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Hosseinkhan N, Najafi L, Jahangiri S, Emami Z, Khamseh ME. Statin use and risk of HCC in patients with MASLD and T2DM: an umbrella review and meta-analysis. BMC Cancer 2025; 25:875. [PMID: 40369443 PMCID: PMC12080120 DOI: 10.1186/s12885-025-14299-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Accepted: 05/08/2025] [Indexed: 05/16/2025] Open
Abstract
BACKGROUND The effect of statin use on hepatocellular carcinoma (HCC) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) or type two diabetes mellitus (T2DM) is still unclear. In this umbrella review, we aimed to assess the available evidence for the association of statin use and HCC risk in the target population. METHODS We carried out an umbrella review of previous systematic reviews/meta-analyses indexed in Cochrane, Embase, Scopus, and PubMed databases and published between Jan 1st, 2013, and Oct 22, 2024. We used random effects models to recalculate summary risk estimates for HCC incidence. Using A Measurement Tool to Assess methodological quality of systematic Review (AMSTAR2) tool, two independent reviewers evaluated each article for eligibility and methodologic quality and gathered data from the included studies. RESULTS Of the initially identified 1,038 systematic reviews/meta-analyses, three non-overlapping studies with medium/high quality were included for qualitative synthesis. Statin use in people with T2DM was reported in six studies belonging to two meta-analyses. The results showed that statins were associated with a decreased risk of HCC (RR: 0.16, 95% CI: [0.03, 0.98]). However, the association was nonsignificant in patients with MASLD comprising five studies from one meta-analysis (RR: 0.89, 95% CI: [0.56, 1.40]). CONCLUSION Statin use is associated with a decreased incidence of HCC in people with T2DM. In patients with MASLD, the association is not significant. However, the effects of other variables including the stage of inflammation and/or liver fibrosis on the outcome need to be explored in future studies.
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Affiliation(s)
- Nazanin Hosseinkhan
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran, No 10, Firoozeh St, Vali Asr Sq
| | - Laily Najafi
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran, No 10, Firoozeh St, Vali Asr Sq
| | - Soodeh Jahangiri
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran, No 10, Firoozeh St, Vali Asr Sq
| | - Zahra Emami
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran, No 10, Firoozeh St, Vali Asr Sq
| | - Mohammad E Khamseh
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran, No 10, Firoozeh St, Vali Asr Sq.
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Zarif Attalla K, Hassan DH, Teaima MH, Yousry C, El-Nabarawi MA, Said MA, Elhabal SF. Enhanced Intranasal Delivery of Atorvastatin via Superparamagnetic Iron-Oxide-Loaded Nanocarriers: Cytotoxicity and Inflammation Evaluation and In Vivo, In Silico, and Network Pharmacology Study for Targeting Glioblastoma Management. Pharmaceuticals (Basel) 2025; 18:421. [PMID: 40143197 PMCID: PMC11944838 DOI: 10.3390/ph18030421] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2025] [Revised: 03/06/2025] [Accepted: 03/11/2025] [Indexed: 03/28/2025] Open
Abstract
Objective: This study aims to develop an intranasal (IN) delivery system for glioblastoma multiforme (GBM) management using repurposed superparamagnetic iron-oxide (SPION) loaded with atorvastatin (ATO)-nanostructured lipid carrier (NLC). Methods: Emulsification and ultrasonication were used to formulate ATO-NLCs, and the best formula was loaded with SPION to make the final atorvastatin/superparamagnetic iron oxide-loaded nanostructured lipid carrier (ASN) formulation. Entrapment efficiency (EE%), particle size (PS), zeta potential (ZP), and drug release after 6 h (Q6h) were evaluated for NLCs. ASN was tested for cytotoxicity on T98G cancer cells, and the cell cycle was examined to determine cell death. Furthermore, the ability of the optimal formulation to suppress the levels of inflammatory biomarkers was investigated in Lipopolysaccharide (LPS)-induced inflammation. The brain-targeting behavior of IN-ASN was visualized in rabbits via confocal laser scanning microscopy (CLSM). Results: The optimum NLC exhibited a spherical shape, EE% of 84.0 ± 0.67%, PS of 282.50 ± 0.51 nm, ZP of -18.40 ± 0.15 mV, and Q6h of 89.23%. The cytotoxicity of ASN against cancer cells was 4.4-fold higher than ATO suspension, with a 1.3-fold increment in cell apoptosis. ASN showed significantly reduced pro-inflammatory biomarkers (IL-β, IL-6, TNF-α, TLR4, NF-қB), whereas CLSM revealed enhanced brain delivery with no observed histopathological nasal irritation. The in silico analysis demonstrated enhanced ATO-ADME (absorption, distribution, metabolism, and excretion) properties, while the network pharmacology study identified 10 target GBM genes, among which MAPK3 was the most prominent with a good binding score as elucidated by the simulated docking study. Conclusions: These findings may present ATO/SPION-NLCs as significant evidence for repurposing atorvastatin in the treatment of glioblastoma multiforme.
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Affiliation(s)
- Kristina Zarif Attalla
- Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Giza 12566, Egypt;
| | - Doaa H. Hassan
- Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Giza 12566, Egypt;
| | - Mahmoud H. Teaima
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt; (M.H.T.); (C.Y.); (M.A.E.-N.)
| | - Carol Yousry
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt; (M.H.T.); (C.Y.); (M.A.E.-N.)
- Department of Pharmaceutics and Industrial Pharmacy, School of Pharmacy, Newgiza University, km. 22 Cairo-Alex Road, Giza P.O. Box 12577, Egypt
| | - Mohamed A. El-Nabarawi
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt; (M.H.T.); (C.Y.); (M.A.E.-N.)
| | - Mohamed A. Said
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt;
| | - Sammar Fathy Elhabal
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Mokattam, Cairo 11571, Egypt
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Chu WM, Chao WC, Chen DY, Ho WL, Chen HH. Incidence and risk factors of mental illnesses among patients with systemic autoimmune rheumatic diseases: an 18-year population-based study. Rheumatology (Oxford) 2025; 64:976-984. [PMID: 38579187 DOI: 10.1093/rheumatology/keae203] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Revised: 03/07/2024] [Accepted: 03/21/2024] [Indexed: 04/07/2024] Open
Abstract
OBJECTIVE This study aimed to assess the incidence and risk factors surrounding mental illnesses in patients diagnosed with systemic autoimmune rheumatic diseases (SARDs). METHODS This retrospective cohort study used nationwide, population-based claim data taken from Taiwan's National Health Insurance Research Database (NHIRD) to identify patients certified as having a catastrophic illness for systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), dermatomyositis (DM), polymyositis (PM) or Sjögren's syndrome (SS) from the years 2002-2020. We furthermore calculated the incidence of mental illness in patients diagnosed with SARDs while exploring factors associated with the development of mental illness using multivariable Cox regression analysis shown as adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS Among the 28 588 participants, the average age was 47.4 (SD 14.9) years, with most participants being female (76.4%). When compared with patients with rheumatoid arthritis, patients with SLE (HR: 1.20, 95% CI: 1.10-1.32), SS (HR: 1.29, 95% CI: 1.19-1.39), and DM (HR: 1.28, 95% CI: 1.04-1.32) showed a significantly increased risk of developing mental illness. Additionally, when compared with patients with rheumatoid arthritis, patients with SLE (HR: 1.32, 95% CI: 1.21-1.44), SSc (HR: 1.20, 95% CI: 1.02-1.41), SS (HR: 1.17, 95% CI: 1.08-1.26), DM (HR: 1.73, 95% CI: 1.44-2.07), and PM (HR: 1.64, 95% CI: 1.32-2.03) showed a significantly increased risk of antidepressant use. CONCLUSION This population-based cohort study revealed that patients diagnosed with SLE, SS, and DM had significantly higher risks of developing mental illness when compared with patients with RA.
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Affiliation(s)
- Wei-Min Chu
- Department of Family Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
- Geriatrics and Gerontology Research Center, College of Medicine, National Chung Hsing University, Taichung, Taiwan
- Department of Epidemiology on Aging, National Center for Geriatrics and Gerontology, Aichi, Japan
| | - Wen-Cheng Chao
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
- Department of Critical Care Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- Big Data Center, National Chung Hsing University, Taichung, Taiwan
- Department of Automatic Control Engineering, Feng Chia University, Taichung, Taiwan
| | - Der-Yuan Chen
- Deparment of Rheumatology and Immunology, China Medical University Hospital, Taichung, Taiwan
- College of Medicine, China Medical University, Taichung, Taiwan
| | - Wei-Li Ho
- Division of Allergy, Immunology and Rheumatology, Chiayi Branch, Taichung Veterans General Hospital, Chiayi, Taiwan
| | - Hsin-Hua Chen
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
- Division of General Medicine, Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine & Big Data Center, Chung Hsing University, Taichung, Taiwan
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Chen Y, Wong CCL. The mechanistic insights behind the anticancer effects of statins in liver cancer. Hepatol Commun 2024; 8:e0519. [PMID: 39225688 PMCID: PMC11371310 DOI: 10.1097/hc9.0000000000000519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 07/10/2024] [Indexed: 09/04/2024] Open
Affiliation(s)
- Yiling Chen
- Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China
| | - Carmen Chak-Lui Wong
- Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China
- Centre for Oncology and Immunology, Hong Kong Science Park, Hong Kong, China
- Department of Clinical Oncology, Shenzhen Key Laboratory for Cancer Metastasis and Personalized Therapy, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
- Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-sen University, Guangzhou, China
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Tsai PC, Huang CF, Yeh ML, Hsieh MH, Kuo HT, Hung CH, Tseng KC, Lai HC, Peng CY, Wang JH, Chen JJ, Lee PL, Chien RN, Yang CC, Lo GH, Kao JH, Liu CJ, Liu CH, Yan SL, Lin CY, Su WW, Chu CH, Chen CJ, Tung SY, Tai C, Lin CW, Lo CC, Cheng PN, Chiu YC, Wang CC, Cheng JS, Tsai WL, Lin HC, Huang YH, Chen CY, Huang JF, Dai CY, Chung WL, Bair MJ, Yu ML, T-COACH Study Group. Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy. Clin Mol Hepatol 2024; 30:468-486. [PMID: 38637957 PMCID: PMC11261235 DOI: 10.3350/cmh.2024.0038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 04/18/2024] [Accepted: 04/18/2025] [Indexed: 04/20/2024] Open
Abstract
BACKGROUND/AIMS Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. METHODS We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan's cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray's cumulative incidence and Cox subdistribution hazards models to analyze HCC development. RESULTS Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. CONCLUSION Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.
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Affiliation(s)
- Pei-Chien Tsai
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Hepatitis Research Centre, School of Medicine and Centre for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Hepatitis Research Centre, School of Medicine and Centre for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Hepatitis Research Centre, School of Medicine and Centre for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Meng-Hsuan Hsieh
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Hepatitis Research Centre, School of Medicine and Centre for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Health Management Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Hsing-Tao Kuo
- Division of Hepatogastroenterology, Department of Internal Medicine, Chi Mei Medical Centre, Tainan, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Kuo-Chih Tseng
- Department of Gastroenterology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| | - Hsueh-Chou Lai
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Cheng-Yuan Peng
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Jing-Houng Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Jyh-Jou Chen
- Division of Gastroenterology and Hepatology, Chi-Mei Medical Centre, Liouying, Tainan, Taiwan
| | - Pei-Lun Lee
- Division of Gastroenterology and Hepatology, Chi-Mei Medical Centre, Liouying, Tainan, Taiwan
| | - Rong-Nan Chien
- Division of Hepatology, Department of Gastroenterology and Hepatology, Linkou Medical Centre, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Chi-Chieh Yang
- Division of Gastroenterology, Department of Internal Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan
| | - Gin-Ho Lo
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital and School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, National Taiwan University Hospital, Taipei, Taiwan
| | - Chen-Hua Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, National Taiwan University Hospital, Taipei, Taiwan
| | - Sheng-Lei Yan
- Division of Gastroenterology, Department of Internal Medicine, Chang Bing Show-Chwan Memorial Hospital, Changhua, Taiwan
| | - Chun-Yen Lin
- Division of Hepatology, Department of Gastroenterology and Hepatology, Linkou Medical Centre, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Wei-Wen Su
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Cheng-Hsin Chu
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
| | - Chih-Jen Chen
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
| | - Shui-Yi Tung
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chi‐Ming Tai
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital and School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Chih-Wen Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital and School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Ching-Chu Lo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Martin De Porres Hospital-Daya, Chiayi, Taiwan
| | - Pin-Nan Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yen-Cheng Chiu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chia-Chi Wang
- Division of Gastroenterology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, New Taipei, Taiwan
| | - Jin-Shiung Cheng
- Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Wei-Lun Tsai
- Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Institute of Clinical Medicine, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chi-Yi Chen
- Department of Internal Medicine, Chiayi Christian Hospital, Chiayi, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Hepatitis Research Centre, School of Medicine and Centre for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Hepatitis Research Centre, School of Medicine and Centre for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chung
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Hepatitis Research Centre, School of Medicine and Centre for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung; Mackay Medical College, Taipei, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Hepatitis Research Centre, School of Medicine and Centre for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Centre of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan
| | - T-COACH Study Group
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Hepatitis Research Centre, School of Medicine and Centre for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Health Management Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Division of Hepatogastroenterology, Department of Internal Medicine, Chi Mei Medical Centre, Tainan, Taiwan
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
- Department of Gastroenterology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- Division of Gastroenterology and Hepatology, Chi-Mei Medical Centre, Liouying, Tainan, Taiwan
- Division of Hepatology, Department of Gastroenterology and Hepatology, Linkou Medical Centre, Chang Gung Memorial Hospital, Keelung, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital and School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, National Taiwan University Hospital, Taipei, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Chang Bing Show-Chwan Memorial Hospital, Changhua, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Martin De Porres Hospital-Daya, Chiayi, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, New Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Institute of Clinical Medicine, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Department of Internal Medicine, Chiayi Christian Hospital, Chiayi, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung; Mackay Medical College, Taipei, Taiwan
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Centre of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan
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Pham N, Benhammou JN. Statins in Chronic Liver Disease: Review of the Literature and Future Role. Semin Liver Dis 2024; 44:191-208. [PMID: 38701856 DOI: 10.1055/a-2319-0694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/05/2024]
Abstract
Chronic liver disease (CLD) is a major contributor to global mortality, morbidity, and healthcare burden. Progress in pharmacotherapeutic for CLD management is lagging given its impact on the global population. While statins are indicated for the management of dyslipidemia and cardiovascular disease, their role in CLD prevention and treatment is emerging. Beyond their lipid-lowering effects, their liver-related mechanisms of action are multifactorial and include anti-inflammatory, antiproliferative, and immune-protective effects. In this review, we highlight what is known about the clinical benefits of statins in viral and nonviral etiologies of CLD and hepatocellular carcinoma (HCC), and explore key mechanisms and pathways targeted by statins. While their benefits may span the spectrum of CLD and potentially HCC treatment, their role in CLD chemoprevention is likely to have the largest impact. As emerging data suggest that genetic variants may impact their benefits, the role of statins in precision hepatology will need to be further explored.
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Affiliation(s)
- Nguyen Pham
- Department of Medicine, University of California, Los Angeles, Los Angeles, California
| | - Jihane N Benhammou
- Department of Medicine, University of California, Los Angeles, Los Angeles, California
- Veterans Affairs Greater Los Angeles, Los Angeles, California
- Comprehensive Liver Research Center at University of California, Los Angeles, Los Angeles, California
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Piscaglia F, Ikeda K, Cheng AL, Kudo M, Ikeda M, Breder V, Ryoo BY, Mody K, Ren M, Ramji Z, Sung MW. Association between treatment-emergent hypertension and survival with lenvatinib treatment for patients with hepatocellular carcinoma in the REFLECT study. Cancer 2024; 130:1281-1291. [PMID: 38261521 DOI: 10.1002/cncr.35185] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 11/13/2023] [Accepted: 11/17/2023] [Indexed: 01/25/2024]
Abstract
BACKGROUND Lenvatinib is approved as a first-line treatment for patients with unresectable and/or recurrent hepatocellular carcinoma (HCC). Lenvatinib achieved promising clinical benefits in REFLECT but was associated with clinically significant treatment-emergent hypertension (CSTE-HTN, a grouped term), a common class effect of tyrosine kinase inhibitors. This post hoc analysis assessed the impact of CSTE-HTN on the efficacy and safety of lenvatinib in HCC. METHODS Patients from REFLECT who received lenvatinib (n = 476) were stratified according to CSTE-HTN. Tumors were assessed by mRECIST. Overall survival (OS) and progression-free survival (PFS) were evaluated using landmark analyses at 4 and 8 weeks. RESULTS A total of 212 patients in the lenvatinib arm developed CSTE-HTN, and 264 did not. CSTE-HTN first occurred at 3.7 weeks (median); the worst grade CSTE-HTN occurred at 4.1 weeks (median). No patients had life-threatening CSTE-HTN and/or died due to CSTE-HTN. Median OS was numerically longer in patients with versus without CSTE-HTN (at 4 weeks: 16.3 vs. 11.6 months; hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.621-1.004; at 8 weeks: 13.5 vs. 11.6 months; HR, 0.87; 95% CI, 0.696-1.089). Median PFS was similar between patients with and without CSTE-HTN (at 4 weeks: 6.6 vs. 6.4 months; HR, 0.887; 95% CI, 0.680-1.157; at 8 weeks: 5.7 vs. 6.4 months; HR, 1.09; 95% CI, 0.84-1.41). Objective response rate was numerically higher in patients with (48.6%) versus without CSTE-HTN (34.5%). CONCLUSIONS In this retrospective analysis, CSTE-HTN was associated with improved OS but not PFS. CSTE-HTN did not impair the outcomes of patients with HCC treated with lenvatinib when detected early and managed appropriately.
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Affiliation(s)
- Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | | | - Ann-Lii Cheng
- National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan
| | | | | | - Valery Breder
- N.N. Blokhin Russian Cancer Research Center, Moscow, Russia
| | - Baek-Yeol Ryoo
- Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | | | - Min Ren
- Eisai Inc, Nutley, New Jersey, USA
| | | | - Max W Sung
- Tisch Cancer Institute at Mount Sinai, New York, New York, USA
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8
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Nguyen P, Singh V, Thakur V, Dwivedi AK, Chattopadhyay M. Effectiveness of HMG-CoA reductase inhibitors on inflammation and metabolic markers in the US-Mexico border Hispanic population. J Investig Med 2024; 72:359-369. [PMID: 38369491 DOI: 10.1177/10815589241234962] [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] [Indexed: 02/20/2024]
Abstract
HMG-CoA reductase inhibitors (statins) are commonly used to manage dyslipidemia to reduce cardiovascular disease (CVD) risk. High-sensitivity C-reactive protein (hs-CRP) is an emerging systematic low-grade inflammatory marker associated with atherosclerotic CVD development. Despite racial/ethnic disparities in the use and response of statins and the anti-inflammatory effects of statins, the effectiveness of statins on inflammation and metabolic markers is unknown among Hispanics. We performed a retrospective cohort study using 150 adult patients scheduled for an annual physical examination at a family medicine clinic between January 1, 2021 and December 31, 2021. Effect size with a 95% confidence interval (CI) was estimated using adjusted regression analyses. Among 150 patients, 52 (34.7%) patients received statins. Patients who received statins had significantly reduced median hs-CRP (1.9 vs 3.2, p = 0.007), mean low-density lipoprotein (LDL-C; 101.2 vs 124.6, p < 0.001), and total cholesterol (172.6 vs 194.5, p < 0.001) concentrations compared to those who did not receive statins. In the propensity-scores matched analysis, lower concentrations of log-transformed hs-CRP (regression coefficient (RC), -0.48; 95% CI: -0.89, -0.07), LDL-C (RC, -19.57; 95% CI: -33.04, -6.10), and total cholesterol (RC, -23.47; 95% CI: -38.96, -7.98) were associated with statin use. In addition, hepatic steatosis (adjusted relative risk (aRR) = 0.25; 95% CI: 0.08, 0.78, p = 0.017) was significantly lower among patients with the use of statins. Our study suggests that HMG-CoA reductase inhibitors may help reduce inflammation among Hispanic patients with dyslipidemia and hypertension. These findings have useful implications for preventing risk and disparities associated with cardiovascular and other inflammatory-induced diseases among the fastest-growing US Hispanic minorities.
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Affiliation(s)
- Phong Nguyen
- Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA
| | - Vishwajeet Singh
- Biostatistics and Epidemiology Consulting Lab, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA
| | - Vikram Thakur
- Department of Molecular and Translational Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA
| | - Alok Kumar Dwivedi
- Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA
- Biostatistics and Epidemiology Consulting Lab, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA
- Department of Molecular and Translational Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA
| | - Munmun Chattopadhyay
- Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA
- Department of Molecular and Translational Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA
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9
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Sonam Dongsar T, Tsering Dongsar T, Gupta G, Alsayari A, Wahab S, Kesharwani P. PLGA nanomedical consignation: A novel approach for the management of prostate cancer. Int J Pharm 2024; 652:123808. [PMID: 38224758 DOI: 10.1016/j.ijpharm.2024.123808] [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: 10/20/2023] [Revised: 12/27/2023] [Accepted: 01/12/2024] [Indexed: 01/17/2024]
Abstract
The malignancy of the prostate is a complicated ailment which impacts millions of male populations around the globe. Despite the multitude of endeavour accomplished within this domain, modalities that are involved in the ameliorative management of predisposed infirmity are still relent upon non-specific and invasive procedures, thus imposing a detrimental mark on the living standard of the individual. Also, the orchestrated therapeutic interventions are still incompetent in substantiating a robust and unabridged therapeutic end point owing to their inadequate solubility, low bioavailability, limited cell assimilation, and swift deterioration, thereby muffling the clinical application of these existing treatment modalities. Nanotechnology has been employed in an array of modalities for the medical management of malignancies. Among the assortment of available nano-scaffolds, nanocarriers composed of a bio-decomposable and hybrid polymeric material like PLGA hold an opportunity to advance as standard chemotherapeutic modalities. PLGA-based nanocarriers have the prospect to address the drawbacks associated with conventional cancer interventions, owing to their versatility, durability, nontoxic nature, and their ability to facilitate prolonged drug release. This review intends to describe the plethora of evidence-based studies performed to validate the applicability of PLGA nanosystem in the amelioration of prostate malignancies, in conjunction with PLGA focused nano-scaffold in the clinical management of prostate carcinoma. This review seeks to explore numerous evidence-based studies confirming the applicability of PLGA nanosystems in ameliorating prostate malignancies. It also delves into the role of PLGA-focused nano-scaffolds in the clinical management of prostate carcinoma, aiming to provide a comprehensive perspective on these advancements.
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Affiliation(s)
- Tenzin Sonam Dongsar
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India
| | - Tenzin Tsering Dongsar
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India
| | - Garima Gupta
- Graphic Era Hill University, Dehradun, 248002, India; School of Allied Medical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Abdulrhman Alsayari
- Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia
| | - Shadma Wahab
- Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia
| | - Prashant Kesharwani
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India.
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10
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Alizadehasl A, Alavi MS, Boudagh S, Alavi MS, Mohebi S, Aliabadi L, Akbarian M, Ahmadi P, Mannarino MR, Sahebkar A. Lipid-lowering drugs and cancer: an updated perspective. Pharmacol Rep 2024; 76:1-24. [PMID: 38015371 DOI: 10.1007/s43440-023-00553-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 10/27/2023] [Accepted: 10/27/2023] [Indexed: 11/29/2023]
Abstract
Statins and non-statin medications used for the management of dyslipidemia have been shown to possess antitumor properties. Since the use of these drugs has steadily increased over the past decades, more knowledge is required about their relationship with cancer. Lipid-lowering agents are heterogeneous compounds; therefore, it remains to be revealed whether anticancer potential is a class effect or related to them all. Here, we reviewed the literature on the influence of lipid-lowering medications on various types of cancer during development or metastasis. We also elaborated on the underlying mechanisms associated with the anticancer effects of antihyperlipidemic agents by linking the reported in vivo and in vitro studies.
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Affiliation(s)
- Azin Alizadehasl
- Cardio-Oncology Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
- Echocardiography Research CenterRajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Maryam Sadat Alavi
- Echocardiography Research CenterRajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Shabnam Boudagh
- Echocardiography Research CenterRajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mohaddeseh Sadat Alavi
- Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Somaye Mohebi
- Echocardiography Research CenterRajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Leila Aliabadi
- Echocardiography Research CenterRajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mahsa Akbarian
- Echocardiography Research CenterRajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Parisa Ahmadi
- Echocardiography Research CenterRajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
| | | | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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11
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Wang J, Liu C, Hu R, Wu L, Li C. Statin therapy: a potential adjuvant to immunotherapies in hepatocellular carcinoma. Front Pharmacol 2024; 15:1324140. [PMID: 38362156 PMCID: PMC10867224 DOI: 10.3389/fphar.2024.1324140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Accepted: 01/23/2024] [Indexed: 02/17/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide and accounts for more than 90% of primary liver cancer. The advent of immune checkpoint inhibitor (ICI)-related therapies combined with angiogenesis inhibition has revolutionized the treatment of HCC in late-stage and unresectable HCC, as ICIs alone were disappointing in treating HCC. In addition to the altered immune microenvironment, abnormal lipid metabolism in the liver has been extensively characterized in various types of HCC. Stains are known for their cholesterol-lowering properties and their long history of treating hypercholesterolemia and reducing cardiovascular disease risk. Apart from ICI and other conventional therapies, statins are frequently used by advanced HCC patients with dyslipidemia, which is often marked by the abnormal accumulation of cholesterol and fatty acids in the liver. Supported by a body of preclinical and clinical studies, statins may unexpectedly enhance the efficacy of ICI therapy in HCC patients through the regulation of inflammatory responses and the immune microenvironment. This review discusses the abnormal changes in lipid metabolism in HCC, summarizes the clinical evidence and benefits of stain use in HCC, and prospects the possible mechanistic actions of statins in transforming the immune microenvironment in HCC when combined with immunotherapies. Consequently, the use of statin therapy may emerge as a novel and valuable adjuvant for immunotherapies in HCC.
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Affiliation(s)
- Jiao Wang
- Department of Laboratory Medicine, Wuhan Hospital of Traditional Chinese and Western Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Chengyu Liu
- Department of Transfusion Medicine, Wuhan Hospital of Traditional Chinese and Western Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ronghua Hu
- Department of Transfusion Medicine, Wuhan Hospital of Traditional Chinese and Western Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Licheng Wu
- School of Clinical Medicine, Nanchang Medical College, Nanchang, China
| | - Chuanzhou Li
- Department of Medical Genetics, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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12
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Piekuś-Słomka N, Mocan LP, Shkreli R, Grapă C, Denkiewicz K, Wesolowska O, Kornek M, Spârchez Z, Słomka A, Crăciun R, Mocan T. Don't Judge a Book by Its Cover: The Role of Statins in Liver Cancer. Cancers (Basel) 2023; 15:5100. [PMID: 37894467 PMCID: PMC10605163 DOI: 10.3390/cancers15205100] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 10/16/2023] [Accepted: 10/20/2023] [Indexed: 10/29/2023] Open
Abstract
Statins, which are inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, are an effective pharmacological tool for lowering blood cholesterol levels. This property makes statins one of the most popular drugs used primarily to prevent cardiovascular diseases, where hyperlipidemia is a significant risk factor that increases mortality. Nevertheless, studies conducted mainly in the last decade have shown that statins might prevent and treat liver cancer, one of the leading causes of cancer-related mortality worldwide. This narrative review summarizes the scientific achievements to date regarding the role of statins in liver tumors. Molecular biology tools have revealed that cell growth and proliferation can be inhibited by statins, which further inhibit angiogenesis. Clinical studies, supported by meta-analysis, confirm that statins are highly effective in preventing and treating hepatocellular carcinoma and cholangiocarcinoma. However, this effect may depend on the statin's type and dose, and more clinical trials are required to evaluate clinical effects. Moreover, their potential hepatotoxicity is a significant caveat for using statins in clinical practice. Nevertheless, this group of drugs, initially developed to prevent cardiovascular diseases, is now a key candidate in hepato-oncology patient management. The description of new drug-statin-like structures, e.g., with low toxicity to liver cells, may bring another clinically significant improvement to current cancer therapies.
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Affiliation(s)
- Natalia Piekuś-Słomka
- Department of Inorganic and Analytical Chemistry, Nicolaus Copernicus University in Toruń, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Jurasza 2, 85-089 Bydgoszcz, Poland;
| | - Lavinia Patricia Mocan
- Department of Histology, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania;
| | - Rezarta Shkreli
- Department of Pharmacy, Faculty of Medical Sciences, Aldent University, 1001-1028 Tirana, Albania;
| | - Cristiana Grapă
- Department of Physiology, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania;
| | - Kinga Denkiewicz
- Department of Pathophysiology, Nicolaus Copernicus University in Toruń, Ludwik Rydygier Collegium Medicum in Bydgoszcz, 85-094 Bydgoszcz, Poland; (K.D.); (O.W.); (A.S.)
| | - Oliwia Wesolowska
- Department of Pathophysiology, Nicolaus Copernicus University in Toruń, Ludwik Rydygier Collegium Medicum in Bydgoszcz, 85-094 Bydgoszcz, Poland; (K.D.); (O.W.); (A.S.)
| | - Miroslaw Kornek
- Department of Internal Medicine I, University Hospital Bonn of the Rheinische Friedrich-Wilhelms-University, 53127 Bonn, Germany;
| | - Zeno Spârchez
- 3rd Medical Department, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania;
| | - Artur Słomka
- Department of Pathophysiology, Nicolaus Copernicus University in Toruń, Ludwik Rydygier Collegium Medicum in Bydgoszcz, 85-094 Bydgoszcz, Poland; (K.D.); (O.W.); (A.S.)
| | - Rareș Crăciun
- 3rd Medical Department, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania;
- Department of Gastroenterology, “Octavian Fodor” Institute for Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
| | - Tudor Mocan
- Department of Gastroenterology, “Octavian Fodor” Institute for Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
- UBBMed Department, Babeș-Bolyai University, 400349 Cluj-Napoca, Romania
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13
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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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14
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Zou B, Odden MC, Nguyen MH. Statin Use and Reduced Hepatocellular Carcinoma Risk in Patients With Nonalcoholic Fatty Liver Disease. Clin Gastroenterol Hepatol 2023; 21:435-444.e6. [PMID: 35158055 DOI: 10.1016/j.cgh.2022.01.057] [Citation(s) in RCA: 47] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Accepted: 01/28/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Recent evidence suggests potential clinical benefits of statin in cancer chemoprevention and treatment. Nonalcoholic fatty liver disease (NAFLD) is expected to become the leading cause of hepatocellular carcinoma (HCC). We aimed to investigate the association between statin initiation and the risk of HCC among patients with NAFLD. METHODS In this study using the Optum de-identified Clinformatics database, Cox proportional hazards regression model was performed to determine the risk of HCC in statin initiators versus nonusers. We incorporated inverse probability of treatment weighting (IPTW) to minimize potential confounding. RESULTS Among 272,431 adults with NAFLD diagnosis, IPTW model shows that statin initiators had 53% less risk of developing HCC compared with nonusers (hazard ratio [HR], 0.47; 95% confidence interval, 0.36-0.60). In the subcohort with fibrosis-4 index data available, statin initiation was associated with 56% hazard reduction of developing HCC in NAFLD after adjusting for fibrosis-4 index score (HR, 0.44; 0.30-0.65). The association between statin initiation and lower risk of HCC development was observed for both lipophilic statin (HR, 0.49; 0.37-0.65) and hydrophilic statin (HR, 0.40; 0.21-0.76). Moreover, we observed greater hazards reduction as the dose and duration of statin use increased. NAFLD patients with more than 600 cumulative defined daily doses of statin had 70% reduction in hazards of developing HCC (HR, 0.30; 0.20-0.43). CONCLUSIONS Our study provides strong evidence for the association between statin initiation and reduced risk of HCC development in NAFLD patients. These findings imply that statin can be used as a protective medication for NAFLD patients to reduce the risk of HCC.
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Affiliation(s)
- Biyao Zou
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, California; Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, California
| | - Michelle C Odden
- Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, California
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, California; Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, California.
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15
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Tsai PC, Kuo HT, Hung CH, Tseng KC, Lai HC, Peng CY, Wang JH, Chen JJ, Lee PL, Chien RN, Yang CC, Lo GH, Kao JH, Liu CJ, Liu CH, Yan SL, Bair MJ, Lin CY, Su WW, Chu CH, Chen CJ, Tung SY, Tai CM, Lin CW, Lo CC, Cheng PN, Chiu YC, Wang CC, Cheng JS, Tsai WL, Lin HC, Huang YH, Yeh ML, Huang CF, Hsieh MH, Huang JF, Dai CY, Chung WL, Chen CY, Yu ML. Metformin reduces hepatocellular carcinoma incidence after successful antiviral therapy in patients with diabetes and chronic hepatitis C in Taiwan. J Hepatol 2023; 78:281-292. [PMID: 36208843 DOI: 10.1016/j.jhep.2022.09.019] [Citation(s) in RCA: 48] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 08/10/2022] [Accepted: 09/14/2022] [Indexed: 01/24/2023]
Abstract
BACKGROUND & AIMS Diabetes mellitus (DM) is known to increase the risk of hepatocellular carcinoma (HCC) among individuals with chronic hepatitis C (CHC). We aimed to evaluate whether metformin reduces HCC risk among individuals with DM and CHC after successful antiviral therapy. METHODS Individuals with CHC who achieved a sustained virological response (SVR) after interferon-based therapy were enrolled in a large-scale, multicenter cohort in Taiwan (T-COACH). Cases of HCC at least 1 year after SVR were identified through linkage to the catastrophic illness and cancer registry databases. RESULTS Of 7,249 individuals with CHC enrolled in the study, 781 (10.8%) had diabetes and 647 (82.8%) were metformin users. During a median follow-up of 4.4 years, 227 patients developed new-onset HCC. The 5-year cumulative HCC incidence was 10.9% in non-metformin users and 2.6% in metformin users, compared to 3.0% in individuals without DM (adjusted hazard ratio [aHR] 2.83; 95% CI 1.57-5.08 and aHR 1.46; 95% CI 0.98-2.19, respectively). Cirrhosis was the most important factor significantly associated with higher HCC risk in Cox regression analysis, followed by DM non-metformin use, older age, male sex, and obesity; whereas hyperlipidemia with statin use was associated with a lower HCC risk. Using the two most crucial risk factors, cirrhosis and DM non-metformin use, we constructed a simple risk model that could predict HCC risk among individuals with CHC after SVR. Metformin use was shown to reduce the risk of all liver-related complications. CONCLUSIONS Metformin use greatly reduced HCC risk after successful antiviral therapy in individuals with diabetes and CHC. A simple risk stratification model comprising cirrhosis and DM non-metformin use could predict long-term outcomes in individuals with CHC after SVR. IMPACT AND IMPLICATIONS The current study provides evidence that metformin could reduce hepatocellular carcinoma (HCC) incidence after successful antiviral therapy among those with diabetes and chronic hepatitis C in a large-scale nationwide cohort study. Although successful antiviral therapy greatly reduces HCC risk in individuals with chronic hepatitis C, those with cirrhosis, diabetes, obesity, and the elderly remain at high risk of HCC development. We demonstrated that a simple risk model composed of two crucial unfavorable factors, cirrhosis and diabetes without metformin use, predicts the risk of HCC and major liver-related complications after successful antiviral therapy in individuals with chronic hepatitis C. Metformin use is highly recommended for individuals with diabetes and chronic hepatitis C after viral eradication to reduce the risk of HCC.
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Affiliation(s)
- Pei-Chien Tsai
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital; Hepatitis Research Center, School of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Health Management Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Hsing-Tao Kuo
- Division of Hepatogastroenterology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan; School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Kuo-Chih Tseng
- Department of Gastroenterology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| | - Hsueh-Chou Lai
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Cheng-Yuan Peng
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Jing-Houng Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jyh-Jou Chen
- Division of Gastroenterology and Hepatology, Chi-Mei Medical Center, Liouying, Tainan, Taiwan
| | - Pei-Lun Lee
- Division of Gastroenterology and Hepatology, Chi-Mei Medical Center, Liouying, Tainan, Taiwan
| | - Rong-Nan Chien
- Division of Hepatology, Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Chi-Chieh Yang
- Division of Gastroenterology, Department of Internal Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan
| | - Gin-Ho Lo
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Division of Gastroenterology and Hepatology, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Division of Gastroenterology and Hepatology, National Taiwan University Hospital, Taipei, Taiwan
| | - Chen-Hua Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Division of Gastroenterology and Hepatology, National Taiwan University Hospital, Taipei, Taiwan
| | - Sheng-Lei Yan
- Division of Gastroenterology, Department of Internal Medicine, Chang Bing Show-Chwan Memorial Hospital, Changhua, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
| | - Chun-Yen Lin
- Division of Hepatology, Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Wei-Wen Su
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Cheng-Hsin Chu
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
| | - Chih-Jen Chen
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
| | - Shui-Yi Tung
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chi-Ming Tai
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Chih-Wen Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Ching-Chu Lo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Martin De Porres Hospital-Daya, Chiayi, Taiwan
| | - Pin-Nan Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yen-Cheng Chiu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chia-Chi Wang
- Division of Gastroenterology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, New Taipei, Taiwan
| | - Jin-Shiung Cheng
- Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Wei-Lun Tsai
- Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, Faculty of Medicine, National Yang Ming, Chiao Tung University, Taipei, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital; Hepatitis Research Center, School of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital; Hepatitis Research Center, School of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Meng-Hsuan Hsieh
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital; Hepatitis Research Center, School of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Health Management Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital; Hepatitis Research Center, School of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital; Hepatitis Research Center, School of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chung
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital; Hepatitis Research Center, School of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chi-Yi Chen
- Department of Internal Medicine, Chiayi Christian Hospital, Chiayi, Taiwan.
| | - Ming-Lung Yu
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital; Hepatitis Research Center, School of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan; School of Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan.
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16
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Ito T, Nguyen MH. Perspectives on the Underlying Etiology of HCC and Its Effects on Treatment Outcomes. J Hepatocell Carcinoma 2023; 10:413-428. [PMID: 36926055 PMCID: PMC10013586 DOI: 10.2147/jhc.s347959] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 02/25/2023] [Indexed: 03/11/2023] Open
Abstract
Hepatocellular carcinoma (HCC) continues to be a serious medical problem with poor prognosis worldwide. The distribution of the major etiologies of HCC is changing due to the progress of anti-viral treatments, including hepatitis B virus (HBV) suppression by nucleoside/nucleotide analogues (NAs) and increased sustained virologic response (SVR) rates by direct-acting antivirals (DAAs) for hepatitis C virus (HCV), as well as the rising trend of nonviral liver disease. Although viral hepatitis remains the most common cause of HCC, non-alcoholic liver disease (NAFLD) with metabolic syndrome and alcohol-associated liver disease (ALD) are increasing. Effective and well-tolerated NAs treatment can slow the disease progression of chronic HBV infection to cirrhosis, end-stage liver disease, and reduce HCC risk. Treatment with NAs is also associated with significant improvement in the long-term survival of patients with HBV infection who already have HCC. DAAs have achieved viral elimination in almost all patients with HCV without significant adverse events, even in patients with decompensated liver cirrhosis and HCC. Similarly, DAA therapy can reduce disease progression, liver and non-liver complications, and improve the long-term survival of patients with chronic HCV infection with or without HCC. Meanwhile, NAFLD is a rapidly increasing cause of HCC along with the epidemics of obesity and type 2 diabetes globally. NAFLD-related HCC can occur in patients without cirrhosis and is known to have a lower survival rate than viral hepatitis-related HCC. Since there is currently no specific pharmacotherapy effective for NAFLD, lifestyle modification and prevention of complications are important to improve prognosis. Additionally, ALD is the second fastest-growing cause of HCC-related deaths, especially with an accelerated trend since the COVID-19 pandemic. This review provides an overview of the epidemiologic trends in the etiologies of HCC, and the progress of treatments for each etiology and the impact on outcome in the patients with HCC.
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Affiliation(s)
- Takanori Ito
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA.,Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, CA, USA
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17
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Pai YY, Wang JD, Ho HE, Chou YJ, Ho WC, Chan WC, Chu WM, Tsan YT. Risk of Fractures, Repeated Fractures and Osteoporotic Fractures among Patients with Hemophilia in Taiwan: A 14-Year Population-Based Cohort Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 20:ijerph20010525. [PMID: 36612847 PMCID: PMC9819339 DOI: 10.3390/ijerph20010525] [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: 11/07/2022] [Revised: 12/22/2022] [Accepted: 12/25/2022] [Indexed: 06/12/2023]
Abstract
The world is aging, and hemophilia patients are as well. The association between patients with hemophilia (PWH) and low bone mineral density is clear. However, the incidence of fractures in patients with hemophilia is inconclusive, and no research has yet explored repeated fractures among PWH. In this study, we investigated the incidence of all-site fractures, repeated fractures and osteoporotic fractures amongst PWH. The study compared the incidence of all-site fractures, repeated fractures and osteoporotic fractures occurring in all PWH who were enrolled in Taiwan's National Health Insurance Research Database between 1997 and 2013 with an age- and gender-matched group from the general population. Eight-hundred thirty-two PWH, along with 8320 members of the general population, were included in the final analysis. After multivariate COX regression analysis with an adjustment for confounding factors, it was found that PWH experienced a higher risk of osteoporotic fracture (HR: 1.25 with 95% CI of 1.03-2.52) but only saw a neutral effect with regards to both all-sites of fracture (HR: 1.00 with 95% CI of 0.92-1.09) and repeated fractures (HR: 1.01 with 95% CI of 0.92-1.10), when compared with the general population. This 14-year population-based cohort study showed that PWH had a higher risk of osteoporotic fracture, but that hemophilia only had a neutral effect in all-sites of fracture and repeated fractures. Screening, prevention and treatment for osteoporosis and further osteoporotic fractures among PWH, in order to improve quality of life and achieve healthy aging in this particular population, remain essential.
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Affiliation(s)
- Yuan-Yi Pai
- Department of Family Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan
- Division of Occupational Medicine, Department of Emergency Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan
| | - Jiaan-Der Wang
- Center for Rare Disease and Hemophilia, Department of Pediatrics, Taichung Veterans General Hospital, Taichung 40705, Taiwan
| | - Hsin-En Ho
- Department of Family Medicine, Taichung Armed Force General Hospital, Taichung 411228, Taiwan
- Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
- School of Medicine, National Defense Medical Center, Taipei 11490, Taiwan
| | - Yi-Jung Chou
- Division of Insurance Services, National Defense Medical Center, Taipei 11490, Taiwan
| | - Wen-Chao Ho
- Department of Public Health, China Medical University, Taichung 406040, Taiwan
| | - Wei-Cheng Chan
- Division of Occupational Medicine, Department of Emergency Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan
| | - Wei-Min Chu
- Department of Family Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 40227, Taiwan
- Education and Innovation Center for Geriatrics and Gerontology, National Center for Geriatrics and Gerontology, Moriokamachi 474-8511, Japan
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
| | - Yu-Tse Tsan
- Division of Occupational Medicine, Department of Emergency Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
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18
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Oura K, Morishita A, Tani J, Masaki T. Antitumor Effects and Mechanisms of Metabolic Syndrome Medications on Hepatocellular Carcinoma. J Hepatocell Carcinoma 2022; 9:1279-1298. [PMID: 36545268 PMCID: PMC9760577 DOI: 10.2147/jhc.s392051] [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: 10/03/2022] [Accepted: 12/04/2022] [Indexed: 12/15/2022] Open
Abstract
Liver cancer has a high incidence and mortality rate worldwide, with hepatocellular carcinoma (HCC) being the most common histological type. With the decrease in the number of newly infected patients and the spread of antiviral therapy, hepatitis virus-negative chronic liver diseases including steatohepatitis are increasingly accounting for a large proportion of HCC, and an important clinical characteristic is the high prevalence of metabolic syndrome including hypertension, type 2 diabetes (T2D), dyslipidemia, and obesity. Since patients with steatohepatitis are less likely to undergo surveillance for early detection of HCC, they may be diagnosed at an advanced stage and have worse prognosis. Therefore, treatment strategies for patients with HCC caused by steatohepatitis, especially in advanced stages, become increasingly important. Further, hypertension, T2D, and dyslipidemia may occur as side effects during systemic treatment, and there will be increasing opportunities to prescribe metabolic syndrome medications, not only for originally comorbid diseases, but also for adverse events during HCC treatment. Interestingly, epidemiological studies have shown that patients taking some metabolic syndrome medications are less likely to develop various types of cancers, including HCC. Basic studies have also shown that these drugs have direct antitumor effects on HCC. In particular, angiotensin II receptor blockers (a drug group for treating hypertension), biguanides (a drug group for treating T2D), and statins (a drug group for treating dyslipidemia) have shown to elucidate antitumor effects against HCC. In this review, we focus on the antitumor effects of metabolic syndrome medications on HCC and their mechanisms based on recent literature. New therapeutic agents are also increasingly being reported. Analysis of the antitumor effects of metabolic syndrome medications on HCC and their mechanisms will be doubly beneficial for HCC patients with metabolic syndrome, and the use of these medications may be a potential strategy against HCC.
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Affiliation(s)
- Kyoko Oura
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa, Japan,Correspondence: Kyoko Oura, Department of Gastroenterology and Neurology, Kagawa University, 1750-1 Ikenobe, Miki, Kida, Kagawa, Japan, Tel +81-87-891-2156, Fax +81-87-891-2158, Email
| | - Asahiro Morishita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Joji Tani
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Tsutomu Masaki
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa, Japan
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19
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Ejam SS, Saleh RO, Catalan Opulencia MJ, Najm MA, Makhmudova A, Jalil AT, Abdelbasset WK, Al-Gazally ME, Hammid AT, Mustafa YF, Sergeevna SE, Karampoor S, Mirzaei R. Pathogenic role of 25-hydroxycholesterol in cancer development and progression. Future Oncol 2022; 18:4415-4442. [PMID: 36651359 DOI: 10.2217/fon-2022-0819] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Accepted: 12/06/2022] [Indexed: 01/19/2023] Open
Abstract
Cholesterol is an essential lipid that serves several important functions, including maintaining the homeostasis of cells, acting as a precursor to bile acid and steroid hormones and preserving the stability of membrane lipid rafts. 25-hydroxycholesterol (25-HC) is a cholesterol derivative that may be formed from cholesterol. 25-HC is a crucial component in various biological activities, including cholesterol metabolism. In recent years, growing evidence has shown that 25-HC performs a critical function in the etiology of cancer, infectious diseases and autoimmune disorders. This review will summarize the latest findings regarding 25-HC, including its biogenesis, immunomodulatory properties and role in innate/adaptive immunity, inflammation and the development of various types of cancer.
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Affiliation(s)
| | - Raed Obaid Saleh
- Department of Pharmacy, Al-Maarif University College, Al-Anbar, Iraq
| | | | - Mazin Aa Najm
- Pharmaceutical Chemistry Department, College of Pharmacy, Al-Ayen University, Thi-Qar, Iraq
| | - Aziza Makhmudova
- Department of Social Sciences & Humanities, Samarkand State Medical Institute, Samarkand, Uzbekistan
- Department of Scientific Affairs, Tashkent State Dental Institute, Makhtumkuli Street 103, Tashkent, 100047, Uzbekistan
| | - Abduladheem Turki Jalil
- Medical Laboratories Techniques Department, Al-Mustaqbal University College, Babylon, Hilla, 51001, Iraq
| | - Walid Kamal Abdelbasset
- Department of Health & Rehabilitation Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al Kharj, Saudi Arabia
- Department of Physical Therapy, Kasr Al-Aini Hospital, Cairo University, Giza, Egypt
| | | | - Ali Thaeer Hammid
- Computer Engineering Techniques Department, Faculty of Information Technology, Imam Ja'afar Al-Sadiq University, Baghdad, Iraq
| | - Yasser Fakri Mustafa
- Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul, 41001, Iraq
| | - Sergushina Elena Sergeevna
- National Research Ogarev Mordovia State University, 68 Bolshevitskaya Street, Republic of Mordovia, Saransk, 430005, Russia
| | - Sajad Karampoor
- Gastrointestinal & Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Rasoul Mirzaei
- Venom & Biotherapeutics Molecules Lab, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
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20
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Shin HS, Jun BG, Yi SW. Impact of diabetes, obesity, and dyslipidemia on the risk of hepatocellular carcinoma in patients with chronic liver diseases. Clin Mol Hepatol 2022; 28:773-789. [PMID: 35934813 PMCID: PMC9597232 DOI: 10.3350/cmh.2021.0383] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 04/20/2022] [Indexed: 01/05/2023] Open
Abstract
Despite the increasing prevalence of metabolic disorders, the potential effects of metabolic factors on hepatocellular carcinoma (HCC) development in individuals with chronic liver diseases (CLDs) are not well understood. For a metabolic factor to be identified as a risk factor for HCC in patients with CLDs, such as hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, there should be a strong synergistic interaction between the carcinogenic mechanisms of the metabolic factor and the CLD itself. This review aims to comprehensively summarize the published data on the relationship between metabolic factors such as diabetes mellitus (DM), obesity, and blood lipids and the risk of HCC in patients with CLDs. DM consistently increases the risk of HCC in patients with CLD. When associated with DM, the risk of HCC seems to be highest in HCV and non-alcoholic fatty liver disease (NAFLD), followed by alcoholic liver disease (ALD) and HBV. Obesity may increase the risk of HCC. Among CLDs, the evidence is relatively consistent and clear for ALD, while clear evidence is limited in other CLDs including HBV, HCV, and NAFLD. Total cholesterol, potentially low-density lipoprotein cholesterol and triglyceride, seems to have strong inverse associations with HCC in individuals with CLDs. Despite evidence from observational studies, statins had no effect in preventing HCC in randomized controlled trials. Whether statins have a preventive effect against HCC is unclear. A better understanding and management of metabolic factors may be beneficial to reduce the risk of HCC in patients with CLDs.
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Affiliation(s)
- Hwang Sik Shin
- Department of Family Medicine, Soonchunhyang University Hospital Cheonan, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Baek Gyu Jun
- Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea,Corresponding author : Baek Gyu Jun Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, 1342 Dongil-ro, Nowon-gu, Seoul 01757, Korea Tel: +82-2-950-8889, Fax: +82-2-950-1955, E-mail:
| | - Sang-Wook Yi
- Department of Preventive Medicine and Public Health, College of Medicine, Catholic Kwandong University, Gangneung, Korea,Sang-Wook Yi Department of Preventive Medicine and Public Health, College of Medicine, Catholic Kwandong University, 24 Beomil-ro 579beon-gil, Gangneung 25601, Korea Tel: +82-33-649-7468, Fax: +82-33-641-1074, E-mail:
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21
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Clark EH, Ahmed ST, Chang E, Chiao EY, White DL. Can statins lessen the burden of virus mediated cancers? Infect Agent Cancer 2022; 17:47. [PMID: 36058947 PMCID: PMC9441070 DOI: 10.1186/s13027-022-00460-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Accepted: 08/22/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Oncogenic viruses, including hepatitis B virus (HBV), hepatitis C virus (HCV), human papillomavirus (HPV), Epstein Barr virus (EBV), and Kaposi Sarcoma Herpes virus (KSHV) contribute to a significant proportion of the world's cancers. Given the sizeable burden of virus mediated cancers, development of strategies to prevent and/or treat these cancers is critical. While large population studies suggest that treatment with hydroxymethylglutaryl-CoA reductase inhibitors, commonly known as statins, may reduce the risk of many cancer types including HBV/HCV related hepatocellular carcinoma, few studies have specifically evaluated the impact of statin use in populations at risk for other types of virus mediated cancers. MAIN BODY Studies of populations with HBV and HCV suggest a protective, dose-dependent effect of statins on hepatocellular carcinoma risk and support the theory that statins may offer clinical benefit if used as chemoprophylactic agents to reduce liver cancer incidence. However, no population level data exists describing the impact of statins on populations with other oncogenic viral infections, such as HPV, EBV, and KSHV. CONCLUSION Further study of statin use in diverse, global populations with or at high risk for oncogenic viral infections is essential to determine the impact of statin therapy on virus mediated cancer risk.
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Affiliation(s)
- Eva H Clark
- Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
- Center for Innovation, Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey VA Medical Center, Houston, TX, USA.
- Section of Pediatric Tropical Medicine, Baylor College of Medicin, Feigin Building Suite 550, Houston, TX, 77030, USA.
| | - Sarah T Ahmed
- Center for Innovation, Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey VA Medical Center, Houston, TX, USA
- Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Elaine Chang
- Center for Innovation, Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey VA Medical Center, Houston, TX, USA
- Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Elizabeth Y Chiao
- Departments of Epidemiology and General Oncology, MD Anderson Cancer Center, Houston, TX, USA
| | - Donna L White
- Center for Innovation, Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey VA Medical Center, Houston, TX, USA
- Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX, USA
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22
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Wang TY, Chen CY, Huang TH, Yang YH, Chen KJ, Chou WC, Lu CH. Protein-bound polysaccharide K prolonged overall survival in gastric cancer patients from a non-Japanese Asian country who received gastrectomy and adjuvant chemotherapy. Medicine (Baltimore) 2022; 101:e29632. [PMID: 35866836 PMCID: PMC9302315 DOI: 10.1097/md.0000000000029632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Revised: 04/19/2022] [Accepted: 05/06/2022] [Indexed: 01/17/2023] Open
Abstract
Adding protein-bound polysaccharide K (PSK) to adjuvant chemotherapy with mitomycin and fluorouracil after gastrectomy for gastric cancer was demonstrated to improve survival in a previous study in Japan. However, the efficacy of PSK outside Japan and in combination with other adjuvant chemotherapeutic agents remains unclear. The aims of this study were to evaluate the efficacy of PSK. We conducted a population-based historical cohort study using the National Health Insurance Research Database of Taiwan. We performed sensitivity analysis with propensity score matching to control for possible confounders. Patients who used PSK (PSK group) were matched at a 1:4 ratio to those who had never used PSK (control group) after adjusting for covariates including sex, age, urbanization, income and comorbidities. The primary outcome was overall survival. Multivariate hazard ratios from competing risk analysis were calculated by adjusting for demographic data and all confounding factors. From 1999 to 2008, we identified 10,617 patients with gastric cancer received gastrectomy and adjuvant chemotherapy. 1295 patients used PSK (PSK group) and 5180 patients never used PSK (control group) were analyzed after propensity score matching. The median overall survival was 6.49 years (95% confidence interval [CI] 5.22-7.63) in the PSK group and 3.59 years (95% CI 3.38-3.80) in the control group. After adjusting for age, sex, urbanization, income, and comorbidities, adding PSK to adjuvant chemotherapy was the most significant prognostic factor for improved survival (hazard ratio 0.76, P < .0001). Adjuvant chemotherapy combined with PSK significantly prolonged overall survival in gastric cancer patients after gastrectomy.
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Affiliation(s)
- Ting-Yao Wang
- Division of Hematology and Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Chao-Yu Chen
- Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Chiayi, Taiwan; Department of Early Childhood Care and Education, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan
| | - Tzu-Hao Huang
- Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Yao-Hsu Yang
- Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan; School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Health Information and Epidemiology Laboratory, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Ko-Jung Chen
- Health Information and Epidemiology Laboratory, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Wen-Chi Chou
- Department of Hematology-Oncology, Chang Gung Memorial Hospital at Linkou and Chang Gung University, College of Medicine, Taoyuan, Taiwan
| | - Chang-Hsien Lu
- Division of Hematology and Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
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23
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Khazaaleh S, Sarmini MT, Alomari M, Al Momani L, El Kurdi B, Asfari M, Almomani Z, Romero-Marrero C. Statin Use Reduces the Risk of Hepatocellular Carcinoma: An Updated Meta-Analysis and Systematic Review. Cureus 2022; 14:e27032. [PMID: 35989795 PMCID: PMC9388192 DOI: 10.7759/cureus.27032] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/21/2022] [Indexed: 11/05/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver resulting in approximately 800,000 deaths annually. A growing body of research investigating statin use and HCC risk has shown conflicting results. We aim to evaluate the current evidence of statin impact on HCC risk. We performed a comprehensive literature search in PubMed, PubMed Central, Embase, and ScienceDirect databases from inception through May 2019 to identify all studies that evaluated the association between statin use and HCC. We included studies that presented an odds ratio (OR) with a 95% confidence interval (CI) or presented data sufficient to calculate the OR with a 95% CI. Statistical analysis was performed using the Comprehensive Meta-Analysis (CMA), Version 3 software, and a Forrest plot was generated. We assessed for publication bias using conventional techniques. Twenty studies (three randomized controlled trials, six cohorts, and 11 case-controls) with 2,668,497 patients including 24,341 cases of HCC were included in the meta-analysis. Our findings indicate a significant risk reduction of HCC among all statin users with a pooled odds ratio of 0.573 (95% CI: 0.491-0.668, I2= 86.57%) compared to non-users. No publication bias was found using Egger’s regression test or on visual inspection of the generated Funnel plot. The results indicate that statin use was associated with a 43% lower risk of HCC compared to statin non-users. Further prospective randomized research is needed to confirm the association.
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Association of statin treatment with hepatocellular carcinoma risk in end-stage kidney disease patients with chronic viral hepatitis. Sci Rep 2022; 12:10807. [PMID: 35752695 PMCID: PMC9233705 DOI: 10.1038/s41598-022-14713-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 06/10/2022] [Indexed: 11/12/2022] Open
Abstract
Statin use in end-stage kidney disease (ESKD) patients are not encouraged due to low cardioprotective effects. Although the risk of hepatocellular carcinoma (HCC), a frequently occurring cancer in East Asia, is elevated in ESKD patients, the relationship between statins and HCC is not known despite its possible chemopreventive effect. The relationship between statin use and HCC development in ESKD patients with chronic hepatitis was evaluated. In total, 6165 dialysis patients with chronic hepatitis B or C were selected from a national health insurance database. Patients prescribed with ≥ 28 cumulative defined daily doses of statins during the first 3 months after dialysis commencement were defined as statin users, while those not prescribed with statins were considered as non-users. Primary outcome was the first diagnosis of HCC. Sub-distribution hazard model with inverse probability of treatment weighting was used to estimate HCC risk considering death as competing risk. During a median follow-up of 2.8 years, HCC occurred in 114 (3.2%) statin non-users and 33 (1.2%) statin users. The HCC risk was 41% lower in statin users than in non-users (sub-distribution hazard ratio, 0.59; 95% confidence interval [CI], 0.42-0.81). The weighted incidence rate of HCC was lower in statin users than in statin non-users (incidence rate difference, - 3.7; 95% CI - 5.7 to - 1.7; P < 0.001). Incidence rate ratio (IRR) was also consistent with other analyses (IRR, 0.56; 95% CI, 0.41 to 0.78; P < 0.001). Statin use was associated with a lower risk of incident HCC in dialysis patients with chronic hepatitis B or C infection.
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Kim DS, Kim HJ, Ahn HS. Statins and the risk of gastric, colorectal, and esophageal cancer incidence and mortality: a cohort study based on data from the Korean national health insurance claims database. J Cancer Res Clin Oncol 2022; 148:2855-2865. [PMID: 35660949 DOI: 10.1007/s00432-022-04075-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Accepted: 05/16/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND This study investigated the association between the use of statins, the incidence of gastric, colorectal, and esophageal cancers, and mortality between January 2005 and June 2013 in South Korea. METHODS We compared patients aged 45-70 years statin users for at least 6 months to non-statin users matched by age and sex, from 2004 to June 2013 using the National Health Insurance database. Main outcomes were gastric, colorectal, and esophageal cancer incidence and mortality. Cox proportional hazard regression was used to calculate the adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) among overall cohort and matched cohort after propensity score matching with a 1:1 ratio. RESULTS Out of 1,008,101 people, 20,473 incident cancers, 3938 cancer deaths occurred and 7669 incident cancer, 1438 cancer death in matched cohort. The aHRs for the association between the risk of cancers and statin use were 0.7 (95% CI 0.65-0.74) for gastric cancer, 0.73 (95% CI 0.69-0.78) for colorectal cancer, and 0.55 (95% CI 0.43-0.71) for esophageal cancer. There were associations between statin use and decreased gastric cancer mortality (HR 0.46, 95% CI 0.52-0.57), colorectal cancer mortality (HR 0.43, 95% CI 0.36-0.51), and esophageal cancer mortality (HR 0.41, 95% CI 0.27-0.50) in the overall cohort and this pattern was similar in the matched cohort. DISCUSSION Statin use for at least 6 months was significantly associated with a lower risk of stomach, colorectal, and esophageal cancer incidence as well as cancer mortality after a diagnosis.
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Affiliation(s)
- Dong-Sook Kim
- Department of Research, Health Insurance Review and Assessment Service, Wonju, Republic of Korea
| | - Hyun Jung Kim
- Department of Preventive Medicine, College of Medicine, Korea University, 126-1, 5-ga, Anam-dong, Sungbuk-gu, Seoul, 136-705, Republic of Korea
| | - Hyeong Sik Ahn
- Department of Preventive Medicine, College of Medicine, Korea University, 126-1, 5-ga, Anam-dong, Sungbuk-gu, Seoul, 136-705, Republic of Korea.
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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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Praveen TK, Gangadharappa HV, Abu Lila AS, Moin A, Mehmood K, Krishna KL, Hussain T, Alafanan A, Shakil S, Rizvi SMD. Inflammation targeted nanomedicines: patents and applications in cancer therapy. Semin Cancer Biol 2022; 86:645-663. [DOI: 10.1016/j.semcancer.2022.04.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 02/08/2022] [Accepted: 04/06/2022] [Indexed: 12/12/2022]
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Singh J, Wozniak A, Cotler SJ, Dhanarajan A, Aldrich D, Park D, Kasia C, Schmidt B, Scaglione S. Combined Use of Aspirin and Statin is Associated With a Decreased Incidence of Hepatocellular Carcinoma. J Clin Gastroenterol 2022; 56:369-373. [PMID: 33883511 DOI: 10.1097/mcg.0000000000001546] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Accepted: 03/05/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a leading cause of cancer and cancer-related mortality worldwide. Studies have suggested that aspirin (ASA) and statins may be associated with a decrease in incident HCC. GOALS We aimed to evaluate the effect of ASA and statin use on the incidence of HCC in a prospective cohort of patients with liver cirrhosis and to identify if there was an increased risk of esophageal variceal hemorrhage (VH) in patients with ASA use. STUDY We conducted a retrospective study of 521 patients with data collected from July 1, 2012 to December 31, 2017. We used competing risk analysis to assess the association between risk factors and HCC; and the association between ASA and VH. RESULTS ASA use alone was associated with a decreased incidence of HCC in the univariate and multivariate models; [hazard ratio (HR) confidence interval (CI): 0.348 (0.124-0.976); P=0.0448] and [HR (CI): 0.266 (0.094-0.755); P=0.0129, respectively]. The combination of ASA and statin use was associated with a decreased hazard of HCC [HR (CI): 0.15 (0.036-0.624); P=0.0090] and this remained statistically significant in the multivariable model [HR (CI): 0.113 (0.026-0.483); P=0.0033]. Among daily ASA users compared with non-users, there was not a significant increase in risk of VH. CONCLUSIONS Daily ASA use was associated with a decrease risk of incident HCC. The combination of daily ASA use and statin use decreased the risk of incident HCC suggesting there is beneficial interaction. Finally, no excess VH was observed in daily ASA users compared with non-users.
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Affiliation(s)
- Jasleen Singh
- Department of Internal Medicine, Loyola University Medical Center
| | - Amy Wozniak
- Clinical Research Office, Biostatistics, Loyola University Chicago, Maywood, IL
| | - Scott J Cotler
- Department of Internal Medicine, Loyola University Medical Center
| | - Asha Dhanarajan
- Department of Internal Medicine, Loyola University Medical Center
| | - Daniel Aldrich
- Department of Internal Medicine, Loyola University Medical Center
| | - David Park
- Department of Internal Medicine, Loyola University Medical Center
| | - Chris Kasia
- Department of Internal Medicine, Loyola University Medical Center
| | - Benjamin Schmidt
- Department of Internal Medicine, Loyola University Medical Center
| | - Steven Scaglione
- Department of Internal Medicine, Loyola University Medical Center
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Wang Y, Wang W, Wang M, Shi J, Jia X, Dang S. A Meta-Analysis of Statin Use and Risk of Hepatocellular Carcinoma. Can J Gastroenterol Hepatol 2022; 2022:5389044. [PMID: 35356132 PMCID: PMC8958112 DOI: 10.1155/2022/5389044] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Revised: 02/25/2022] [Accepted: 02/26/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND The use of statins is a potential protective factor against the development of hepatocellular carcinoma. Therefore, we conducted a meta-analysis to evaluate the contribution of statins to the risk of hepatocellular carcinoma. METHODS We searched for PubMed and EMBASE through January 2021. RESULTS Thirty-two studies (eighteen cohort, eleven case-control, and three randomized controlled trials) reporting 56,838 cases of hepatocellular carcinoma in 4,963,518 persons were included. Statin users were less likely to develop hepatocellular carcinoma than nonusers (adjusted odds ratio, 0.58; 95% CI: 0.51-0.67). Stratified analysis showed that statins reduced the risk of hepatocellular carcinoma in Asian and Western populations (odds ratio, 0.54 vs. 0.60). Besides, statins have protective effects against hepatocellular carcinoma after hepatitis B virus (odds ratio, 0.44; 95% CI: 0.22-0.85) and hepatitis C virus infections (odds ratio, 0.53; 95% CI: 0.49-0.57). Statins have protective effects on people with chronic liver disease (odds ratio, 0.52; 95% CI: 0.40-0.68) and on the general population (odds ratio, 0.60; 95% CI: 0.50-0.72). Lipophilic statins can prevent hepatocellular carcinoma (odds ratio, 0.51, 95% CI: 0.46-0.57), while hydrophilic statins cannot (odds ratio, 0.77, 95% CI: 0.58-1.02). The single-drug analyses showed that simvastatin (odds ratio, 0.53, 95% CI: 0.48-0.59), atorvastatin (odds ratio, 0.54, 95% CI: 0.45-0.64), rosuvastatin (odds ratio, 0.55, 95% CI: 0.37-0.83), lovastatin (odds ratio, 0.30, 95% CI: 0.15-0.62), and pitavastatin (odds ratio, 0.36, 95% CI: 0.17-0.75) had significant benefits. Further studies have shown that those in the high-dose group experienced better effects in preventing hepatocellular carcinoma (adjusted hazard ratio, 0.38 vs. 0.55). Further research found that the combined use of aspirin did not increase the chemoprevention effect of liver cancer (odds ratio, 0.57; 95% CI: 0.40-0.81). In addition, the preventive effect of statins improved with the extension of follow-up time (odds ratio, 0.54 vs. 0.65). CONCLUSION Our meta-analysis shows that the use of statins 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 710004, China
| | - Wenjun Wang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China
| | - Muqi Wang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China
| | - Juanjuan Shi
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China
| | - Xiaoli Jia
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China
| | - Shuangsuo Dang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China
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Hajifathalian K, Tafesh Z, Rosenblatt R, Kumar S, Homan EA, Sharaiha RZ, Cohen DE, Brown RS, Fortune BE. Effect of Statin Use on Cancer-related Mortality in Nonalcoholic Fatty Liver Disease: A Prospective United States Cohort Study. J Clin Gastroenterol 2022; 56:173-180. [PMID: 33606428 DOI: 10.1097/mcg.0000000000001503] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 12/22/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND Indications for use of statins are common among patients with nonalcoholic fatty liver disease (NAFLD). Epidemiologic studies have suggested a possible association between statins and decreased risk of malignancies. We hypothesized that statin use has a protective effect on cancer mortality in patients with NAFLD. METHODS Participants with NAFLD in 8 rounds of National Health and Nutrition Examination Survey (NHANES) were included in this study. Mortality data were obtained by linking the NHANES data to National Death Index. NAFLD was defined using the previously validated Hepatic Steatosis Index model. RESULTS A total of 10,821 participants with NAFLD were included and 23% were statin users (n=2523). Statin use was associated with a 43% lower risk of cancer mortality [hazard ratio (HR)=0.57, 95% confidence interval (CI): 0.43-0.75, P<0.001] in multivariable analysis. Statin use under 1 year did not show a significant effect on cancer mortality (HR=0.72, 95% CI: 0.46-1.12), while statin use for 1 to 5 years decreased cancer mortality by 35% (HR=0.65, 95% CI: 0.42-0.99, P=0.46), and statin use >5 years decreased cancer mortality by 56% (HR=0.44, 95% CI: 0.29-0.66, P<0.001). Statin use was associated with a significant decrease in the risk of cancer mortality in NAFLD patients with both low and high risk of liver fibrosis (HR=0.55, 95% CI: 0.38-0.81; and HR=0.53, 95% CI: 0.31-0.89, respectively). CONCLUSION Using a large US prospective cohort, we showed statin use is associated with a considerable decrease in cancer-related mortality among patients with NAFLD. These results are important for clinical decision making, as statin indications are prevalent among NAFLD patients, but many do not receive benefit in the event that the statin is discontinued due to liver test abnormalities.
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Affiliation(s)
| | - Zaid Tafesh
- Divisions of Gastroenterology and Hepatology
| | | | - Sonal Kumar
- Divisions of Gastroenterology and Hepatology
| | - Edwin A Homan
- Cardiology, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY
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Khajeh E, Moghadam AD, Eslami P, Ali-Hasan-Al-Saegh S, Ramouz A, Shafiei S, Ghamarnejad O, Dezfouli SA, Rupp C, Springfeld C, Carvalho C, Probst P, Mousavizadeh SM, Mehrabi A. Statin use is associated with the reduction in hepatocellular carcinoma recurrence after liver surgery. BMC Cancer 2022; 22:91. [PMID: 35062904 PMCID: PMC8781082 DOI: 10.1186/s12885-022-09192-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 01/05/2022] [Indexed: 02/06/2023] Open
Abstract
Abstract
Background
Hepatocellular carcinoma (HCC) is the sixth most common form of cancer worldwide. Although surgical treatments have an acceptable cure rate, tumor recurrence is still a challenging issue. In this meta-analysis, we investigated whether statins prevent HCC recurrence following liver surgery.
Methods
PubMed, Web of Science, EMBASE and Cochrane Central were searched. The Outcome of interest was the HCC recurrence after hepatic surgery. Pooled estimates were represented as hazard ratios (HRs) and odds ratios (ORs) using a random-effects model. Summary effect measures are presented together with their corresponding 95% confidence intervals (CI). The certainty of evidence was evaluated using the Grades of Research, Assessment, Development and Evaluation (GRADE) approach.
Results
The literature search retrieved 1362 studies excluding duplicates. Nine retrospective studies including 44,219 patients (2243 in the statin group and 41,976 in the non-statin group) were included in the qualitative analysis. Patients who received statins had a lower rate of recurrence after liver surgery (HR: 0.53; 95% CI: 0.44–0.63; p < 0.001). Moreover, Statins decreased the recurrence 1 year after surgery (OR: 0.27; 95% CI: 0.16–0.47; P < 0.001), 3 years after surgery (OR: 0.22; 95% CI: 0.15–0.33; P < 0.001), and 5 years after surgery (OR: 0.28; 95% CI: 0.19–0.42; P < 0.001). The certainty of evidence for the outcomes was moderate.
Conclusion
Statins increase the disease-free survival of patients with HCC after liver surgery. These drugs seem to have chemoprevention effects that decrease the probability of HCC recurrence after liver transplantation or liver resection.
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Shen YC, Hsu HC, Lin TM, Chang YS, Hu LF, Chen LF, Lin SH, Kuo PI, Chen WS, Lin YC, Chen JH, Liang YC, Chang CC. H1-Antihistamines Reduce the Risk of Hepatocellular Carcinoma in Patients With Hepatitis B Virus, Hepatitis C Virus, or Dual Hepatitis B Virus-Hepatitis C Virus Infection. J Clin Oncol 2022; 40:1206-1219. [PMID: 35044851 PMCID: PMC8987217 DOI: 10.1200/jco.21.01802] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
H1-antihistamines (AHs) may exert protective effects against cancer. This study investigated the association of AH use with the risk of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV), hepatitis C virus (HCV), or dual HBV-HCV virus infection.
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Affiliation(s)
- Yu-Chuan Shen
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Hui-Ching Hsu
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.,Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Tzu-Min Lin
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Division of Rheumatology, Immunology, and Allergy, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - Yu-Sheng Chang
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan
| | - Li-Fang Hu
- Division of Rheumatology, Immunology, and Allergy, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - Lung-Fang Chen
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.,Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Sheng-Hong Lin
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan
| | - Pei-I Kuo
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Cardinal Tien Hospital, Yonghe Branch, Taipei, Taiwan
| | - Wei-Sheng Chen
- Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan
| | - Yi-Chun Lin
- Biostatistics Center, College of Management, Taipei Medical University, Taipei, Taiwan
| | - Jin-Hua Chen
- Biostatistics Center, College of Management, Taipei Medical University, Taipei, Taiwan.,Graduate Institute of Data Science, College of Management, Taipei Medical University, Taipei, Taiwan
| | - Yu-Chih Liang
- School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.,Ph.D. Program in Medical Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.,Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan
| | - Chi-Ching Chang
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Division of Rheumatology, Immunology, and Allergy, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
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Uemura N, Hayashi H, Baba H. Statin as a therapeutic agent in gastroenterological cancer. World J Gastrointest Oncol 2022; 14:110-123. [PMID: 35116106 PMCID: PMC8790423 DOI: 10.4251/wjgo.v14.i1.110] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 06/19/2021] [Accepted: 11/25/2021] [Indexed: 02/06/2023] Open
Abstract
Statins inhibit 3-hydroxy-3-methylglutaryl-CoA reductase, the rate-limiting enzyme of the mevalonate pathway, and are widely used as an effective and safe approach handle hypercholesterolemia. The mevalonate pathway is a vital metabolic pathway that uses acetyl-CoA to generate isoprenoids and sterols that are crucial to tumor growth and progression. Multiple studies have indicated that statins improve patient prognosis in various carcinomas. Basic research on the mechanisms underlying the antitumor effects of statins is underway. The development of new anti-cancer drugs is progressing, but increasing medical costs from drug development have become a major obstacle. Readily available, inexpensive and well-tolerated drugs like statins have not yet been successfully repurposed for cancer treatment. Identifying the cancer patients that may benefit from statins is key to improved patient treatment. This review summarizes recent advances in statin research in cancer and suggests important considerations for the clinical use of statins to improve outcomes for cancer patients.
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Affiliation(s)
- Norio Uemura
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan
| | - Hiromitsu Hayashi
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan
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Goh MJ, Sinn DH. Statin and aspirin for chemoprevention of hepatocellular carcinoma: Time to use or wait further? Clin Mol Hepatol 2022; 28:380-395. [PMID: 35021597 PMCID: PMC9293618 DOI: 10.3350/cmh.2021.0366] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Accepted: 01/08/2022] [Indexed: 11/20/2022] Open
Abstract
Preclinical studies highlighted potential therapeutic applications of aspirin and statins as anticancer agents based on their pleiotropic effects. Epidemiologic studies suggested the role of aspirin and statins in the chemoprevention of hepatocellular carcinoma (HCC). However, observational data is prone to bias, and no prospective randomized trials are currently available to assess the risks and benefits of statin or aspirin therapy for chemoprevention of HCC. It is therefore important for clinicians and researchers to be aware of the quality of current evidence regarding this issue. In this review, we summarize currently available evidence to assist clinicians with their decision to use statin or aspirin and provide information for further clinical investigations.
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Affiliation(s)
- Myung Ji Goh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Ha J, Choi DW, Kim KJ, Cho SY, Kim H, Kim KY, Koh Y, Nam CM, Kim E. Association of metformin use with Alzheimer's disease in patients with newly diagnosed type 2 diabetes: a population-based nested case-control study. Sci Rep 2021; 11:24069. [PMID: 34912022 PMCID: PMC8674300 DOI: 10.1038/s41598-021-03406-5] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Accepted: 11/22/2021] [Indexed: 01/08/2023] Open
Abstract
Metformin reduces insulin resistance, which constitutes a pathophysiological connection of diabetes with Alzheimer’s disease (AD), but the evidence of metformin on AD development was still insufficient and conflicting. We investigated AD risk in patients with newly diagnosed type 2 DM treated with metformin. This retrospective, observational, nested case–control study included patients with newly diagnosed type 2 DM obtained from the Korean National Health Insurance Service DM cohort (2002–2017). Among 70,499 dementia-free DM patients, 1675 AD cases were matched to 8375 controls for age, sex, and DM onset and duration. The association between AD and metformin was analyzed by multivariable regression analyses, adjusted for comorbidities and cardiometabolic risk profile. Metformin use was associated with an increased odds of AD (adjusted odds ratio [AOR] 1.50; 95% CI 1.23–1.83). The risk of AD was higher in patients with a longer DM duration. Furthermore, AD risk was significantly high in DM patients with depression (AOR 2.05; 95% CI 1.02–4.12). Given the large number of patients with DM who are taking metformin worldwide, a double-blinded, prospective study is required to determine the long-term cognitive safety of metformin.
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Affiliation(s)
- Junghee Ha
- Department of Psychiatry, Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Dong-Woo Choi
- Cancer Big Data Center, National Cancer Control Institute, National Cancer Center, Gyeonggi-do, Republic of Korea
| | - Kwang Joon Kim
- Division of Geriatrics, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - So Yeon Cho
- Department of Psychiatry, Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.,Brain Korea 21 FOUR Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hyunjeong Kim
- Department of Psychiatry, Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Keun You Kim
- Department of Psychiatry, Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Youngseung Koh
- Department of Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Chung Mo Nam
- Department of Preventive Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
| | - Eosu Kim
- Department of Psychiatry, Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea. .,Brain Korea 21 FOUR Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.
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Wang J, Li X. Impact of statin use on the risk and prognosis of hepatocellular carcinoma: a meta-analysis. Eur J Gastroenterol Hepatol 2021; 33:1603-1609. [PMID: 33405428 DOI: 10.1097/meg.0000000000002040] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND Previous studies have demonstrated that statin use might be associated with a reduced risk of hepatocellular carcinoma (HCC). However, the value of statin on the prognosis still needs to be evaluated. Based on the above considerations, we conducted a meta-analysis regarding the value of statin on the prevention and prognosis of HCC. METHODS Articles regarding the impact of statin use on the risk, prognosis of HCC and published before October 2020 were searched in the five databases. We computed odds ratio (OR)/relative risk (RR) or hazard ratio (HR) and 95% confidence intervals (CIs) regarding the association between statin use and the risk or prognosis of HCC by using STATA 12.0 software. RESULTS Twenty-six studies (including 1772 463 participants) detected the association between statin use and risk of HCC. Additionally, seven studies (including 8925 statin users and 76 487 no-statin users) explored the association between statin use and mortality of HCC. The meta-analysis showed that statin use was associated with lower risk and all-cause mortality of HCC with random effects models (risk: OR/RR = 0.57, 95% CI 0.49-0.65, I2 = 86.0%, P < 0.0001; all-cause mortality: HR = 0.80, 95% CI 0.68-0.94, I2 = 77.6%, P < 0.0001). However, statin use was not associated with cancer-specific mortality of HCC with a random effects model (HR = 0.80, 95% CI 0.62-1.03, I2 = 73.9%, P = 0.002). CONCLUSION In conclusion, our results have demonstrated the salutary effect of statin on the prevention and prognosis of HCC.
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Affiliation(s)
- Jianfeng Wang
- Department of Gastroenterology, Baoshan Branch of Shanghai Renji Hospital, Shanghai, China
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Francis P, Forman LM. Statins Show Promise Against Progression of Liver Disease. Clin Liver Dis (Hoboken) 2021; 18:280-287. [PMID: 34976372 PMCID: PMC8688902 DOI: 10.1002/cld.1143] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Revised: 04/28/2021] [Accepted: 05/05/2021] [Indexed: 02/04/2023] Open
Abstract
Content available: Audio Recording.
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Affiliation(s)
- Prashanth Francis
- Division of Gastroenterology and HepatologyUniversity of ColoradoAuroraCO
| | - Lisa M. Forman
- Division of Gastroenterology and HepatologyUniversity of ColoradoAuroraCO
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Prevention of NAFLD-associated HCC: Role of lifestyle and chemoprevention. J Hepatol 2021; 75:1217-1227. [PMID: 34339764 DOI: 10.1016/j.jhep.2021.07.025] [Citation(s) in RCA: 89] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 07/13/2021] [Accepted: 07/15/2021] [Indexed: 02/07/2023]
Abstract
In many countries worldwide, the burden of hepatocellular carcinoma (HCC) associated with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) is increasing. Preventive strategies are needed to counteract this trend. In this review, we provide an overview of the evidence on preventive strategies in NAFLD-associated HCC. We consider the impact of lifestyle factors such as weight loss, physical activity, smoking, dietary patterns and food items, including coffee and alcohol, on both HCC and NAFLD/NASH. Furthermore, evidence on chemopreventive treatments, including aspirin, antidiabetic treatments and statins is summarised. The role of adjuvant therapies for tertiary prevention of HCC is briefly reviewed.
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Chiu WC, Shan JC, Yang YH, Chen VCH, Chen PC. Statins and the risks of decompensated liver cirrhosis and hepatocellular carcinoma determined in patients with alcohol use disorder. Drug Alcohol Depend 2021; 228:109096. [PMID: 34600254 DOI: 10.1016/j.drugalcdep.2021.109096] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 08/12/2021] [Accepted: 08/28/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND Alcohol-related liver disease (ALD) is the most common cause of liver disease. No medication can improve ALD and abstinence from alcohol is the sole effective strategy. Statin use has been demonstrated to have protective effects against liver cirrhosis and hepatocellular carcinoma (HCC) in patients with virus-related liver diseases. Whether statin use has a similar association among patients with alcohol use disorder (AUD) that can lead to ALD, is unknown. METHOD We conducted a population-based cohort study using Taiwan's National Health Insurance Research Database from 1997 to 2013 to compare risks of decompensated liver cirrhosis and hepatocellular carcinoma (HCC) between the statin exposed and unexposed groups in the patients with AUD. The incidence rates of decompensated liver cirrhosis and HCC were calculated between patients exposed and unexposed to statins with 1:4 propensity score matching. Cox proportional hazard regressions were performed to evaluate hazard ratios (HRs). RESULTS The incidence rates of decompensated liver cirrhosis and HCC in the statin-exposed group differed from those in the unexposed group (decompensated cirrhosis: 269.9 vs. 628.9 cases per 100,000 person-years; HCC: 116.7 vs. 318.3 cases per 100,000 person-years). The HRs for decompensated liver cirrhosis and HCC were 0.43 (95% CI, 0.37-0.51) and 0.40 (95% CI, 0.31-0.51), respectively, after adjustment. CONCLUSIONS Statin use was associated with reduced risk of decompensated liver cirrhosis and HCC among AUD patients in a cumulative dose effect manner. Statins might have some potential effects on mitigating ALD progression beside abstinence from alcohol. Further research is needed.
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Affiliation(s)
- Wei-Che Chiu
- Department of Psychiatry, Cathay General Hospital, Taipei, Taiwan; School of Medicine, Fu Jen Catholic University, Taipei, Taiwan
| | - Jia-Chi Shan
- Department of Psychiatry, Cathay General Hospital, Taipei, Taiwan; Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Yao-Hsu Yang
- Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chia-Yi, Taiwan; Center of Excellence for Chang Gung Research Datalink, Chang Gung Memorial Hospital, Chia-Yi, Taiwan; School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Vincent Chin-Hung Chen
- Department of Psychiatry, Chang Gung Medical Foundation, Chiayi Chang Gung Memorial Hospital, Chia-Yi, Taiwan; School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Pau-Chung Chen
- Institute of Environmental and Occupational Health Sciences, National Taiwan University College of Public Health, Taipei, Taiwan; Department of Environmental and Occupational Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan; Department of Public Health, National Taiwan University College of Public Health, Taipei, Taiwan; National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan.
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Choi WM, Kim HJ, Jo AJ, Choi SH, Han S, Ko MJ, Lim YS. Association of aspirin and statin use with the risk of liver cancer in chronic hepatitis B: A nationwide population-based study. Liver Int 2021; 41:2777-2785. [PMID: 34242482 DOI: 10.1111/liv.15011] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Revised: 06/08/2021] [Accepted: 07/05/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Aspirin and statins have been suggested to prevent hepatocellular carcinoma (HCC). However, the combined effects of aspirin and statins on HCC risk in patients with chronic hepatitis B (CHB) are not clear. METHODS A nationwide nested case-control study was performed with data from the National Health Insurance Service gathered between 2005 and 2015 in Korea. In a cohort of 538,135 treatment-naïve, non-cirrhotic patients with CHB, 6,539 HCC cases were matched to 26,156 controls and were analysed by conditional logistic regression. Separate historical cohort studies for each drug were analysed by time-dependent Cox regression as a sensitivity analysis. RESULTS In the nested case-control study, statins (OR 0.34; 95% CI 0.32-0.37) and aspirin (OR 0.92; 95% CI 0.85-0.99) were significantly associated with a HCC risk reduction. However, dose-dependent risk reduction was observed only with statins. By sensitivity analysis in the historical cohorts, statin users (n = 244,455; HR 0.67; 95% CI 0.66-0.68) and aspirin users (n = 288,777; HR 0.81; 95% CI 0.80-0.82) had significantly lower HCC risk. In the drug-stratified analyses, statins were associated with significantly reduced risk of HCC regardless of aspirin, whereas aspirin did not show such associations. CONCLUSIONS In this nationwide population-based study of patients with CHB, statin use was consistently associated with a significant and dose-dependent reduction in HCC risk. In contrast, the association between aspirin use and HCC risk reduction was not dose-dependent and was suggested to be confounded by statins.
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Affiliation(s)
- Won-Mook Choi
- Liver Center, Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hyo Jeong Kim
- Division for Healthcare Technology Assessment Research, National Evidence-Based Healthcare Collaborating Agency, Seoul, Republic of Korea
| | - Ae Jeong Jo
- Division for Healthcare Technology Assessment Research, National Evidence-Based Healthcare Collaborating Agency, Seoul, Republic of Korea
| | - So Hyun Choi
- Division for Healthcare Technology Assessment Research, National Evidence-Based Healthcare Collaborating Agency, Seoul, Republic of Korea.,Department of Statistics, Kyungpook National University, Daegu, Republic of Korea
| | - Seungbong Han
- Department of Biostatistics, Korea University College of Medicine, Seoul, Republic of Korea
| | - Min Jung Ko
- Division for Healthcare Technology Assessment Research, National Evidence-Based Healthcare Collaborating Agency, Seoul, Republic of Korea
| | - Young-Suk Lim
- Liver Center, Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Tsai MC, Wang CC, Lee WC, Lin CC, Chang KC, Chen CH, Hung CH, Lin MT, Hsiao CC, Chen CL, Chien RN, Hu TH. Tenofovir Is Superior to Entecavir on Tertiary Prevention for BCLC Stage 0/A Hepatocellular Carcinoma after Curative Resection. Liver Cancer 2021; 11:22-37. [PMID: 35222505 PMCID: PMC8820175 DOI: 10.1159/000518940] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 08/09/2021] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND It is unclear whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) have different effects on hepatocellular carcinoma (HCC) recurrence and death in patients receiving curative hepatectomy for hepatitis B virus (HBV)-related HCC. AIMS The aim of this study was to compare the long-term efficacy of ETV and TDF in HCC recurrence and overall survival (OS) of patients after curative hepatectomy. METHODS From January 2010 to December 2019, 20,572 patients with HCC who received hepatectomy were screened for study eligibility. Finally, a total of 219 consecutive patients treated with ETV (n = 146) or TDF (n = 73) after curative hepatectomy for HBV-related HCC of Barcelona Clinic Liver Cancer stage 0 or A were analyzed by propensity score matching (PSM) (2:1) analysis and competing risk analysis. HCC recurrence and OS of patients were compared between ETV and TDF groups. RESULT After a median follow-up of 52.2 months, 81 patients (37.0%) had HCC recurrence, 33 (15.1%) died, and 5 (2.3%) received liver transplantation. TDF therapy was an independent protective factor for HCC recurrence compared with ETV therapy (HR, 1.687; 95% CI, 1.027-2.770, p = 0.039); however, no difference in the risk of death or liver transplantation. Results were similar in competing risk analysis. We further found that TDF therapy was significantly associated with a lower risk of late recurrence (HR, 4.705; 95% CI, 1.763-12.558, p = 0.002), but not in early recurrence. CONCLUSIONS TDF therapy is associated with a significantly lower risk of HCC recurrence, especially of late recurrence, than ETV therapy among patients who undergo curative hepatectomy for HBV-related early-stage HCC.
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Affiliation(s)
- Ming-Chao Tsai
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan,Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chih-Chi Wang
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Wei-Chen Lee
- Division of Liver and Transplantation Surgery, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Chih-Che Lin
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Kuo-Chin Chang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chien-Hung Chen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chao-Hung Hung
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ming-Tsung Lin
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chang-Chun Hsiao
- Division of Pulmonary and Critical Care Medicine, Graduate Institute of Clinical Medical Sciences, College of Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, Kaohsiung, Taiwan
| | - Chao-Long Chen
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Rong-Nan Chien
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Linko Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Tsung-Hui Hu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan,*Tsung-Hui Hu,
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Hepatic Interactions in Atherosclerotic Heart Disease. Am J Med Sci 2021; 363:104-113. [PMID: 34547286 DOI: 10.1016/j.amjms.2021.07.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 04/19/2021] [Accepted: 07/16/2021] [Indexed: 12/20/2022]
Abstract
Atherosclerotic heart disease remains a major cause of morbidity and mortality worldwide. The past few decades have seen the emergence of chronic inflammation as a mediator of atherosclerosis. Although the heart and vascular system remain the organ systems most affected in the atherosclerotic process, chronic inflammation and ischemia trigger a systemic multi-organ response. The liver is a critical organ for systemic hemostasis and recent developments have established an important role of the liver in response to atherosclerosis and myocardial ischemia. In addition, the rapid emergence of systemic liver diseases has unraveled a pathophysiological link with heart disease with therapeutic implications. In this review, we explore the relationship between the liver and the heart in myocardial ischemia, describe epidemiological associations between various liver pathologies and coronary heart disease, and elucidate practical challenges in the clinical management of patients with concomitant coronary heart disease and hepatic abnormalities.
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Clinical Presentation of Hepatocellular Carcinoma in African Americans vs. Caucasians: A Retrospective Analysis. PATHOPHYSIOLOGY 2021; 28:387-399. [PMID: 35366282 PMCID: PMC8830457 DOI: 10.3390/pathophysiology28030026] [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: 03/22/2021] [Revised: 08/10/2021] [Accepted: 08/19/2021] [Indexed: 12/27/2022] Open
Abstract
Hepatocellular carcinoma (HCC) remains an important form of cancer-related morbidity and mortality in the U.S. and worldwide. Previous U.S.-based studies on survival suggest ethnic disparities in HCC patients, but the complex interplay of multiple factors that contribute are still incompletely understood. Here we considered the influences of risk factors contributing towards HCC survival, including ethnic background, over ten years at a premier academic medical center with a majority (57.20%) African American (AA) population. Retrospective HCC data were collected from 2008–2018 at LSUHSC-Shreveport, an urban tertiary medical center. Data included demographics, comorbidities, liver disease characteristics, and tumor parameters. Statistical analysis was performed using Chi Square and one-way ANOVA. Results: 229 HCC patients were identified (male 78.6%). The mean HCC age at diagnosis was 61 years (SD = 7.3). Compared to non-Hispanic Caucasians (42.7%), AA patients (57.2% of total) were older at presentation, had more frequent diabetes/dyslipidemia/NAFLD (45 (34.3%) compared with 19 (19.3%) in non-Hispanic Caucasians, p = 0.02), and had a larger HCC burden at diagnosis. We conclude that compared to white patients, despite having similar BMI and MELD scores and rates of portal vein thrombosis, AA patients with HCC in our cohort were older at presentation, had a significantly increased incidence of modifiable metabolic risk factors including diabetes, higher AFP values, increased incidence of gallstones, and larger sized HCCs, and were more likely to be outside Milan criteria. These findings have important prognostic and diagnostic implications for developing a more targeted HCC surveillance program.
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Wong YJ, Qiu TY, Ng GK, Zheng Q, Teo EK. Efficacy and Safety of Statin for Hepatocellular Carcinoma Prevention Among Chronic Liver Disease Patients: A Systematic Review and Meta-analysis. J Clin Gastroenterol 2021; 55:615-623. [PMID: 33606427 DOI: 10.1097/mcg.0000000000001478] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 10/29/2020] [Indexed: 02/05/2023]
Abstract
INTRODUCTION AND AIM Hepatocellular carcinoma (HCC) is a deadly complication among patients with chronic liver disease (CLD). Controversies on the efficacy and safety of statin to prevent HCC among patients with CLD remain despite the growing evidences. We aim to investigate the efficacy and safety of using statin for HCC prevention among adult with CLD. METHODS We performed a systematic search of 4 electronic databases (PubMed/MEDLINE, EMBASE, Cochrane library, and ClinicalTrial.gov) up to April 15, 2020. We selected all types of studies evaluating the statin use and the risk of HCC among CLD patients, regardless of language, region, publication date, or status. The primary endpoint was the pooled risk of HCC. The secondary endpoint was the risk of statin-associated myopathy. RESULT From 583 citations, we included a total of 13 studies (1,742,260 subjects, 7 types of statins), fulfilling the inclusion criteria, evaluating efficacy and safety of statin in CLD patients for HCC prevention. All studies were observational (2 nested case-control studies, 11 cohort studies), and no randomised trial was identified. We found that statin user has a lower pooled risk of HCC development (hazard ratio=0.57, 95% confidence interval: 0.52-0.62, I2=42%). HCC reduction was consistent among statin users in cirrhosis, hepatitis B virus, and hepatitis C virus infections. The risk of statin-associated myopathy was similar between statin user and nonuser (hazard ratio=1.07, 95% confidence interval=0.91-1.27). CONCLUSION Statin use was safe and associated with a lower pooled risk of HCC development among adults with CLD. Given the bias with observation studies, prospective randomised trial is needed to confirm this finding.
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Affiliation(s)
- Yu-Jun Wong
- Department of Gastroenterology and Hepatology, Changi General Hospital
- Yong Loo Lin School of Medicine, National University of Singapore
| | - Tian-Yu Qiu
- Department of Gastroenterology and Hepatology, Changi General Hospital
| | | | | | - Eng Kiong Teo
- Department of Gastroenterology and Hepatology, Changi General Hospital
- Yong Loo Lin School of Medicine, National University of Singapore
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Magnasco L, Sepulcri C, Antonello RM, Di Bella S, Labate L, Luzzati R, Giacobbe DR, Bassetti M. The role of PCSK9 in infectious diseases. Curr Med Chem 2021; 29:1000-1015. [PMID: 34269657 DOI: 10.2174/0929867328666210714160343] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 05/01/2021] [Accepted: 05/13/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND In recent years, many aspects of the physiological role of PCSK9 have been elucidated, particularly regarding its role in lipid metabolism, cardiovascular risk, and its role in innate immunity. Increasing evidence is available about the involvement of PCSK9 in the pathogenesis of viral infections, mainly HCV, and the regulation of host response to bacterial infections, primarily sepsis and septic shock. Moreover, the action of PCSK9 has been investigated as a crucial step in the pathogenesis of malaria infection and disease severity. OBJECTIVE This paper aims to review the available published literature on the role of PCSK9 in a wide array of infectious diseases. CONCLUSION Besides the ongoing investigation on PCSK9 inhibition among HIV-infected patients to treat HIV- and ART-related hyperlipidemia, preclinical studies indicate how PCSK9 is involved in reducing the replication of HCV. Interestingly, high plasmatic PCSK9 levels have been described in patients with sepsis. Moreover, a protective role of PCSK9 inhibition has also been proposed against dengue and SARS-CoV-2 viral infections. Finally, a loss of function in the PCSK9-encoding gene has been reported to reduce malaria infection mortality.
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Affiliation(s)
- Laura Magnasco
- Infectious Diseases Unit, San Martino Policlinico Hospital - IRCCS, Genoa, Italy
| | - Chiara Sepulcri
- Infectious Diseases Unit, San Martino Policlinico Hospital - IRCCS, Genoa, Italy
| | | | | | - Laura Labate
- Infectious Diseases Unit, San Martino Policlinico Hospital - IRCCS, Genoa, Italy
| | - Roberto Luzzati
- Clinical Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy
| | | | - Matteo Bassetti
- Infectious Diseases Unit, San Martino Policlinico Hospital - IRCCS, Genoa, Italy
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Hartl L, Elias J, Prager G, Reiberger T, Unger LW. Individualized treatment options for patients with non-cirrhotic and cirrhotic liver disease. World J Gastroenterol 2021; 27:2281-2298. [PMID: 34040322 PMCID: PMC8130039 DOI: 10.3748/wjg.v27.i19.2281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Revised: 03/19/2021] [Accepted: 04/25/2021] [Indexed: 02/06/2023] Open
Abstract
The obesity pandemic has led to a significant increase in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). While dyslipidemia, type 2 diabetes mellitus and cardiovascular diseases guide treatment in patients without signs of liver fibrosis, liver related morbidity and mortality becomes relevant for MAFLD's progressive form, non-alcoholic steatohepatitis (NASH), and upon development of liver fibrosis. Statins should be prescribed in patients without significant fibrosis despite concomitant liver diseases but are underutilized in the real-world setting. Bariatric surgery, especially Y-Roux bypass, has been proven to be superior to conservative and/or medical treatment for weight loss and resolution of obesity-associated diseases, but comes at a low but existent risk of surgical complications, reoperations and very rarely, paradoxical progression of NASH. Once end-stage liver disease develops, obese patients benefit from liver transplantation (LT), but may be at increased risk of perioperative infectious complications. After LT, metabolic comorbidities are commonly observed, irrespective of the underlying liver disease, but MAFLD/NASH patients are at even higher risk of disease recurrence. Few studies with low patient numbers evaluated if, and when, bariatric surgery may be an option to avoid disease recurrence but more high-quality studies are needed to establish clear recommendations. In this review, we summarize the most recent literature on treatment options for MAFLD and NASH and highlight important considerations to tailor therapy to individual patient's needs in light of their risk profile.
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Affiliation(s)
- Lukas Hartl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna A-1090, Austria
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna A-1090, Austria
| | - Joshua Elias
- Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, United Kingdom
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Addenbrooke’s Hospital, Cambridge CB2 0QQ, United Kingdom
| | - Gerhard Prager
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna A-1090, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna A-1090, Austria
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna A-1090, Austria
| | - Lukas W Unger
- Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, United Kingdom
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna A-1090, Austria
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48
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Chen Z, Chen L, Sun B, Liu D, He Y, Qi L, Li G, Han Z, Zhan L, Zhang S, Zhu K, Luo Y, Chen L, Zhang N, Guo H. LDLR inhibition promotes hepatocellular carcinoma proliferation and metastasis by elevating intracellular cholesterol synthesis through the MEK/ERK signaling pathway. Mol Metab 2021; 51:101230. [PMID: 33823318 PMCID: PMC8102998 DOI: 10.1016/j.molmet.2021.101230] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 03/23/2021] [Accepted: 03/30/2021] [Indexed: 12/14/2022] Open
Abstract
Objective Adaptive rewiring of cancer energy metabolism has received increasing attention. By binding with LDLs, LDLRs make most of the circulating cholesterol available for cells to utilize. However, it remains unclear how LDLR works in HCC development by affecting cholesterol metabolism. Methods Database analyses and immunohistochemical staining were used to identify the clinical significance of LDLR in HCC. A transcriptome analysis was used to reveal the mechanism of LDLR aberration in HCC progression. A liver orthotopic transplantation model was used to evaluate the role of LDLR in HCC progression in vivo. Results Downregulation of LDLR was identified as a negative prognostic factor in human HCC. Reduced expression of LDLR in HCC cell lines impaired LDL uptake but promoted proliferation and metastasis in vitro and in vivo. Mechanistically, increasing intracellular de novo cholesterol biosynthesis was the chief contributor to malignant behaviors caused by LDLR inhibition, which could be rescued by simvastatin. Activation of the MEK/ERK pathway by LDLR downregulation partially contributed to intracellular cholesterol synthesis in HCC. Conclusions Downregulation of LDLR may elevate intracellular cholesterol synthesis to accelerate proliferation and motility through a mechanism partially attributed to stimulation of the MEK/ERK signaling pathway. Repression of intracellular cholesterol synthesis with statins may constitute a targetable liability in the context of lower LDLR expression in HCC.
Downregulation of LDLR is identified as a negative prognostic factor in human HCC. LDLR inhibition facilitates the proliferation and metastasis of HCC cells. Increased cholesterol synthesis chiefly contributes to the malignant behaviors caused by LDLR reduction. Blockade of cholesterol synthesis by simvastatin attenuates HCC progression under lower LDLR. Activation of the MEK/ERK pathway by LDLR downregulation promotes cholesterol synthesis in HCC.
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Affiliation(s)
- Ziye Chen
- Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Lu Chen
- Department of Hepatobiliary Cancer, Liver Cancer Research Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Bo Sun
- The Second Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Dongming Liu
- Department of Hepatobiliary Cancer, Liver Cancer Research Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Yuchao He
- Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Lisha Qi
- Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Guangtao Li
- Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Zhiqiang Han
- Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Linlin Zhan
- Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Su Zhang
- Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Keyun Zhu
- Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Yi Luo
- Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Liwei Chen
- Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Ning Zhang
- Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China; Translational Cancer Research Center, Peking University First Hospital, Beijing 100034, China.
| | - Hua Guo
- Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China.
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Chen CY, Wang TY, Chen WM, Chen KH, Yang YH, Chen PC, Chen VCH. Bilateral oophorectomy and the risk of hepatocellular carcinoma in women with hepatitis C: A population-based study. Maturitas 2021; 146:11-17. [PMID: 33722359 DOI: 10.1016/j.maturitas.2020.12.006] [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: 05/15/2020] [Revised: 12/21/2020] [Accepted: 12/22/2020] [Indexed: 01/17/2023]
Abstract
OBJECTIVE Patients with chronic hepatitis C virus (HCV) infection are at high risk of developing hepatocellular carcinoma (HCC). Previous studies suggested that menopause may increase the risk of HCC. We investigated the association between bilateral oophorectomy (BO) and the risk of HCC in women with HCV infection. STUDY DESIGN We used data from the National Health Insurance Research Database of Taiwan and conducted a matched cohort study. MAIN OUTCOME MEASURES The main outcome was HCC. We used a competing risk model to adjust for potential confounding factors. RESULTS From 1997-2013, we identified 2176 patients with BO and 8704 controls. A total of 107 HCC cases (4.9 %, 107/2176) were identified in the BO group compared with 465 HCC cases (5.3 %, 465/8704) in the control group. The incidence rates were 506.3 and 538.9 cases per 100,000 person-years among the HCV-infected patients with and without BO, respectively. The competing risk model showed that BO did not increase the risk of developing HCC. Furthermore, a sub-analysis of only women under 50 years of age similarly showed that BO did not increase the risk of developing HCC after adjusting for additional covariates. The log-rank test revealed that whether or not the patients had received HRT, patients with BO did not have an increased risk of developing HCC (non-BO vs BO with HRT, p = 0.10; non-BO vs BO without HRT, p = 0.09). The use of HRT after BO did not influence the risk of developing HCC. CONCLUSIONS This study examined a large dataset with a long follow-up period to test the relationship between BO and the risk of HCC in HCV-infected women. Our findings suggest that BO did not increase the risk of HCC, regardless of HRT usage, in these women.
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Affiliation(s)
- Chao-Yu Chen
- Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Ting-Yao Wang
- Division of Hematology and Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Wei-Ming Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan; Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Kai-Hua Chen
- Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Yao-Hsu Yang
- Health Information and Epidemiology Laboratory, Chang Gung Memorial Hospital, Chiayi County, Taiwan; Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan; School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Pau-Chung Chen
- Institute of Environmental and Occupational Health Sciences, National Taiwan University College of Public Health, Taipei, Taiwan; Department of Public Health, National Taiwan University College of Public Health, Taipei, Taiwan; Department of Environmental and Occupational Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Office of Occupational Safety and Health, National Taiwan University Hospital, Taipei, Taiwan
| | - Vincent Chin-Hung Chen
- Department of Psychiatry, Chang Gung Memorial Hospital, Chiayi and Chang Gung University, Taoyuan, Taiwan.
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50
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Franco-Peláez JA, Esteban-Lucia L, Zambrano Chacón MDLÁ, Pello-Lázaro AM, Venegas Rodriguez AM, Nieto Roca L, García-Talavera CS, Kallmeyer Mayor A, Villar Alvarez F, Fernandez Roblas R, Gonzalez-Lorenzo O, Tuñón J, Ibañez B, Aceña A. Statin use is associated with reduced mortality after respiratory viral infection. ERJ Open Res 2021; 7:00365-2020. [PMID: 33569498 PMCID: PMC7861028 DOI: 10.1183/23120541.00365-2020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 11/05/2020] [Indexed: 12/15/2022] Open
Abstract
Background Several studies suggest that statins, besides reducing cardiovascular disease, have anti-inflammatory properties which might provide a benefit in downregulating the immune response after a respiratory viral infection (RVI) and, hence, decreasing subsequent complications. We aim to analyse the effect of statins on mortality after RVI. Methods A single-centre, observational and retrospective study was carried out including all adult patients with a RVI confirmed by PCR tests from October 2, 2017 to May 20, 2018. Patients were divided between statin users and non-statin users and followed-up for 1 year, and all causes of death were recorded. In order to analyse the effect of statin treatment on mortality after RVI we planned two different approaches, a multivariate Cox regression model with the overall population and a univariate Cox model with a propensity-score matched population. Results We included 448 patients, 154 (34.4%) of whom were under statin treatment. Statin users had a worse clinical profile (older population with more comorbidities). During the 1-year follow-up, 67 patients died, 17 (11.0%) in the statin group and 50 (17.1%) in the non-statin group. Multivariate Cox analysis showed that statins were associated with mortality benefit (HR 0.47, 95% CI 0.26–0.83; p=0.01). In a matched population (101 statins users and 101 non-statins users) statins also remained associated with mortality benefit (HR 0.32, 95% CI 0.14–0.72; p=0.006). Differences were mainly driven by non-cardiovascular mortality (HR 0.31, 95% CI 0.13–0.73; p=0.004). Conclusions Chronic statin treatment was associated with reduced 1-year mortality in patients with laboratory-confirmed RVI. Further studies are needed to determine the exact role of statin therapy after RVI. Statin treatment is associated with reduced 1-year mortality after respiratory viral infections, despite the higher risk profile of patients on statins. Statins seem a good candidate to be tested during the current global pandemic.https://bit.ly/36t0tDh
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Affiliation(s)
| | - Laura Esteban-Lucia
- Dept of Cardiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Madrid, Spain
| | | | - Ana María Pello-Lázaro
- Dept of Cardiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Madrid, Spain
| | | | - Luis Nieto Roca
- Dept of Cardiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Madrid, Spain
| | | | - Andrea Kallmeyer Mayor
- Dept of Cardiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Madrid, Spain
| | - Felipe Villar Alvarez
- Dept of Pneumology, Instituto de Investigación Sanitaria -Fundación Jiménez Díaz, Madrid, Spain.,Autonoma University, Madrid, Spain.,CIBERES, Madrid, Spain
| | - Ricardo Fernandez Roblas
- Dept of Microbiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Madrid, Spain
| | - Oscar Gonzalez-Lorenzo
- Dept of Cardiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Madrid, Spain
| | - José Tuñón
- Dept of Cardiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Madrid, Spain.,Autonoma University, Madrid, Spain.,CIBERCV, Madrid, Spain
| | - Borja Ibañez
- Dept of Cardiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Madrid, Spain.,CIBERCV, Madrid, Spain.,Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
| | - Alvaro Aceña
- Dept of Cardiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Madrid, Spain.,Autonoma University, Madrid, Spain
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