takuma Nakatsuka
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Masaya Sato
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Koji Uchino
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kenichiro Enooku
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hayato Nakagawa
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hidetaka Fujinaga
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Masashi Izumiya
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazuyuki Hanajiri
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- Department of Gastroenterology, Sanraku Hospital, Tokyo, Japan
| | - Yoshinari Asaoka
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Yuji Kondo
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- Department of Gastroenterology and Hepatology, Kyoundo Hospital, Tokyo, Japan
| | - Yasuo Tanaka
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Motoyuki Otsuka
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Takamasa Ohki
- Department of Gastroenterology, Mitsui Memorial Hospital, Tokyo, Japan
| | - Masahiro Arai
- Department of Gastroenterology, Toshiba General Hospital, Toshiba, Japan
| | - Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Kiyomi Yasuda
- Department of Gastroenterology, Kiyokawa Hospital, Tokyo, Japan
| | - Hideaki Miura
- Department of Gastroenterology, Tokyo Yamate Medical Center, Tokyo, Japan
| | - Itsuro Ogata
- Department of Gastroenterology, Kawakita General Hospital, Tokyo, Japan
| | - Toshiro Kamoshida
- Department of Gastroenterology, Hitachi General Hospital, Hitachi, Japan
| | - Kazuaki Inoue
- Department of Gastroenterology, Showa University Fujigaoka Hospital, Yokohama, Japan
| | - Yukihiro Koike
- Department of Gastroenterology, Kanto Central Hospital of the Mutual Aid Association of Public School Teacher, Tokyo, Japan
| | | | - Hiroshi Mitsui
- Department of Gastroenterology, Tokyo Teishin Hospital, Tokyo, Japan
| | - Hajime Fujie
- Department of Gastroenterology, Tokyo Shinjuku Medical Center, Tokyo, Japan
| | - Keiji Ogura
- Department of Gastroenterology, Tokyo Metropolitan Police Hospital, Tokyo, Japan
| | - Hideo Yoshida
- Department of Gastroenterology, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Tomonori Wada
- Department of Gastroenterology, Sanraku Hospital, Tokyo, Japan
| | | | - Hisato Maekawa
- Department of Gastroenterology and Hepatology, Tokyo Takanawa Hospital, Tokyo, Japan
| | - Shuntaro Obi
- Department of Gastroenterology and Hepatology, Kyoundo Hospital, Tokyo, Japan
| | - Takuma Teratani
- Department of Hepato-Biliary-Pancreatic medicine, NTT Medical Center Tokyo, Tokyo, Japan
| | - Naohiko Masaki
- Clinical Laboratory Department, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan
| | - Kayo Nagashima
- Department of Gastroenterology, National Disaster Medical Center, Tachikawa, Japan
| | | | - Naoya Kato
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kyoji Moriya
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroshi Yotsuyanagi
- Division of Infectious Disease and Applied Immunology, The Institute of Medical Science Research Hospital, The University of Tokyo, Tokyo, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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Lou W, Wang W, Chen J, Wang S, Huang Y. ncRNAs-mediated high expression of SEMA3F correlates with poor prognosis and tumor immune infiltration of hepatocellular carcinoma. MOLECULAR THERAPY. NUCLEIC ACIDS 2021; 24:845-855. [PMID: 34026328 PMCID: PMC8121632 DOI: 10.1016/j.omtn.2021.03.014] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Accepted: 03/25/2021] [Indexed: 01/04/2023]
Abstract
Hepatocellular carcinoma (HCC) is notorious for its poor prognosis. Increasing evidence has demonstrated that semaphorin 3F (SEMA3F) plays key roles in initiation and progression of several types of human cancer. However, the specific role and mechanism of SEMA3F in HCC remains not fully determined. In this study, we first performed pan-cancer analysis for SEMA3F's expression and prognosis using The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) data and found that SEMA3F might be a potential oncogene in HCC. Subsequently, noncoding RNAs (ncRNAs) contributing to SEMA3F overexpression were identified by a combination of a series of in silico analyses, including expression analysis, correlation analysis, and survival analysis. Finally, the TMPO-AS1/SNHG16-let-7c-5p axis was identified as the most potential upstream ncRNA-related pathway of SEMA3F in HCC. Moreover, SEMA3F level was significantly positively associated with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression. Collectively, our findings elucidated that ncRNAs-mediated upregulation of SEMA3F correlated with poor prognosis and tumor immune infiltration in HCC.
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Affiliation(s)
- Weiyang Lou
- Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003 Zhejiang, China
| | - Wenlong Wang
- Intensive Care Unit, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, China
| | - Jing Chen
- Department of Oncology, The First Affiliated Hospital of Jiaxing University, Jiaxing, 314000 Zhejiang, China
| | - Shuqian Wang
- Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003 Zhejiang, China
| | - Yuan Huang
- Department of Breast Medical Oncology, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, 310022 Zhejiang, China
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Fouad Y, Lazarus JV, Negro F, Peck-Radosavljevic M, Sarin SK, Ferenci P, Esmat G, Ghazinian H, Nakajima A, Silva M, Lee S, Colombo M. MAFLD considerations as a part of the global hepatitis C elimination effort: an international perspective. Aliment Pharmacol Ther 2021; 53:1080-1089. [PMID: 33751604 DOI: 10.1111/apt.16346] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 02/17/2021] [Accepted: 03/09/2021] [Indexed: 12/09/2022]
Abstract
BACKGROUND The World Health Organization (WHO) set a goal to eliminate hepatitis C (HCV) infection globally by 2030, with specific targets to reduce new viral hepatitis infections by 80% and reduce related deaths by 65%. However, an overlooked aspect that may hinder these efforts is the impact other liver diseases could have by continuing to drive liver disease progression and offset the beneficial impact of DAAs on end-stage liver disease and hepatocellular carcinoma (HCC). In particular, the decrease in HCV prevalence has been countered by a marked increase in the prevalence of metabolic-associated fatty liver disease (MAFLD). AIMS To review the potential interaction of HCV and MAFLD. METHODS We have reviewed the literature relating to an arrange of interaction of HCV, metabolic dysfunction and MAFLD. RESULTS In this viewpoint, international experts suggest a holistic and multidisciplinary approach for the management of the growing number of treated HCV patients who achieved SVR, taking into consideration the overlooked impact of MAFLD for reducing morbidity and mortality in people who have had HCV. CONCLUSIONS This will strengthen and improve the continuum of care cascade for patients with liver disease(s) and holds the potential to alleviate the cost burden of disease; and increase quality of life for patients following DAAs treatment.
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Alcohol Intake and Mortality in Patients With Chronic Viral Hepatitis: A Nationwide Cohort Study. Am J Gastroenterol 2021; 116:329-335. [PMID: 33038136 DOI: 10.14309/ajg.0000000000000966] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Accepted: 08/26/2020] [Indexed: 12/11/2022]
Abstract
INTRODUCTION We evaluated the association between alcohol intake and all-cause and cause-specific mortality in subjects with chronic viral hepatitis, using nationwide population-based cohort study. METHODS A total of 364,361 men and women aged 40-84 years who underwent health screening examination between January 2002 and December 2013 that included assessment of frequency and amount of alcohol consumption were assessed for all-cause and cause-specific mortality. RESULTS In participants without chronic viral hepatitis, the fully adjusted hazard ratios (HRs) for all-cause mortality comparing light, moderate, and heavy drinkers with nondrinkers were 0.92 (95% confidence interval [CI] 0.87-0.98), 1.08 (95% CI 1.01-1.16), and 1.51 (95% CI 1.33-1.72), respectively. In participants with chronic viral hepatitis, the corresponding HRs were 1.19 (95% CI 1.05-1.36), 1.23 (95% CI 1.06-1.43), and 1.69 (95% CI 1.28-2.24), respectively (P value for alcohol intake by chronic viral hepatitis interaction <0.001). Compared with participants without chronic viral hepatitis, those with chronic viral hepatitis had substantially elevated liver cancer or liver disease (HR 10.85, 95% CI 9.74-12.09) and extrahepatic cancer mortality (HR 1.37, 95% CI 1.26-1.49). In patients with chronic viral hepatitis, the high mortality due to liver cancer or liver disease and the positive association of alcohol intake with liver cancer or liver disease mortality explained the positive association of alcohol intake with all-cause mortality. DISCUSSION Even light to moderate alcohol intake was associated with increased all-cause mortality in individuals with chronic viral hepatitis. Clinicians and public health campaigns should advise against any amount of alcohol intake in individuals with chronic viral hepatitis.
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Osna NA, Ganesan M, Seth D, Wyatt TA, Kidambi S, Kharbanda KK. Second hits exacerbate alcohol-related organ damage: an update. Alcohol Alcohol 2021; 56:8-16. [PMID: 32869059 PMCID: PMC7768623 DOI: 10.1093/alcalc/agaa085] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 06/09/2020] [Accepted: 07/31/2020] [Indexed: 02/05/2023] Open
Abstract
Chronic and excessive alcohol abuse cause direct and indirect detrimental effects on a wide range of body organs and systems and accounts for ~4% of deaths worldwide. Many factors influence the harmful effects of alcohol. This concise review presents newer insights into the role of select second hits in influencing the progression of alcohol-induced organ damage by synergistically acting to generate a more dramatic downstream biological defect. This review specifically addresses on how a lifestyle factor of high fat intake exacerbates alcoholic liver injury and its progression. This review also provides the mechanistic insights into how increasing matrix stiffness during liver injury promotes alcohol-induced fibrogenesis. It also discusses how hepatotropic viral (HCV, HBV) infections as well as HIV (which is traditionally not known to be hepatotropic), are potentiated by alcohol exposure to promote hepatotoxicity and fibrosis progression. Finally, this review highlights the impact of reactive aldehydes generated during alcohol and cigarette smoke coexposure impair innate antimicrobial defense and increased susceptibility to infections. This review was inspired by the symposium held at the 17th Congress of the European Society for Biomedical research on Alcoholism in Lille, France entitled 'Second hits in alcohol-related organ damage'.
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Affiliation(s)
- Natalia A Osna
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, Nebraska 68105, USA
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA
| | - Murali Ganesan
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, Nebraska 68105, USA
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA
| | - Devanshi Seth
- Drug Health Services, Royal Prince Alfred Hospital, Missenden Road, Camperdown, New South Wales 2050, Australia
- Centenary Institute of Cancer Medicine and Cell Biology, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales 2006, Australia
| | - Todd A Wyatt
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, Nebraska 68105, USA
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA
- Department of Environmental, Agricultural and Occupational Health, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA
| | - Srivatsan Kidambi
- Department of Chemical and Biomolecular Engineering, University of Nebraska-Lincoln, Lincoln, Nebraska 68588, USA
| | - Kusum K Kharbanda
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, Nebraska 68105, USA
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA
- Department of Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA
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35
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Matsuura T, Ohfuji S, Enomoto M, Tamori A, Kubo S, Kioka K, Kawada N, Fukushima W. Risk factors for hepatocellular carcinoma in treated chronic hepatitis C patients-Relationship to smoking and alcohol. JGH Open 2020; 4:867-875. [PMID: 33102757 PMCID: PMC7578324 DOI: 10.1002/jgh3.12331] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2019] [Revised: 03/03/2020] [Accepted: 03/13/2020] [Indexed: 01/19/2023]
Abstract
BACKGROUND AND AIM The purpose of this study was to identify lifestyle risk factors, such as cigarette smoking and alcohol consumption, in relation to the development of hepatocellular carcinoma (HCC) among chronic hepatitis C patients who have achieved a sustained virologic response (SVR). METHODS This cross-sectional study was conducted between 2014 and 2017 using self-administered questionnaires and medical information at two tertiary hospitals in Osaka, Japan. Study subjects were chronic hepatitis C patients who had achieved SVR without HCC following antiviral treatment that was completed more than 1 year earlier. A logistic regression model was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the development of post-SVR HCC for each factor. RESULTS Of 202 participants, 18 patients were diagnosed with post-SVR HCC. After considering potential confounders, former drinkers at the time of SVR (OR, 9.51; 95% CI, 1.08-83.90) and patients with a history of gastric or duodenal ulcer (OR, 4.14; 95% CI, 1.37-12.46) were significantly associated with HCC. In addition, among patients with severe fibrosis, current smokers at the time of SVR had an increased OR for HCC compared with never smokers, with marginal significance (OR, 5.61; 95% CI, 0.97-32.63). CONCLUSIONS In chronic hepatitis C patients with severe fibrosis, continuing smoking after achieving SVR could be a risk factor for post-SVR HCC. The relationship between gastric or duodenal ulcer history and post-SVR HCC should be investigated further.
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Affiliation(s)
- Tomoka Matsuura
- Department of Public HealthOsaka City University Graduate School of MedicineOsakaJapan
- Department of HepatologyOsaka City University Graduate School of MedicineOsakaJapan
| | - Satoko Ohfuji
- Department of Public HealthOsaka City University Graduate School of MedicineOsakaJapan
| | - Masaru Enomoto
- Department of HepatologyOsaka City University Graduate School of MedicineOsakaJapan
| | - Akihiro Tamori
- Department of HepatologyOsaka City University Graduate School of MedicineOsakaJapan
| | - Shoji Kubo
- Department of Hepato‐Biliary‐Pancreatic SurgeryOsaka City University Graduate School of MedicineOsakaJapan
| | - Kiyohide Kioka
- Department of HepatologyOsaka City General HospitalOsakaJapan
| | - Norifumi Kawada
- Department of HepatologyOsaka City University Graduate School of MedicineOsakaJapan
| | - Wakaba Fukushima
- Department of Public HealthOsaka City University Graduate School of MedicineOsakaJapan
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Zou RC, Li LL, Yuan HL. Current Status of Research on the Role of Circular RNAs in Hepatocellular Carcinoma and Clinical Implications. Med Sci Monit 2020; 26:e923832. [PMID: 32779638 PMCID: PMC7441742 DOI: 10.12659/msm.923832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Accepted: 06/03/2020] [Indexed: 12/24/2022] Open
Abstract
The latest statistics show that rates of morbidity and mortality for hepatocellular carcinoma are gradually increasing over time. Accumulating evidence indicates that circular RNAs (circRNAs) participate in the regulation of gene transcription and translation and exert a crucial role in endogenous RNA network. circRNAs are implicated in the pathogenesis of numerous tumors including hepatocellular carcinoma (HCC), gastric carcinoma and bladder cancer. Of note, the effect of circRNAs in HCC has drawn increasing public attention. Previous studies revealed that the function of circRNAs mainly consists of sponges of miRNA and RNA-binding proteins, alternative splicing of pre-mRNAs, transcriptional and translational regulators, and potential to encode proteins. In addition, recent research data indicate that the expression level of circRNAs is closely correlated with metastasis, invasion, and occurrence of HCC in patients. These findings imply that circRNAs may be useful as biomarkers for diagnosis and prediction of prognosis of HCC. In this review, we have systemically summarized current viewpoints regarding the role of circRNAs expression in HCC to provide an important reference illustrating the underlying mechanism of HCC.
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Affiliation(s)
- Ren-Chao Zou
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China
| | - Ling-Lin Li
- Department of Nephrology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China
- Department of Nephrology, The Third People’s Hospital of Yunnan Province, Kunming, Yunnan, P.R. China
| | - Hong-Ling Yuan
- Department of Nephrology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China
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37
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Sims OT, Wang K, Chandler R, Melton PA, Truong DN. A descriptive analysis of concurrent alcohol and substance use among patients living with HIV/HCV co-infection. SOCIAL WORK IN HEALTH CARE 2020; 59:525-541. [PMID: 32873213 PMCID: PMC9494867 DOI: 10.1080/00981389.2020.1814938] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/08/2023]
Abstract
The objectives of this study were to estimate the prevalence of concurrent alcohol and substance use among patients living with HIV/HCV co-infection and to compare demographic and clinical characteristics of those with concurrent alcohol and substance to those with alcohol or substance use, and to those who were abstinent. We conducted an analysis of patient reported outcomes data of patients living with HIV/HCV co-infection (n = 327) who transitioned from primary care to sub-specialty care for evaluation of candidacy for HCV treatment at a university-affiliated HIV Clinic. The prevalence of self-reported concurrent alcohol and substance use was 33%. A higher proportion of those with concurrent alcohol and substance use were currently smoking tobacco, and those who were abstinent had higher ratings of health-related quality of life compared to those with alcohol or substance use. To reduce patients' risk for progression to advanced stages of HIV, HCV, and liver-related disease due to continued alcohol and substance and tobacco use, social workers and other health care professionals are encouraged to develop and implement intervention strategies to assist patients living with HIV/HCV co-infection in efforts to achieve behavioral change.
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Affiliation(s)
- Omar T Sims
- Department of Social Work, College of Arts and Sciences, University of Alabama at Birmingham , Birmingham, AL, USA
- Department of Health Behavior, School of Public Health, University of Alabama at Birmingham , Birmingham, AL, USA
- Integrative Center for Healthy Aging, School of Medicine, University of Alabama at Birmingham , Birmingham, AL, USA
- Center for AIDS Research, School of Medicine, University of Alabama at Birmingham , Birmingham, AL, USA
- Center for AIDS Prevention Studies, Division of Prevention Science, Department of Medicine, University of California San Francisco , San Francisco, CA, USA
| | - Kaiying Wang
- Department of Health Behavior, School of Public Health, University of Alabama at Birmingham , Birmingham, AL, USA
- Department of Mathematics and Statistics, College of Arts and Sciences, Georgia State University , Atlanta, GA, USA
| | - Rasheeta Chandler
- Center for AIDS Prevention Studies, Division of Prevention Science, Department of Medicine, University of California San Francisco , San Francisco, CA, USA
- School of Nursing, Emory University , Atlanta, GA, USA
| | - Pamela A Melton
- School of Social Work, Tulane University , New Orleans, LA, USA
| | - Duong N Truong
- Department of Health Care Organization and Policy, School of Public Health, University of Alabama at Birmingham , Birmingham, AL, USA
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Classification and mutation prediction based on histopathology H&E images in liver cancer using deep learning. NPJ Precis Oncol 2020; 4:14. [PMID: 32550270 PMCID: PMC7280520 DOI: 10.1038/s41698-020-0120-3] [Citation(s) in RCA: 121] [Impact Index Per Article: 24.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Accepted: 05/07/2020] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common subtype of liver cancer, and assessing its histopathological grade requires visual inspection by an experienced pathologist. In this study, the histopathological H&E images from the Genomic Data Commons Databases were used to train a neural network (inception V3) for automatic classification. According to the evaluation of our model by the Matthews correlation coefficient, the performance level was close to the ability of a 5-year experience pathologist, with 96.0% accuracy for benign and malignant classification, and 89.6% accuracy for well, moderate, and poor tumor differentiation. Furthermore, the model was trained to predict the ten most common and prognostic mutated genes in HCC. We found that four of them, including CTNNB1, FMN2, TP53, and ZFX4, could be predicted from histopathology images, with external AUCs from 0.71 to 0.89. The findings demonstrated that convolutional neural networks could be used to assist pathologists in the classification and detection of gene mutation in liver cancer.
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Artenie AA, Cunningham EB, Dore GJ, Conway B, Dalgard O, Powis J, Bruggmann P, Hellard M, Cooper C, Read P, Feld JJ, Hajarizadeh B, Amin J, Lacombe K, Stedman C, Litwin AH, Marks P, Matthews GV, Quiene S, Erratt A, Bruneau J, Grebely J. Patterns of Drug and Alcohol Use and Injection Equipment Sharing Among People With Recent Injecting Drug Use or Receiving Opioid Agonist Treatment During and Following Hepatitis C Virus Treatment With Direct-acting Antiviral Therapies: An International Study. Clin Infect Dis 2020; 70:2369-2376. [PMID: 31300820 PMCID: PMC7245153 DOI: 10.1093/cid/ciz633] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 07/10/2019] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND In many settings, recent or prior injection drug use remains a barrier to accessing direct-acting antiviral treatment (DAA) for hepatitis C virus (HCV) infection. We examined patterns of drug and alcohol use and injection equipment sharing among people with recent injecting drug use or receiving opioid agonist treatment (OAT) during and following DAA-based treatment. METHODS SIMPLIFY and D3FEAT are phase 4 trials evaluating the efficacy of DAA among people with past 6-month injecting drug use or receiving OAT through a network of 25 international sites. Enrolled in 2016-2017, participants received sofosbuvir/velpatasvir (SIMPLIFY) or paritaprevir/ritonavir/dasabuvir/ombitasvir ± ribavirin (D3FEAT) for 12 weeks and completed behavioral questionnaires before, during, and up to 2 years posttreatment. The impact of time in HCV treatment and follow-up on longitudinally measured longitudinally measured behaviors was estimated using generalized estimating equations. RESULTS At screening, of 190 participants (mean age, 47 years; 74% male), 62% reported any past-month injecting 16% past-month injection equipment sharing, and 61% current OAT. Median alcohol use was 2 (Alcohol Use Disorders Identification Test-Consumption; range, 1-12). During follow-up, opioid injecting (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.92-0.99) and sharing (OR, 0.87; 95% CI, 0.80-0.94) decreased, whereas no significant changes were observed for stimulant injecting (OR, 0.98; 95% CI, 0.94-1.02) or alcohol use (OR, 0.99; 95% CI, 0.95-1.04). CONCLUSIONS Injecting drug use and risk behaviors remained stable or decreased following DAA-based HCV treatment. Findings further support expanding HCV treatment to all, irrespective of injection drug use. CLINICAL TRIALS REGISTRATION SIMPLIFY, NCT02336139; D3FEAT, NCT02498015.
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Affiliation(s)
- Andreea A Artenie
- Department of Social and Preventive Medicine, School of Public Health, Université de Montréal, Canada
- Research Centre, Centre Hospitalier de l’Université de Montréal, Canada
| | | | - Gregory J Dore
- Kirby Institute, University of New South Wales, Australia
- Department of Infectious Diseases, St Vincent’s Hospital, Sydney, Australia
| | | | - Olav Dalgard
- Department of Infectious Disease, Akershus University Hospital, Oslo, Norway
| | - Jeff Powis
- South Riverdale Community Health Centre, Toronto, Canada
| | | | - Margaret Hellard
- Centre for Population Health, Burnet Institute, Australia
- Department of Infectious Diseases, Alfred Hospital, Melbourne, Victoria, Australia
| | | | - Philip Read
- Kirby Institute, University of New South Wales, Australia
- Kirketon Road Centre, Sydney, Australia
| | | | | | - Janaki Amin
- Kirby Institute, University of New South Wales, Australia
- Department of Health Systems and Populations, Macquarie University, Sydney, Australia
| | - Karine Lacombe
- Department of Infectious and Tropical Diseases, Saint-Antoine Hospital, Paris, France
- Institut Pierre Louis d’Épidémiologie et de Santé Publique, INSERM, Sorbonne Université, Paris, France
| | | | - Alain H Litwin
- Department of Medicine, School of Medicine Greenville, University of South Carolina
- Department of Medicine, School of Health Research, Clemson University, Greenville, South Carolina
- Prisma Health—Upstate, Greenville, South Carolina
| | - Pip Marks
- Kirby Institute, University of New South Wales, Australia
| | - Gail V Matthews
- Kirby Institute, University of New South Wales, Australia
- Department of Infectious Diseases, St Vincent’s Hospital, Sydney, Australia
| | - Sophie Quiene
- Kirby Institute, University of New South Wales, Australia
| | - Amanda Erratt
- Kirby Institute, University of New South Wales, Australia
| | - Julie Bruneau
- Department of Social and Preventive Medicine, School of Public Health, Université de Montréal, Canada
- Research Centre, Centre Hospitalier de l’Université de Montréal, Canada
| | - Jason Grebely
- Kirby Institute, University of New South Wales, Australia
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Ronis MJ, Mercer KE, Shankar K, Pulliam C, Pedersen K, Ingelman-Sundberg M, Friso S, Samuelson D, Del Valle L, Taylor C, Welsh DA. Potential role of gut microbiota, the proto-oncogene PIKE (Agap2) and cytochrome P450 CYP2W1 in promotion of liver cancer by alcoholic and nonalcoholic fatty liver disease and protection by dietary soy protein. Chem Biol Interact 2020; 325:109131. [PMID: 32417163 DOI: 10.1016/j.cbi.2020.109131] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Accepted: 05/06/2020] [Indexed: 12/12/2022]
Abstract
We have previously demonstrated promotion of diethylnitrosamine (DEN) initiated liver tumorigenesis after feeding diets high in fat or ethanol (EtOH) to male mice. This was accompanied by hepatic induction of the proto-oncogene PIKE (Agap2). Switch of dietary protein from casein to soy protein isolate (SPI) significantly reduced tumor formation in these models. We have linked EtOH consumption in mice to microbial dysbiosis. Adoptive transfer studies demonstrate that microbiota from mice fed ethanol can induce hepatic steatosis in the absence of ethanol suggesting that microbiota or the microbial metabolome play key roles in development of fatty liver disease. Feeding SPI significantly changed gut bacteria in mice increasing alpha diversity (P < 0.05) and levels of Clostidiales spp. Feeding soy formula to piglets also resulted in significant changes in microbiota, the pattern of bile acid metabolites and in inhibition of the intestinal-hepatic FXR/FGF19-SHP pathway which has been linked to both steatosis and hepatocyte proliferation. Moreover, feeding SPI also resulted in induction of hepatic PPARα signaling and inhibition of PIKE mRNA expression coincident with inhibition of steatosis and cancer prevention. Feeding studies in the DEN model with differing dietary fats demonstrated tumor promotion specific to the saturated fat, cocoa butter relative to diets containing olive oil or corn oil associated with microbial dysbiosis including dramatic increases in Lachnospiraceae particularly from the genus Coprococcus. Immunohistochemical analysis demonstrated that tumors from EtOH-fed mice and patients with alcohol-associated HCC also expressed high levels of a novel cytochrome P450 enzyme CYP2W1. Additional adoptive transfer experiments and studies in knockout mice are required to determine the exact relationship between soy effects on the microbiota, expression of PIKE, CYP2W1, PPARα activation and prevention of tumorigenesis.
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Affiliation(s)
- Martin J Ronis
- Louisiana State University Health Sciences Center, New Orleans, USA.
| | | | | | - Casey Pulliam
- Louisiana State University Health Sciences Center, New Orleans, USA
| | - Kim Pedersen
- Louisiana State University Health Sciences Center, New Orleans, USA
| | | | | | | | - Luis Del Valle
- Louisiana State University Health Sciences Center, New Orleans, USA
| | - Chris Taylor
- Louisiana State University Health Sciences Center, New Orleans, USA
| | - David A Welsh
- Louisiana State University Health Sciences Center, New Orleans, USA
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Kåberg M, Larsson SB, Jerkeman A, Nystedt A, Duberg AS, Kövamees J, Ydreborg M, Aleman S, Büsch K, Alanko Blomé M, Weiland O, Söderholm J. High risk of non-alcoholic liver disease mortality in patients with chronic hepatitis C with illicit substance use disorder. Scand J Gastroenterol 2020; 55:574-580. [PMID: 32356496 DOI: 10.1080/00365521.2020.1754456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Aims: Hepatitis C virus (HCV) is a slowly progressive disease, often transmitted among people who inject drugs (PWID). Mortality in PWID is high, with an overrepresentation of drug-related causes. This study investigated the risk of death in patients with chronic hepatitis C virus (HCV) infection with or without illicit substance use disorder (ISUD).Methods: Patients with HCV were identified using the Swedish National Patient Registry according to the International Classification of Diseases-10 (ICD-10) code B18.2, with ≤5 matched comparators from the general population. Patients with ≥2 physician visits with ICD-10 codes F11, F12, F14, F15, F16, or F19 were considered to have ISUD. The underlying cause of death was analyzed for alcoholic liver disease, non-alcoholic liver disease, liver cancer, drug-related and external causes, non-liver cancers, or other causes. Mortality risks were assessed using the standardized mortality ratio (SMR) with 95% CIs and Cox regression analyses for cause-specific hazard ratios.Results: In total, 38,186 patients with HCV were included, with 31% meeting the ISUD definition. Non-alcoholic liver disease SMRs in patients with and without ISUD were 123.2 (95% CI, 103.7-145.2) and 69.4 (95% CI, 63.8-75.3), respectively. The significant independent factors associated with non-alcoholic liver disease mortality were older age, being unmarried, male sex, and having ISUD.Conclusions: The relative risks for non-alcoholic liver disease mortality were elevated for patients with ISUD. Having ISUD was a significant independent factor for non-alcoholic liver disease. Thus, patients with HCV with ISUD should be given HCV treatment to reduce the risk for liver disease.
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Affiliation(s)
- Martin Kåberg
- Department of Medicine Huddinge, Division of Infectious Diseases, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden.,Stockholm Needle Exchange, Stockholm Centre for Dependency Disorders, Stockholm, Sweden
| | - Simon B Larsson
- Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Department of Addiction, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Anna Jerkeman
- Department of Translational Medicine, Section of Infectious Disease, Malmö, Lund University, Malmö, Sweden
| | - Anders Nystedt
- Center for Communicable Disease Control, Region Norrbotten, Sweden
| | - Ann-Sofi Duberg
- Department of Infectious Diseases, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | | | - Magdalena Ydreborg
- Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Soo Aleman
- Department of Medicine Huddinge, Division of Infectious Diseases, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden
| | - Katharina Büsch
- AbbVie AB, Stockholm, Sweden.,Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet at Karolinska University Hospital, Huddinge, Stockholm, Sweden
| | - Marianne Alanko Blomé
- Department of Translational Medicine, Section of Infectious Disease, Malmö, Lund University, Malmö, Sweden.,Center for Communicable Disease Control, Region Skåne, Sweden
| | - Ola Weiland
- Department of Medicine Huddinge, Division of Infectious Diseases, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden
| | - Jonas Söderholm
- AbbVie AB, Stockholm, Sweden.,Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet at Karolinska University Hospital, Huddinge, Stockholm, Sweden
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42
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Liu Z, Suo C, Mao X, Jiang Y, Jin L, Zhang T, Chen X. Global incidence trends in primary liver cancer by age at diagnosis, sex, region, and etiology, 1990-2017. Cancer 2020; 126:2267-2278. [PMID: 32201944 DOI: 10.1002/cncr.32789] [Citation(s) in RCA: 85] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2019] [Revised: 01/15/2020] [Accepted: 01/31/2020] [Indexed: 12/31/2022]
Abstract
BACKGROUND The incidence of primary liver cancer (PLC) continues to increase worldwide. The incidence trends and patterns of PLC associated with different age at diagnosis remain unknown. METHODS We collected detailed information on PLC between 1990 and 2017 from Global Burden of Disease Study 2017. Estimated annual percentage changes in the PLC age-standardized incidence rate (ASR) diagnosed by age, sex, region, and etiology were calculated to quantify the temporal trends in PLC ASR. RESULTS Globally, the number of PLC cases for which the age at diagnosis was <30 years decreased from 17,381 in 1990 to 14,661 in 2017, whereas the number of PLC cases diagnosed at age 30 to 59 and ≥60 years old increased from 216,561 and 241,189 in 1990 to 359,770 and 578,344 in 2017, respectively. The ASR of PLC cases with age at diagnosis <30 years and between 30 and 59 years decreased in both sexes, whereas the ASR of PLC with age at diagnosis ≥60 years increased in males and remained stable in females at the global level. Males had a more dramatic increase in PLC diagnosed at age ≥60 years but a milder decrease in PLC diagnosed between 30 and 59 years of age. This decrease was attributed largely to the reduction in PLC caused by hepatitis B and hepatitis C and was consistent in most regions except for developed countries, in which the ASR of PLC increased irrespective of sex and age. The ASR of PLC due to nonalcoholic steatohepatitis (NASH) increased by the greatest magnitude in most regions. CONCLUSION PLC in highly endemic regions has been partly alleviated due to the potent control of hepatitis, especially among young and middle-aged people. However, an unfavorable trend was observed in most developed countries and in elderly populations. As such, PLC prevention schedules should give more attention to NASH and elderly patients.
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Affiliation(s)
- Zhenqiu Liu
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, Fudan University, Shanghai, China.,School of Life Sciences, Fudan University, Shanghai, China.,Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Chen Suo
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.,Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, China
| | - Xianhua Mao
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, Fudan University, Shanghai, China.,School of Life Sciences, Fudan University, Shanghai, China.,Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Yanfeng Jiang
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, Fudan University, Shanghai, China.,School of Life Sciences, Fudan University, Shanghai, China.,Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Li Jin
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, Fudan University, Shanghai, China.,School of Life Sciences, Fudan University, Shanghai, China.,Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Tiejun Zhang
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.,Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, China
| | - Xingdong Chen
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, Fudan University, Shanghai, China.,School of Life Sciences, Fudan University, Shanghai, China.,Fudan University Taizhou Institute of Health Sciences, Taizhou, China
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Kim NJ, Pearson M, Vutien P, Su F, Moon AM, Berry K, Green PK, Williams EC, Ioannou GN. Alcohol Use and Long-Term Outcomes Among U.S. Veterans Who Received Direct-Acting Antivirals for Hepatitis C Treatment. Hepatol Commun 2020; 4:314-324. [PMID: 32025613 PMCID: PMC6996340 DOI: 10.1002/hep4.1464] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Accepted: 11/26/2019] [Indexed: 12/12/2022] Open
Abstract
Outcomes related to alcohol use after hepatitis C virus (HCV) treatment are unknown in the direct‐acting antiviral (DAA) era. We assessed levels of alcohol use before and after HCV treatment and their association with long‐term outcomes in a cohort of U.S. veterans. In this retrospective cohort analysis, 29,037 patients who initiated DAA regimens between 2013 and 2015 were followed for a mean of 3.04 years. We categorized alcohol use into three categories (nondrinking, low‐level drinking, and unhealthy drinking) using Alcohol Use Disorders Identification Test‐Consumption questionnaires administered within 1 year before (baseline) and after treatment. Multivariable Cox proportional hazards regression was used to determine the associations between alcohol use and mortality or liver‐related outcomes. Before DAA treatment, 68% of veterans reported nondrinking, 22.9% reported low‐level drinking, and 9.1% reported unhealthy drinking. Compared to patients with baseline non‐drinking, those with unhealthy drinking had a higher risk of mortality (adjusted hazard ratio [HR] 1.53, 95% confidence interval [CI]: 1.34‐1.75) and decompensated cirrhosis (adjusted HR 1.30, 95% CI: 1.06‐1.59) and lower likelihood of liver transplantation (adjusted HR 0.24, 95% CI: 0.06‐0.92). These associations were greater in patients without sustained virologic response than in those with sustained virologic response. When alcohol use before and after treatment was modeled as a time‐varying covariate, similar associations were observed. Survival analysis also found that unhealthy drinking was significantly associated with a lower probability of survival compared with nondrinking. Low‐level alcohol use was not associated with increased risk of adverse outcomes. Conclusion: In this large cohort of U.S. veterans with HCV who received DAAs, unhealthy drinking was common and associated with a higher risk of posttreatment mortality. Interventions to achieve alcohol cessation before and during antiviral treatment should be encouraged.
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Affiliation(s)
- Nicole J Kim
- Division of Gastroenterology University of Washington Seattle WA
| | - Meredith Pearson
- Division of Gastroenterology University of Washington Seattle WA
| | - Philip Vutien
- Division of Gastroenterology University of Washington Seattle WA
| | - Feng Su
- Division of Gastroenterology University of Washington Seattle WA
| | - Andrew M Moon
- Division of Gastroenterology University of North Carolina Chapel Hill NC
| | - Kristin Berry
- Health Service Research and Development Veterans Affairs Puget Sound Health Care System Seattle WA
| | - Pamela K Green
- Health Service Research and Development Veterans Affairs Puget Sound Health Care System Seattle WA
| | - Emily C Williams
- Health Service Research and Development Veterans Affairs Puget Sound Health Care System Seattle WA.,Department of Health Services University of Washington Seattle WA
| | - George N Ioannou
- Division of Gastroenterology University of Washington Seattle WA.,Division of Gastroenterology Veterans Affairs Puget Sound Health Care System Seattle WA
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44
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Zhang G, Cao F, Shi L, Ma T, Zhang L. Contribution of high body mass index and alcohol use to liver cancer-related mortality: A study based on 195 countries or territories. Dig Liver Dis 2020; 52:221-231. [PMID: 31744773 DOI: 10.1016/j.dld.2019.10.012] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Revised: 09/05/2019] [Accepted: 10/12/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND High body mass index (BMI) and alcohol use are well-defined risk factors for liver cancer. AIMS We aim to describe the contribution of high BMI and alcohol use to liver-cancer-related death at the global and national levels. METHODS The data of liver cancer-related mortality attributable to all known risk factors, high BMI, and alcohol use were collected from the Global Burden of Disease database. The estimated average percentage change was used to quantify the liver cancer age-standardized mortality rate (ASMR) trends. RESULTS Globally, approximately 819,435 liver cancer-related deaths occurred in 2017, among which 415,867, 98,552, and 129,287 deaths could be ascribed to all 9 known risk factors, high BMI, and alcohol use, respectively. The overall ASMR increased from 4.42 per 100,000 to 5.17 per 100,000 in the study period. The liver cancer ASMR attributable to high BMI consistently increased at the global level and in most countries. The alcohol use-related liver cancer mortality decreased by 0.17% per year during the study period. However, a significant increase was found after 2008. CONCLUSION The increase in high BMI-related liver cancer mortality suggests scarce attention to overweight and highlights its priority in future prevention schedules for liver cancer. Effective prevention measures are still needed to mitigate the adverse impact of alcohol consumption.
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Affiliation(s)
- Guoyao Zhang
- Department of Oncology, Luohe Central Hospital, Luohe, China
| | - Fei Cao
- Department of Oncology, Luohe Central Hospital, Luohe, China
| | - Lei Shi
- Department of Oncology, Luohe Central Hospital, Luohe, China
| | - Tianjiang Ma
- Department of Oncology, Luohe Central Hospital, Luohe, China
| | - Lei Zhang
- Department of Oncology, Luohe Central Hospital, Luohe, China.
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45
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Sagnelli E, Macera M, Russo A, Coppola N, Sagnelli C. Epidemiological and etiological variations in hepatocellular carcinoma. Infection 2020; 48:7-17. [PMID: 31347138 DOI: 10.1007/s15010-019-01345-y] [Citation(s) in RCA: 147] [Impact Index Per Article: 29.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Accepted: 07/16/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer and a leading cause of cancer-related deaths worldwide. The major risk factors for HCC development are chronic liver disease and cirrhosis due to hepatitis B virus (HBV) and/or hepatitis C virus (HCV), alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), steatohepatitis, intake of aflatoxin-contaminated food, diabetes, and obesity. RESULTS In Western countries, the number of NASH-related HCC cases is increasing, that of HBV- or HCV-related cases is declining due to the wide application of HBV universal vaccination and the introduction of effective therapies against HBV and HCV infections, and that of alcohol-related cases remaining substantially unchanged. Nevertheless, the burden of HCC is expected to increase worldwide in the next few decades, due to the population growth and aging expected in coming years. Overall, the abovementioned changes and future variations in lifestyle and in the impact of environmental factors in Western countries and a decreasing exposure to dietary aflatoxins and improved socio-economic conditions in developing countries will create new HCC epidemiology in the next few decades. CONCLUSION A substantial further reduction in cases of HCC requires a wider application of universal HBV vaccination and effective treatment of HBV- and HCV-related chronic hepatitis and cirrhosis, more effective campaigns to favor correct dietary habits and reduce alcohol consumption and the intensification of studies on HCC pathogenesis for future optimized prevention strategies.
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Affiliation(s)
- Evangelista Sagnelli
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80131, Naples, Italy.
| | - Margherita Macera
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80131, Naples, Italy
| | - Antonio Russo
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80131, Naples, Italy
| | - Nicola Coppola
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80131, Naples, Italy
| | - Caterina Sagnelli
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80131, Naples, Italy
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Nahon P, Ganne-Carrié N. Management of patients with pre-therapeutic advanced liver fibrosis following HCV eradication. JHEP Rep 2019; 1:480-489. [PMID: 32039400 PMCID: PMC7005771 DOI: 10.1016/j.jhepr.2019.11.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Revised: 10/30/2019] [Accepted: 11/06/2019] [Indexed: 12/19/2022] Open
Abstract
Patients with HCV-related bridging fibrosis or cirrhosis remain at risk of developing life-threatening complications even after achieving a sustained virological response. Although it is reduced, the risk of liver-related events in these patients justifies their inclusion in surveillance programmes dedicated to the early detection of hepatocellular carcinoma and the screening for portal hypertension. Biochemical parameters or non-invasive tests might indicate the potential progression of liver injury despite viral clearance. Specific attention must be focused on the management of comorbidities, while dedicated educational programmes must be encouraged to increase compliance and commitment to surveillance. Better knowledge of the long-term evolution of these patients, who now live longer, is essential to improve risk stratification and refine screening strategies in this growing population.
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Key Words
- AFP, alpha-fetoprotein
- ALT, alanine aminotransferase
- APRI, AST-to-platelet ratio index
- AST, aspartate aminotransferase
- DAAs, direct-acting antivirals
- EHC, extrahepatic cancer
- FIB-4, fibrosis-4
- HCC, hepatocellular carcinoma
- HCV
- HR, hazard ratio
- Hepatocellular carcinoma
- LSM, liver stiffness measurement
- Liver failure
- MACEs, major adverse cardiovascular events
- PHT, portal hypertension
- Portal hypertension
- SMR, standardised mortality ratio
- SVR
- SVR, sustained virological response
- surveillance
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Affiliation(s)
- Pierre Nahon
- AP-HP, Hôpital Jean Verdier, Liver Unit, Bondy, France
- University Paris 13, Sorbonne Paris Cité, “équipe labellisée Ligue Contre le Cancer”, F-93000 Bobigny, France
- INSERM UMR-1162: Functional Genomics of Solid Tumours, F-75010, Paris, France
| | - Nathalie Ganne-Carrié
- AP-HP, Hôpital Jean Verdier, Liver Unit, Bondy, France
- University Paris 13, Sorbonne Paris Cité, “équipe labellisée Ligue Contre le Cancer”, F-93000 Bobigny, France
- INSERM UMR-1162: Functional Genomics of Solid Tumours, F-75010, Paris, France
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47
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Huang PS, Wang CS, Yeh CT, Lin KH. Roles of Thyroid Hormone-Associated microRNAs Affecting Oxidative Stress in Human Hepatocellular Carcinoma. Int J Mol Sci 2019; 20:E5220. [PMID: 31640265 PMCID: PMC6834183 DOI: 10.3390/ijms20205220] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Revised: 10/17/2019] [Accepted: 10/18/2019] [Indexed: 02/07/2023] Open
Abstract
Oxidative stress occurs as a result of imbalance between the generation of reactive oxygen species (ROS) and antioxidant genes in cells, causing damage to lipids, proteins, and DNA. Accumulating damage of cellular components can trigger various diseases, including metabolic syndrome and cancer. Over the past few years, the physiological significance of microRNAs (miRNA) in cancer has been a focus of comprehensive research. In view of the extensive level of miRNA interference in biological processes, the roles of miRNAs in oxidative stress and their relevance in physiological processes have recently become a subject of interest. In-depth research is underway to specifically address the direct or indirect relationships of oxidative stress-induced miRNAs in liver cancer and the potential involvement of the thyroid hormone in these processes. While studies on thyroid hormone in liver cancer are abundantly documented, no conclusive information on the potential relationships among thyroid hormone, specific miRNAs, and oxidative stress in liver cancer is available. In this review, we discuss the effects of thyroid hormone on oxidative stress-related miRNAs that potentially have a positive or negative impact on liver cancer. Additionally, supporting evidence from clinical and animal experiments is provided.
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Affiliation(s)
- Po-Shuan Huang
- Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 33302, Taiwan.
- Department of Biomedical Sciences, College of Medicine, Chang-Gung University, Taoyuan 33302, Taiwan.
| | - Chia-Siu Wang
- Department of General Surgery, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan.
| | - Chau-Ting Yeh
- Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan 33302, Taiwan.
| | - Kwang-Huei Lin
- Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 33302, Taiwan.
- Department of Biomedical Sciences, College of Medicine, Chang-Gung University, Taoyuan 33302, Taiwan.
- Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan 33302, Taiwan.
- Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 33302, Taiwan.
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Pocha C, Xie C. Hepatocellular carcinoma in alcoholic and non-alcoholic fatty liver disease-one of a kind or two different enemies? Transl Gastroenterol Hepatol 2019; 4:72. [PMID: 31728429 DOI: 10.21037/tgh.2019.09.01] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Accepted: 08/22/2019] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular cancer (HCC) is a cancer with an overall poor prognosis and an alarming globally rising incidence. While viral etiology of chronic liver disease and HCC is down-trending, alcohol and excess calorie intake have emerged as major culprits. Alcohol related liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) share similar pathogenetic mechanism of hepatic injury and in promoting development of HCC; yet some genetic and epigenetic features are distinct and may promise clinical utility. Population based intervention are urgently needed to reduce alcohol use and improve metabolic factors such as obesity and diabetes. The goal is to identify at-risk patients, to link these patients to care and to provide effective management of chronic liver disease and HCC. This review focuses on the epidemiology, pathophysiology including genetic and epigenetic altercation as well as clinical aspects of ALD and NAFLD associated HCC.
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Affiliation(s)
- Christine Pocha
- Avera McKennnan Hospital and University Medical Center, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, USA.,Department of Gastroenterology and Hepatology, Thomas Jefferson University, Philadelphia, PA, USA
| | - Chencheng Xie
- Avera McKennnan Hospital and University Medical Center, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, USA.,Department of Gastroenterology and Hepatology, Thomas Jefferson University, Philadelphia, PA, USA
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49
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Xiong M, Li J, Yang S, Zeng F, Ji Y, Liu J, Wu Q, He Q, Tang X, Jiang R, Zhou F, Chen Y, Wen W, Chen J, Hou J. Impacts of cigarette smoking on liver fibrosis and its regression under therapy in male patients with chronic hepatitis B. Liver Int 2019; 39:1428-1436. [PMID: 30920714 DOI: 10.1111/liv.14108] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 03/22/2019] [Accepted: 03/23/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS The role of cigarette smoking in the development of chronic hepatitis B (CHB) remains poorly understood. We assessed the potential contributions of cigarette smoking to liver fibrosis and its regression after starting antiviral therapy in CHB patients. METHODS In this cohort study, 2144 consecutive male CHB patients under no antiviral therapy were evaluated and 206 patients with significant liver fibrosis (≥F2) initiating antiviral therapy had longitudinal follow-up. Liver fibrosis was measured by liver stiffness measurement using transient elastography. To adjust for imbalances between smoking history and never smoking groups, propensity score (PS) matching model with 1:1 ratios were performed. Cigarette smoking history and intensity (pack-years) were collected and documented using a standardized questionnaire. RESULTS Before PS matching, 432/2144 patients had advanced fibrosis in prevalence cohort. Patients with smoking history (n = 1002) had a greater prevalence of advanced fibrosis than those without (n = 1142) (24.4% vs 16.5%, P = 0.001). Multivariate logistic regression analysis demonstrated that smoking contributed to advanced fibrosis (OR, 1.458; 95% CI, 1.114-1.908). In longitudinal cohort, multivariate logistic regression analysis demonstrated retarded fibrosis regression in patients with history of smoking ≥10 pack-years (OR, 0.288; 95% CI, 0.1-0.825). After PS matching, patients with smoking history had higher prevalence of advanced fibrosis (22.8% vs 18%, P = 0.024) than those non-smokers. In post-PS-matching logistic regression, the effect of smoking on advanced fibrosis persisted (OR, 1.415; 95% CI, 1.047-1.912; P = 0.024). CONCLUSIONS Cigarette smoking in male CHB patients aggravated liver fibrosis prior to and delayed fibrosis regression under antiviral therapy.
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Affiliation(s)
- Ming Xiong
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Junying Li
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Shuling Yang
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Fansen Zeng
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
- Department of Infectious Diseases, Guangzhou Women and Children's Medical Center, Guangzhou, China
| | - Yali Ji
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jiang Liu
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Qiaoping Wu
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Qingjun He
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xiaoting Tang
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ronglong Jiang
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Fuyuan Zhou
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yongpeng Chen
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Weiqun Wen
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jinjun Chen
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jinlin Hou
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
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50
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Gao Y, Zhou Z, Ren T, Kim SJ, He Y, Seo W, Guillot A, Ding Y, Wu R, Shao S, Wang X, Zhang H, Wang W, Feng D, Xu M, Han E, Zhong W, Zhou Z, Pacher P, Niu J, Gao B. Alcohol inhibits T-cell glucose metabolism and hepatitis in ALDH2-deficient mice and humans: roles of acetaldehyde and glucocorticoids. Gut 2019; 68:1311-1322. [PMID: 30121625 PMCID: PMC6582747 DOI: 10.1136/gutjnl-2018-316221] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Revised: 07/16/2018] [Accepted: 07/20/2018] [Indexed: 12/14/2022]
Abstract
OBJECTIVE Aldehyde dehydrogenase 2 (ALDH2), a key enzyme to detoxify acetaldehyde in the liver, exists in both active and inactive forms in humans. Individuals with inactive ALDH2 accumulate acetaldehyde after alcohol consumption. However, how acetaldehyde affects T-cell hepatitis remains unknown. DESIGN Wild-type (WT) and Aldh2 knockout (Aldh2-/-) mice were subjected to chronic ethanol feeding and concanavalin A (ConA)-induced T-cell hepatitis. Effects of acetaldehyde on T-cell glucose metabolism were investigated in vitro. Human subjects were recruited for binge drinking and plasma cortisol and corticosterone measurement. RESULTS Ethanol feeding exacerbated ConA-induced hepatitis in WT mice but surprisingly attenuated it in Aldh2-/- mice despite higher acetaldehyde levels in Aldh2-/- mice. Elevation of serum cytokines and their downstream signals in the liver post-ConA injection was attenuated in ethanol-fed Aldh2-/- mice compared to WT mice. In vitro exposure to acetaldehyde inhibited ConA-induced production of several cytokines without affecting their mRNAs in mouse splenocytes. Acetaldehyde also attenuated interferon-γ production in phytohaemagglutinin-stimulated human peripheral lymphocytes. Mechanistically, acetaldehyde interfered with glucose metabolism in T cells by inhibiting aerobic glycolysis-related signal pathways. Finally, compared to WT mice, ethanol-fed Aldh2-/- mice had higher levels of serum corticosterone, a well-known factor that inhibits aerobic glycolysis. Blockade of corticosterone partially restored ConA-mediated hepatitis in ethanol-fed Aldh2-/- mice. Acute alcohol drinking elevated plasma cortisol and corticosterone levels in human subjects with higher levels in those with inactive ALDH2 than those with active ALDH2. CONCLUSIONS ALDH2 deficiency is associated with elevated acetaldehyde and glucocorticoids post-alcohol consumption, thereby inhibiting T-cell activation and hepatitis.
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Affiliation(s)
- Yanhang Gao
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
- Department of Hepatology, First Affiliated Hospital, Jilin University, Changchun, China
| | - Zhou Zhou
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
| | - Tianyi Ren
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
- Department of Hepatology, First Affiliated Hospital, Jilin University, Changchun, China
| | - Seung-Jin Kim
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
| | - Yong He
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
| | - Wonhyo Seo
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
| | - Adrien Guillot
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
| | - Yanhua Ding
- Department of Hepatology, First Affiliated Hospital, Jilin University, Changchun, China
| | - Ruihong Wu
- Department of Hepatology, First Affiliated Hospital, Jilin University, Changchun, China
| | - Shuang Shao
- Department of Hepatology, First Affiliated Hospital, Jilin University, Changchun, China
| | - Xiaomei Wang
- Department of Hepatology, First Affiliated Hospital, Jilin University, Changchun, China
| | - Hong Zhang
- Department of Hepatology, First Affiliated Hospital, Jilin University, Changchun, China
| | - Wei Wang
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
| | - Dechun Feng
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
| | - Mingjiang Xu
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
| | - Elaine Han
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
| | - Wei Zhong
- Center for Translational Biomedical Research, University of North Carolina at Greensboro, Kannapolis, North Carolina, USA
| | - Zhanxiang Zhou
- Center for Translational Biomedical Research, University of North Carolina at Greensboro, Kannapolis, North Carolina, USA
| | - Pal Pacher
- Laboratory of Cardiovascular Physiology and Tissue Injury, National Institutes of Health/NIAAA, Bethesda, Maryland, USA
| | - Junqi Niu
- Department of Hepatology, First Affiliated Hospital, Jilin University, Changchun, China
| | - Bin Gao
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
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