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Cheraghpour M, Hatami B, Singal AG. Lifestyle and Pharmacologic Approaches to Prevention of Metabolic Dysfunction-associated Steatotic Liver Disease-related Hepatocellular Carcinoma. Clin Gastroenterol Hepatol 2025; 23:685-694.e6. [PMID: 39800201 DOI: 10.1016/j.cgh.2024.09.041] [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: 08/03/2024] [Revised: 09/19/2024] [Accepted: 09/30/2024] [Indexed: 01/15/2025]
Abstract
Hepatocellular carcinoma (HCC) is a major concern for public health. Fatty liver disease, related to alcohol misuse or metabolic syndrome, has become the leading cause of chronic liver disease and HCC. The strong association between type 2 diabetes mellitus and HCC can be partly attributed to the development of metabolic dysfunction-associated steatotic liver disease (MASLD). There is a strong interest in strategies that may mitigate HCC risk and reduce HCC incidence in this growing population of at-risk individuals. In this review, we describe the pathogenesis of HCC in patients with MASLD and discuss potential emerging pharmacological and lifestyle interventions for MASLD-related HCC. HCC risk has been observed to be lower with healthy lifestyle behaviors, such as healthy dietary patterns (eg, high consumption of vegetables, whole grains, fish and poultry, yogurt, and olive oil, and low consumption of red and processed meats and dietary sugar) and increased physical activity. Selecting an appropriate pharmacologic approach for individuals with MASLD may also decrease the occurrence of HCC. Metformin, PPAR activators, sodium-glucose cotransporter 2 inhibitors, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, aspirin, and statins have all shown promise to reduce the risk of HCC, although guidelines do not recommend their use for the sole purpose of chemoprevention at this time, given a dearth of data defining their risk-benefit ratio.
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Affiliation(s)
- Makan Cheraghpour
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Behzad Hatami
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amit G Singal
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
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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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López-Cánovas JL, Naranjo-Martínez B, Diaz-Ruiz A. Fasting in combination with the cocktail Sorafenib:Metformin blunts cellular plasticity and promotes liver cancer cell death via poly-metabolic exhaustion. Cell Oncol (Dordr) 2025; 48:161-182. [PMID: 38990489 PMCID: PMC11850423 DOI: 10.1007/s13402-024-00966-2] [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] [Accepted: 05/31/2024] [Indexed: 07/12/2024] Open
Abstract
PURPOSE Dual-Interventions targeting glucose and oxidative metabolism are receiving increasing attention in cancer therapy. Sorafenib (S) and Metformin (M), two gold-standards in liver cancer, are known for their mitochondrial inhibitory capacity. Fasting, a glucose-limiting strategy, is also emerging as chemotherapy adjuvant. Herein, we explore the anti-carcinogenic response of nutrient restriction in combination with sorafenib:metformin (NR-S:M). RESULTS Our data demonstrates that, independently of liver cancer aggressiveness, fasting synergistically boosts the anti-proliferative effects of S:M co-treatment. Metabolic and Cellular plasticity was determined by the examination of mitochondrial and glycolytic activity, cell cycle modulation, activation of cellular apoptosis, and regulation of key signaling and metabolic enzymes. Under NR-S:M conditions, early apoptotic events and the pro-apoptotic Bcl-xS/Bcl-xL ratio were found increased. NR-S:M induced the highest retention in cellular SubG1 phase, consistent with the presence of DNA fragments from cellular apoptosis. Mitochondrial functionality, Mitochondrial ATP-linked respiration, Maximal respiration and Spare respiratory capacity, were all found blunted under NR-S:M conditions. Basal Glycolysis, Glycolytic reserve, and glycolytic capacity, together with the expression of glycogenic (PKM), gluconeogenic (PCK1 and G6PC3), and glycogenolytic enzymes (PYGL, PGM1, and G6PC3), were also negatively impacted by NR-S:M. Lastly, a TMT-proteomic approach corroborated the synchronization of liver cancer metabolic reprogramming with the activation of molecular pathways to drive a quiescent-like status of energetic-collapse and cellular death. CONCLUSION Altogether, we show that the energy-based polytherapy NR-S:M blunts cellular, metabolic and molecular plasticity of liver cancer. Notwithstanding the in vitro design of this study, it holds a promising therapeutic tool worthy of exploration for this tumor pathology.
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Affiliation(s)
- Juan L López-Cánovas
- Laboratory of Cellular and Molecular Gerontology, Precision Nutrition and Aging Program, Institute IMDEA Food (CEI UAM+CSIC), Crta. de Canto Blanco nº 8, Madrid, E-28049, Spain
| | - Beatriz Naranjo-Martínez
- Laboratory of Cellular and Molecular Gerontology, Precision Nutrition and Aging Program, Institute IMDEA Food (CEI UAM+CSIC), Crta. de Canto Blanco nº 8, Madrid, E-28049, Spain
| | - Alberto Diaz-Ruiz
- Laboratory of Cellular and Molecular Gerontology, Precision Nutrition and Aging Program, Institute IMDEA Food (CEI UAM+CSIC), Crta. de Canto Blanco nº 8, Madrid, E-28049, Spain.
- CIBER Pathophysiology of Obesity and Nutrition (CIBERobn), Córdoba, Spain.
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Polpichai N, Saowapa S, Danpanichkul P, Chan SY, Sierra L, Blagoie J, Rattananukrom C, Sripongpun P, Kaewdech A. Beyond the Liver: A Comprehensive Review of Strategies to Prevent Hepatocellular Carcinoma. J Clin Med 2024; 13:6770. [PMID: 39597914 PMCID: PMC11594971 DOI: 10.3390/jcm13226770] [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: 10/16/2024] [Revised: 11/06/2024] [Accepted: 11/08/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND/OBJECTIVES Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, primarily developing in the context of chronic liver disease. Traditional prevention has focused on liver-specific interventions like antiviral therapies and surveillance. However, extrahepatic factors also significantly contribute to HCC risk. This review explores comprehensive strategies for HCC prevention, including both hepatic and extrahepatic factors. METHODS An extensive literature search of peer-reviewed articles up to October 2024 was conducted, focusing on studies addressing HCC prevention strategies. Studies that focused on both hepatic and extrahepatic factors were included. Data were extracted and synthesized to provide an overview of current prevention strategies and their effectiveness in reducing HCC incidence. RESULTS Hepatitis B vaccination and antiviral treatments for hepatitis B and C significantly reduce HCC incidence. Lifestyle modifications-such as reducing alcohol consumption, maintaining a healthy weight through diet and exercise, and smoking cessation-are crucial in lowering HCC risk. Environmental measures to limit exposure to aflatoxins and other hazards also contribute to prevention. Regular surveillance of high-risk groups enables early detection and improves survival rates. Emerging strategies like immunotherapy and gene therapy show potential for further reducing HCC risk. CONCLUSIONS A comprehensive approach combining medical interventions, lifestyle changes, and environmental controls is essential for effectively decreasing HCC incidence globally. Implementing these combined measures could significantly reduce the global burden of HCC.
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Affiliation(s)
- Natchaya Polpichai
- Department of Medicine, Weiss Memorial Hospital, Chicago, IL 60640, USA; (N.P.); (S.-Y.C.); (J.B.)
| | - Sakditad Saowapa
- Department of Medicine, Texas Tech University Health Science Center, Lubbock, TX 79430, USA; (S.S.); (P.D.)
| | - Pojsakorn Danpanichkul
- Department of Medicine, Texas Tech University Health Science Center, Lubbock, TX 79430, USA; (S.S.); (P.D.)
| | - Shu-Yen Chan
- Department of Medicine, Weiss Memorial Hospital, Chicago, IL 60640, USA; (N.P.); (S.-Y.C.); (J.B.)
| | - Leandro Sierra
- Department of Medicine, Cleveland Clinic Foundation, Cleveland, OH 44195, USA;
| | - Johanna Blagoie
- Department of Medicine, Weiss Memorial Hospital, Chicago, IL 60640, USA; (N.P.); (S.-Y.C.); (J.B.)
| | - Chitchai Rattananukrom
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Srinagarind Hospital, Khon Kaen University, Khon Kaen 40002, Thailand;
| | - Pimsiri Sripongpun
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand;
| | - Apichat Kaewdech
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand;
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Wang K, Chen Y, Zhang M, Wang S, Yao S, Gong Z, Fei B, Huang Z. Metformin suppresses gastric cancer progression by disrupting the STAT1-PRMT1 axis. Biochem Pharmacol 2024; 226:116367. [PMID: 38876258 DOI: 10.1016/j.bcp.2024.116367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 05/24/2024] [Accepted: 06/11/2024] [Indexed: 06/16/2024]
Abstract
Gastric cancer (GC) is a common form of cancer and the leading cause of cancer-related deaths worldwide. Chemotherapy is the primary treatment for patients with unresectable or partially resectable GC. However, its adverse effects and chemoresistance greatly restrict its applicability and efficacy. Although HER2-targeted therapy and immunotherapy have been successfully used for GC treatment, their beneficial population is limited. To expand the range of cancer treatments, drug repurposing has emerged as a promising strategy. In this study, we evaluated the potential of Metformin, an oral anti-hyperglycemic agent, to suppress GC progression both in vivo and in vitro. Functional investigations showed that Metformin significantly inhibits GC proliferation and migration. Furthermore, we discovered that Metformin bound and disrupted STAT1 phosphorylation, inhibiting PRMT1 expression and consequently GC progression. In conclusion, our study not only provides further evidence for the anti-GC role of Metformin but also identifies the direct target mediating the tumor-inhibitory effects of Metformin in GC.
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Affiliation(s)
- Kaiqing Wang
- Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu, China; Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, Jiangsu, China; Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu, China
| | - Yanyan Chen
- Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu, China; Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, Jiangsu, China
| | - Meimei Zhang
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi University of Chinese Medicine, Xi'an 712046, Shaanxi, China
| | - Suzeng Wang
- Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu, China; Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, Jiangsu, China; Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu, China
| | - Surui Yao
- Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu, China; Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, Jiangsu, China
| | - Zhicheng Gong
- Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu, China; Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, Jiangsu, China.
| | - Bojian Fei
- Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu, China.
| | - Zhaohui Huang
- Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu, China; Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, Jiangsu, China.
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Ding X, Deng L, Cen C, Yang Y. Association Between Prediabetes and Risk, Mortality of Hepatocellular Carcinoma: A Meta-Analysis. Endocr Res 2024; 49:186-192. [PMID: 38830240 DOI: 10.1080/07435800.2024.2361160] [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: 01/03/2024] [Revised: 05/18/2024] [Accepted: 05/23/2024] [Indexed: 06/05/2024]
Abstract
BACKGROUND As the high-risk stage of diabetes, the role of prediabetes in the development of hepatocellular carcinoma (HCC) remains unclear. To address this knowledge gap, we undertook a meta-analysis to investigate the potential association between the prediabetic stage and HCC. METHODS In this study, two independent investigators conducted a comprehensive search for relevant articles published up until May 2023 in several databases, including PubMed, Web of Science, Medline, EMBASE, and Google Scholar. The results were then summarized using STATA 12.0 software. RESULTS Our analysis included a total of 6 cohort studies involving 1,490,752 participants, as well as 1 case-control study with 220 participants. The research aimed to examine the association between prediabetes and the risk of HCC. Our meta-analysis revealed that prediabetes was significantly associated with an elevated risk of HCC (odds ratio (OR)/relative risk (RR) = 1.25, 95% confidence interval (CI) 1.06 to 1.48, I2 = 57.2%, p = 0.012), using a random-effects model. Moreover, four cohort studies, encompassing 1,362,847 participants, explored the relationship between prediabetes and HCC mortality. The meta-analysis showed that prediabetes was associated with a higher mortality rate of HCC, also utilizing a random-effects model (hazard ratio (HR) = 1.36, 95% CI 1.02 to 1.81, I2 = 55.8%, p = 0.060). CONCLUSIONS Overall, our findings highlight a significant association between prediabetes and an increased risk of HCC and suggest that prediabetes may also contribute to higher mortality rates among HCC patients.
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Affiliation(s)
- Xin Ding
- Department of Gastroenterology, Zhongshan City People's Hospital, Zhongshan, Guangdong, China
| | - Li Deng
- Radiotherapy Department of Nasopharyngeal Head and Neck Tumors, Zhongshan City People's Hospital, Zhongshan, Guangdong, China
| | - Chuan Cen
- Department of Gastroenterology, Zhongshan City People's Hospital, Zhongshan, Guangdong, China
| | - Yuyu Yang
- Department of Gastroenterology, Zhongshan City People's Hospital, Zhongshan, Guangdong, China
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7
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Zhang Z, Wu W, Wu Z, He Y, Chang X, Deng S, Zhou R, Chen Y, Zhang H. Bridging the gap: exploring the causal relationship between metformin and tumors. Front Genet 2024; 15:1397390. [PMID: 38962452 PMCID: PMC11220117 DOI: 10.3389/fgene.2024.1397390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Accepted: 06/03/2024] [Indexed: 07/05/2024] Open
Abstract
Objective Numerous studies have reported that metformin can reduce the risk of tumor development. However, some of the results of these studies are conflicting, necessitating a more reliable evaluation. Methods We conducted a Mendelian randomization phenome-wide association study (MR-PheWAS) of tumors to explore the causal relationship between metformin and tumors. Two cohorts of patients taking metformin were obtained from the UK Biobank. Complete phenotype data of the tumors were obtained from FinnGen_R10. We elucidated the causal relationship using a two-sample Mendelian randomization (MR) analysis. More importantly, we conducted a meta-analysis to ensure relatively unbiased results. In the MR analysis, we used the inverse-variance weighted (IVW) method as the main outcome indicator. Subsequently, two cohorts were integrated for the meta-analysis. Finally, we investigated the mechanisms through mediational MR analysis. Results MR analysis revealed that metformin might have a causal relationship with 13 tumor-associated phenotypes in the training cohort. Four phenotypes were validated in the testing cohort. In the training and testing cohorts, metformin exhibited a protective effect against brain meningiomas and malignant neoplasms of the breast (HER-positive), oral cavity, tonsils, and the base of the tongue. Intriguingly, after integrating the results of the two cohorts for the meta-analysis, 12 results were statistically significant. Mediational MR analysis suggested that the effects of metformin on brain meningiomas may be weakened by the presence of the family Oxalobacteraceae. Conclusion Metformin exhibits potential preventive and therapeutic effects on four types of tumors: brain meningioma, malignant neoplasms of the breast (HER-positive), oral cavity and tonsils, and the base of the tongue. Large randomized controlled trials are required to confirm these findings.
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Affiliation(s)
- Zexin Zhang
- The Second Clinical School of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Wenfeng Wu
- The Second Clinical School of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Zexia Wu
- The Second Clinical School of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yihan He
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xuesong Chang
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Shenyuan Deng
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Rui Zhou
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yadong Chen
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Haibo Zhang
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, China
- Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou, China
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
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8
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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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9
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Qin S, Wang J, Yuan H, He J, Luan S, Deng Y. Liver function indicators and risk of hepatocellular carcinoma: a bidirectional mendelian randomization study. Front Genet 2024; 14:1260352. [PMID: 38318289 PMCID: PMC10839095 DOI: 10.3389/fgene.2023.1260352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Accepted: 12/29/2023] [Indexed: 02/07/2024] Open
Abstract
Observational studies have shown an association between liver dysfunction and hepatocellular carcinoma (HCC), but the causality relationship between them is unclear. We aimed to determine whether there is a bidirectional causal relationship between liver function indicators (alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; γ-glutamyltransferase, GGT) and HCC. Our two-sample Mendelian randomization (MR) study acquired single nucleotide polymorphisms (SNPs) associated with liver function indicators (ALT, n = 134,182; AST, n = 134,154; GGT, n = 118,309; ALP, n = 105,030) and with HCC (n = 197,611) from publicly available genome-wide association studies (GWAS) of East Asian ancestry in Japan (BioBank Japan, BBJ). Univariable MR analyses were performed to identify whether the genetic evidence of exposure was significantly associated with outcome. Multivariable MR analysis was conducted to estimate the independent effects of exposures on outcome. Univariable MR analysis indicated that the level of ALT, AST, and GGT was the risk factor for HCC incidence. Meanwhile, multivariable MR analysis revealed that AST was an independent risk factor for HCC. The hazard ratio (HR) of the probability of HCC was 3.045 [95% confidence interval (95%CI), 1.697-5.463, p = 0.003] for AST. The results of reverse MR analyses showed that gene-predictive HCC incidence could increase the levels of AST (HR = 1.031, 95%CI: 1.009-1.054, p = 2.52 × 10-4) and ALT (HR = 1.040, 95%CI: 1.019-1.063, p = 0.005). Meanwhile, HCC may be negatively correlated with ALP levels (HR = 0.971, 95%CI: 0.947-0.995, p = 0.018). This study provides evidence to support that genetically predicted higher levels of AST are related to increased risk of HCC, with no strong evidence of a causal effect of genetically predicted ALP, ALP, and GGT on HCC. In addition, genetic predisposition to HCC could influence blood concentration of ALT, AST, and ALP. Thus, this may create a vicious cycle.
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Affiliation(s)
- Shanshan Qin
- Department of Radiology, Qilu Hospital of Shandong University, Jinan, China
| | - Jing Wang
- Shandong Medical College, Jinan, China
| | - Haiqing Yuan
- Intensive Care Unit, Weifang People’s Hospital, Weifang, Shandong, China
| | - Jingzhen He
- Department of Radiology, Qilu Hospital of Shandong University, Jinan, China
| | - Shoujing Luan
- Department of Endocrinology and Metabolism, Weifang People’s Hospital, Weifang, Shandong, China
| | - Yan Deng
- Department of Radiology, Qilu Hospital of Shandong University, Jinan, China
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10
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Eguia E, Baker T, Baker M. Hepatocellular Carcinoma: Surgical Management and Evolving Therapies. Cancer Treat Res 2024; 192:185-206. [PMID: 39212922 DOI: 10.1007/978-3-031-61238-1_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the eighth most common cancer in women worldwide. It is also the second leading cause of cancer death worldwide, with 780,000 deaths in 2018. Seventy-two percent of HCC cases occur in Asia, 10% in Europe, 8% in Africa, 5% in North America, and 5% in Latin America (Singal et al. in J Hepatol 72(2):250-261, 2020 [1]).
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Affiliation(s)
- Emanuel Eguia
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Talia Baker
- Huntsman Cancer Center, University of Utah Eccles School of Medicine, Salt Lake City, UT, USA
| | - Marshall Baker
- Huntsman Cancer Center, University of Utah Eccles School of Medicine, Salt Lake City, UT, USA.
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11
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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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12
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Huang SC, Kao JH. The interplay between chronic hepatitis B and diabetes mellitus: A narrative and concise review. Kaohsiung J Med Sci 2024; 40:6-10. [PMID: 37732697 DOI: 10.1002/kjm2.12762] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Revised: 09/02/2023] [Accepted: 09/05/2023] [Indexed: 09/22/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder among individuals with chronic hepatitis B (CHB), contributing to additional adverse impacts on both hepatic and extrahepatic systems. Existing evidence suggests a potential positive association between CHB and the development of insulin resistance and T2DM. The presence of T2DM in CHB patients is associated with an increased risk of liver fibrosis, cirrhosis, decompensation, and hepatocellular carcinoma (HCC) occurrence. Moreover, it elevates the risk of non-liver cancers and all-cause mortality in this population. T2DM also serves as the key element in metabolic dysfunction-associated steatotic liver disease, which is prevalent in the CHB population. Although specific guidelines for managing T2DM in CHB patients have not been proposed, some studies indicated that intensive glycemic control may benefit the prognosis of these patients. Additionally, specific antidiabetic agents, such as metformin and thiazolidinediones, promise to reduce HCC risk. However, unresolved questions, including the optimal glycemic control target and the selection of antidiabetic agents for CHB patients, remain and thus warrant further investigations through well-designed prospective trials. Implementing a standardized protocol encompassing regular monitoring, risk stratification, and early intervention using a multidisciplinary framework may improve the outcomes of diabetic CHB patients.
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Affiliation(s)
- Shang-Chin Huang
- Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
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13
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Sacco M, Ribaldone DG, Saracco GM. Metformin and Hepatocellular Carcinoma Risk Reduction in Diabetic Patients with Chronic Hepatitis C: Fact or Fiction? Viruses 2023; 15:2451. [PMID: 38140692 PMCID: PMC10748230 DOI: 10.3390/v15122451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Revised: 12/07/2023] [Accepted: 12/15/2023] [Indexed: 12/24/2023] Open
Abstract
BACKGROUND Patients with chronic hepatitis C (CHC) and concomitant type 2 diabetes mellitus (DM) show a higher risk of developing hepatocellular carcinoma (HCC). Successful antiviral therapy has reduced the incidence of post-therapy HCC, but the presence of DM still represents an unfavourable predictive factor even in cured patients. Metformin (MET) is recommended as a first-line therapy for DM, and its use is associated with a significant reduction in HCC among diabetic patients with chronic liver disease of different etiology, but very few studies specifically address this issue in patients with CHC. AIM the aim of this review is to evaluate whether the use of MET induces a significant decrease in HCC in diabetic patients with CHC, treated or untreated with antiviral therapy. METHODS A search of PubMed, Medline, Web of Sciences and Embase was conducted for publications evaluating the role of MET in reducing the risk of HCC in patients with DM and CHC, with no language and study type restrictions up to 30 June 2023. Only studies fulfilling the following inclusion criteria were considered: (1) data on the incidence of HCC in the follow-up of diabetic patients with CHC only; (2) follow-up ≥24 months; (3) sufficient data to establish the rate of diabetic patients with CHC treated with metformin or other antidiabetic medications; and (4) data on the type of antiviral treatment and the clinical outcome. RESULTS Three studies met the inclusion criteria. A prospective cohort study considering only patients with DM and untreated advanced CHC, or non-responders to interferon (IFN) therapy, showed that the use of MET was associated with a significant decrease in HCC incidence, liver-related death and liver transplants. A recent retrospective study focusing on a large-scale nationwide cohort of patients with CHC in Taiwan successfully treated with IFN-based therapy stratified patients into 3 groups: non-MET users, MET users and non-diabetic patients, with 5-year cumulative rates of HCC of 10.9%, 2.6% and 3.0%, respectively, showing a significantly higher HCC risk in non-MET users compared with MET users and with non-diabetic patients, while it was not significantly different between MET users and non-diabetic patients. In a recent Italian cohort study focusing on 7007 patients with CHC treated and cured with direct-acting antiviral agents (DAAs), a combined effect of DM and MET therapy was found, showing a higher incidence of HCC in diabetic patients not taking MET compared with those without DM and those with DM taking MET. CONCLUSION according to the current evidence, the use of MET should be encouraged in diabetic patients with CHC in order to reduce the risk of HCC; however, a well-designed randomized controlled trial is needed to establish the generalizability of the beneficial effects of MET in this particular subset of patients.
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Affiliation(s)
| | | | - Giorgio Maria Saracco
- Gastro-Hepatoloy Unit, Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (M.S.); (D.G.R.)
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He W, Wang X, Chen M, Li C, Chen W, Pan L, Cui Y, Yu Z, Wu G, Yang Y, Xu M, Dong Z, Ma K, Wang J, He Z. Metformin reduces hepatocarcinogenesis by inducing downregulation of Cyp26a1 and CD8 + T cells. Clin Transl Med 2023; 13:e1465. [PMID: 37997519 PMCID: PMC10668005 DOI: 10.1002/ctm2.1465] [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: 04/14/2023] [Revised: 10/12/2023] [Accepted: 10/19/2023] [Indexed: 11/25/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a highly heterogeneous cancer with major challenges in both prevention and therapy. Metformin, adenosine monophosphate-activated protein kinase (AMPK) activator, has been suggested to reduce the incidence of HCC when used for patients with diabetes in preclinical and clinical studies. However, the possible effects of metformin and their mechanisms of action in non-diabetic HCC have not been adequately investigated. METHODS Fah-/- mice were used to construct a liver-injury-induced non-diabetic HCC model for exploring hepatocarcinogenesis and therapeutic potential of metformin. Changes in relevant tumour and biochemical indicators were measured. Bulk and single-cell RNA-sequencing analyses were performed to validate the crucial role of proinflammatory/pro-tumour CD8+ T cells. In vitro and in vivo experiments were performed to confirm Cyp26a1-related antitumour mechanisms of metformin. RESULTS RNA-sequencing analysis showed that chronic liver injury led to significant changes in AMPK-, glucose- and retinol metabolism-related pathways in Fah-/- mice. Metformin prevented the formation of non-diabetic HCC in Fah-/- mice with chronic liver injury. Cyp26a1 ddexpression in hepatocytes was significantly suppressed after metformin treatment. Moreover, downregulation of Cyp26a1 occurred in conjunction with increased levels of all-trans-retinoic acid (atRA), which is involved in the activation of metformin-suppressed hepatocarcinogenesis in Fah-/- mice. In contrast, both CD8+ T-cell infiltration and proinflammatory/pro-tumour cytokines in the liver were significantly upregulated in Fah-/- mice during chronic liver injury, which was notably reversed by either metformin or atRA treatment. Regarding mechanisms, metformin regulated the decrease in Cyp26a1 enzyme expression and increased atRA expression via the AMPK/STAT3/Gadd45β/JNK/c-Jun pathway. CONCLUSIONS Metformin inhibits non-diabetic HCC by upregulating atRA levels and downregulating CD8+ T cells. This is the first reporting that the traditional drug metformin regulates the metabolite atRA via the Cyp26a1-involved pathway. The present study provides a potential application of metformin and atRA in non-diabetic HCC.
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Affiliation(s)
- Weizhi He
- Institute for Regenerative Medicine, Ji'an Hospital, Shanghai East HospitalSchool of Life Sciences and TechnologyTongji University School of MedicineShanghaiChina
- Shanghai Engineering Research Center of Stem Cells Translational MedicineShanghaiChina
- Fudan University Shanghai Cancer Center, International Co‐Laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Shanghai Medical College of Fudan University, Institutes of Biomedical SciencesShanghai Key Laboratory of Medical EpigeneticsShanghaiChina
| | - Xicheng Wang
- Institute for Regenerative Medicine, Ji'an Hospital, Shanghai East HospitalSchool of Life Sciences and TechnologyTongji University School of MedicineShanghaiChina
- Shanghai Engineering Research Center of Stem Cells Translational MedicineShanghaiChina
| | - Miaomiao Chen
- Institute for Regenerative Medicine, Ji'an Hospital, Shanghai East HospitalSchool of Life Sciences and TechnologyTongji University School of MedicineShanghaiChina
- Shanghai Engineering Research Center of Stem Cells Translational MedicineShanghaiChina
| | - Chong Li
- Zhoupu Community Health Service Center of Pudong New AreaShanghaiChina
| | - Wenjian Chen
- Institute for Regenerative Medicine, Ji'an Hospital, Shanghai East HospitalSchool of Life Sciences and TechnologyTongji University School of MedicineShanghaiChina
- Shanghai Engineering Research Center of Stem Cells Translational MedicineShanghaiChina
| | - Lili Pan
- Institute for Regenerative Medicine, Ji'an Hospital, Shanghai East HospitalSchool of Life Sciences and TechnologyTongji University School of MedicineShanghaiChina
- Shanghai Engineering Research Center of Stem Cells Translational MedicineShanghaiChina
| | - Yangyang Cui
- Institute for Regenerative Medicine, Ji'an Hospital, Shanghai East HospitalSchool of Life Sciences and TechnologyTongji University School of MedicineShanghaiChina
- Postgraduate Training Base of Shanghai East HospitalJinzhou Medical UniversityJinzhouLiaoningChina
| | - Zhao Yu
- Institute for Regenerative Medicine, Ji'an Hospital, Shanghai East HospitalSchool of Life Sciences and TechnologyTongji University School of MedicineShanghaiChina
- Shanghai Engineering Research Center of Stem Cells Translational MedicineShanghaiChina
| | - Guoxiu Wu
- Institute for Regenerative Medicine, Ji'an Hospital, Shanghai East HospitalSchool of Life Sciences and TechnologyTongji University School of MedicineShanghaiChina
- Shanghai Engineering Research Center of Stem Cells Translational MedicineShanghaiChina
| | - Yang Yang
- Institute for Regenerative Medicine, Ji'an Hospital, Shanghai East HospitalSchool of Life Sciences and TechnologyTongji University School of MedicineShanghaiChina
- Shanghai Engineering Research Center of Stem Cells Translational MedicineShanghaiChina
| | - Mingyang Xu
- Institute for Regenerative Medicine, Ji'an Hospital, Shanghai East HospitalSchool of Life Sciences and TechnologyTongji University School of MedicineShanghaiChina
- Shanghai Engineering Research Center of Stem Cells Translational MedicineShanghaiChina
| | - Zhaoxuan Dong
- Institute for Regenerative Medicine, Ji'an Hospital, Shanghai East HospitalSchool of Life Sciences and TechnologyTongji University School of MedicineShanghaiChina
- Shanghai Engineering Research Center of Stem Cells Translational MedicineShanghaiChina
| | - Keming Ma
- Institute for Regenerative Medicine, Ji'an Hospital, Shanghai East HospitalSchool of Life Sciences and TechnologyTongji University School of MedicineShanghaiChina
- Shanghai Engineering Research Center of Stem Cells Translational MedicineShanghaiChina
| | - Jinghan Wang
- Department of Hepatobiliary and Pancreatic SurgeryShanghai East Hospital, Tongji UniversityShanghaiChina
| | - Zhiying He
- Institute for Regenerative Medicine, Ji'an Hospital, Shanghai East HospitalSchool of Life Sciences and TechnologyTongji University School of MedicineShanghaiChina
- Shanghai Engineering Research Center of Stem Cells Translational MedicineShanghaiChina
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Khajeh E, Aminizadeh E, Moghadam AD, Ramouz A, Klotz R, Golriz M, Merle U, Springfeld C, Chang D, Longerich T, Büchler MW, Mehrabi A. Association of perioperative use of statins, metformin, and aspirin with recurrence after curative liver resection in patients with hepatocellular carcinoma: A propensity score matching analysis. Cancer Med 2023; 12:19548-19559. [PMID: 37737550 PMCID: PMC10587989 DOI: 10.1002/cam4.6569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Revised: 08/22/2023] [Accepted: 09/11/2023] [Indexed: 09/23/2023] Open
Abstract
BACKGROUND Statins, metformin, and aspirin have been reported to reduce the incidence of hepatocellular carcinoma (HCC). However, the effect of their perioperative use on survival outcomes of HCC patients following curative liver resection still remains unclear. METHOD Three hundred and fifty three patients with a first diagnosis of HCC who underwent curative liver resection were included. Propensity score matching analysis with a users: nonusers ratio of 1:2 were performed for each of the medications (statins, metformin, and aspirin). Overall survival (OS) and recurrence-free survival (RFS) were evaluated and multivariable Cox proportional hazard analysis was performed. RESULTS Sixty two patients received statins, 48 patients used metformin, and 53 patients received aspirin for ≥90 days before surgery. None of the medications improved OS. RFS of statin users was significantly longer than that of nonusers (p = 0.021) in the matched cohort. Users of hydrophilic statins, but not lipophilic ones had a significantly longer RFS than nonusers. Multivariable analysis showed that statin use significantly improved RFS (hazard ratio [HR]: 0.41, 95% confidence interval [CI]: 0.17-0.97, p = 0.044). No difference was seen in RFS between metformin users and nonusers. Among patients with diabetes, RFS was nonsignificantly longer in metformin users than in non-metformin users (84.1% vs. 60.85%, p = 0.069) in the matched cohort. No difference in postoperative RFS was seen between aspirin users and nonusers. CONCLUSION Preoperative use of statins in patients with HCC can increase RFS after curative liver resection, but metformin and aspirin were not associated with improved survival. Randomized controlled trials are needed to confirm the findings of the present study.
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Affiliation(s)
- Elias Khajeh
- Department of General, Visceral, and Transplantation SurgeryHeidelberg University HospitalHeidelbergGermany
| | - Ehsan Aminizadeh
- Department of General, Visceral, and Transplantation SurgeryHeidelberg University HospitalHeidelbergGermany
| | - Arash Dooghaie Moghadam
- Department of General, Visceral, and Transplantation SurgeryHeidelberg University HospitalHeidelbergGermany
| | - Ali Ramouz
- Department of General, Visceral, and Transplantation SurgeryHeidelberg University HospitalHeidelbergGermany
| | - Rosa Klotz
- Department of General, Visceral, and Transplantation SurgeryHeidelberg University HospitalHeidelbergGermany
| | - Mohammad Golriz
- Department of General, Visceral, and Transplantation SurgeryHeidelberg University HospitalHeidelbergGermany
- Liver Cancer Center Heidelberg (LCCH)Heidelberg University HospitalHeidelbergGermany
| | - Uta Merle
- Liver Cancer Center Heidelberg (LCCH)Heidelberg University HospitalHeidelbergGermany
- Department of Internal Medicine IV, Gastroenterology & HepatologyHeidelberg University HospitalHeidelbergGermany
| | - Christoph Springfeld
- Liver Cancer Center Heidelberg (LCCH)Heidelberg University HospitalHeidelbergGermany
- Department of Medical OncologyNational Center for Tumor Diseases Heidelberg University HospitalHeidelbergGermany
| | - De‐Hua Chang
- Liver Cancer Center Heidelberg (LCCH)Heidelberg University HospitalHeidelbergGermany
- Department of Diagnostic and Interventional RadiologyHeidelberg University HospitalHeidelbergGermany
| | - Thomas Longerich
- Liver Cancer Center Heidelberg (LCCH)Heidelberg University HospitalHeidelbergGermany
- Institute of PathologyHeidelberg University HospitalHeidelbergGermany
| | - Markus W. Büchler
- Department of General, Visceral, and Transplantation SurgeryHeidelberg University HospitalHeidelbergGermany
| | - Arianeb Mehrabi
- Department of General, Visceral, and Transplantation SurgeryHeidelberg University HospitalHeidelbergGermany
- Liver Cancer Center Heidelberg (LCCH)Heidelberg University HospitalHeidelbergGermany
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Abdalla MMI. Serum resistin and the risk for hepatocellular carcinoma in diabetic patients. World J Gastroenterol 2023; 29:4271-4288. [PMID: 37545641 PMCID: PMC10401662 DOI: 10.3748/wjg.v29.i27.4271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 06/11/2023] [Accepted: 06/27/2023] [Indexed: 07/13/2023] Open
Abstract
Hepatocellular carcinoma (HCC), the predominant type of liver cancer, is a major contributor to cancer-related fatalities across the globe. Diabetes has been identified as a significant risk factor for HCC, with recent research indicating that the hormone resistin could be involved in the onset and advancement of HCC in diabetic individuals. Resistin is a hormone that is known to be involved in inflammation and insulin resistance. Patients with HCC have been observed to exhibit increased resistin levels, which could be correlated with more severe disease stages and unfavourable prognoses. Nevertheless, the exact processes through which resistin influences the development and progression of HCC in diabetic patients remain unclear. This article aims to examine the existing literature on the possible use of resistin levels as a biomarker for HCC development and monitoring. Furthermore, it reviews the possible pathways of HCC initiation due to elevated resistin and offers new perspectives on comprehending the fundamental mechanisms of HCC in diabetic patients. Gaining a better understanding of these processes may yield valuable insights into HCC’s development and progression, as well as identify possible avenues for prevention and therapy.
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Affiliation(s)
- Mona Mohamed Ibrahim Abdalla
- Department of Human Biology, School of Medicine, International Medical University, Bukit Jalil 57000, Kuala Lumpur, Malaysia
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17
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Wang S, Zuo L, Lin Z, Yang Z, Chen R, Xu Y. The relationship between aspirin consumption and hepatocellular carcinoma: a systematic review and meta-analysis. Eur J Med Res 2023; 28:226. [PMID: 37422691 DOI: 10.1186/s40001-023-01204-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 06/29/2023] [Indexed: 07/10/2023] Open
Abstract
BACKGROUND Recent studies have shown that aspirin consumption may reduce the risk of hepatocellular carcinoma (HCC), but their correlation is still not fully understood. This meta-analysis aimed to investigate the correlation between aspirin consumption and HCC. METHODS A systematic literature search was conducted on PubMed, Scopus, Cochrane Library, EMBASE, and Web of Science databases. The search period was from the establishment of the database to July 1, 2022 with no language restrictions. RESULTS A total of 19 studies including three prospective studies and 16 retrospective ones with 2,217,712 patients were included. Compared with those who did not take aspirin, those who took aspirin had a 30% lower risk of HCC (hazard ratio [HR] = 0.70, 95% confidence interval [CI] 0.63-0.76, I2 = 84.7%, P < 0.001). Subgroup analysis showed that aspirin significantly reduced the risk of HCC by 19% in Asia (HR = 0.81, 95% CI 0.80-0.82, I2 = 85.2%, P < 0.001) and by 33% (HR = 0.67, 95% CI 0.61-0.73, I2 = 43.6%, P = 0.150) in Europe and the U.S with no significant difference. Moreover, in patients with HBV or HCV infection, aspirin reduced 19% and 24% of the risk of HCC, respectively. However, aspirin administration might increase risks of gastrointestinal bleeding in patients with chronic liver disease (HR = 1.14, 95% CI 0.99-1.31, I2 = 0.0%, P = 0.712). Sensitivity analysis showed no significant difference of results after excluding individual studies, suggesting that the results were robust. CONCLUSION Aspirin may reduce the risk of HCC in both healthy population and patients with chronic liver disease. However, attention should be paid to adverse events such as gastrointestinal bleeding in patients with chronic liver disease.
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Affiliation(s)
- Shuai Wang
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun, 130033, Jilin, China
| | - Lijuan Zuo
- Department of Gastroenterology, The First Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Zhaojin Lin
- Department of Anesthesiology, The First Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Zhiqin Yang
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun, 130033, Jilin, China
| | - Ran Chen
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun, 130033, Jilin, China
| | - Yan Xu
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun, 130033, Jilin, China.
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Abdelmalak J, Tan N, Con D, Eslick G, Majeed A, Kemp W, Roberts SK. The Effect of Aspirin Use on Incident Hepatocellular Carcinoma-An Updated Systematic Review and Meta-Analysis. Cancers (Basel) 2023; 15:3518. [PMID: 37444628 PMCID: PMC10341252 DOI: 10.3390/cancers15133518] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 07/02/2023] [Accepted: 07/04/2023] [Indexed: 07/15/2023] Open
Abstract
An increasing number of observational studies have described an association between aspirin use and a reduced risk of incident hepatocellular carcinoma. We performed this meta-analysis to provide a comprehensive and updated aggregate assessment of the effect of aspirin on HCC incidence. Two independent authors performed a systematic search of the literature, utilising the Medline, Embase, Scopus, and PubMed databases. A total of 16 studies (12 cohort studies, and 4 case-control studies) were selected for inclusion, with a large number of studies excluded, due to an overlapping study population. The pooled analysis of cohort studies involving a total population of approximately 2.5 million subjects, 822,680 aspirin users, and 20,626 HCC cases demonstrated a 30% reduced risk of HCC associated with aspirin use (adjusted HR 0.70, 95%CI 0.60-0.81). There was a similar but non-significant association observed across the case-control studies (adjusted OR 0.60, 95%CI 0.32-1.15, p = 0.13), which involved a total of 1961 HCC cases. In a subgroup meta-analysis of patients with cirrhosis, the relationship between aspirin use and incident HCC diminished to non-significance (adjusted HR 0.96, 95%CI 0.84-1.09). Aspirin use was associated with a statistically significant increase in bleeding events when all relevant studies were pooled together (adjusted HR 1.11, 95%CI 1.02-1.22). Prospectively collected data should be sought, to define the optimal patient group in which aspirin is safe and effective for the chemoprophylaxis of HCC.
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Affiliation(s)
- Jonathan Abdelmalak
- Department of Gastroenterology, Alfred Health, Melbourne, VIC 3004, Australia; (J.A.); (N.T.); (A.M.); (W.K.)
- Department of Medicine, Central Clinical School, Monash University, Melbourne, VIC 3145, Australia
| | - Natassia Tan
- Department of Gastroenterology, Alfred Health, Melbourne, VIC 3004, Australia; (J.A.); (N.T.); (A.M.); (W.K.)
- Department of Medicine, Central Clinical School, Monash University, Melbourne, VIC 3145, Australia
| | - Danny Con
- Department of Gastroenterology, Austin Health, Heidelberg, VIC 3084, Australia;
| | - Guy Eslick
- Clinical Links Using Evidence-Based Data (CLUED) Pty. Ltd., Sydney, NSW 2060, Australia;
| | - Ammar Majeed
- Department of Gastroenterology, Alfred Health, Melbourne, VIC 3004, Australia; (J.A.); (N.T.); (A.M.); (W.K.)
- Department of Medicine, Central Clinical School, Monash University, Melbourne, VIC 3145, Australia
| | - William Kemp
- Department of Gastroenterology, Alfred Health, Melbourne, VIC 3004, Australia; (J.A.); (N.T.); (A.M.); (W.K.)
- Department of Medicine, Central Clinical School, Monash University, Melbourne, VIC 3145, Australia
| | - Stuart K. Roberts
- Department of Gastroenterology, Alfred Health, Melbourne, VIC 3004, Australia; (J.A.); (N.T.); (A.M.); (W.K.)
- Department of Medicine, Central Clinical School, Monash University, Melbourne, VIC 3145, Australia
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Scheen AJ. Pharmacokinetic, toxicological, and clinical considerations for the treatment of type 2 diabetes in patients with liver disease: a comprehensive update. Expert Opin Drug Metab Toxicol 2023; 19:543-553. [PMID: 37620287 DOI: 10.1080/17425255.2023.2252333] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Revised: 08/22/2023] [Accepted: 08/23/2023] [Indexed: 08/26/2023]
Abstract
INTRODUCTION Type 2 diabetes and liver disease, mainly metabolic-associated fatty liver disease (MAFLD) and more rarely cirrhosis, coexist in many patients. This duality has direct implications for the physician when choosing glucose-lowering agents, with classical concerns but also recent new hopes. AREAS COVERED This updated comprehensive review will consider the pharmacokinetics, the tolerance/safety profile, the benefit/risk balance in cirrhosis, the effects on MAFLD and the risk of hepatocellular carcinoma of old and new glucose-lowering compounds in patients with liver disease, with a special focus on glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors. EXPERT OPINION We are currently facing a new paradigm in the management of patients with diabetes and liver disease. From previous reluctance when using antidiabetic agents (except insulin) in diabetic patients with hepatic impairment because of safety concerns, the commercialization of novel glucose-lowering agents has changed the scene. These agents, which have a good safety profile, are associated with weight loss and pleiotropic effects. They have proven their efficacy in improving MAFLD. However, more specific studies are still needed to prove their efficacy in preventing the progression to fibrosis/cirrhosis and confirm this new opportunity for the management of patients with diabetes and liver disease.
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Affiliation(s)
- André J Scheen
- Division of Clinical Pharmacology, Centre for Interdisciplinary Research on Medicines (CIRM), Liège University, Liège, Belgium
- Division of Diabetes, Nutrition and Metabolic Disorders, CHU Liège, Liège, Belgium
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Pan GQ, Jiao Y, Meng GX, Dong ZR, Li T. The relationship between the serum lipid profile and hepatocellular carcinoma in east Asian population: A mendelian randomization study. Heliyon 2023; 9:e17126. [PMID: 37484252 PMCID: PMC10361312 DOI: 10.1016/j.heliyon.2023.e17126] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 06/07/2023] [Accepted: 06/08/2023] [Indexed: 07/25/2023] Open
Abstract
BACKGROUND Although several studies have found that the serum lipid profile may be correlated with hepatocellular carcinoma (HCC), the causal relationships between the serum lipid profile and HCC have not been determined due to potential confounder. Here, Mendelian randomization (MR) analysis was performed to identify the relationship between the serum lipid profile and HCC in the East Asian population. METHOD Our study made a MR analysis with the validation of two data sets. We obtained genome-wide association study (GWAS) data related to the serum lipid profile from Asian Genetic Epidemiology Network (AGEN). Then, the data from a recent large GWAS of the East Asian ancestry in Japan (BioBank Japan, BBJ) were extracted. Summary-level statistical data for HCC were obtained from a large GWAS of the East Asian ancestry in Japan. Univariable MR analysis were performed to identify whether the genetic evidence of serum lipid profile was significantly associated with HCC risk. Multivariable MR analysis was conducted to estimate the independent effects of exposures on HCC. RESULTS Univariable and multivariable MR analyses indicated that the serum lipid profile was not a risk factor for HCC incidence in either data set based on the East Asian population. Multivariable MR analysis revealed that the hazard ratios of the probability of HCC in AGEN were 1.134 (95% confidence interval (CI), 0.903-1.424) for TG, 1.010 (95% CI: 0.824-1.237) for HDL-C, 0.974 (95% CI: 0.746-1.271) for TC, 0.918 (95% CI: 0.734-1.147) for LDL-C, while the results in BBJ were also non-significant: 1.111 (95% CI: 0.869-1.419) for TG, 0.957 (95% CI: 0.790-1.158) for HDL-C, 0.917 (95% CI: 0.643-1.308) for TC, 0.932 (95% CI: 0.699-1.243) for LDL-C. CONCLUSION Our MR study with the validation of two data sets found no strong evidence to support causal associations between the serum lipid profile and HCC risk.
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Affiliation(s)
- Guo-Qiang Pan
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, China
| | - Yan Jiao
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, China
| | - Guang-Xiao Meng
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, China
| | - Zhao-Ru Dong
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, China
| | - Tao Li
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, China
- Department of Hepatobiliary Surgery, The Second Hospital of Shandong University, Jinan, 250012, China
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21
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Lai HC, Lin HJ, Shih YH, Chou JW, Lin KW, Jeng LB, Huang ST. LipoCol Forte capsules reduce the risk of liver cancer: A propensity score-matched, nationwide, population-based cohort study. World J Gastrointest Oncol 2023; 15:828-842. [PMID: 37275448 PMCID: PMC10237025 DOI: 10.4251/wjgo.v15.i5.828] [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: 01/25/2023] [Revised: 03/03/2023] [Accepted: 04/19/2023] [Indexed: 05/12/2023] Open
Abstract
BACKGROUND Liver cancer is among the top five most common cancers globally. Lipid-lowering drugs such as statins can lower the risk of liver cancer, but may also cause liver damage. LipoCol Forte capsules (LFC), a red yeast rice product, have demonstrated significant antihypercholesterolemic effects and a good safety profile in clinical studies.
AIM To evaluate whether LFC lowers the risk of liver cancer in adults in this propensity score-matched, nationwide, population-based cohort study.
METHODS We used data from Taiwan’s National Health Insurance Research Database, which includes electronic medical records for up to 99.99% of Taiwan’s population. LFC users and LFC non-users were matched 1:1 by propensity scores between January 2010 and December 2017. All had follow-up data for at least 1 year. Statistical analyses compared demographic distributions including sex, age, comorbidities, and prescribed medications. Cox regression analyses estimated adjusted hazard ratios (aHRs) after adjusting for potential confounders.
RESULTS We enrolled 33231 LFC users and 33231 non-LFC users (controls). No significant differences between the study cohorts were identified regarding comorbidities and medications [standardized mean difference (SMD) < 0.05]. At follow-up, the overall incidence of liver cancer was significantly lower in the LFC cohort compared with controls [aHR 0.91; 95% confidence interval (CI): 0.86-0.95; P < 0.001]. The risk of liver cancer was significantly reduced in both females (aHR 0.87; 95%CI: 0.8-0.94; P < 0.001) and males (aHR 0.93; 95%CI: 0.87-0.98; P < 0.01) in the LFC cohort compared with their counterparts in the non-LFC cohort. The antitumor protective effects applied to patients with comorbidities (including hypertension, ischemic stroke, diabetes mellitus, hyperlipidemia, hepatitis B infection and hepatitis C infection). Those using LFC for more than 84 drug days had a 0.64-fold lower risk of liver cancer compared with controls (P < 0.001). Compared with controls, the risk of developing liver cancer in the LFC cohort progressively decreased over time; the lowest incidence of liver cancer occurred in LFC users followed-up for more than 6 years (27.44 vs 31.49 per 1,000 person-years; aHR 0.75; 95%CI: 0.68-0.82; P < 0.001).
CONCLUSION This retrospective cohort study indicates that LFC has a significantly protective effect on lowering the risk of liver cancer, in a dose-dependent and time-dependent manner.
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Affiliation(s)
- Hsiang-Chun Lai
- Graduate Institute of Chinese Medicine, School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40447, Taiwan
| | - Hung-Jen Lin
- School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan
| | - Ying-Hsiu Shih
- Management Office for Health Data, China Medical University Hospital, Taichung 40447, Taiwan
| | - Jen-Wei Chou
- Department of Internal Medicine, China Medical University Hospital, Taichung 40447, Taiwan
| | - Kuan-Wen Lin
- Department of Surgery, China Medical University Hospital, Taichung 40447, Taiwan
| | - Long-Bin Jeng
- Organ Transplantation Center, China Medical University Hospital, Taichung 40447, Taiwan
| | - Sheng-Teng Huang
- Department of Chinese Medicine, China Medical University Hospital, Taichung 40447, Taiwan
- Cancer Research Center for Traditional Chinese Medicine, Department of Medical Research, China Medical University Hospital, Taichung 40447, Taiwan
- An-Nan Hospital, China Medical University, Tainan 709204, Taiwan
- School of Chinese Medicine, China Medical University, Taichung 40447, Taiwan
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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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23
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Zeng RW, Yong JN, Tan DJH, Fu CE, Lim WH, Xiao J, Chan KE, Tan C, Goh XL, Chee D, Syn N, Tan EX, Muthiah MD, Ng CH, Tamaki N, Lee SW, Kim BK, Nguyen MH, Loomba R, Huang DQ. Meta-analysis: Chemoprevention of hepatocellular carcinoma with statins, aspirin and metformin. Aliment Pharmacol Ther 2023; 57:600-609. [PMID: 36625733 PMCID: PMC10792521 DOI: 10.1111/apt.17371] [Citation(s) in RCA: 50] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 11/12/2022] [Accepted: 12/11/2022] [Indexed: 01/11/2023]
Abstract
BACKGROUND Emerging data suggest that statins, aspirin and metformin may protect against hepatocellular carcinoma (HCC) development. However, prior meta-analyses were limited by heterogeneity and inclusion of studies without adequate adjustment for baseline risks. AIM To examine by an updated meta-analysis the association between these medications and HCC risk. METHODS Medline and Embase databases were searched from inception to March 2022 for studies that balanced baseline risks between study groups via propensity score matching or inverse probability of treatment weighting, that reported the impact of statins, aspirin or metformin on HCC risk. Multivariable-adjusted hazard ratios (HRs) for HCC were pooled using a random effects model. RESULTS Statin use was associated with reduced HCC risk overall (HR: 0.52; 95% CI: 0.37-0.72) (10 studies, 1,774,476), and in subgroup analyses for cirrhosis, hepatitis B/C, non-alcoholic fatty liver disease, studies accounting for concurrent aspirin and metformin consumption and lipophilic statins. Aspirin use was associated with reduced HCC risk overall (HR: 0.48; 95% CI: 0.27-0.87) (11 studies, 2,190,285 patients) but not in studies accounting for concurrent statin and metformin use. Metformin use was not associated with reduced HCC risk overall (HR: 0.57; 95% CI: 0.31-1.06) (3 studies, 125,458 patients). Most analyses had moderate/substantial heterogeneity, except in follow-up <60 months for aspirin (I2 = 0%). CONCLUSION Although statin and aspirin use were associated with reduced HCC risk, only statin use was significant in subgroup analyses accounting for concurrent medications. Metformin use was not associated with reduced HCC risk. These data have implications for future clinical trial design.
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Affiliation(s)
- Rebecca W. Zeng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Jie Ning Yong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Darren J. H. Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Clarissa E. Fu
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Jieling Xiao
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Kai En Chan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Caitlyn Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Xin Lei Goh
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Douglas Chee
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Nicholas Syn
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Eunice X. Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Mark D. Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Sung Won Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
- The Catholic University Liver Research Centre, Seoul, Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Mindie H. Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
| | - Rohit Loomba
- NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California at San Diego, San Diego, California, USA
| | - Daniel Q. Huang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
- NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California at San Diego, San Diego, California, USA
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24
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Tseng CH. Metformin Reduces the Risk of Hearing Loss: A Retrospective Cohort Study. Otolaryngol Head Neck Surg 2023; 168:1389-1400. [PMID: 36939574 DOI: 10.1002/ohn.232] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 11/22/2022] [Accepted: 11/30/2022] [Indexed: 01/30/2023]
Abstract
OBJECTIVE To compare the risk of hearing loss with regard to metformin exposure. STUDY DESIGN Retrospective cohort. SETTING Taiwan's National Health Insurance database. METHODS We enrolled 292,071 ever users and 18,200 never users of metformin with new-onset diabetes mellitus from 1999 to 2005 and followed them for hearing loss from January 1, 2006, to December 31, 2011. Hazard ratios (HRs) weighted by propensity score were estimated. RESULTS Hearing loss was newly diagnosed in 10,085 ever users and 1072 never users. Their respective incidence rates (per 100,000 person-years) were 738.09 and 1366.83. The HR comparing ever-to-never users was 0.534 (95% confidence interval [CI]: 0.501-0.569]. The HR (95% CI) for the first (<27.07 months), second (27.07-59.13 months), and third (>59.13 months) tertiles of cumulative duration of metformin therapy were 0.912 (0.852-0.975), 0.544 (0.508-0.582), and 0.275 (0.255-0.295), respectively; and were 0.900 (0.841-0.962), 0.531 (0.496-0.569), and 0.293 (0.273-0.315), respectively, for the first (<796.70 g), second (796.70-2020.15 g), and third (>2020.15 g) tertiles of cumulative dose. The magnitude of risk reduction became more remarkable in corresponding to the increasing tertiles of the defined daily dose prescribed. Subtype analyses suggested that the risk reduction was more significant for sensorineural than conductive hearing loss. Findings derived from a propensity score-matched cohort did not substantially change the conclusions, and the risk reduction for mixed hearing loss was not statistically significant in the matched cohort as significantly observed in the unmatched cohort. CONCLUSION The risk of hearing loss is reduced in a dose-response pattern in patients who use metformin.
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Affiliation(s)
- Chin-Hsiao Tseng
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Internal Medicine, Division of Endocrinology and Metabolism, National Taiwan University Hospital, Taipei, Taiwan.,National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Taiwan
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25
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Teng PC, Huang DQ, Lin TY, Noureddin M, Yang JD. Diabetes and Risk of Hepatocellular Carcinoma in Cirrhosis Patients with Nonalcoholic Fatty Liver Disease. Gut Liver 2023; 17:24-33. [PMID: 36530125 PMCID: PMC9840929 DOI: 10.5009/gnl220357] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Revised: 09/09/2022] [Accepted: 09/19/2022] [Indexed: 12/23/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the world. NAFLD is a hepatic manifestation of insulin resistance, the core pathophysiology of diabetes. Multiple clinical studies show that diabetes increases the risk of liver disease progression and cirrhosis development in patients with NAFLD. Diabetes has causal associations with many different cancers, including hepatocellular carcinoma (HCC). More recent studies demonstrate that diabetes increases the risk of HCC in patients with underlying NAFLD cirrhosis, confirming the direct hepatocarcinogenic effect of diabetes among cirrhosis patients. Diabetes promotes hepatocarcinogenesis via the activation of inflammatory cascades producing reactive oxygen species and proinflammatory cytokines, leading to genomic instability, cellular proliferation, and inhibition of apoptosis. Given the global increase in the burden of NAFLD and HCC, high-risk patients such as older diabetic individuals should be carefully monitored for HCC development. Future larger studies should explore whether the effect of diabetes on HCC risk in NAFLD cirrhosis is modifiable by the type of antidiabetic medication and the effectiveness of diabetes control.
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Affiliation(s)
- Pai-Chi Teng
- Division of Urology, Department of Surgery, Cardinal Tien Hospital, New Taipei, Taiwan,Department of Urology, National Taiwan University Hospital, Taipei, Taiwan,Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Daniel Q. Huang
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore,Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore
| | - Ting-Yi Lin
- Doctoral Degree Program of Translational Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei, Taiwan
| | - Mazen Noureddin
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Ju Dong Yang
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA,Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA,Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA,Corresponding AuthorJu Dong Yang, ORCIDhttps://orcid.org/0000-0001-7834-9825, E-mail
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26
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Garg K, Lingaraj A, Havangi S, Satheesha A, Naidu A, Garg B. Metformin use and Occurrence of Hepatocellular Carcinoma in Patients with Type II Diabetes Mellitus: A Systematic Review. JOURNAL OF RADIATION AND CANCER RESEARCH 2023. [DOI: 10.4103/jrcr.jrcr_65_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
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Does aspirin reduce the incidence, recurrence, and mortality of hepatocellular carcinoma? A GRADE-assessed systematic review and dose-response meta-analysis. Eur J Clin Pharmacol 2023; 79:39-61. [PMID: 36334108 DOI: 10.1007/s00228-022-03414-y] [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: 07/30/2022] [Accepted: 11/01/2022] [Indexed: 11/08/2022]
Abstract
PURPOSE Aspirin has been suggested to reduce the risk of cancer. However, previous studies have been inconsistent regarding the relationship between aspirin use and the risk of occurrence of hepatocellular carcinoma (HCC). The purpose of this study was to assess the effect of aspirin on clinical outcomes in patients with HCC in a meta-analysis and to explore the possible dose-response relationship. METHODS A systematic literature search was conducted in 10 electronic databases and 4 registries. The combined hazard ratios (HRs) were calculated using a random-effects model with 95% confidence interval (CIs) to assess the effect of aspirin on the risk of HCC. Relevant subgroup analyses and sensitivity analyses were performed. RESULTS The results show that aspirin use correlated with lower incidence of HCC (HR: 0.75, 95% CI: 0.71-0.80), decreased risk of HCC recurrence (HR: 0.79, 95% CI: 0.65-0.96), and reduced mortality (HR: 0.72, 95% CI: 0.60-0.87). The results of the subgroup analysis showed that aspirin use was consistently associated with reduced incidence of HCC across different regions, study designs, and populations. A linear relationship was found for both dosage and duration of aspirin use. An increased of bleeding with aspirin use among patients was also observed (HR 1.10, 95% CI: 1.02-1.20). CONCLUSIONS This meta-analysis found that aspirin use was independently associated with a reduced risk of HCC incidence, recurrence, and death. Furthermore, aspirin use influenced HCC occurrence in a dose-dependent and duration-dependent manner. However, an increased risk of bleeding with aspirin use was noted.
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28
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Jaffe A, Taddei TH, Giannini EG, Ilagan-Ying YC, Colombo M, Strazzabosco M. Holistic management of hepatocellular carcinoma: The hepatologist's comprehensive playbook. Liver Int 2022; 42:2607-2619. [PMID: 36161463 PMCID: PMC10878125 DOI: 10.1111/liv.15432] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 08/26/2022] [Accepted: 09/21/2022] [Indexed: 12/12/2022]
Abstract
Hepatocellular carcinoma (HCC) is a common complication in patients with chronic liver disease and leads to significant morbidity and mortality. Liver disease and liver cancer are preventable by mitigating and managing common risk factors, including chronic hepatitis B and C infection, alcohol use, diabetes, obesity and other components of the metabolic syndrome. The management of patients with HCC requires treatment of the malignancy and adequate control of the underlying liver disease, as preserving liver function is critical for successful cancer treatment and may have a relevant prognostic role independent of HCC management. Hepatologists are the ideal providers to guide the care of patients with HCC as they are trained to identify patients at risk, apply appropriate surveillance strategies, assess and improve residual liver function, evaluate candidacy for transplant, provide longitudinal care to optimize and preserve liver function during and after HCC treatment, survey for cancer recurrence and manage its risk factors, and prevent and treat decompensating events. We highlight the need for a team-based holistic approach to the patient with liver disease and HCC and identify necessary gaps in current care and knowledge.
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Affiliation(s)
- Ariel Jaffe
- Liver Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
- Smilow Cancer Hospital and Liver Cancer Program, New Haven, CT, USA
| | - Tamar H. Taddei
- Liver Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
| | - Edoardo G. Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Ysabel C. Ilagan-Ying
- Liver Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
| | | | - Mario Strazzabosco
- Liver Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
- Smilow Cancer Hospital and Liver Cancer Program, New Haven, CT, USA
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29
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Plaz Torres MC, Jaffe A, Perry R, Marabotto E, Strazzabosco M, Giannini EG. Diabetes medications and risk of HCC. Hepatology 2022; 76:1880-1897. [PMID: 35239194 PMCID: PMC9790535 DOI: 10.1002/hep.32439] [Citation(s) in RCA: 59] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 02/23/2022] [Accepted: 02/24/2022] [Indexed: 02/06/2023]
Abstract
Type 2 diabetes mellitus is a recognized risk factor for HCC in patients with liver disease, independent from the etiology of their liver disease. Hence, prevention and treatment of type 2 diabetes mellitus and its underlying cause, insulin resistance, should be considered a treatment target for patients with liver disease. The drug armamentarium for diabetes is wide and consists of agents with insulin-sensitizing activity, agents that stimulate insulin secretion, insulin itself, and agents that reduce gastrointestinal and urinary glucose absorption. From an endocrinology perspective, the main goal of treatment is the achievement of euglycemia; however, in patients at risk of, or with known underlying liver disease, the choice of diabetic medication as it relates to potential hepatic carcinogenesis remains complex and should be carefully considered. In the last decade, increasing evidence has suggested that metformin may reduce the risk of HCC, whereas evidence for other classes of diabetic medications, particularly some of the newer agents including the sodium glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, is fewer and often inconsistent. In this review, we aim to summarize the current evidence on the potential effects of the most widely used diabetic agents on liver cancer tumorigenesis.
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Affiliation(s)
- Maria Corina Plaz Torres
- Gastroenterology Unit, Department of Internal MedicineIRCCS—Ospedale Policlinico San Martino, University of GenoaGenoaItaly
| | - Ariel Jaffe
- Liver CenterDepartment of Internal MedicineYale University School of MedicineNew HavenConnecticutUSA
| | - Rachel Perry
- Liver CenterDepartment of Internal MedicineYale University School of MedicineNew HavenConnecticutUSA
- Section of EndocrinologyDepartment of Internal MedicineYale University School of MedicineNew HavenConnecticutUSA
- Department of Cellular and Molecular PhysiologyYale University School of MedicineNew HavenConnecticutUSA
| | - Elisa Marabotto
- Gastroenterology Unit, Department of Internal MedicineIRCCS—Ospedale Policlinico San Martino, University of GenoaGenoaItaly
| | - Mario Strazzabosco
- Liver CenterDepartment of Internal MedicineYale University School of MedicineNew HavenConnecticutUSA
| | - Edoardo G. Giannini
- Gastroenterology Unit, Department of Internal MedicineIRCCS—Ospedale Policlinico San Martino, University of GenoaGenoaItaly
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30
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Tseng CH. The Risk of Multiple Myeloma Is Reduced in Metformin Initiators: A Retrospective Cohort Study in Taiwanese Patients with Type 2 Diabetes Mellitus. Cancers (Basel) 2022; 14:5637. [PMID: 36428730 PMCID: PMC9688273 DOI: 10.3390/cancers14225637] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/08/2022] [Accepted: 11/14/2022] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Whether metformin might reduce the risk of multiple myeloma (MM) has not been extensively researched in humans. METHODS The study subjects were enrolled from the reimbursement database of Taiwan's National Health Insurance. A total of 739,553 patients who had a new diagnosis of type 2 diabetes mellitus during 1999-2009 were identified. They were categorized as metformin initiators (metformin (+)) and non-metformin initiators (metformin (-)) based on the prescriptions of antidiabetic drugs that included metformin and did not include metformin within the initial 12 months, respectively. MM incidence was calculated after the initial 12 months of treatment group assignment until 31 December 2011. Hazard ratios based on intention-to-treat (ITT) and per-protocol (PP) approaches were estimated by Cox regression weighted by propensity scores. RESULTS In the ITT analyses, the respective incidence rates for 497,248 metformin (+) and 242,305 metformin (-) were 9.97 and 14.33 per 100,000 person-years. The hazard ratio that compared metformin (+) to metformin (-) in the ITT analysis was 0.710 (95% confidence interval 0.593-0.850). In the PP analysis, the respective incidence rates were 5.14 and 13.98 per 100,000 person-years, and the hazard ratio was 0.355 (95% confidence interval, 0.270-0.466). The lower risk of MM among metformin (+) was supported by subgroup and sensitivity analyses. CONCLUSIONS Type 2 diabetes patients who are initiated with metformin treatment have a significantly lower risk of MM, especially when they adhere to metformin treatment.
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Affiliation(s)
- Chin-Hsiao Tseng
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei 10051, Taiwan;
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan
- National Institute of Environmental Health Sciences, Zhunan 35053, Taiwan
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31
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Yan LJ, Yao SY, Li HC, Meng GX, Liu KX, Ding ZN, Hong JG, Chen ZQ, Dong ZR, Li T. Efficacy and Safety of Aspirin for Prevention of Hepatocellular Carcinoma: An Updated Meta-analysis. J Clin Transl Hepatol 2022; 10:835-846. [PMID: 36304506 PMCID: PMC9547262 DOI: 10.14218/jcth.2021.00257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 09/30/2021] [Accepted: 12/15/2021] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND AND AIMS Previous meta-analyses have shown that aspirin use may reduce the risk of hepatocellular carcinoma (HCC). However, the optimal dose, frequency, and duration of aspirin use or the safety and efficacy of aspirin in target populations for HCC prevention remain unclear. The study aim was to investigate the efficacy and safety of aspirin for prevention of HCC. METHODS Publications were retrieved by a comprehensive literature research of several databases. Based on a random-effects model, hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were used to assess the pooled risk. The dose-response relationship between aspirin use and HCC risk was assessed with a restricted cubic spline model. RESULTS Twenty-two studies were included in the meta-analysis. Aspirin use was associated with a reduced risk of HCC (HR=0.64, 95% CI: 0.56-0.75). The effect was robust across sex and age; however, women and the non-elderly had the greatest benefit from aspirin use. The preventive effect was well reproduced in those with comorbidities. Daily use and long-term use of aspirin appeared to offer greater benefits. Aspirin 100 mg/d was associated with maximum reduction of HCC risk. Aspirin use did slightly increase the risk of bleeding (HR=1.14, 95% CI: 1.02-1.27). CONCLUSIONS Our meta-analysis confirmed that use of aspirin significantly reduced the incident risk of HCC. Regular and long-term aspirin use offers a greater advantage. Aspirin use was associated with an increased risk of bleeding. We recommend 100 mg/d aspirin as a feasible dose for further research on primary prevention of HCC in a broad at-risk population.
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Affiliation(s)
- Lun-Jie Yan
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Sheng-Yu Yao
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Hai-Chao Li
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Guang-Xiao Meng
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Kai-Xuan Liu
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Zi-Niu Ding
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Jian-Guo Hong
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Zhi-Qiang Chen
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Zhao-Ru Dong
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Tao Li
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
- Department of Hepatobiliary Surgery, The second Hospital of Shandong University, Jinan, Shandong, China
- Correspondence to: Tao Li, Department of General Surgery, Qilu Hospital, Shandong University 107 West Wen Hua Road, Jinan, Shandong 250012, China. ORCID: https://orcid.org/0000-0002-5108-1774. Tel/Fax: +86-531-82166341, E-mail: mailto:
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Tseng CH. Metformin and risk of gingival/periodontal diseases in diabetes patients: A retrospective cohort study. Front Endocrinol (Lausanne) 2022; 13:1036885. [PMID: 36277720 PMCID: PMC9583654 DOI: 10.3389/fendo.2022.1036885] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Accepted: 09/20/2022] [Indexed: 12/03/2022] Open
Abstract
AIM To compare the risk of gingival and periodontal diseases (GPD) between ever users and never users of metformin in patients with type 2 diabetes mellitus. METHODS The Taiwan's National Health Insurance database was used to enroll 423,949 patients with new onset diabetes mellitus from 1999 to 2005. After excluding ineligible patients, 60,309 ever users and 5578 never users were followed up for the incidence of GPD from January 1, 2006 until December 31, 2011. Propensity score-weighted hazard ratios were estimated by Cox regression. RESULTS GPD was newly diagnosed in 18,528 ever users (incidence: 7746.51 per 100,000 person-years) and 2283 never users (incidence: 12158.59 per 100,000 person-years). The hazard ratio that compared ever users to never users was 0.627 (95% confidence interval: 0.600-0.655). When metformin use was categorized by tertiles of cumulative duration and cumulative dose, the risk significantly reduced in a dose-response pattern when the cumulative duration reached approximately 2 years or the cumulative dose reached 670 grams. Analyses on the tertiles of defined daily dose of metformin showed that the reduction of GPD risk could be seen in all three subgroups but the benefit would be greater when the daily dose increased. CONCLUSION Long-term use of metformin is associated with a significantly reduced risk of GPD.
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Affiliation(s)
- Chin-Hsiao Tseng
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
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Metformin administration is associated with enhanced response to transarterial chemoembolization for hepatocellular carcinoma in type 2 diabetes patients. Sci Rep 2022; 12:14482. [PMID: 36008432 PMCID: PMC9411109 DOI: 10.1038/s41598-022-18341-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 08/09/2022] [Indexed: 12/09/2022] Open
Abstract
Transarterial chemoembolization (TACE) is often used as a locoregional therapy for early hepatocellular carcinoma (HCC) when local ablation or resection are not feasible, but incomplete response and recurrence are commonly observed. In this study, we sought to determine the association between metformin administration and TACE outcomes for single nodular HCC in patients with type 2 diabetes mellitus (T2DM). The retrospective cohort analysis included 164 T2DM patients with single nodular HCC who underwent TACE as an initial treatment, and 91 were exposed to metformin before and after TACE. Propensity score (PS) matching was used to balance covariates. Logistic regression analysis was used to determine the predictors of tumor response after TACE, and Cox regression analysis assessed independent predictors of local tumor recurrence (LTR) in patients with complete response after TACE. Metformin use was associated with significantly higher objective response rate (ORR) in the overall and PS-matched cohort (79.1% vs. 60.3 and 78.7% vs. 57.5%; p = 0.008 and p = 0.029, respectively). Logistic regression analysis showed that metformin use was an independent predictor of ORR in all and PS-matched patients (odds ratio = 2.65 and 3.06; p = 0.016 and 0.034, respectively). Cox regression analysis showed metformin administration was an independent predictor for lower LTR in all and PS-matched patients (hazard ratio = 0.28 and 0.27; p = 0.001 and 0.007, respectively). Metformin administration is associated with better initial response and lower local recurrence after TACE for single nodular HCC in T2DM.
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Wang Y, Wang M, Liu C, Wang W, Shi J, Dang S. Aspirin Use and the Risk of Hepatocellular Carcinoma: A Meta-analysis. J Clin Gastroenterol 2022; 56:e293-e302. [PMID: 35316225 DOI: 10.1097/mcg.0000000000001693] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 02/12/2022] [Indexed: 12/11/2022]
Abstract
INTRODUCTION AND AIM The use of aspirin is a potential protective factor against the development of hepatocellular carcinoma (HCC). Therefore, we conducted a meta-analysis to evaluate the contribution of aspirin to the risk of HCC. METHODS We searched for PubMed and EMBASE through September 2021. RESULTS Eighteen studies (16 cohort, 2 case-control) were included. Aspirin users were less likely to develop HCC than nonusers [adjusted odds ratio (OR), 0.54; 95% confidence interval (CI): 0.44-0.66]. Stratified analysis showed that aspirin reduced the risk of HCC in Asian and Western populations (OR, 0.59 vs. 0.67). Besides, aspirin has protective effects against HCC after hepatitis B virus (OR, 0.70; 95% CI: 0.52-0.93) and hepatitis C virus infections (OR, 0.41; 95% CI: 0.23-0.73). Aspirin has protective effects on people with chronic liver disease (OR, 0.46; 95% CI: 0.31-0.67) and on the general population (OR, 0.65; 95% CI: 0.54-0.79). In addition, confounding factors have an important impact on the results of aspirin prevention of liver cancer before (OR, 0.28; 95% CI: 0.06-1.27) and after (OR, 0.58; 95% CI: 0.47-0.71) adjustment. Further studies have shown that those in the long duration group do not experience better effects in preventing HCC (OR, 0.62 vs. 0.63). A further meta-analysis of 3 articles showed that the use of aspirin did not increase the risk of bleeding in patients with HCC (OR, 1.19; 95% CI: 0.87-1.64). CONCLUSION Our meta-analysis shows that the use of aspirin is associated with a lower risk of liver cancer.
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Affiliation(s)
- Yikai Wang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China
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Liu L, Liao R. Clinical features and outcomes of NAFLD-related hepatocellular carcinoma. Lancet Oncol 2022; 23:e243. [PMID: 35654060 DOI: 10.1016/s1470-2045(22)00272-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Accepted: 04/14/2022] [Indexed: 02/06/2023]
Affiliation(s)
- Lei Liu
- Department of Hepatobiliary Surgery, the People's Hospital of Yubei District of Chongqing City, Chongqing, China
| | - Rui Liao
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
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Cisneros-Garza L, González-Huezo M, Moctezuma-Velázquez C, Ladrón de Guevara-Cetina L, Vilatobá M, García-Juárez I, Alvarado-Reyes R, Álvarez-Treviño G, Allende-Pérez S, Bornstein-Quevedo L, Calderillo-Ruiz G, Carrillo-Martínez M, Castillo-Barradas M, Cerda-Reyes E, Félix-Leyva J, Gabutti-Thomas J, Guerrero-Ixtlahuac J, Higuera-de-la-Tijera F, Huitzil-Meléndez D, Kimura-Hayama E, López-Hernández P, Malé-Velázquez R, Méndez-Sánchez N, Morales-Ruiz M, Ruíz-García E, Sánchez-Ávila J, Torrecillas-Torres L. The second Mexican consensus on hepatocellular carcinoma. Part I: Epidemiology and diagnosis. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2022; 87:216-234. [DOI: 10.1016/j.rgmxen.2021.10.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 10/21/2021] [Indexed: 12/24/2022] Open
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Cisneros-Garza LE, González-Huezo MS, Moctezuma-Velázquez C, Ladrón de Guevara-Cetina L, Vilatobá M, García-Juárez I, Alvarado-Reyes R, Álvarez-Treviño GA, Allende-Pérez S, Bornstein-Quevedo L, Calderillo-Ruiz G, Carrillo-Martínez MA, Castillo-Barradas M, Cerda-Reyes E, Félix-Leyva JA, Gabutti-Thomas JA, Guerrero-Ixtlahuac J, Higuera-de-la-Tijera F, Huitzil-Meléndez D, Kimura-Hayama E, López-Hernández PA, Malé-Velázquez R, Méndez-Sánchez N, Morales-Ruiz MA, Ruíz-García E, Sánchez-Ávila JF, Torrecillas-Torres L. The second Mexican consensus on hepatocellular carcinoma. Part I: Epidemiology and diagnosis. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2022; 87:216-234. [PMID: 35431142 DOI: 10.1016/j.rgmx.2021.10.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 10/21/2021] [Indexed: 01/04/2025]
Abstract
Hepatocellular carcinoma (HCC) is more frequently manifesting as one of the main complications of cirrhosis of the liver, its principal risk factor. There have been modifications in its incidence over the past decade, related to an epidemiologic transition in the etiology of cirrhosis, with a decrease in the prevalence of hepatitis C and an increase in nonalcoholic fatty liver disease (NAFLD) as a cause, as well as the development of HCC in the non-cirrhotic liver due to NAFLD. Genetic markers associated with the disease have been identified, and surveillance and diagnosis have improved. Regarding treatment, surgical techniques, in both resection and transplantation, have advanced and radiologic techniques, at the curative stage of the disease, have enhanced survival in those patients. And finally, there have been radical changes in the systemic approach, with much more optimistic expectations, when compared with the options available a decade ago. Therefore, the Asociación Mexicana de Hepatología decided to carry out the Second Mexican Consensus on Hepatocellular Carcinoma, which is an updated review of the available national and international evidence on the epidemiology, risk factors, surveillance, diagnosis, and treatment of the disease, to offer the Mexican physician current information on the different topics regarding hepatocellular carcinoma. In this first part of the document, the topics related to epidemiology and diagnosis are presented.
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Affiliation(s)
- L E Cisneros-Garza
- Hospital Christus Muguerza Alta Especialidad, Monterrey, Nuevo León, Mexico
| | | | - C Moctezuma-Velázquez
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | - M Vilatobá
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - I García-Juárez
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | - G A Álvarez-Treviño
- Unidad de Medicina de Alta Especialidad 25 IMSS, Monterrey, Nuevo León, Mexico
| | | | - L Bornstein-Quevedo
- InmunoQ, Laboratorio de Patología, Inmunohistoquímica y Biología Molecular, Mexico City, Mexico
| | | | | | | | | | | | - J A Gabutti-Thomas
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | - D Huitzil-Meléndez
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | - P A López-Hernández
- Unidad de Medicina de Alta Especialidad 25 IMSS, Monterrey, Nuevo León, Mexico
| | - R Malé-Velázquez
- Instituto de Salud Digestiva y Hepática SA de CV, Guadalajara, Jalisco, Mexico
| | | | - M A Morales-Ruiz
- Centro Oncológico Estatal Issemym, Toluca, Estado de México, Mexico
| | - E Ruíz-García
- Instituto Nacional de Cancerología, Mexico City, Mexico
| | - J F Sánchez-Ávila
- Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Monterrey, Nuevo León, Mexico
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Di Ciaula A, Bonfrate L, Krawczyk M, Frühbeck G, Portincasa P. Synergistic and Detrimental Effects of Alcohol Intake on Progression of Liver Steatosis. Int J Mol Sci 2022; 23:2636. [PMID: 35269779 PMCID: PMC8910376 DOI: 10.3390/ijms23052636] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 02/24/2022] [Accepted: 02/25/2022] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are the most common liver disorders worldwide and the major causes of non-viral liver cirrhosis in the general population. In NAFLD, metabolic abnormalities, obesity, and metabolic syndrome are the driving factors for liver damage with no or minimal alcohol consumption. ALD refers to liver damage caused by excess alcohol intake in individuals drinking more than 5 to 10 daily units for years. Although NAFLD and ALD are nosologically considered two distinct entities, they show a continuum and exert synergistic effects on the progression toward liver cirrhosis. The current view is that low alcohol use might also increase the risk of advanced clinical liver disease in NAFLD, whereas metabolic factors increase the risk of cirrhosis among alcohol risk drinkers. Therefore, special interest is now addressed to individuals with metabolic abnormalities who consume small amounts of alcohol or who binge drink, for the role of light-to-moderate alcohol use in fibrosis progression and clinical severity of the liver disease. Evidence shows that in the presence of NAFLD, there is no liver-safe limit of alcohol intake. We discuss the epidemiological and clinical features of NAFLD/ALD, aspects of alcohol metabolism, and mechanisms of damage concerning steatosis, fibrosis, cumulative effects, and deleterious consequences which include hepatocellular carcinoma.
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Affiliation(s)
- Agostino Di Ciaula
- Clinica Medica “Augusto Murri”, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School—Piazza Giulio Cesare 11, 70124 Bari, Italy; (A.D.C.); (L.B.)
| | - Leonilde Bonfrate
- Clinica Medica “Augusto Murri”, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School—Piazza Giulio Cesare 11, 70124 Bari, Italy; (A.D.C.); (L.B.)
| | - Marcin Krawczyk
- Department of Medicine II Saarland University Medical Center, Saarland University, 66424 Homburg, Germany;
- Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Centre for Preclinical Research, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Gema Frühbeck
- Department of Endocrinology & Nutrition, Clínica Universidad de Navarra, 31008 Pamplona, Spain;
- Metabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), ISCIII, 31009 Pamplona, Spain
- Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31009 Pamplona, Spain
| | - Piero Portincasa
- Clinica Medica “Augusto Murri”, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School—Piazza Giulio Cesare 11, 70124 Bari, Italy; (A.D.C.); (L.B.)
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Chemopreventive Effects of Concomitant or Individual Use of Statins, Aspirin, Metformin, and Angiotensin Drugs: A Study Using Claims Data of 23 Million Individuals. Cancers (Basel) 2022; 14:cancers14051211. [PMID: 35267516 PMCID: PMC8909564 DOI: 10.3390/cancers14051211] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 02/09/2022] [Accepted: 02/22/2022] [Indexed: 12/14/2022] Open
Abstract
Despite previous studies on statins, aspirin, metformin, and angiotensin-converting-enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs), little has been studied about all their possible combinations for chemoprevention against cancers. This study aimed to comprehensively analyze the composite chemopreventive effects of all the combinations. In this case-control study, health records were retrieved from claims databases of Taiwan’s Health and Welfare Data Science Center. Eligible cases were matched at a 1:4 ratio with controls for age and sex. Both cases and controls were categorized into 16 exposure groups based on medication use. A total of 601,733 cancer cases were identified. Cancer risks (denoted by adjusted odds ratio; 99% confidence interval) were found to be significantly decreased: overall risk of all cancers in statin-alone (0.864; 0.843, 0.886), aspirin-alone (0.949; 0.939, 0.958), and ACEIs/ARBs (0.982; 0.978, 0.985) users; prostate (0.924; 0.889, 0.962) and female breast (0.967; 0.936, 1.000) cancers in metformin-alone users; gastrointestinal, lung, and liver cancers in aspirin and/or ACEIs/ARBs users; and liver cancer (0.433; 0.398, 0.471) in statin users. In conclusion, the results found no synergistic effect of multiple use of these agents on cancer prevention. Use of two (statins and aspirin, statins and metformin, statins and ACEIs/ARBs, and aspirin and ACEIS/ARBs) showed chemopreventive effects in some combinations, while the use of four, in general, did not.
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Yen FS, Hsu CC, Wei JCC, Hou MC, Hwu CM. Selection and Warning of Evidence-Based Antidiabetic Medications for Patients With Chronic Liver Disease. Front Med (Lausanne) 2022; 9:839456. [PMID: 35252271 PMCID: PMC8888965 DOI: 10.3389/fmed.2022.839456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 01/26/2022] [Indexed: 11/13/2022] Open
Abstract
The global prevalence of chronic liver disease and diabetes mellitus (DM) has gradually increased potentially due to changes in diet and lifestyle. The choice of antidiabetic medications for patients with coexisting DM and chronic liver disease is complicated. Severe liver injury may decrease the metabolism of antidiabetic medications, resulting in elevated drug concentrations and adverse effects. The choice of antidiabetic medications in patients with chronic liver disease has not been well studied. The long-term outcomes of antidiabetic medications in patients with chronic liver disease have gained attention recently. Herein, we reviewed relevant articles to extend our understanding on the selection and warning of antidiabetic medications for patients with chronic liver disease.
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Affiliation(s)
| | - Chih-Cheng Hsu
- Institute of Population Health Sciences, National Health Research Institute, Miaoli, Taiwan
- Department of Health Services Administration, China Medical University, Taichung, Taiwan
- Department of Family Medicine, Min-Sheng General Hospital, Taoyuan, Taiwan
| | - James Cheng-Chung Wei
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Department of Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
- Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
| | - Ming-Chih Hou
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chii-Min Hwu
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
- Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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Li Q, Xu H, Sui C, Zhang H. Impact of metformin use on risk and mortality of hepatocellular carcinoma in diabetes mellitus. Clin Res Hepatol Gastroenterol 2022; 46:101781. [PMID: 34332136 DOI: 10.1016/j.clinre.2021.101781] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 06/22/2021] [Accepted: 07/07/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND The views regarding the associations between metformin use and hepatocellular carcinoma (HCC) among diabetes mellitus (DM) patients are divisive. Thus we summarized all available published studies evaluating the relationship between metformin therapy and HCC survival and risk, and aim to conduct an updated meta-analysis study to more accurately clarify the association. METHODS We searched for articles regarding impact of metformin use on risk and mortality of HCC in DM and published before April 2021 in databases (PubMed and Web of Science). We used STATA 12.0 software to compute odds ratios (ORs)/relative risks (RRs) or hazard ratios (HRs) and their 95% confidence intervals (CIs) to generate a computed effect size and 95% CI. RESULTS The present study showed that metformin use was associated with a decreased risk of HCC in DM with a random effects model (OR/RR = 0.59, 95% CI 0.51-0.68, I2 = 96.5%, p < 0.001). In addition, the study indicated that metformin use was associated with a decreased all-cause mortality of HCC in DM with a random effects model (HR = 0.74, 95% CI 0.66-0.83, I2 = 49.6%, p = 0.037). CONCLUSION In conclusion, our studies support that the use of metformin in DM patients is significantly associated with reduced risk and all-cause mortality of HCC. And more prospective studies focusing on the metformin therapy as a protective factor for HCC are needed to verify the accuracy of the findings.
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Affiliation(s)
- Qiaomei Li
- Department of Hepatic Surgery, The Third Affiliated Hospital of Naval Medical University, 201805 Shanghai, China
| | - Hairong Xu
- Second department of biliary tract, The Third Affiliated Hospital of Naval Medical University, 201805 Shanghai, China
| | - Chengjun Sui
- Department of special treatment, The Third Affiliated Hospital of Naval Medical University, 201805 Shanghai, China
| | - Hongjuan Zhang
- Department of Oncology Biotherapy, The Third Affiliated Hospital of Naval Medical University, No. 700 North Moyu road, Jiading district, 201805 Shanghai, China.
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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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Maddah R, Shariati P, Arabpour J, Bazireh H, Shadpirouz M, Kafraj AS. Identification of critical genes and pathways associated with hepatocellular carcinoma and type 2 diabetes mellitus using integrated bioinformatics analysis. INFORMATICS IN MEDICINE UNLOCKED 2022. [DOI: 10.1016/j.imu.2022.100956] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
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Valenti L, Pelusi S, Aghemo A, Gritti S, Pasulo L, Bianco C, Iegri C, Cologni G, Degasperi E, D'Ambrosio R, Del Poggio P, Soria A, Puoti M, Carderi I, Pigozzi MG, Carriero C, Spinetti A, Zuccaro V, Memoli M, Giorgini A, Viganò M, Rumi MG, Re T, Spinelli O, Colombo MC, Quirino T, Menzaghi B, Lorini G, Pan A, D'Arminio Monforte A, Buscarini E, Autolitano A, Bonfanti P, Terreni N, Aimo G, Mendeni M, Prati D, Lampertico P, Colombo M, Fagiuoli S. Dysmetabolism, Diabetes and Clinical Outcomes in Patients Cured of Chronic Hepatitis C: A Real-Life Cohort Study. Hepatol Commun 2021; 6:867-877. [PMID: 34811949 PMCID: PMC8948549 DOI: 10.1002/hep4.1851] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Revised: 09/21/2021] [Accepted: 09/26/2021] [Indexed: 12/14/2022] Open
Abstract
The aim of this study was to examine the impact of features of dysmetabolism on liver disease severity, evolution, and clinical outcomes in a real‐life cohort of patients treated with direct acting antivirals for chronic hepatitis C virus (HCV) infection. To this end, we considered 7,007 patients treated between 2014 and 2018, 65.3% with advanced fibrosis, of whom 97.7% achieved viral eradication (NAVIGATORE‐Lombardia registry). In a subset (n = 748), liver stiffness measurement (LSM) was available at baseline and follow‐up. Higher body mass index (BMI; odds ratio [OR] 1.06 per kg/m2, 1.03‐1.09) and diabetes (OR 2.01 [1.65‐2.46]) were independently associated with advanced fibrosis at baseline, whereas statin use was protective (OR 0.46 [0.35‐0.60]; P < 0.0001 for all). The impact of BMI was greater in those without diabetes (P = 0.003). Diabetes was independently associated with less pronounced LSM improvement after viral eradication (P = 0.001) and in patients with advanced fibrosis was an independent predictor of the most frequent clinical events, namely de novo hepatocellular carcinoma (HCC; hazard ratio [HR] 2.09 [1.20‐3.63]; P = 0.009) and cardiovascular events (HR 2.73 [1.16‐6.43]; P = 0.021). Metformin showed a protective association against HCC (HR 0.32 [0.11‐0.96]; P = 0.043), which was confirmed after adjustment for propensity score (P = 0.038). Diabetes diagnosis further refined HCC prediction in patients with compensated advanced chronic liver disease at high baseline risk (P = 0.024). Conclusion: Metabolic comorbidities were associated with advanced liver fibrosis at baseline, whereas statins were protective. In patients with advanced fibrosis, diabetes increased the risk of de novo HCC and of cardiovascular events. Optimization of metabolic comorbidities treatment by a multi‐disciplinary management approach may improve cardiovascular and possibly liver‐related outcomes.
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Affiliation(s)
- Luca Valenti
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milano, Italy.,Precision Medicine Lab, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Milano, Italy
| | - Serena Pelusi
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milano, Italy.,Precision Medicine Lab, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Milano, Italy
| | - Alessio Aghemo
- Department of Internal Medicine and Hepatology, Humanitas University and Research Hospital, Rozzano, Italy
| | - Sara Gritti
- Fondazione Ricerca Ospedale di Bergamo, Papa Giovanni Hospital, Bergamo, Italy
| | - Luisa Pasulo
- Department of Gastroenterology and Hepatology, Papa Giovanni Hospital, Bergamo, Italy
| | - Cristiana Bianco
- Precision Medicine Lab, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Milano, Italy
| | - Claudia Iegri
- Department of Gastroenterology and Hepatology, Papa Giovanni Hospital, Bergamo, Italy
| | - Giuliana Cologni
- Department of Internal Medicine, Papa Giovanni Hospital, Bergamo, Italy
| | - Elisabetta Degasperi
- Division of Gastroenterology & Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Milano, Italy
| | - Roberta D'Ambrosio
- Division of Gastroenterology & Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Milano, Italy
| | - Paolo Del Poggio
- Department of Gastroenterology and Hepatology, Papa Giovanni Hospital, Bergamo, Zingonia, Italy
| | - Alessandro Soria
- Division of Infectious Diseases, San Gerardo Hospital-ASST Monza, Monza, Italy
| | - Massimo Puoti
- Department of Infectious Diseases, Hepatitis Center, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
| | | | | | - Canio Carriero
- Department of Infectious Diseases, Spedali Civili Hospital-ASST Brescia, Brescia, Italy
| | - Angiola Spinetti
- Department of Infectious Diseases, Spedali Civili Hospital-ASST Brescia, Brescia, Italy
| | - Valentina Zuccaro
- Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo di Pavia, Pavia, Italy
| | - Massimo Memoli
- Liver Center, San Raffaele Scientific Institute IRCCS, Milano, Italy
| | - Alessia Giorgini
- Department of Gastroenterology and Hepatology, San Paolo Hospital, ASST Santi Paolo e Carlo, Milan, Italy
| | - Mauro Viganò
- Department of Gastroenterology and Hepatology, San Giuseppe Hospital, Milan, Italy
| | - Maria Grazia Rumi
- Department of Gastroenterology and Hepatology, San Giuseppe Hospital, Milan, Italy
| | - Tiziana Re
- Department of Gastroenterology and Hepatology, Legnano Hospital-ASST Milano Ovest, Milan, Italy
| | - Ombretta Spinelli
- Department of Gastroenterology and Hepatology, Lariana Como Hospital, Milan, Italy
| | - Maria Chiara Colombo
- Department of Gastroenterology and Hepatology, Lariana Como Hospital, Milan, Italy
| | - Tiziana Quirino
- Department of Gastroenterology and Hepatology, Busto Arsizio Hospital ASST Valle Olona, Milan, Italy
| | - Barbara Menzaghi
- Department of Gastroenterology and Hepatology, Busto Arsizio Hospital ASST Valle Olona, Milan, Italy
| | - Gianpaolo Lorini
- Department of Gastroenterology and Hepatology, ASST Franciacorta, Milan, Italy
| | - Angelo Pan
- Department of Internal Medicine, Ospedale di Cremona, Cremona, Italy
| | | | | | | | - Paolo Bonfanti
- Division of Infectious Diseases, ASST Lecco, Lecco, Italy
| | | | | | | | - Daniele Prati
- Precision Medicine Lab, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Milano, Italy
| | - Pietro Lampertico
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milano, Italy.,Division of Gastroenterology & Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Milano, Italy.,CRC "AM. and A. Migliavacca" Center for Liver Disease, Università degli Studi di Milano, Milano, Italy
| | - Massimo Colombo
- Liver Center, San Raffaele Scientific Institute IRCCS, Milano, Italy
| | - Stefano Fagiuoli
- Department of Gastroenterology and Hepatology, Papa Giovanni Hospital, Bergamo, Italy
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Philips CA, Rajesh S, Nair DC, Ahamed R, Abduljaleel JK, Augustine P. Hepatocellular Carcinoma in 2021: An Exhaustive Update. Cureus 2021; 13:e19274. [PMID: 34754704 PMCID: PMC8569837 DOI: 10.7759/cureus.19274] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/04/2021] [Indexed: 02/06/2023] Open
Abstract
Primary liver cancer is a challenging global health concern with an estimated more than a million persons to be affected annually by the year 2025. The commonest type is hepatocellular carcinoma (HCC), which has been increasing in incidence the world over, mostly due to chronic viral hepatitis B infection. In the last decade, paradigm changes in the etiology, understanding of molecular biology, and pathogenesis, including the role of gut microbiota; medical and surgical treatments, and outcome trends are notable. The application of omics-based technology has helped us unlock the molecular and immune landscape of HCC, through which novel targets for drug treatment such as immune-checkpoint inhibitors have been identified. Novel tools for the surveillance and diagnosis of HCC include protein-, genomics-, and composite algorithm-based clinical/biomarker panels. Magnetic resonance imaging-based novel techniques have improved HCC diagnosis through ancillary features that enhance classical criteria while positron emission tomography has shown value in prognostication. Identification of the role of gut microbiota in the causation and progression of HCC has opened areas for novel therapeutic research. A select group of patients still benefit from modified surgical and early interventional radiology treatments. Improvements in radiotherapy protocols, identification of parameters of futility among radiological interventions, and the emergence of novel first-line systemic therapies that include a combination of antiangiogenic and immune-checkpoint inhibitors have seen a paradigm change in progression-free and overall survival. The current review is aimed at providing exhaustive updates on the etiology, molecular biology, biomarker diagnosis, imaging, and recommended treatment options in patients with HCC.
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Affiliation(s)
- Cyriac A Philips
- Clinical and Translational Hepatology, The Liver Institute, Center of Excellence in GI Sciences, Rajagiri Hospital, Aluva, IND
| | - Sasidharan Rajesh
- Interventional Hepatobiliary Radiology, Center of Excellence in GI Sciences, Rajagiri Hospital, Aluva, IND
| | - Dinu C Nair
- Interventional Hepatobiliary Radiology, Center of Excellence in GI Sciences, Rajagiri Hospital, Aluva, IND
| | - Rizwan Ahamed
- Gastroenterology and Advanced Gastrointestinal (GI) Endoscopy, Center of Excellence in GI Sciences, Rajagiri Hospital, Aluva, IND
| | - Jinsha K Abduljaleel
- Gastroenterology and Advanced Gastrointestinal (GI) Endoscopy, Center of Excellence in GI Sciences, Rajagiri Hospital, Aluva, IND
| | - Philip Augustine
- Gastroenterology and Advanced Gastrointestinal (GI) Endoscopy, Center of Excellence in GI Sciences, Rajagiri Hospital, Aluva, IND
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Yip TC, Chan RNC, Wong VW, Tse Y, Liang LY, Hui VW, Zhang X, Li G, Chan HL, Wong GL. Association of metformin use on metabolic acidosis in diabetic patients with chronic hepatitis B-related cirrhosis and renal impairment. Health Sci Rep 2021; 4:e352. [PMID: 34401527 PMCID: PMC8358231 DOI: 10.1002/hsr2.352] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 07/01/2021] [Accepted: 07/22/2021] [Indexed: 12/02/2022] Open
Abstract
BACKGROUND AND AIMS Metformin is an oral anti-hyperglycemic recommended by the American Diabetes Association (ADA) as a preferred initial pharmacologic agent for type 2 diabetes. Metabolic acidosis is a rare yet severe side effect of it. We examined the association of metformin use and dosage on the risk of metabolic acidosis in diabetic patients with different degrees of chronic hepatitis B (CHB)-related cirrhosis and chronic kidney disease (CKD). METHODS Metabolic acidosis was defined by blood pH ≤7.35, together with lactate >5 mmol/L or arterial bicarbonate ≤18 mmol/L or venous bicarbonate ≤21 mmol/L, and/or diagnosis codes. Child-Pugh class and CKD stage were included in the model as time-dependent covariates. Age, gender, comorbidities, and use of relevant medications were adjusted as covariates. Maximum daily dose of metformin was classified into ≤1000 mg and >1000 mg. RESULTS We identified 4431 diabetic patients with CHB-related cirrhosis between 2000 and 2017 from a territory-wide database in Hong Kong. The risk of metabolic acidosis increased with Child-Pugh class B and C cirrhosis regardless of CKD stage (adjusted subdistribution hazard ratio [aSHR] ranged from 3.50 to 86.16). Metformin use was associated with a higher risk in patients with Child-Pugh class B or C cirrhosis and stage 3A CKD or above (aSHR ranged from 1.55 to 2.46). In stage 4/5 CKD, a daily dose of metformin ≤1000 mg was still associated with a higher risk of metabolic acidosis regardless of the severity of cirrhosis (aSHR ranged from 2.45 to 3.92). CONCLUSION In conclusion, patients with Child-Pugh class B cirrhosis or above were at a higher risk of metabolic acidosis. Metformin further increased the risk in patients with Child-Pugh class B cirrhosis or above and stage 3A CKD or above. Dose adjustment in stage 4/5 CKD did not reduce the risk of metabolic acidosis.
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Affiliation(s)
- Terry Cheuk‐Fung Yip
- Department of Medicine and TherapeuticsThe Chinese University of Hong KongHong KongChina
- Medical Data Analytics Centre (MDAC)The Chinese University of Hong KongHong KongChina
- Institute of Digestive Disease, The Chinese University of Hong KongHong KongChina
| | - Raymond Ngai Chiu Chan
- Department of Medicine and TherapeuticsThe Chinese University of Hong KongHong KongChina
| | - Vincent Wai‐Sun Wong
- Department of Medicine and TherapeuticsThe Chinese University of Hong KongHong KongChina
- Medical Data Analytics Centre (MDAC)The Chinese University of Hong KongHong KongChina
- Institute of Digestive Disease, The Chinese University of Hong KongHong KongChina
| | - Yee‐Kit Tse
- Department of Medicine and TherapeuticsThe Chinese University of Hong KongHong KongChina
- Medical Data Analytics Centre (MDAC)The Chinese University of Hong KongHong KongChina
- Institute of Digestive Disease, The Chinese University of Hong KongHong KongChina
| | - Lilian Yan Liang
- Department of Medicine and TherapeuticsThe Chinese University of Hong KongHong KongChina
| | - Vicki Wing‐Ki Hui
- Department of Medicine and TherapeuticsThe Chinese University of Hong KongHong KongChina
| | - Xinrong Zhang
- Department of Medicine and TherapeuticsThe Chinese University of Hong KongHong KongChina
| | - Guan‐Lin Li
- Department of Medicine and TherapeuticsThe Chinese University of Hong KongHong KongChina
| | - Henry Lik‐Yuen Chan
- Medical Data Analytics Centre (MDAC)The Chinese University of Hong KongHong KongChina
- Faculty of MedicineThe Chinese University of Hong KongHong KongChina
- Department of Internal MedicineUnion HospitalHong Kong
| | - Grace Lai‐Hung Wong
- Department of Medicine and TherapeuticsThe Chinese University of Hong KongHong KongChina
- Medical Data Analytics Centre (MDAC)The Chinese University of Hong KongHong KongChina
- Institute of Digestive Disease, The Chinese University of Hong KongHong KongChina
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Shimada S, Kamiyama T, Orimo T, Nagatsu A, Kamachi H, Taketomi A. High HbA1c is a risk factor for complications after hepatectomy and influences for hepatocellular carcinoma without HBV and HCV infection. Hepatobiliary Surg Nutr 2021; 10:454-463. [PMID: 34430524 DOI: 10.21037/hbsn.2020.01.03] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Accepted: 12/04/2019] [Indexed: 12/11/2022]
Abstract
Background Currently, the population with type 2 diabetes mellitus (DM) is increasing worldwide. However, the influence of DM or hyperglycemia on the outcome of resected hepatocellular carcinoma (HCC) is unclear. Methods We analyzed 756 patients with HCC who underwent hepatectomy. These patients were assigned to an HbA1c ≥7.0% (H-A1c; n=100) or HbA1c <7.0% (L-A1c; n=656) group depending on their HbA1c level at admission. We investigated prognoses, clinicopathological characteristics and surgical outcomes including morbidities of HCC patients with high HbA1c, prognoses according to the treatment for DM were also investigated. Results Among all patients and those with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, overall survival (OS) and relapse-free survival (RFS) did not differ significantly between the H-A1c and L-A1c groups. In contrast, the 5-year OS rate of the H-A1c group was 55% and that of the L-A1c group 71% among patients without HBV and HCV (NBNC patients) (P=0.03). Among NBNC patients, the median RFS of the H-A1c group was 13 months, and that of the L-A1c group was 26 months (P=0.02). In addition, metformin use was an independent favorable factor for both OS and RFS. The H-A1c group had significantly higher rates of hyperbilirubinemia, wound infection, and pneumonia. Conclusions HCC patients with high HbA1c might have poor prognoses for both survival and recurrence in NBNC-HCC. High HbA1c may also be a risk factor for morbidities after hepatectomy. Metformin use may constitute a good option for NBNC patients with HCC.
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Affiliation(s)
- Shingo Shimada
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Toshiya Kamiyama
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Tatsuya Orimo
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Akihisa Nagatsu
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Hirofumi Kamachi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
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Tseng CH. Metformin and Risk of Malignant Brain Tumors in Patients with Type 2 Diabetes Mellitus. Biomolecules 2021; 11:1226. [PMID: 34439890 PMCID: PMC8391370 DOI: 10.3390/biom11081226] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 08/09/2021] [Accepted: 08/12/2021] [Indexed: 12/29/2022] Open
Abstract
The risk of malignant brain tumors associated with metformin use has rarely been investigated in humans. This retrospective cohort study investigated such an association. Patients with new-onset type 2 diabetes mellitus diagnosed from 1999 to 2005 in the nationwide database of Taiwan's national health insurance were used to enroll study subjects. We first identified an unmatched cohort of 153,429 ever users and 16,222 never users of metformin. A cohort of 16,222 ever users and 16,222 never users matched on propensity score was then created from this unmatched cohort. All patients were followed up from 1 January 2006 until 31 December 2011. The incidence density was calculated and hazard ratios were derived from Cox regression incorporated with the inverse probability of treatment weighting using a propensity score. The results showed that 27 never users and 155 ever users developed malignant brain tumors in the unmatched cohort. The incidence rate was 37.11 per 100,000 person-years in never users and 21.39 per 100,000 person-years in ever users. The overall hazard ratio comparing ever users versus never users was 0.574 (95% confidence interval: 0.381-0.863). The respective hazard ratios comparing the first (<27.13 months), second (27.13-58.33 months), and third (>58.33 months) tertiles of cumulative duration of metformin therapy versus never users were 0.897 (0.567-1.421), 0.623 (0.395-0.984), and 0.316 (0.192-0.518). In the matched cohort, the overall hazard ratio was 0.317 (0.149-0.673) and the respective hazard ratios were 0.427 (0.129-1.412), 0.509 (0.196-1.322), and 0.087 (0.012-0.639) for the first, second, and third tertile of cumulative duration of metformin therapy. In conclusion, this study shows a risk reduction of malignant brain tumors associated with metformin use in a dose-response pattern. The risk reduction is more remarkable when metformin has been used for approximately 2-5 years.
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Affiliation(s)
- Chin-Hsiao Tseng
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei 10051, Taiwan;
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei 10051, Taiwan
- Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan 350, Taiwan
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Management of diabetes mellitus in patients with cirrhosis: An overview and joint statement. DIABETES & METABOLISM 2021; 47:101272. [PMID: 34363981 DOI: 10.1016/j.diabet.2021.101272] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 06/25/2021] [Accepted: 07/12/2021] [Indexed: 12/18/2022]
Abstract
Type 2 diabetes mellitus (T2DM) is a frequent comorbidity in patients with cirrhosis that is projected to rise in prevalence due to the worldwide burden of obesity, insulin-resistance and non-alcoholic fatty liver disease. The management of T2DM in patients with cirrhosis is complex given the requirement for accurate adaptation according to the level of liver function impairment, with lack of summary of the little evidence available in the literature. Here, we summarise the data available with respect to the epidemiology and the impact of T2DM in patients with cirrhosis, as well as those on the management of T2DM in these patients. We provide guidance for the diagnosis of T2DM and the monitoring of glycaemic control in patients with cirrhosis, and for the management of nutrition and pharmacological treatments in relation to the level of liver dysfunction.
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Elsayed M, Wagstaff W, Behbahani K, Villalobos A, Bercu Z, Majdalany BS, Akce M, Schuster DM, Mao H, Kokabi N. Improved Tumor Response in Patients on Metformin Undergoing Yttrium-90 Radioembolization Segmentectomy for Hepatocellular Carcinoma. Cardiovasc Intervent Radiol 2021; 44:1937-1944. [PMID: 34312687 DOI: 10.1007/s00270-021-02916-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2020] [Accepted: 06/21/2021] [Indexed: 01/01/2023]
Abstract
PURPOSE Metformin is associated with improved outcomes after external radiation and chemotherapy but has not been studied for Y-90 radiation segmentectomy (RS). This study evaluates the effect of metformin on tumor response after Y-90 RS in patients with hepatocellular carcinoma (HCC). METHODS AND MATERIALS A retrospective analysis of patients with HCC who underwent Y-90 RS between 2014-2018 was performed. Comparisons were made between all patients taking and not taking metformin, and diabetic patients taking and not taking metformin. Tumor response was analyzed with logistic regression to compare absolute and percent change in total tumor diameter (TTD) and modified Response Evaluation Criteria in Solid Tumors (mRECIST). Overall survival (OS) was evaluated using Kaplan-Meier estimation and log-rank analysis. RESULTS A total of 106 patients underwent 112 Y-90 RS, of which 40 were diabetic (38.8%) and 19 (18.4%) were on metformin. At baseline, the two groups of patients on metformin and not on metformin had no significant difference in age, Child-Pugh score, MELD score, ALBI grade, total tumor diameter, and size of dominant tumor. The only significant baseline difference was ECOG status. Uni- and multivariate analysis demonstrated a larger reduction in TTD and objective response by mRECIST criteria for patients undergoing Y-90 RS on metformin compared to those not on metformin. OS was similar between patients taking and not taking metformin (p = 0.912). CONCLUSION Metformin may be associated with increased tumor response after Y-90 RS in patients with HCC. LEVEL OF EVIDENCE III, Retrospective Study.
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Affiliation(s)
- Mohammad Elsayed
- Division of Interventional Radiology and Image-Guided Medicine, Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA.
| | - William Wagstaff
- Division of Interventional Radiology and Image-Guided Medicine, Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA
| | - Keywan Behbahani
- Division of Interventional Radiology and Image-Guided Medicine, Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA
| | - Alexander Villalobos
- Division of Interventional Radiology and Image-Guided Medicine, Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA
| | - Zachary Bercu
- Division of Interventional Radiology and Image-Guided Medicine, Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA
| | - Bill S Majdalany
- Division of Interventional Radiology and Image-Guided Medicine, Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA
| | - Mehmet Akce
- Department of Hematology and Medical Oncology, Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA
| | - David M Schuster
- Division of Nuclear Medicine and Molecular Imaging, Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA
| | - Hui Mao
- Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA
| | - Nima Kokabi
- Division of Interventional Radiology and Image-Guided Medicine, Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA
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