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Jani CT, Mouchati C, Abdallah N, Jani R, Kakoullis L, Chen LH. Do Statins Affect Viral Infections Encountered by International Travelers? Trop Med Infect Dis 2025; 10:73. [PMID: 40137827 PMCID: PMC11946866 DOI: 10.3390/tropicalmed10030073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 03/06/2025] [Accepted: 03/08/2025] [Indexed: 03/29/2025] Open
Abstract
Statins are among the most frequently prescribed medications. In addition to their well-established effectiveness in lowering total cholesterol, LDL, and triglycerides, statins have been described to have immunomodulatory and anti-inflammatory properties and have been associated with improved endothelial functions. Given the common use of statins, we sought to evaluate the effect of statins on some viral infections encountered by residents in tropical areas or by international travelers. A literature search was performed in PubMED/MEDLINE focusing on keywords that included statins and the viruses of interest, including SARS-CoV-2, influenza, yellow fever, dengue, Zika, tick-borne encephalitis, hemorrhagic fever viruses, hepatitis A, norovirus, hepatitis B, hepatitis C, measles, and herpesviruses; findings were synthesized for each virus into a summary. The effects of statins on viral infections vary depending on the specific virus. While some studies indicate potential benefits in chronic HBV and HCV infections, evidence regarding SARS-CoV-2 and influenza remains inconclusive due to mixed findings from observational studies and randomized controlled trials. The role of statins in other viral infections is largely unexplored, with preclinical data available for only a few viruses. Given the conflicting evidence, further prospective studies and randomized controlled trials are warranted to elucidate statins' role in viral infections, particularly in modulating inflammation, endothelial dysfunction, and immune responses. Future research should aim to define the optimal patient populations, target viruses, statin types, and treatment durations that may confer benefits in specific viral infections.
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Affiliation(s)
- Chinmay T. Jani
- Division of Medical Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA;
| | - Christian Mouchati
- Division of Neurology, University of Connecticut, Farmington, CT 06030, USA;
| | - Nour Abdallah
- Department of Medicine, University of Connecticut, Farmington, CT 06030, USA;
| | - Ruchi Jani
- Department of Medicine, Smt NHL Municipal Medical College, Ahmedabad 380006, Gujarat, India;
| | - Loukas Kakoullis
- Department of Medicine, Mount Auburn Hospital, Cambridge, MA 02138, USA;
- Harvard Medical School, Boston, MA 02115, USA
| | - Lin H. Chen
- Department of Medicine, Mount Auburn Hospital, Cambridge, MA 02138, USA;
- Harvard Medical School, Boston, MA 02115, USA
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Jiang C, Zhang ZH, Li JX. Current status of drug therapy for chronic hepatitis B. World J Gastroenterol 2025; 31:99443. [PMID: 39811512 PMCID: PMC11684199 DOI: 10.3748/wjg.v31.i2.99443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 11/04/2024] [Accepted: 11/25/2024] [Indexed: 12/18/2024] Open
Abstract
In this editorial, we comment on the article by Meng et al. Chronic hepatitis B (CHB) is a significant global health problem, particularly in developing countries. Hepatitis B virus (HBV) infection is one of the most important risk factors for cirrhosis and hepatocellular carcinoma. Prevention and treatment of HBV are key measures to reduce complications. At present, drug therapy can effectively control virus replication and slow disease progression, but completely eliminating the virus remains a challenge. Anti-HBV treatment is a long-term process, and there are many kinds of antiviral drugs with different mechanisms of action, it is essential to evaluate the safety and efficacy of these drugs to reduce side effects and improve patients' compliance. We will summarize the current status of CHB drug treatment, hoping to provide a reference for the selection of clinical antiviral drugs.
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Affiliation(s)
- Chuang Jiang
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Zhi-Hong Zhang
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jia-Xin Li
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
- Department of General Surgery, Dafang County People's Hospital, Bijie 551600, Guizhou Province, China
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Li F, Wu M, Wang F, Luo L, Wu Z, Huang Z, Wen Z. Unveiling the endocrine connections of NAFLD: evidence from a comprehensive mendelian randomization study. Biomed Eng Lett 2025; 15:239-248. [PMID: 39781064 PMCID: PMC11704114 DOI: 10.1007/s13534-024-00442-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Revised: 10/17/2024] [Accepted: 10/29/2024] [Indexed: 01/03/2025] Open
Abstract
Background NAFLD is gaining recognition as a complex, multifactorial condition with suspected associations with endocrine disorders. This investigation employed MR analysis to explore the potential causality linking NAFLD to a spectrum of endocrine diseases, encompassing T1D, T2D, obesity, graves' disease, and acromegaly. Methods Our methodology leveraged a stringent IV selection process, adhering to the STROBE-MR guidelines. The MR analysis was conducted utilizing three distinct methods: IVW, WM, and MR-Egger. The IVW method was prioritized as the primary analytical approach. We conducted MR analyses to analyze the causal relationship between NAFLD and metabolic disorders. We also examined 1400 metabolites implicated in NAFLD. Metabolic pathway analysis was performed using the MetaboAnalyst database. Results The findings indicated that T2D (OR = 1.211, 95%CI: 0.836-1.585) and obesity (OR = 1.245, 95%CI: 0.816-1.674) are associated with an increased risk of NAFLD development. Further exploration into the the 1400 metabolites revealed that cys-gly and diacetylornithine are predictive of NAFLD, T2D, and obesity, whereas isovalerylcarnitine exhibited an inverse association, potentially inhibiting disease development. Metabolic pathways involving alanine, aspartate, and glutamate metabolism were identified as pivotal regulators in the pathophysiology of NAFLD, T2D, and obesity. Conclusion The present study generated innovative viewpoints on the etiology of NAFLD. Our findings underscore the significant role of T2D and obesity in NAFLD pathogenesis through metabolic pathways, presenting opportunities for targeted therapeutic strategies and warranting further investigation. Supplementary Information The online version contains supplementary material available at 10.1007/s13534-024-00442-8.
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Affiliation(s)
- Fan Li
- Department of Gastroenterology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006 China
| | - Mingjun Wu
- Nanchang Hongdu Hospital of Traditional Chinese Medicine, Nanchang, China
| | - Fenfen Wang
- Department of Gastroenterology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006 China
| | - Linfei Luo
- Department of Gastroenterology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006 China
| | - Zhengqiang Wu
- Department of Gastroenterology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006 China
| | - Zixiang Huang
- Department of Gastroenterology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006 China
| | - Zhili Wen
- Department of Gastroenterology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006 China
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Lee CH, Huang YH, Hsu TJ, Yen TH, Hsieh SY. Statin Monotherapy Not Inferior to Aspirin or Combined Aspirin and Statins Reducing the Incidences of Cirrhosis, HCC, and Mortality in MAFLD/MASH Patients: A Population Cohort Study. Int J Gen Med 2024; 17:6495-6511. [PMID: 39742030 PMCID: PMC11687094 DOI: 10.2147/ijgm.s481724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Accepted: 12/07/2024] [Indexed: 01/03/2025] Open
Abstract
Purpose Metabolic dysfunction-associated fatty liver disease (MAFLD) and metabolic dysfunction-associated steatohepatitis (MASH) pose significant risks for liver cirrhosis and hepatocellular carcinoma (HCC). Daily aspirin and statins could reduce HCC in patients with MAFLD/MASH. We aimed to clarify whether combined aspirin and statins exert a synergistic effect on prevention of cirrhosis and HCC in patients with MAFLD/MASH. Patients and Methods Patients and their clinical data were collected from the National Health Insurance Research Database (NHIRD), encompassing about 20 million population. A total of 735,574 MAFLD/MASH patients between January 1, 2009, and December 31, 2020 were identified. After applying exclusion criteria, 662,004 cases were enrolled, with a follow-up period of 3 years. Propensity score matching was employed for comparative analysis. Results Our findings indicate that combined statin and aspirin use significantly reduced the incidence of liver cirrhosis (p < 0.001) compared to statin or aspirin alone, or non-use of both drugs. However, the combined therapy did not confer additional benefits in reducing mortality rates and HCC. Furthermore, statin monotherapy exhibited a more pronounced effect in reducing mortality and HCC compared to aspirin alone or combined therapy. Conclusion Our study underscores that statin monotherapy was not inferior to aspirin or aspirin-statin combined therapies in terms of chemoprevention of cirrhosis, HCC, and overall mortality in MAFLD/MASH patients.
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Affiliation(s)
- Chern-Horng Lee
- Department of Geriatric Medicine and General Internal Medicine, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, 333, Taiwan
| | - Yu-Han Huang
- Department of Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan, College of Medicine, China Medical University, Taichung, Taiwan
| | - Tzu-Ju Hsu
- Management Office for Health Data (DryLab), Clinical Trial Research Center (CTC), China Medical University Hospital, Taichung, Taiwan
| | - Tzung-Hai Yen
- Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuanm, 333, Taiwan
| | - Sen-Yung Hsieh
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, 333, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan
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Protopapas AA, Tsankof A, Papagiouvanni I, Kaiafa G, Skoura L, Savopoulos C, Goulis I. Outpatient management after hospitalisation for acute decompensation of cirrhosis: A practical guide. World J Hepatol 2024; 16:1377-1394. [DOI: 10.4254/wjh.v16.i12.1377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 10/24/2024] [Accepted: 11/20/2024] [Indexed: 11/29/2024] Open
Abstract
Acute decompensation in cirrhotic patients signifies the onset of clinically evident events due to portal hypertension. The transition from compensated to decompensated cirrhosis involves hemodynamic changes leading to multiorgan dysfunction, managed predominantly in outpatient settings with regular monitoring. The mortality risk is elevated in decompensated patients. Therefore, diligent outpatient management should focus on regular medical follow-ups, medication adjustments, patient education, addressing emergent issues and evaluation for liver transplantation. The ultimate goal is to improve quality of life, prevent disease progression, reduce complications, and assess possible recompensation. This guide provides valuable recommendations for medical experts managing decompensated cirrhotic patients post-hospitalization.
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Affiliation(s)
- Adonis A Protopapas
- First Propaedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki 54636, Greece
| | - Alexandra Tsankof
- First Propaedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki 54636, Greece
| | - Ioanna Papagiouvanni
- Fourth Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital, Thessaloniki 54642, Greece
| | - Georgia Kaiafa
- First Propaedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki 54636, Greece
| | - Lemonia Skoura
- Department of Microbiology, Aristotle University οf Thessaloniki, AHEPA University Hospital, Thessaloniki 54636, Greece
| | - Christos Savopoulos
- First Propaedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki 54636, Greece
| | - Ioannis Goulis
- Fourth Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital, Thessaloniki 54642, Greece
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Tien P, Bih ZL, Chen WM, Shia BC, Wu SY, Chiang CW. Aspirin use reduces cancer risk in betel nut chewers: a nationwide population-based cohort study. Am J Cancer Res 2024; 14:5921-5934. [PMID: 39803639 PMCID: PMC11711529 DOI: 10.62347/jxmi9007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Accepted: 11/10/2024] [Indexed: 01/16/2025] Open
Abstract
Betel nut chewing, common in several Asian populations, is linked to increased cancer risk, including oral, esophageal, gastric, and hepatocellular carcinoma. Aspirin shows potential as a chemopreventive agent. This study investigates the association between aspirin use and cancer risk among betel nut chewers. Betel nut chewers aged 18 and older were included, with aspirin use defined as at least 28 cumulative defined daily doses (cDDDs). Propensity score matching and Cox proportional hazards models, adjusted for time-varying covariates, were used to assess cancer risk. The study included 46,302 betel nut chewers, equally divided between aspirin users and non-users. Aspirin use was associated with a 31% reduction in overall cancer risk (adjusted hazard ratio [aHR], 0.69; 95% confidence interval [CI], 0.66 to 0.73; P<0.0001). A dose-response relationship was observed, with higher cDDDs of aspirin corresponding to greater reductions in cancer risk. The highest quartile of aspirin use (Quartile 4) showed a 62% reduction in cancer risk (aHR, 0.38; 95% CI, 0.34 to 0.41; P<0.0001). Daily aspirin intensity was also associated with a significant reduction in cancer risk, with doses greater than 1 DDD showing an aHR of 0.54 (95% CI, 0.47 to 0.61; P<0.0001) compared to 1 DDD or less. Aspirin use significantly reduces cancer risk among betel nut chewers in a dose-dependent manner. These findings suggest aspirin as a potential chemopreventive agent in high-risk populations, warranting further investigation.
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Affiliation(s)
- Peng Tien
- Department of Otorhinolaryngology, Lo-Hsu Medical Foundation, Lotung Poh-Ai HospitalYilan 265, Taiwan
| | - Zen Lang Bih
- Department of Emergency Medicine, Lo-Hsu Medical Foundation, Lotung Poh-Ai HospitalYilan 265, Taiwan
| | - Wan-Ming Chen
- Graduate Institute of Business Administration, College of Management, Fu Jen Catholic UniversityTaipei 242, Taiwan
- Artificial Intelligence Development Center, Fu Jen Catholic UniversityTaipei 242, Taiwan
| | - Ben-Chang Shia
- Graduate Institute of Business Administration, College of Management, Fu Jen Catholic UniversityTaipei 242, Taiwan
- Artificial Intelligence Development Center, Fu Jen Catholic UniversityTaipei 242, Taiwan
| | - Szu-Yuan Wu
- Department of Food Nutrition and Health Biotechnology, College of Medical and Health Science, Asia UniversityTaichung 413, Taiwan
- Division of Radiation Oncology, Lo-Hsu Medical Foundation, Lotung Poh-Ai HospitalYilan 265, Taiwan
- Big Data Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai HospitalYilan 265, Taiwan
- Department of Healthcare Administration, College of Medical and Health Science, Asia UniversityTaichung 413, Taiwan
- Cancer Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai HospitalYilan 265, Taiwan
- Centers for Regional Anesthesia and Pain Medicine, Taipei Municipal Wan Fang Hospital, Taipei Medical UniversityTaipei 116, Taiwan
| | - Ching-Wen Chiang
- Department of Otorhinolaryngology, Lo-Hsu Medical Foundation, Lotung Poh-Ai HospitalYilan 265, Taiwan
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Chang CC, Yeh CC, Tiong C, Sun MF, Lin JG, Cherng YG, Chen TL, Liao CC. Real-World Risk and Outcome of Liver Cirrhosis in Patients with Hyperlipidemia Treated with Red Yeast Rice: A Retrospective Cohort Study. J Multidiscip Healthc 2024; 17:3727-3738. [PMID: 39100903 PMCID: PMC11297496 DOI: 10.2147/jmdh.s466696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 07/17/2024] [Indexed: 08/06/2024] Open
Abstract
Objective Sustained hyperlipidemia contributes to fatty liver and liver cirrhosis. Red yeast rice (RYR) effectively improved the lipid profile; however, the effects of RYR on the risk of incident liver cirrhosis remain to be elucidated. We aimed to evaluate the beneficial effects of RYR use on the risk and outcome of liver cirrhosis. Patients and methods We identified 156,587 adults who had newly diagnosed hyperlipidemia in 2010-2016 from health insurance data in this retrospective cohort study. Using propensity score matching, we selected 34,367 patients who used RYR and 34,367 patients who used lovastatin. Events of incident liver cirrhosis that occurred in the two cohorts during the follow-up period of 2010-2019 were identified. We calculated adjusted hazard ratios (HRs) and 95% confidence intervals (Cis) for liver cirrhosis risk associated with RYR use in the multiple Cox proportional hazard model. Results Compared with patients who used lovastatin, patients who used RYR had a decreased risk of liver cirrhosis (HR 0.60, 95% CI 0.57-0.63), and this association was significant in various subgroups. A biological gradient relationship between the frequency of RYR use and decreased liver cirrhosis was observed (p for trend < 0.0001). Reduced postcirrhosis jaundice (HR 0.56, 95% CI 0.43-0.72), ascites (HR 0.37, 95% CI 0.28-0.50), hepatic coma (HR 0.36, 95% CI 0.26-0.50), and mortality (HR 0.48, 95% CI 0.38-0.61) were also associated with RYR use. Conclusion We demonstrated the beneficial effects of RYR use on the risk and outcome of liver cirrhosis; however, the lack of compliance data should be considered. However, our study did not infer causality or claim the superiority of RYR over lovastatin.
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Affiliation(s)
- Chuen-Chau Chang
- Department of Anesthesiology, Taipei Medical University Hospital, Taipei, Taiwan
- Anesthesiology and Health Policy Research Center, Taipei Medical University Hospital, Taipei, Taiwan
- Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Chun-Chieh Yeh
- Department of Surgery, China Medical University Hospital, Taichung, Taiwan
- Department of Surgery, University of Illinois, Chicago, IL, USA
| | - Cheng Tiong
- Division of Gastroenterology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
- Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Mao-Feng Sun
- School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan
| | - Jaung-Geng Lin
- School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan
| | - Yih-Giun Cherng
- Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Department of Anesthesiology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan
| | - Ta-Liang Chen
- Anesthesiology and Health Policy Research Center, Taipei Medical University Hospital, Taipei, Taiwan
- Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Department of Anesthesiology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Chien-Chang Liao
- Department of Anesthesiology, Taipei Medical University Hospital, Taipei, Taiwan
- Anesthesiology and Health Policy Research Center, Taipei Medical University Hospital, Taipei, Taiwan
- Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan
- Research Center of Big Data and Meta-Analysis, Wan Fang Hospital, Taipei Medical University, Taipei, 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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9
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Mellemkjær A, Kjær MB, Haldrup D, Grønbæk H, Thomsen KL. Management of cardiovascular risk in patients with metabolic dysfunction-associated steatotic liver disease. Eur J Intern Med 2024; 122:28-34. [PMID: 38008609 DOI: 10.1016/j.ejim.2023.11.012] [Citation(s) in RCA: 15] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Revised: 11/06/2023] [Accepted: 11/08/2023] [Indexed: 11/28/2023]
Abstract
The novel term Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is proposed to replace non-alcoholic fatty liver disease (NAFLD) to highlight the close association with the metabolic syndrome. MASLD encompasses patients with liver steatosis and at least one of five cardiometabolic risk factors which implies that these patients are at increased risk of cardiovascular disease (CVD). Indeed, the prevalence of CVD in MASLD patients is increased and CVD is recognized as the most common cause of death in MASLD patients. We here present an update on the pathophysiology of CVD in MASLD, discuss the risk factors, and suggest screening for CVD in patients with MASLD. Currently, there is no FDA-approved pharmacological treatment for MASLD, and no specific treatment recommended for CVD in patients with MASLD. Thus, the treatment strategy is based on weight loss and a reduction and treatment of CVD risk factors. We recommend screening of MASLD patients for CVD using the SCORE2 system with guidance to specific treatment algorithms. In all patients with CVD risk factors, lifestyle intervention to induce weight loss through diet and exercise is recommended. Especially a Mediterranean diet may improve hyperlipidemia and if further treatment is needed, statins should be used as first-line treatment. Further, anti-hypertensive drugs should be used to treat hypertension. With the epidemic of obesity and type 2 diabetes mellitus (T2DM) the risk of MASLD and CVD is expected to increase, and preventive measures, screening, and effective treatments are highly needed to reduce morbidity and mortality in MASLD patients.
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Affiliation(s)
- Anders Mellemkjær
- Department of Hepatology & Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Mikkel Breinholt Kjær
- Department of Hepatology & Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - David Haldrup
- Department of Hepatology & Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Henning Grønbæk
- Department of Hepatology & Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
| | - Karen Louise Thomsen
- Department of Hepatology & Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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10
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Sharma R, Simon TG, Hagström H, Lochhead P, Roelstraete B, Söderling J, Verna EC, Emond J, Ludvigsson JF. Statins Are Associated With a Decreased Risk of Severe Liver Disease in Individuals With Noncirrhotic Chronic Liver Disease. Clin Gastroenterol Hepatol 2024; 22:749-759.e19. [PMID: 37121528 DOI: 10.1016/j.cgh.2023.04.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 02/07/2023] [Accepted: 04/03/2023] [Indexed: 05/02/2023]
Abstract
BACKGROUND & AIMS Little is known about the potential impact of statins on the progression of noncirrhotic chronic liver diseases (CLDs) to severe liver disease. METHODS Using liver histopathology data in a nationwide Swedish cohort, we identified 3862 noncirrhotic individuals with CLD and statin exposure, defined as a statin prescription filled for 30 or more cumulative defined daily doses. Statin users were matched to 3862 (statin) nonusers with CLD through direct 1:1 matching followed by propensity score matching. Cox regression was used to estimate hazard ratios (HRs) for the primary outcome of incident severe liver disease (a composite of cirrhosis, hepatocellular carcinoma, and liver transplantation/liver-related mortality). RESULTS A total of 45.3% of CLD patients had nonalcoholic fatty liver disease, 21.9% had alcohol-related liver disease, 17.7% had viral hepatitis, and 15.1% had autoimmune hepatitis. During follow-up evaluation, 234 (6.1%) statin users vs 276 (7.1%) nonusers developed severe liver disease. Statin use was associated with a decreased risk of developing severe liver disease (HR, 0.60; 95% CI, 0.48-0.74). Statistically significantly lower rates of severe liver disease were seen in alcohol-related liver disease (HR, 0.30; 95% CI, 0.19-0.49) and in nonalcoholic fatty liver disease (HR, 0.68; 95% CI, 0.45-1.00), but not in viral hepatitis (HR, 0.76; 95% CI, 0.51-1.14) or autoimmune hepatitis (HR, 0.88; 95% CI, 0.48-1.58). Statin use had a protective association in both prefibrosis and fibrosis stages at diagnosis. Statin use was associated with lower rates of progression to cirrhosis (HR, 0.62; 95% CI, 0.49-0.78), hepatocellular carcinoma (HR, 0.44; 95% CI, 0.27-0.71), and liver-related mortality (HR, 0.55; 95% CI, 0.36-0.82). CONCLUSIONS Among individuals with noncirrhotic CLD, incident statin use was linked to lower rates of severe liver disease, suggesting a potential disease-modifying role.
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Affiliation(s)
- Rajani Sharma
- Center for Liver Disease and Transplantation, Division of Digestive and Liver Diseases, Columbia University Irving Medical Center, New York, New York; Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York.
| | - Tracey G Simon
- Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts
| | - Hannes Hagström
- Unit of Hepatology, Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden; Division of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden
| | | | - Bjorn Roelstraete
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Jonas Söderling
- Division of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
| | - Elizabeth C Verna
- Center for Liver Disease and Transplantation, Division of Digestive and Liver Diseases, Columbia University Irving Medical Center, New York, New York; Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York
| | - Jean Emond
- Center for Liver Disease and Transplantation, Division of Digestive and Liver Diseases, Columbia University Irving Medical Center, New York, New York
| | - Jonas F Ludvigsson
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, United Kingdom
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11
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Terbah R, Testro A, Gow P, Majumdar A, Sinclair M. Portal Hypertension in Malnutrition and Sarcopenia in Decompensated Cirrhosis-Pathogenesis, Implications and Therapeutic Opportunities. Nutrients 2023; 16:35. [PMID: 38201864 PMCID: PMC10780673 DOI: 10.3390/nu16010035] [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: 12/03/2023] [Revised: 12/18/2023] [Accepted: 12/19/2023] [Indexed: 01/12/2024] Open
Abstract
Malnutrition and sarcopenia are highly prevalent in patients with decompensated cirrhosis and are associated with poorer clinical outcomes. Their pathophysiology is complex and multifactorial, with protein-calorie malnutrition, systemic inflammation, reduced glycogen stores and hormonal imbalances all well reported. The direct contribution of portal hypertension to these driving factors is however not widely documented in the literature. This review details the specific mechanisms by which portal hypertension directly contributes to the development of malnutrition and sarcopenia in cirrhosis. We summarise the existing literature describing treatment strategies that specifically aim to reduce portal pressures and their impact on nutritional and muscle outcomes, which is particularly relevant to those with end-stage disease awaiting liver transplantation.
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Affiliation(s)
- Ryma Terbah
- Liver Transplant Unit, Austin Health, 145 Studley Road, Heidelberg, VIC 3084, Australia; (R.T.); (A.T.); (P.G.); (A.M.)
- Department of Medicine, The University of Melbourne, Parkville, VIC 3050, Australia
| | - Adam Testro
- Liver Transplant Unit, Austin Health, 145 Studley Road, Heidelberg, VIC 3084, Australia; (R.T.); (A.T.); (P.G.); (A.M.)
- Department of Medicine, The University of Melbourne, Parkville, VIC 3050, Australia
| | - Paul Gow
- Liver Transplant Unit, Austin Health, 145 Studley Road, Heidelberg, VIC 3084, Australia; (R.T.); (A.T.); (P.G.); (A.M.)
- Department of Medicine, The University of Melbourne, Parkville, VIC 3050, Australia
| | - Avik Majumdar
- Liver Transplant Unit, Austin Health, 145 Studley Road, Heidelberg, VIC 3084, Australia; (R.T.); (A.T.); (P.G.); (A.M.)
- Department of Medicine, The University of Melbourne, Parkville, VIC 3050, Australia
| | - Marie Sinclair
- Liver Transplant Unit, Austin Health, 145 Studley Road, Heidelberg, VIC 3084, Australia; (R.T.); (A.T.); (P.G.); (A.M.)
- Department of Medicine, The University of Melbourne, Parkville, VIC 3050, Australia
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12
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Shaffer LR, Mahmud N. Statins in Cirrhosis: Hope or Hype? J Clin Exp Hepatol 2023; 13:1032-1046. [PMID: 37975036 PMCID: PMC10643276 DOI: 10.1016/j.jceh.2023.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Accepted: 05/01/2023] [Indexed: 11/19/2023] Open
Abstract
In recent years, studies have demonstrated the benefits of statins in a range of chronic diseases separate from cardiovascular outcomes. Early studies in the context of chronic liver disease have suggested favorable effects of statins leading to slowed fibrosis progression, reduced portal pressures, decreased rates of hepatic decompensation, and improved survival. This has increased interest in the potential role that statins may have in the management of chronic liver disease and cirrhosis, though many questions remain unanswered, including concerns regarding the safety of higher dose statins in patients with advanced decompensated cirrhosis. In this review, we provide an update on the current literature addressing the use of statins in patients with cirrhosis and highlight areas in which additional studies are needed.
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Affiliation(s)
- Lauren R. Shaffer
- Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Nadim Mahmud
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
- Gastroenterology Section, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA
- Leonard David Institute of Health Economics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
- Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA, USA
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13
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Wu SY, Chen WM, Chiang MF, Lo HC, Wu MS, Lee MC, Soong RS. Protective effects of statins on the incidence of NAFLD-related decompensated cirrhosis in T2DM. Liver Int 2023; 43:2232-2244. [PMID: 37381761 DOI: 10.1111/liv.15656] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 06/02/2023] [Accepted: 06/12/2023] [Indexed: 06/30/2023]
Abstract
BACKGROUND AND AIMS Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome and poses a significant threat to patients with type 2 diabetes mellitus (T2DM) and metabolic dysregulation. Statins exert anti-inflammatory, antioxidative and antithrombotic effects that target mechanisms underlying NAFLD. However, the protective effects of the different doses, intensities and types of statins on the incidence of NAFLD-related decompensated liver cirrhosis (DLC) in patients with T2DM remain unclear. METHODS This study used the data of patients with T2DM who were non-HBV and non-HCV carriers from a national population database to examine the protective effects of statin use on DLC incidence through propensity score matching. The incidence rate (IR) and incidence rate ratios (IRRs) of DLC in patients with T2DM with or without statin use were calculated. RESULTS A higher cumulative dose and specific types of statins, namely rosuvastatin, pravastatin, atorvastatin, simvastatin and fluvastatin, reduced the risk of DLC in patients with T2DM. Statin use was associated with a significant reduction in the risk of DLC (HR: .65, 95% CI: .61-.70). The optimal daily intensity of statin use with the lowest risk of DLC was .88 defined daily dose (DDD). CONCLUSIONS The results revealed the protective effects of specific types of statins on DLC risk in patients with T2DM and indicated a dose-response relationship. Additional studies are warranted to understand the specific mechanisms of action of different types of statins and their effect on DLC risk in patients with T2DM.
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Affiliation(s)
- Szu-Yuan Wu
- Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, New Taipei City, Taiwan
- Artificial Intelligence Development Center, Fu Jen Catholic University, New Taipei City, Taiwan
- Department of Food Nutrition and Health Biotechnology, College of Medical and Health Science, Asia University, Taichung City, Taiwan
- Big Data Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Taiwan
- Division of Radiation Oncology, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan
- Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung City, Taiwan
- Centers for Regional Anesthesia and Pain Medicine, Taipei Municipal Wan Fang Hospital, Taipei Medical University, Taipei City, Taiwan
| | - Wan-Ming Chen
- Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, New Taipei City, Taiwan
- Artificial Intelligence Development Center, Fu Jen Catholic University, New Taipei City, Taiwan
| | - Ming-Feng Chiang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan
| | - Hung-Chieh Lo
- Department of Traumatology, Wan Fang Hospital, Taipei Medical University, Taipei City, Taiwan
| | - Ming-Shun Wu
- Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei City, Taiwan
| | - Ming-Che Lee
- Division of General Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei City, Taiwan
- College of Medicine, Taipei Medical University, Taipei City, Taiwan
- Division of Transplantation Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei City, Taiwan
- TMU Research Center for Organ Transplantation, College of Medicine, Taipei Medical University, Taipei City, Taiwan
- Taipei Cancer Center, Taipei Medical University, Taipei City, Taiwan
| | - Ruey-Shyang Soong
- Division of General Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei City, Taiwan
- College of Medicine, Taipei Medical University, Taipei City, Taiwan
- Division of Transplantation Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei City, Taiwan
- TMU Research Center for Organ Transplantation, College of Medicine, Taipei Medical University, Taipei City, Taiwan
- Taipei Cancer Center, Taipei Medical University, Taipei City, Taiwan
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14
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Kumar R, Kumar S, Prakash SS. Compensated liver cirrhosis: Natural course and disease-modifying strategies. World J Methodol 2023; 13:179-193. [PMID: 37771878 PMCID: PMC10523240 DOI: 10.5662/wjm.v13.i4.179] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Revised: 06/05/2023] [Accepted: 06/27/2023] [Indexed: 09/20/2023] Open
Abstract
Compensated liver cirrhosis (CLC) is defined as cirrhosis with one or more decompensating events, such as ascites, variceal haemorrhage, or hepatic encephalopathy. Patients with CLC are largely asymptomatic with preserved hepatic function. The transition from CLC to decompensated cirrhosis occurs as a result of a complex interaction between multiple predisposing and precipitating factors. The first decompensation event in CLC patients is considered a significant turning point in the progression of cirrhosis, as it signals a drastic decline in median survival rates from 10-12 years to only 1-2 years. Furthermore, early cirrhosis has the potential to regress as liver fibrosis is a dynamic condition. With the advent of effective non-invasive tools for detecting hepatic fibrosis, more and more patients with CLC are currently being recognised. This offers clinicians a unique opportunity to properly manage such patients in order to achieve cirrhosis regression or, at the very least, prevent its progression. There are numerous emerging approaches for preventing or delaying decompensation in CLC patients. A growing body of evidence indicates that treating the underlying cause can lead to cirrhosis regression, and the use of non-selective beta-blockers can prevent decompensation by lowering portal hypertension. Additionally, addressing various cofactors (such as obesity, diabetes, dyslipidaemia, and alcoholism) and precipitating factors (such as infection, viral hepatitis, and hepatotoxic drugs) that have a detrimental impact on the natural course of cirrhosis may benefit patients with CLC. However, high-quality data must be generated through well-designed and adequately powered randomised clinical trials to validate these disease-modifying techniques for CLC patients. This article discussed the natural history of CLC, risk factors for its progression, and therapeutic approaches that could alter the trajectory of CLC evolution and improve outcomes.
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Affiliation(s)
- Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
| | - Sudhir Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
| | - Sabbu Surya Prakash
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
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15
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Gratacós-Ginès J, Pose E. Review of the role of statins in cirrhosis and portal hypertension. Clin Liver Dis (Hoboken) 2023; 22:50-57. [PMID: 37663550 PMCID: PMC10473354 DOI: 10.1097/cld.0000000000000015] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 12/23/2022] [Indexed: 09/05/2023] Open
Affiliation(s)
- Jordi Gratacós-Ginès
- Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Catalonia, Spain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Catalonia, Spain
| | - Elisa Pose
- Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Catalonia, Spain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Catalonia, Spain
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16
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Cui JJ, Li R, Ma XL, Yu HY, Luo ZG, Du P, Ren L, Ding X, Guo XP, Zheng WS, Jiang JD, Che Y, Wang LL. Prebiotic‐Based Nanoamorphous Atorvastatin Attenuates Nonalcoholic Fatty Liver Disease by Retrieving Gut and Liver Health. SMALL STRUCTURES 2023; 4. [DOI: 10.1002/sstr.202200312] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
The pathogenesis of nonalcoholic fatty liver disease (NAFLD) is multifactorial and composite, with the disorder of lipid metabolism‐induced lipotoxicity being one of the main risk factors. Atorvastatin (AT), the most widely prescribed lipid‐lowering drug, has pleiotropic actions benefiting NAFLD treatment. However, low absorption rate in the gut and potential disruption of AT on gut flora hindered its further applications. Notably, gut dysbiosis is involved in and is thus a promising management strategy for NAFLD. In this study, we constructed a prebiotic‐based AT nanoamorphous (PANA) to improve the efficacy of AT against NAFLD by retrieving liver and gut health. After oral administration, PANA showed superior drug accumulation in the liver tissue compared with pure AT. Moreover, PANA intervention effectively restored gut healthiness, indicated by reconstructed gut flora, and improved intestinal immunity, barrier integrity, and inflammation. Consequently, compared with AT, PANA treatment caused profound inhibition of weight gain and fat deposition, decreased plasma lipid levels, and alleviated hepatic steatosis and liver inflammation. The transcriptome analysis in the gut and liver tissues identified improved immunity and inflammation as potential mechanisms. This study suggests a promising strategy to treat NAFLD, assisted with nanotechnology in synergy with functional biomaterials.
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Affiliation(s)
- Jin-Jin Cui
- Institute of Medicinal Biotechnology Chinese Academy of Medical Science and Peking Union Medical College Beijing 100050 China
| | - Rui Li
- Institute of Medicinal Biotechnology Chinese Academy of Medical Science and Peking Union Medical College Beijing 100050 China
| | - Xiao-Lei Ma
- Institute of Materia Medica Chinese Academy of Medical Science and Peking Union Medical College Beijing 100050 China
| | - Hao-Yang Yu
- Institute of Medicinal Biotechnology Chinese Academy of Medical Science and Peking Union Medical College Beijing 100050 China
| | - Zhi-Gang Luo
- Institute of Materia Medica Chinese Academy of Medical Science and Peking Union Medical College Beijing 100050 China
| | - Peng Du
- Institute of Materia Medica Chinese Academy of Medical Science and Peking Union Medical College Beijing 100050 China
| | - Ling Ren
- Institute of Medicinal Biotechnology Chinese Academy of Medical Science and Peking Union Medical College Beijing 100050 China
| | - Xiao Ding
- State Key Laboratory of Phytochemistry and Plant Resource in West China Kunming Institute of Botany Chinese Academy of Sciences Kunming 650201 China
| | - Xiu-Ping Guo
- Institute of Medicinal Biotechnology Chinese Academy of Medical Science and Peking Union Medical College Beijing 100050 China
| | - Wen-Sheng Zheng
- Institute of Materia Medica Chinese Academy of Medical Science and Peking Union Medical College Beijing 100050 China
| | - Jian-Dong Jiang
- Institute of Medicinal Biotechnology Chinese Academy of Medical Science and Peking Union Medical College Beijing 100050 China
- Institute of Materia Medica Chinese Academy of Medical Science and Peking Union Medical College Beijing 100050 China
| | - Yongsheng Che
- Institute of Medicinal Biotechnology Chinese Academy of Medical Science and Peking Union Medical College Beijing 100050 China
| | - Lu-Lu Wang
- Institute of Medicinal Biotechnology Chinese Academy of Medical Science and Peking Union Medical College Beijing 100050 China
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17
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Bitto N, Ghigliazza G, Lavorato S, Caputo C, La Mura V. Improving Management of Portal Hypertension: The Potential Benefit of Non-Etiological Therapies in Cirrhosis. J Clin Med 2023; 12:jcm12030934. [PMID: 36769582 PMCID: PMC9917703 DOI: 10.3390/jcm12030934] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 01/17/2023] [Accepted: 01/20/2023] [Indexed: 01/27/2023] Open
Abstract
Portal hypertension is the consequence of cirrhosis and results from increased sinusoidal vascular resistance and hepatic blood inflow. Etiological therapies represent the first intervention to prevent a significant increase in portal pressure due to chronic liver damage. However, other superimposed pathophysiological drivers may worsen liver disease, including inflammation, bacterial translocation, endothelial dysfunction, and hyperactivation of hemostasis. These mechanisms can be targeted by a specific class of drugs already used in clinical practice. Albumin, rifaximin, statins, aspirin, and anticoagulants have been tested in cirrhosis and were a topic of discussion in the last Baveno consensus as non-etiological therapies. Based on the pathogenesis of portal hypertension in cirrhosis, our review summarizes the main mechanisms targeted by these drugs as well as the clinical evidence that considers them a valid complementary option to manage patients with cirrhosis and portal hypertension.
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Affiliation(s)
- Niccolò Bitto
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, 20122 Milan, Italy
| | - Gabriele Ghigliazza
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Division of Sub-Intensive Care Medicine, 20122 Milan, Italy
| | - Stanislao Lavorato
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, 20122 Milan, Italy
| | - Camilla Caputo
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, 20122 Milan, Italy
| | - Vincenzo La Mura
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, 20122 Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy
- Correspondence:
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18
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Lee HA, Chang Y, Sung PS, Yoon EL, Lee HW, Yoo JJ, Lee YS, An J, Song DS, Cho YY, Kim SU, Kim YJ. Therapeutic mechanisms and beneficial effects of non-antidiabetic drugs in chronic liver diseases. Clin Mol Hepatol 2022; 28:425-472. [PMID: 35850495 PMCID: PMC9293616 DOI: 10.3350/cmh.2022.0186] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 06/29/2022] [Indexed: 11/05/2022] Open
Abstract
The global burden of chronic liver disease (CLD) is substantial. Due to the limited indication of and accessibility to antiviral therapy in viral hepatitis and lack of effective pharmacological treatment in nonalcoholic fatty liver disease, the beneficial effects of antidiabetics and non-antidiabetics in clinical practice have been continuously investigated in patients with CLD. In this narrative review, we focused on non-antidiabetic drugs, including ursodeoxycholic acid, silymarin, dimethyl4,4'-dimethoxy-5,6,5',6'-dimethylenedixoybiphenyl-2,2'-dicarboxylate, L-ornithine L-aspartate, branched chain amino acids, statin, probiotics, vitamin E, and aspirin, and summarized their beneficial effects in CLD. Based on the antioxidant, anti-inflammatory properties, and regulatory functions in glucose or lipid metabolism, several non-antidiabetic drugs have shown beneficial effects in improving liver histology, aminotransferase level, and metabolic parameters and reducing risks of hepatocellular carcinoma and mortality, without significant safety concerns, in patients with CLD. Although the effect as the centerpiece management in patients with CLD is not robust, the use of these non-antidiabetic drugs might be potentially beneficial as an adjuvant or combined treatment strategy.
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Affiliation(s)
- Han Ah Lee
- Departments of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Young Chang
- Department of Internal Medicine, Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Pil Soo Sung
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.,The Catholic University Liver Research Center, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Eileen L Yoon
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Jeong-Ju Yoo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Young-Sun Lee
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Jihyun An
- Department of Gastroenterology and Hepatology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Do Seon Song
- Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Young Youn Cho
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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19
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Yun B, Ahn SH, Yoon JH, Kim BK. Statin use and risk of progression to liver cirrhosis in chronic hepatitis B independent of conventional risk factors: A nationwide study. Hepatol Commun 2022; 6:2455-2464. [PMID: 35766457 PMCID: PMC9426396 DOI: 10.1002/hep4.2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 05/15/2022] [Accepted: 05/30/2022] [Indexed: 11/08/2022] Open
Abstract
Many studies have elucidated the protective associations of statin use with liver cancer or mortality, but studies examining statin's effect on the risk of progression to liver cirrhosis considering medical/metabolic conditions or lifestyle factors are lacking. We aimed to assess statin's benefit independent of conventional risk factors. We identified 25,033 pairs of statin users (using statins for ≥90 days) and nonusers among patients with chronic hepatitis B (CHB) in the Republic of Korea's National Health Insurance Service database from 2010 to 2018. The primary endpoint was progression to cirrhosis from an inactive carrier or simple CHB. The cumulative probability was plotted using the Kaplan-Meier method. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated using the multivariable Cox proportional hazard model. During a 218,472 person-year follow-up, 2210 incident cases of progression to cirrhosis occurred. The 5-year cumulative risks were 4.0% and 6.3% in statin users and nonusers, respectively (p < 0.001). Statin use was significantly associated with a decreased risk of progression to cirrhosis (aHR, 0.59; 95% CI, 0.55-0.65; p < 0.001), after adjusting for age, sex, hypertension, diabetes, dyslipidemia, antiviral therapy, aspirin use, metformin use, nonstatin medication for dyslipidemia, smoking, drinking, obesity, exercise, and liver dysfunction. This protective association was still significant in a dose-response manner and with different time lags for outcomes. Conclusion: Statin use is associated with a decreased risk of progression to cirrhosis among patients with CHB, independent of metabolic and lifestyle factors. Future studies are required to validate this observation.
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Affiliation(s)
- Byungyoon Yun
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Jin-Ha Yoon
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Institute for Occupational Health, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
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20
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Wang J, Liu D, Chen S, Qi X. Aspirin for patients after TIPS: an old dog with new tricks? Hepatol Int 2022; 16:1244-1245. [PMID: 35767174 DOI: 10.1007/s12072-022-10383-y] [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: 05/22/2022] [Accepted: 06/14/2022] [Indexed: 11/04/2022]
Affiliation(s)
- Jitao Wang
- Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, Gansu, China.,Xingtai Key Laboratory of Precision Medicine for Liver Cirrhosis and Portal Hypertension, Xingtai People's Hospital of Hebei Medical University, Xingtai, 054001, Hebei, China
| | - Dengxiang Liu
- Xingtai Key Laboratory of Precision Medicine for Liver Cirrhosis and Portal Hypertension, Xingtai People's Hospital of Hebei Medical University, Xingtai, 054001, Hebei, China
| | - Shubo Chen
- Xingtai Key Laboratory of Precision Medicine for Liver Cirrhosis and Portal Hypertension, Xingtai People's Hospital of Hebei Medical University, Xingtai, 054001, Hebei, China
| | - Xiaolong Qi
- Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, Gansu, China.
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21
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Li H. Intercellular crosstalk of liver sinusoidal endothelial cells in liver fibrosis, cirrhosis and hepatocellular carcinoma. Dig Liver Dis 2022; 54:598-613. [PMID: 34344577 DOI: 10.1016/j.dld.2021.07.006] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 07/09/2021] [Accepted: 07/12/2021] [Indexed: 12/12/2022]
Abstract
Intercellular crosstalk among various liver cells plays an important role in liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Capillarization of liver sinusoidal endothelial cells (LSECs) precedes fibrosis and accumulating evidence suggests that the crosstalk between LSECs and other liver cells is critical in the development and progression of liver fibrosis. LSECs dysfunction, a key event in the progression from fibrosis to cirrhosis, and subsequently obstruction of hepatic sinuses and increased intrahepatic vascular resistance (IHVR) contribute to development of portal hypertension (PHT) and cirrhosis. More importantly, immunosuppressive tumor microenvironment (TME), which is closely related to the crosstalk between LSECs and immune liver cells like CD8+ T cells, promotes advances tumorigenesis, especially HCC. However, the connections within the crosstalk between LSECs and other liver cells during the progression from liver fibrosis to cirrhosis to HCC have yet to be discussed. In this review, we first summarize the current knowledge of how different crosstalk between LSECs and other liver cells, including hepatocytes, hepatic stellate cells (HSCs), macrophoges, immune cells in liver and extra cellular matrix (ECM) contribute to the physiological function and the progrssion from liver fibrosis to cirrhosis, or even to HCC. Then we examine current treatment strategies for LSECs crosstalk in liver fibrosis, cirrhosis and HCC.
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Affiliation(s)
- Hui Li
- Central Laboratory, Hospital of Chengdu University of Traditional Chinese Medicine, NO. 39 Shi-er-qiao Road, Chengdu, 610072, Sichuan Province, PR China.
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22
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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: 5] [Impact Index Per Article: 1.3] [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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Kronborg TM, Ytting H, Hobolth L, Møller S, Kimer N. Novel Anti-inflammatory Treatments in Cirrhosis. A Literature-Based Study. Front Med (Lausanne) 2021; 8:718896. [PMID: 34631742 PMCID: PMC8495012 DOI: 10.3389/fmed.2021.718896] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 08/26/2021] [Indexed: 12/11/2022] Open
Abstract
Liver cirrhosis is a disease characterised by multiple complications and a poor prognosis. The prevalence is increasing worldwide. Chronic inflammation is ongoing in liver cirrhosis. No cure for the inflammation is available, and the current treatment of liver cirrhosis is only symptomatic. However, several different medical agents have been suggested as potential healing drugs. The majority are tested in rodents, but few human trials are effectuated. This review focuses on medical agents described in the literature with supposed alleviating and curing effects on liver cirrhosis. Twelve anti-inflammatory, five antioxidative, and three drugs with effects on gut microflora and the LPS pathway were found. Two drugs not categorised by the three former categories were found in addition. In total, 42 rodent studies and seven human trials were found. Promising effects of celecoxib, aspirin, curcumin, kahweol, pentoxifylline, diosmin, statins, emricasan, and silymarin were found in cirrhotic rodent models. Few indices of effects of etanercept, glycyrrhizin arginine salt, and mitoquinone were found. Faecal microbiota transplantation is in increasing searchlight with a supposed potential to alleviate cirrhosis. However, human trials are in demand to verify the findings in this review.
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Affiliation(s)
- Thit Mynster Kronborg
- Gastro Unit, Medical Division, Amager-Hvidovre University Hospital, Hvidovre, Denmark
| | - Henriette Ytting
- Gastro Unit, Medical Division, Amager-Hvidovre University Hospital, Hvidovre, Denmark
| | - Lise Hobolth
- Gastro Unit, Medical Division, Amager-Hvidovre University Hospital, Hvidovre, Denmark
| | - Søren Møller
- Department of Clinical Physiology and Nuclear Medicine 260, Center for Functional and Diagnostic Imaging and Research, Amager-Hvidovre Hospital, Hvidovre, Denmark.,Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Nina Kimer
- Gastro Unit, Medical Division, Amager-Hvidovre University Hospital, Hvidovre, Denmark.,Novo Nordisk Foundation Centre for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
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Ciardullo S, Perseghin G. Statin use is associated with lower prevalence of advanced liver fibrosis in patients with type 2 diabetes. Metabolism 2021; 121:154752. [PMID: 33716004 DOI: 10.1016/j.metabol.2021.154752] [Citation(s) in RCA: 68] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 02/25/2021] [Accepted: 03/04/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Patients with type 2 diabetes (T2D) are at increased risk of both cardiovascular disease (CVD) and advanced liver fibrosis related to non-alcoholic fatty liver disease (NAFLD). Statin use is known to reduce the incidence of CVD while evidence on an effect on NAFLD severity is limited. METHODS This is a cross-sectional study performed with data from the 2017-2018 cycle of the National Health and Nutrition Examination Survey (NHANES). The target population consisted in adult patients with T2D and reliable vibration-controlled transient elastography (VCTE) results. Presence of liver fibrosis and steatosis were assessed by the median values of liver stiffness measurement (LSM) and controlled attenuation parameter (CAP), respectively. Patients with evidence of viral hepatitis and significant alcohol consumption were excluded. Logistic regression analysis was performed to evaluate the association between statin treatment and both steatosis and advanced (≥F3) liver fibrosis after adjustment for potential confounders. RESULTS The study population consisted in 744 patients (age: 61 ± 1 years, BMI: 33.3 ± 0.5 kg/m2). NAFLD (CAP≥274 dB/m) was present in 74.9% of patients (95% CI 69.2-79.8) and 14.5% (95% CI 10.8-19.2) had advanced fibrosis (LSM ≥ 9.7 kPa). After adjustment for age, sex, race-ethnicity, BMI, albumin, total cholesterol, HbA1c, triglycerides and liver enzymes, statin use was associated with lower odds of advanced fibrosis (OR 0.35, 95% CI 0.13-0.90, p = 0.03). No significant interaction was found between statin use and steatosis. CONCLUSION Given the absence of approved therapies for NAFLD-fibrosis, it would be reasonable to initiate specific randomized controlled trials with statins.
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Affiliation(s)
- Stefano Ciardullo
- Department of Medicine and Rehabilitation, Policlinico di Monza, Italy; Department of Medicine and Surgery, Università degli Studi di Milano Bicocca, Italy
| | - Gianluca Perseghin
- Department of Medicine and Rehabilitation, Policlinico di Monza, Italy; Department of Medicine and Surgery, Università degli Studi di Milano Bicocca, Italy.
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Muñoz AE, Pollarsky FD, Marino M, Cartier M, Vázquez H, Salgado P, Romero G. Addition of statins to the standard treatment in patients with cirrhosis: Safety and efficacy. World J Gastroenterol 2021; 27:4639-4652. [PMID: 34366626 PMCID: PMC8326251 DOI: 10.3748/wjg.v27.i28.4639] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Revised: 02/26/2021] [Accepted: 07/05/2021] [Indexed: 02/06/2023] Open
Abstract
This review summarizes the safety and efficacy of statins in patients with cirrhosis. Due to concerns about the safety of statins in patients with impaired liver function, they have recently been investigated as a potential treatment option in cirrhosis. The most clinically significant adverse event is statin-related myopathy, and this may be related to the high serum statin concentrations in the setting of severely impaired liver function. Rhabdomyolysis is the most serious and potentially life-threatening manifestation. It has recently been demonstrated that the recommended dose of simvastatin in patients with decompensated cirrhosis would be 20 mg/d because higher values, such as 40 mg/d, are associated with many adverse events, especially muscle injury. Likewise, simvastatin should not be administered to patients with Model for End-stage Liver Disease score > 12 and/or Child-Pugh class C because of the high risk of severe muscle injury. Due to the pleiotropic effects, the focus on statins has shifted from being considered harmful to something useful. Through these effects, statins could prevent liver-related morbidity and mortality in cirrhotic patients. Observational studies in large populations of patients with cirrhosis have shown that treatment with statins to decrease high cholesterol levels was associated with a reduced risk of hepatic decompensation, hepatocellular carcinoma development and death. The few randomized controlled trials in patients with cirrhosis and portal hypertension showed that statins lower portal pressure, quite likely through a reduction in hepatic resistance. Another large randomized controlled trial in patients with variceal bleeding showed that simvastatin in addition to standard of care did not prevent rebleeding but improved survival rate. Despite these encouraging outcomes, the quality of the evidence regarding the use of statins is low or very low due to the observational characteristics of most of the studies involved. Therefore, it is advisable to perform further randomized controlled trials on a large series of patients with hard clinical endpoints, using different statin types and varying doses. The objectives would be to prevent liver-related morbidity and mortality rather than treating cirrhosis complications to take additional information that makes it possible to add statins to the standard of care of these patients.
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Affiliation(s)
- Alberto E Muñoz
- Sección Hepatología, Hospital de Gastroenterología Dr. Carlos Bonorino Udaondo, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires 1264, Argentina
- Instituto de Investigaciones en Salud Pública, Facultad de Odontología, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires 1122, Argentina
| | - Florencia D Pollarsky
- Sección Hepatología, Hospital de Gastroenterología Dr. Carlos Bonorino Udaondo, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires 1264, Argentina
| | - Mónica Marino
- Sección Hepatología, Hospital de Gastroenterología Dr. Carlos Bonorino Udaondo, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires 1264, Argentina
| | - Mariano Cartier
- Sección Hepatología, Hospital de Gastroenterología Dr. Carlos Bonorino Udaondo, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires 1264, Argentina
| | - Horacio Vázquez
- Unidad Clínica, Hospital de Gastroenterología Dr. Carlos Bonorino Udaondo, Investigador Asociado del Gobierno de la Ciudad Autónoma de Buenos Aires, Ciudad Autónoma de Buenos Aires 1264, Argentina
| | - Pablo Salgado
- Instituto de Investigaciones en Salud Pública, Facultad de Odontología, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires 1122, Argentina
| | - Gustavo Romero
- Sección Hepatología, Hospital de Gastroenterología Dr. Carlos Bonorino Udaondo, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires 1264, Argentina
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The effect of statin therapy on disease-related outcomes in idiopathic pulmonary fibrosis: A systematic review and meta-analysis. Respir Med Res 2021; 80:100792. [PMID: 34091200 DOI: 10.1016/j.resmer.2020.100792] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 09/15/2020] [Accepted: 09/24/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Idiopathic pulmonary fibrosis is a progressive disease and antifibrotic therapies do not reverse existing fibrosis. There has been emerging evidence of potential role for statins in idiopathic pulmonary fibrosis. The aim of this review is to synthesise the evidence on the efficacy of statins in idiopathic pulmonary fibrosis, focusing on associations with all-cause mortality, disease-specific mortality and change in pulmonary function. METHODS Medline and Embase were reviewed to identify relevant publications. Studies were selected if they examined disease-related outcomes including mortality, pulmonary function and adverse events in people with idiopathic pulmonary fibrosis receiving statin therapy. RESULTS Five studies with a total of 3407 people with IPF were selected and analysed. The overall risk of bias of five included studies was moderate to serious. In the fixed effect meta-analysis, statin use was associated with a reduction in mortality (RR 0.8; 95% CI 0.72-0.99). However, in the random effects model, there was no longer any significant association between statin use and all-cause mortality (RR 0.87; 95% CI 0.68-1.12). There was no statistically significant association between statin use and decline in FVC % predicted. CONCLUSION There is currently insufficient evidence to conclude the effect of statin therapy on disease-related outcomes in idiopathic pulmonary fibrosis. Considering the limitations of available literature, we would recommend a prospective cohort study with capture of dosage and preparation of statin, statin adherence and use of concurrent antifibrotic treatment. PROSPERO REGISTRATION NUMBER CRD42019122745.
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27
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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: 2] [Impact Index Per Article: 0.5] [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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Abstract
PURPOSE OF REVIEW Statins are a class of lipid lower medications used primarily in patients with high-risk cardiovascular disease. Since their development, statins have been considered to be harmful in patients with liver disease, and many of the prescribing information labels consider them to be contraindicated in patients with active liver disease. However, recent studies have shown the contrary, warranting further investigation and discussion. This review aims to describe the latest literature on the mechanism, safety profile and potential benefits of statins use on the natural history of chronic liver disease (CLD) progression and its complications. RECENT FINDINGS A number of recently published studies have added to the existing body of literature supporting the concept that statins are safe and likely to be beneficial for treating patients with CLD. Patients with CLD including hepatitis B virus infection, hepatitis C virus infection, nonalcoholic fatty liver disease and alcohol on statins have been shown to have a lower rate of decompensating events, lower incidence of hepatocellular cancer, a lower rate of infections, and increased survival. However, the majority of the available literature supporting statin use in patients with liver disease comes from retrospective observational studies with high potential for bias. SUMMARY Statins appear to be safe in patients with compensated cirrhosis, and evidence suggests that they may reduce fibrosis, even in patients with advanced fibrosis and cirrhosis. Further high-quality research on this topic is needed to fully delineate the effect of statins in patients with liver disease.
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Affiliation(s)
- Mohamad Kareem Marrache
- Digestive Disease Research Center, Medical University of South Carolina, Charleston, South Carolina, USA
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Huang CY, Wu MY, Wang HC, Liao YC, Tou SI, Yen HR. Chinese Herbal Medicine Decreases Incidence of Cirrhosis in Patients with Non-Alcoholic Fatty Liver Disease in Taiwan: A Propensity Score-Matched Cohort Study. J Altern Complement Med 2021; 27:596-605. [PMID: 33913734 DOI: 10.1089/acm.2020.0494] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Objective: Chinese herbal medicine (CHM) is quite popular in Asia. The purpose of this study is to investigate the benefits of decreasing the risk of cirrhosis in patients with non-alcoholic fatty liver disease (NAFLD) by using CHM. Design: We performed a 1:3 propensity score-matched cohort study to analyze patients with NAFLD diagnosed between January 1, 1997 and December 31, 2011 through the Taiwanese National Health Insurance Research Database. Patients who received CHM therapy from the initial date of diagnosis of NAFLD to December 31, 2011 were included in the CHM group. Patients who were not treated with CHM during the same interval were categorized in the non-CHM group. Cox regression model was used to adjust for sex, age, comorbidities, and drug use. Hazard ratios were also compared between the two groups. Results: A total of 13,072 patients were identified after 1:3 propensity score matching. The patients had similar basic characteristics. A lower cumulative incidence of cirrhosis was found in the CHM cohort (log-rank test, p < 0.0001). Finally, 176 patients in the CHM cohort (4.66 per 1000 person-years) and 582 patients in the non-CHM cohort (7.92 per 1000 person-years) developed cirrhosis (adjusted hazard ratios 0.63, 95% confidence interval 0.53-0.75). The effect of CHM to lower cirrhosis incidence was independent of sex, drug use, and comorbidities, including diabetes mellitus, hypertension, and cardiovascular diseases. Patients older than 40 years of age and without comorbidities such as chronic obstructive pulmonary disease, hyperlipidemia, alcoholism, tobacco use, or obesity also benefited from CHM. Conclusions: Our study is the first large-scale investigation in Taiwan that shows the association between patients with NAFLD and cirrhosis prevention after CHM intervention. The results may be useful for treatment and for decision making for patients and clinical doctors. Further restricted trials are needed to support our findings.
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Affiliation(s)
- Chia-Yu Huang
- Department of Family Medicine, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan.,School of Medicine, Tzu Chi University, Hualien, Taiwan.,Graduate Institute of Chinese Medicine, School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan
| | - Mei-Yao Wu
- Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan.,School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.,Research Center for Traditional Chinese Medicine, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
| | - Hsiang-Chi Wang
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan.,College of Medicine, China Medical University, Taichung, Taiwan
| | - Yuan-Ching Liao
- Graduate Institute of Chinese Medicine, School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.,Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Sio-Ian Tou
- Department of Pediatrics, Chung Kang Branch, Cheng-Ching General Hospital, Taichung, Taiwan
| | - Hung-Rong Yen
- Graduate Institute of Chinese Medicine, School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.,Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan.,Research Center for Traditional Chinese Medicine, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.,Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
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Chou AH, Lin YS, Wu VCC, Chen FT, Yang CH, Chen DY, Chen SW. Effect of medications after cardiac surgery on long-term outcomes in patients with cirrhosis. Medicine (Baltimore) 2021; 100:e23075. [PMID: 33592816 PMCID: PMC7870262 DOI: 10.1097/md.0000000000023075] [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: 08/03/2020] [Accepted: 10/13/2020] [Indexed: 01/05/2023] Open
Abstract
The aim of this study was to evaluate the effect of beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) after cardiac surgery in the liver cirrhosis (LC) patients. We conducted a population-based cohort study using data from the Taiwanese National Health Insurance Research Database (NHIRD) from 2001 to 2013. The outcomes of interest included all-cause mortality, major adverse cardiac and cerebrovascular events (MACCE) and liver and renal outcomes. Among 1470 LC patients, 35.6% (n = 524) received beta-blockers and 33.4% (n = 491) were prescribed ACEIs and/or ARBs after cardiac surgery. The risk of negative liver outcomes was significantly lower in the ARB group compared with the ACEI group (9.6% vs 22.7%, hazard ratio [HR] 0.50, 95% confidence interval [CI] 0.31-0.83). Furthermore, the risk of MACCE (44.2% vs 54.7%, HR 0.79, 95% CI 0.65-0.96), all-cause mortality (35.3% vs 46.4%, HR 0.74, 95% CI 0.60-0.92), composite liver outcomes (9.6% vs 16.5%, HR 0.56, 95% CI 0.38-0.85) and hepatic encephalopathy (2.7% vs 5.7%, HR 0.45, 95% CI 0.21-0.94) were lower in the ARB group than the control group. Our study demonstrated that ARBs provide a greater protective effect than ACEIs in regard to long-term outcomes following cardiac surgery in patients with LC.
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Affiliation(s)
- An-Hsun Chou
- Department of Anesthesiology, Chang Gung Memorial Hospital, Linkou Medical, Center
- Collage of Medicine, Chang Gung University, Taoyuan City
| | - Yu-Sheng Lin
- Department of Cardiology, Chiayi Branch, Chiayi City
| | | | - Fang-Ting Chen
- Department of Anesthesiology, Chang Gung Memorial Hospital, Linkou Medical, Center
| | | | | | - Shao-Wei Chen
- Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou Medical Center
- Graduate Institute of Clinical Medical Sciences, College of medicine, Chang Gung, University, Taoyuan City, Taiwan
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Liver stiffness across different chronic liver disease under therapy with statin in a real life cohort. Eur J Gastroenterol Hepatol 2021; 32:223-229. [PMID: 32282399 DOI: 10.1097/meg.0000000000001719] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
INTRODUCTION Statins have been associated with improved clinical outcomes in patients with viral hepatitis and after variceal bleeding. Still, the clinical benefit of statins is not well defined for different liver diseases. Moreover, associations between statin use and liver stiffness as well as event free survival have not been established. METHODS Liver stiffness was evaluated in 6490 patients with liver disease (January 2012 till December 2016). Two hundred thirty-four of those received statin therapy, 468 controls without statins were selected by a 1:2 case by case matching using age, sex, underlying liver disease and BMI. RESULTS Statins were given to 234 patients with chronic virus hepatitis (n = 104), nonalcoholic fatty liver disease (n = 52), autoimmune liver disease including autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis (n = 31) and hepatitis of unknown origin (n = 47). Follow-up data were available for 96 and 119 pairs (mean follow-up 2 years). Statin users showed reduced inflammatory activity. Elevated liver enzymes were reported in 57% of statin-treated compared with 70% of controls (mean alanine aminotransferase level 53 vs. 74 U/l; P < 0.001). Statin use was well tolerated in this cohort. Mean liver stiffness values were 10.7 kPa (SEM 0.7) and 15.5 kPa (SEM 0.7) accordingly (P < 0.0001). Decompensation was less likely to occur in the statin group, both groups do not defer in the incidence of liver tumor occurrence, transplantation or death (odds ratio = 1, P = nonsignificant). CONCLUSIONS Use of statins was well tolerated irrespective of liver disease. Statin users showed reduced hepatic inflammatory activity, less severe markers of liver stiffness and portal hypertension. There might be a beneficial effect of statin on the risk to experience hepatic decompensation.
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Effects of Statin Use on the Development and Progression of Nonalcoholic Fatty Liver Disease: A Nationwide Nested Case-Control Study. Am J Gastroenterol 2021; 116:116-124. [PMID: 33027082 DOI: 10.14309/ajg.0000000000000845] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Accepted: 06/03/2020] [Indexed: 02/06/2023]
Abstract
INTRODUCTION The use of statins in nonalcoholic fatty liver disease (NAFLD) may reduce cardiovascular morbidity, although their effect on NAFLD itself is not well known. We aimed to investigate the role of statins on the development of de novo NAFLD and progression of significant liver fibrosis. METHODS This study included 11,593,409 subjects from the National Health Information Database of the Republic of Korea entered in 2010 and followed up until 2016. NAFLD was diagnosed by calculating fatty liver index (FLI), and significant liver fibrosis was evaluated using the BARD score. Controls were randomly selected at a ratio of 1:5 from individuals who were at risk of becoming the case subjects at the time of selection. RESULTS Among 5,339,901 subjects that had a FLI < 30 and included in the non-NAFLD cohort, 164,856 subjects eventually had NAFLD developed. The use of statin was associated with a reduced risk of NAFLD development (adjusted odds ratio [AOR] 0.66; 95% confidence interval [CI] 0.65-0.67) and was independent of associated diabetes mellitus (DM) (with DM: AOR 0.44; 95% CI 0.41-0.46, without DM: AOR 0.71; 95% CI 0.69-0.72). From 712,262 subjects with a FLI > 60 and selected in the NAFLD cohort, 111,257 subjects showed a BARD score ≥ 2 and were defined as liver fibrosis cases. The use of statins reduced the risk of significant liver fibrosis (AOR 0.43; 95% CI 0.42-0.44), independent of DM (with DM: AOR 0.31; 95% CI 0.31-0.32, without DM: AOR 0.52; 95% CI 0.51-0.52). DISCUSSION In this large population-based study, statin use decreased the risk of NAFLD occurrence and the risk of liver fibrosis once NAFLD developed.
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Zhang Q, Gao F, Yang X, Hu Y, Liu Y, Hou Y, Li Y, Zhu B, Niu S, Huang Y, Wang X. Protective Effect of Probiotics against Esophagogastric Variceal Rebleeding in Patients with Liver Cirrhosis after Endoscopic Therapy. Med Sci Monit 2020; 26:e924040. [PMID: 32769964 PMCID: PMC7433391 DOI: 10.12659/msm.924040] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 05/28/2020] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Probiotic therapy has been shown to be beneficial against some liver diseases. However, there is still uncertainty regarding the clinical efficacy of probiotics for the treatment of variceal rebleeding. This research explored the efficacy of probiotics in variceal rebleeding. MATERIAL AND METHODS This was a retrospective study of 704 consecutive patients with liver cirrhosis who recovered from esophagogastric variceal bleeding after endoscopic treatment. Patients were subdivided into a probiotics cohort (n=214) and a non-probiotics cohort (n=490) based on the cumulative defined daily dose (cDDD) of probiotics received during follow-up. Propensity score matching was utilized to obtain a relatively balanced cohort of 200 patients per group for the analysis. Patients were monitored for rebleeding during the one-year follow-up. RESULTS Multivariate Cox regression analysis revealed that probiotic therapy (≥28cDDD) was an independent protector against rebleeding (AHR=0.623; 95% CI=0.488-0.795; P<0.001). After propensity score matching, Kaplan-Meier analysis revealed that the rebleeding rate was higher in the non-probiotics cohort (n=200) than in the probiotics cohort (n=200) (56.0% vs. 44.0%, P=0.002). The incidence of rebleeding decreased with increased probiotic dosage (56.0%, 48.5%, 43.3%, and 38.1% in <28 cDDD, 28-60 cDDD, 61-90 cDDD, and >90 cDDD groups, respectively; P=0.011). The median rebleeding interval in the probiotics cohort (n=95) was significantly longer than that in the non-probiotics cohort (n=261) (147.0 vs. 91.0 days; P<0.001). CONCLUSIONS Adjuvant probiotic therapy significantly reduced the incidence of variceal rebleeding and delayed rebleeding after endotherapy in patients with cirrhosis.
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Affiliation(s)
- Qun Zhang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, P.R. China
| | - Fangyuan Gao
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, P.R. China
| | - Xue Yang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, P.R. China
| | - Ying Hu
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, P.R. China
| | - Yao Liu
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, P.R. China
| | - Yixin Hou
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, P.R. China
| | - Yuxin Li
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, P.R. China
| | - Bingbing Zhu
- Department of Gastroenterology, Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, P.R. China
| | - Shuaishuai Niu
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, P.R. China
| | - Yunyi Huang
- Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, P.R. China
| | - Xianbo Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, P.R. China
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Sung SF, Hsieh CY, Hu YH. Two Decades of Research Using Taiwan's National Health Insurance Claims Data: Bibliometric and Text Mining Analysis on PubMed. J Med Internet Res 2020; 22:e18457. [PMID: 32543443 PMCID: PMC7327589 DOI: 10.2196/18457] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 04/12/2020] [Accepted: 04/16/2020] [Indexed: 12/18/2022] Open
Abstract
Background Studies using Taiwan’s National Health Insurance (NHI) claims data have expanded rapidly both in quantity and quality during the first decade following the first study published in 2000. However, some of these studies were criticized for being merely data-dredging studies rather than hypothesis-driven. In addition, the use of claims data without the explicit authorization from individual patients has incurred litigation. Objective This study aimed to investigate whether the research output during the second decade after the release of the NHI claims database continues growing, to explore how the emergence of open access mega journals (OAMJs) and lawsuit against the use of this database affect the research topics and publication volume and to discuss the underlying reasons. Methods PubMed was used to locate publications based on NHI claims data between 1996 and 2017. Concept extraction using MetaMap was employed to mine research topics from article titles. Research trends were analyzed from various aspects, including publication amount, journals, research topics and types, and cooperation between authors. Results A total of 4473 articles were identified. A rapid growth in publications was witnessed from 2000 to 2015, followed by a plateau. Diabetes, stroke, and dementia were the top 3 most popular research topics whereas statin therapy, metformin, and Chinese herbal medicine were the most investigated interventions. Approximately one-third of the articles were published in open access journals. Studies with two or more medical conditions, but without any intervention, were the most common study type. Studies of this type tended to be contributed by prolific authors and published in OAMJs. Conclusions The growth in publication volume during the second decade after the release of the NHI claims database was different from that during the first decade. OAMJs appeared to provide fertile soil for the rapid growth of research based on NHI claims data, in particular for those studies with two or medical conditions in the article title. A halt in the growth of publication volume was observed after the use of NHI claims data for research purposes had been restricted in response to legal controversy. More efforts are needed to improve the impact of knowledge gained from NHI claims data on medical decisions and policy making.
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Affiliation(s)
- Sheng-Feng Sung
- Division of Neurology, Department of Internal Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi City, Taiwan.,Department of Information Management, Institute of Healthcare Information Management, National Chung Cheng University, Chiayi County, Taiwan
| | - Cheng-Yang Hsieh
- Department of Neurology, Tainan Sin Lau Hospital, Tainan, Taiwan.,School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ya-Han Hu
- Department of Information Management, National Central University, Taoyuan City, Taiwan.,Center for Innovative Research on Aging Society, National Chung Cheng University, Chiayi County, Taiwan.,MOST AI Biomedical Research Center, National Cheng Kung University, Tainan, Taiwan
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Frankul L, Frenette CT. Spotlight on Impactful Research: Utilization of Aspirin and Statin in Management of Coronary Artery Disease in Patients With Cirrhosis Undergoing Liver Transplant Evaluation. Clin Liver Dis (Hoboken) 2020; 15:69-70. [PMID: 32226618 PMCID: PMC7098668 DOI: 10.1002/cld.899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Accepted: 11/02/2019] [Indexed: 02/04/2023] Open
Abstract
http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-2-reading-frankul a video presentation of this article http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-2-interview-frenette an interview with the author Answer questions and earn https://www.wileyhealthlearning.com/Activity/7036138/disclaimerspopup.aspx.
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Affiliation(s)
- Leana Frankul
- Scripps Center for Organ TransplantationScripps Clinic/Green HospitalLa JollaCA
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Trivella JP, Martin P, Carrion AF. Novel targeted therapies for the management of liver fibrosis. Expert Opin Emerg Drugs 2020; 25:59-70. [PMID: 32098512 DOI: 10.1080/14728214.2020.1735350] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Juan P. Trivella
- Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Paul Martin
- Division of Gastroenterology and Hepatology, University of Miami, Miller School of Medicine, Miami, FL, USA
| | - Andres F. Carrion
- Division of Gastroenterology and Hepatology, University of Miami, Miller School of Medicine, Miami, FL, USA
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Francis P, Forman L. Use of Statins in Patients With and Without Liver Disease. Clin Liver Dis (Hoboken) 2020; 15:40-45. [PMID: 32104577 PMCID: PMC7041958 DOI: 10.1002/cld.866] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2019] [Accepted: 06/27/2019] [Indexed: 02/04/2023] Open
Affiliation(s)
- Prashanth Francis
- Division of Gastroenterology and HepatologyUniversity of Colorado Anschutz Medical CampusAuroraCO
| | - Lisa Forman
- Division of Gastroenterology and HepatologyUniversity of Colorado Anschutz Medical CampusAuroraCO
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Sheu MJ, Liang FW, Li ST, Li CY, Lu TH. Validity of ICD-10-CM Codes Used to Identify Patients with Chronic Hepatitis B and C Virus Infection in Administrative Claims Data from the Taiwan National Health Insurance Outpatient Claims Dataset. Clin Epidemiol 2020; 12:185-192. [PMID: 32110110 PMCID: PMC7039074 DOI: 10.2147/clep.s236823] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Accepted: 02/02/2020] [Indexed: 12/20/2022] Open
Abstract
PURPOSE To validate the use of International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes to identify patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in the Taiwan National Health Insurance (NHI) Outpatient Claims Dataset. METHODS We conducted a retrospective study using results of HBV surface antigen (HBsAg), HBV e antigen (HBeAg), and anti-HCV antibody tests in the NHI Lab & Exam Dataset from January 1 to March 31, 2018, as the reference standard to confirm HBV and HCV infection cases. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) to assess the performance of HBV infection-specific ICD-10-CM codes (B180, B181, and B191) and HCV infection-specific ICD-10-CM codes (B182 and B192) recorded in the NHI Outpatient Claims Dataset to identify patients with HBV or HCV infection. RESULTS In total, 196,635 and 120,628 patients had analyzable results for HBsAg/HBeAg tests and anti-HCV tests, respectively. Moreover, 44,574 and 14,443 were confirmed to have HBV and HCV infection, respectively. The sensitivity, specificity, PPV, and NPV were, respectively, 46%, 83%, 45%, and 84% for HBV infection-specific ICD-10-CM codes and 47%, 99%, 81%, and 93% for HCV infection-specific ICD-10-CM codes. The sensitivity demonstrated great variation by region, clinical setting, and physician specialty. CONCLUSION The HBV and HCV infection-specific ICD-10-CM codes recorded by physicians in Taiwan NHI outpatient claims data in 2018 had moderate sensitivity and high specificity for both HBV and HCV infection. The PPV was high for HCV ICD-10-CM codes, yet moderate for HBV ICD-10-CM codes.
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Affiliation(s)
- Ming-Jen Sheu
- Division of Gastroenterology and Hepatology, Chi Mei Medical Center, Tainan, Taiwan
- Department of Medicinal Chemistry, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Fu-Weng Liang
- Department of Public Health, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Sheng-Tun Li
- Department of Industrial and Information Management, College of Management, National Cheng Kung University, Tainan, Taiwan
| | - Chung-Yi Li
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan
- Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan
| | - Tsung-Hsueh Lu
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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Abstract
The hydroxymethyglutaryl-coenzyme A reductase inhibitors (statins) are a commonly prescribed class of medication for the treatment of hyperlipidemia and coronary artery disease. This class of medication has several proven benefits, including reduction of mortality related to coronary artery disease. A major consideration when prescribing these drugs are the potential for adverse effects, mainly myalgias, myopathy, and hepatotoxicity. In this article, we summarize current data on statin-associated hepatotoxicity and highlight that the risk of clinically significant idiosyncratic drug-induced liver injury is actually quite small. We also review preclinical data suggesting potential hepatoprotective effects of statin therapy.
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Affiliation(s)
- Lindsay Meurer
- Department of Internal Medicine, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - Stanley Martin Cohen
- University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Digestive Health Institute, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
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Hung TH, Tsai CC, Lee HF. Effects of poor hepatic reserve in cirrhotic patients with bacterial infections: A population-based study. Tzu Chi Med J 2020; 32:47-52. [PMID: 32110520 PMCID: PMC7015002 DOI: 10.4103/tcmj.tcmj_142_18] [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: 08/09/2018] [Revised: 09/18/2018] [Accepted: 10/03/2018] [Indexed: 11/04/2022] Open
Abstract
OBJECTIVE Ascites, hepatic encephalopathy, hepatorenal syndrome, spontaneous bacterial peritonitis, and esophageal variceal bleeding are major complications associated with cirrhosis. The presence of these complications indicates poor hepatic reserve. This study aimed to identify the effects of poor hepatic reserve on mortality in cirrhotic patients with bacterial infections. PATIENTS AND METHODS The Taiwan National Health Insurance Database was used to identify 43,042 cirrhotic patients with bacterial infections hospitalized between January 1, 2010, and December 31, 2013, after propensity score matching analysis. Of these, 21,521 cirrhotic patients had major cirrhotic-related complications and were considered to have poor hepatic reserve. RESULTS Mortality rates at 30 and 90 days were 24.2% and 39.5% in the poor hepatic reserve group and 12.8% and 21.7% in the good hepatic reserve group, respectively (P < 0.001 for each group). The cirrhotic patients with poor hepatic reserve (hazard ratio [HR], 2.10; 95% confidence interval [CI] = 2.03-2.18; P < 0.001) had significantly increased mortality at 90 days. The mortality HRs in patients with one, two, and three or more complications compared to patients without complications were 1.92 (95% CI = 1.85-1.99, P < 0.001), 2.61 (95% CI = 2.47-2.77, P < 0.001), and 3.81 (95% CI = 3.18-4.57, P < 0.001), respectively. CONCLUSION In cirrhotic patients with bacterial infections, poor hepatic reserve is associated with a poor prognosis. The presence of three or more cirrhotic-related complications increases mortality almost four folds.
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Affiliation(s)
- Tsung-Hsing Hung
- Division of Gastroenterology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Chih-Chun Tsai
- Department of Mathematics, Tamkang University, New Taipei, Taiwan
| | - Hsing-Feng Lee
- Division of Gastroenterology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
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Gu Y, Yang X, Liang H, Li D. Comprehensive evaluation of effects and safety of statin on the progression of liver cirrhosis: a systematic review and meta-analysis. BMC Gastroenterol 2019; 19:231. [PMID: 31888534 PMCID: PMC6938024 DOI: 10.1186/s12876-019-1147-1] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Accepted: 12/17/2019] [Indexed: 02/07/2023] Open
Abstract
Background Statin has been more and more widely used in chronic liver disease, however, existed studies have attained contradictory results. According to the present study, we aimed to test the efficacy and safety of statin via a meta-analysis. Methods Different databases were searched for full-text publication based on inclusion and exclusion criteria. For data-pooling, fixed-effect model was applied if heterogeneity wasn’t detected. Otherwise, random-effect model was adopted. Heterogeneity was detected by I squire (I2) test. All results of analysis were illustrated as forest plots. Publication bias was assessed using the Begg’s adjusted rank correlation test. Standard mean difference (SMD) was calculated in continuous variables. Pooled hazard ratio or odds ratio was calculated in catergorical variables. Results Seventeen clinical studies were finally included. Hepatic portal hemodynamic parameters were improved in statin users for a short-term response. For a long-term follow-up, statin treatment surprisingly decreased mortality rate (HR = 0.782, 95% CI: 0.718–0.846, I2 > 50%) and lower the occurrence of hepatocellular carcinoma (HR = 0.75, 95% CI: 0.64–0.86, I2 > 50%) in liver cirrhosis. Statin seemed not to decrease the risk of esophageal variceal bleeding and spontaneous bacterial peritonitis. However, statin was proved to decrease the risk of hepatic encephalopathy and ascites. Incidence of drug related adverse events didn’t increase in statin users. Dose-dependent effects of statin on hepatocellular carcinoma development, decompensated cirrhosis events occurrence, and liver cirrhosis progression. Conclusion Statin influenced parameters of hepatic portal vessel pressure in short-term treatment. Prognosis of liver cirrhosis benefited from statin treatment in long term follow-up. The efficacy and safety of statin in liver cirrhosis treatment is confirmed. To date, similar study is hardly seen before.
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Affiliation(s)
- Yue Gu
- Department of Hepatobiliary and Pancreatic Surgery, First Hospital of Jilin University, Changchun, Jilin, China
| | - Xueqin Yang
- Department of Traditional Chinese Medicine, First Hospital of Jilin University, Changchun, Jilin, China
| | - Hang Liang
- Department of Pediatric Respiratory II, First Hospital of Jilin University, No. 1 Xinmin Street, Changchun, 130021, Jilin, China
| | - Deli Li
- Department of Pediatric Respiratory II, First Hospital of Jilin University, No. 1 Xinmin Street, Changchun, 130021, Jilin, China.
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Chinese Herbal Medicine Ameliorated the Development of Chronic Kidney Disease in Patients with Chronic Hepatitis C: A Retrospective Population-Based Cohort Study. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2019; 2019:5319456. [PMID: 31871483 PMCID: PMC6906860 DOI: 10.1155/2019/5319456] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/22/2019] [Revised: 09/15/2019] [Accepted: 10/17/2019] [Indexed: 12/28/2022]
Abstract
Chronic kidney disease (CKD) is a serious complication affecting patients with chronic hepatitis. The effectiveness of CHM for the prevention of CKD in hepatitis patients remains unclear. Therefore, we conducted a retrospective cohort study to investigate the effectiveness of CHM in preventing the development of CKD in hepatitis patients. From a subdataset of the Taiwan National Health Insurance Research Database (NHIRD), we included 19,409 patients newly diagnosed with hepatitis B and hepatitis C between the years 2000 and 2010. After exclusion criteria and 1 : 1 propensity score matching process, we compared demographic factors, comorbidities, and correlated drugs between the CHM and non-CHM cohorts. Statistical analysis was applied to evaluate the differences in characteristic distributions and to compare the cumulative incidence of CKD between the CHM and non-CHM cohorts. This study showed that the patients suffering from hepatitis C with CHM treatment more than 90 days as an adjuvant therapy combined with western medical treatment modalities exhibited a decreased risk of developing CKD (hazard ratio (HR) = 0.40, 95% confidence interval (CI) = 0.21–0.76, p value <0.01). The Kaplan–Meier curve revealed a lower cumulative incidence rate of CKD (p value = 0.004) for the CHM cohort. For further reference, we herein offer the ten most frequently prescribed single herbs and herbal formulas; as such, Salviae miltiorrhizae and Jia-Wei-Xiao-Yao-San were the most commonly prescribed single herb and formula, respectively. This nationwide retrospective cohort study provides evidence that CHM is an effective adjuvant treatment to decrease the risk of developing CKD in hepatitis C patients.
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Newman CB, Preiss D, Tobert JA, Jacobson TA, Page RL, Goldstein LB, Chin C, Tannock LR, Miller M, Raghuveer G, Duell PB, Brinton EA, Pollak A, Braun LT, Welty FK. Statin Safety and Associated Adverse Events: A Scientific Statement From the American Heart Association. Arterioscler Thromb Vasc Biol 2019; 39:e38-e81. [PMID: 30580575 DOI: 10.1161/atv.0000000000000073] [Citation(s) in RCA: 435] [Impact Index Per Article: 72.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
One in 4 Americans >40 years of age takes a statin to reduce the risk of myocardial infarction, ischemic stroke, and other complications of atherosclerotic disease. The most effective statins produce a mean reduction in low-density lipoprotein cholesterol of 55% to 60% at the maximum dosage, and 6 of the 7 marketed statins are available in generic form, which makes them affordable for most patients. Primarily using data from randomized controlled trials, supplemented with observational data where necessary, this scientific statement provides a comprehensive review of statin safety and tolerability. The review covers the general patient population, as well as demographic subgroups, including the elderly, children, pregnant women, East Asians, and patients with specific conditions such as chronic disease of the kidney and liver, human immunodeficiency viral infection, and organ transplants. The risk of statin-induced serious muscle injury, including rhabdomyolysis, is <0.1%, and the risk of serious hepatotoxicity is ≈0.001%. The risk of statin-induced newly diagnosed diabetes mellitus is ≈0.2% per year of treatment, depending on the underlying risk of diabetes mellitus in the population studied. In patients with cerebrovascular disease, statins possibly increase the risk of hemorrhagic stroke; however, they clearly produce a greater reduction in the risk of atherothrombotic stroke and thus total stroke, as well as other cardiovascular events. There is no convincing evidence for a causal relationship between statins and cancer, cataracts, cognitive dysfunction, peripheral neuropathy, erectile dysfunction, or tendonitis. In US clinical practices, roughly 10% of patients stop taking a statin because of subjective complaints, most commonly muscle symptoms without raised creatine kinase. In contrast, in randomized clinical trials, the difference in the incidence of muscle symptoms without significantly raised creatinine kinase in statin-treated compared with placebo-treated participants is <1%, and it is even smaller (0.1%) for patients who discontinued treatment because of such muscle symptoms. This suggests that muscle symptoms are usually not caused by pharmacological effects of the statin. Restarting statin therapy in these patients can be challenging, but it is important, especially in patients at high risk of cardiovascular events, for whom prevention of these events is a priority. Overall, in patients for whom statin treatment is recommended by current guidelines, the benefits greatly outweigh the risks.
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Kim GA, Shim JJ, Lee JS, Kim BH, Kim JW, Oh CH, Oh CM, Oh IH, Park SY. Effect of Statin Use on Liver Cancer Mortality Considering Hypercholesterolemia and Obesity in Patients with Non-Cirrhotic Chronic Hepatitis B. Yonsei Med J 2019; 60:1203-1208. [PMID: 31769252 PMCID: PMC6881704 DOI: 10.3349/ymj.2019.60.12.1203] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Revised: 09/17/2019] [Accepted: 10/16/2019] [Indexed: 01/01/2023] Open
Abstract
Little is known about the benefits of statin use on liver cancer mortality among patients with chronic hepatitis B (CHB) considering hypercholesterolemia and obesity. A nationwide retrospective cohort study was conducted using data from a Health Examination Cohort of the National Health Insurance Service of Korea. Data on CHB patients with no other concurrent liver disease were acquired, and statin use was defined as a cumulative daily dose ≥28. A 3-year landmark analysis was performed to avoid immortal time bias. Patients who started statin therapy within the landmark date were considered statin users. A Cox regression analysis was applied to assess associations between statin use and liver cancer mortality considering hypercholesterolemia and obesity. Among 13063 patients, 193 (1.5%) died of liver cancer during the mean follow-up period of 10.6 years. After adjusting for demographic and metabolic factors, statin use [hazard ratio (HR), 0.17; 95% confidence interval (CI), 0.04-0.70] and hypercholesterolemia (HR, 0.46; 95% CI, 0.24-0.88 for total cholesterol ≥240 mg/dL) were associated with a decreased risk of liver cancer mortality, whereas body mass index (BMI) ≥30 kg/m² was associated with an increased risk of liver cancer mortality (HR, 2.46; 95% CI, 1.20-5.06). This study showed that statin use was associated with decreased liver cancer mortality when adjusting for cholesterol levels and BMI. This study found that hypercholesterolemia was independently associated with decreased liver cancer mortality regardless of statin use.
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Affiliation(s)
- Gi Ae Kim
- Department of Internal Medicine, School of Medicine, Kyung Hee University, Seoul, Korea
| | - Jae Jun Shim
- Department of Internal Medicine, School of Medicine, Kyung Hee University, Seoul, Korea.
| | - Ji Sung Lee
- Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Clinical Research Center, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Byung Ho Kim
- Department of Internal Medicine, School of Medicine, Kyung Hee University, Seoul, Korea
| | - Jung Wook Kim
- Department of Internal Medicine, School of Medicine, Kyung Hee University, Seoul, Korea
| | - Chi Hyuk Oh
- Department of Internal Medicine, School of Medicine, Kyung Hee University, Seoul, Korea
| | - Chang Mo Oh
- Department of Preventive Medicine, School of Medicine, Kyung Hee University, Seoul, Korea
| | - In Hwan Oh
- Department of Preventive Medicine, School of Medicine, Kyung Hee University, Seoul, Korea
| | - So Youn Park
- Department of Medical Education and Humanities, School of Medicine, Kyung Hee University, Seoul, Korea
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Guideline-conform statin use reduces overall mortality in patients with compensated liver disease. Sci Rep 2019; 9:11674. [PMID: 31406146 PMCID: PMC6690990 DOI: 10.1038/s41598-019-47943-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Accepted: 07/10/2019] [Indexed: 02/06/2023] Open
Abstract
Statins reduce cardiovascular risk. However, “real-life” data on statin use in patients with chronic liver disease and its impact on overall and liver-related survival are limited. Therefore, we assessed 1265 CLD patients stratified as advanced (ACLD) or non-advanced (non-ACLD) stage. Statin indication was evaluated according to the 2013 ACC/AHA guidelines and survival-status was verified by national death registry data. Overall, 122 (9.6%) patients had an indication for statin therapy but did not receive statins, 178 (14.1%) patients were on statins and 965 (76.3%) patients had no indication for statins. Statin underutilization was 34.2% in non-ACLD and 48.2% in ACLD patients. In non-ACLD patients, survival was worse without a statin despite indication as compared to patients on statin or without indication (log-rank p = 0.018). In ACLD patients, statin use did not significantly impact on survival (log-rank p = 0.264). Multivariate cox regression analysis confirmed improved overall survival in patients with statin as compared to patients with indication but no statin (HR 0.225; 95%CI 0.053–0.959; p = 0.044) and a trend towards reduced liver-related mortality (HR 0.088; 95%CI 0.006–1.200; p = 0.068). This was not observed in ACLD patients. In conclusion, guideline-confirm statin use is often withhold from patients with liver disease and this underutilization is associated with impaired survival in non-ACLD patients.
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Kaplan DE, Serper MA, Mehta R, Fox R, John B, Aytaman A, Baytarian M, Hunt K, Albrecht J, Njei B, Taddei TH. Effects of Hypercholesterolemia and Statin Exposure on Survival in a Large National Cohort of Patients With Cirrhosis. Gastroenterology 2019; 156:1693-1706.e12. [PMID: 30660733 DOI: 10.1053/j.gastro.2019.01.026] [Citation(s) in RCA: 92] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Revised: 12/17/2018] [Accepted: 01/09/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS Concerns related to hepatotoxicity frequently lead to discontinuation or non-initiation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase therapy in patients with cirrhosis despite data supporting statin use. We investigated the independent effects of hyperlipidemia and statin exposure on mortality, hepatic decompensation, and hepatocellular carcinoma development in a large national cohort of patients with cirrhosis. METHODS We performed a retrospective cohort study of patients with newly diagnosed cirrhosis from January 1, 2008 through June 30, 2016 in the Veterans Health Administration. Subjects were divided into 2 cohorts: 21,921 patients with prior statin exposure (existing users) and 51,023 statin-naïve individuals, of whom 8794 subsequently initiated statin therapy (new initiators) and 44,269 did not (non-initiators). Multivariable Cox proportional hazard models with inverse probability weighting were constructed to assess the effects of time-updating lipid profiles and cumulative exposure to statins on survival and hepatic decompensation. Statin-naïve new initiators were propensity matched with non-initiators to simulate a randomized controlled trial of statin use in cirrhosis. RESULTS In statin-naïve subjects, every 10-mg/dL increase in baseline total cholesterol was associated with a 3.6% decrease in mortality. In existing users, each year of continued statin exposure was associated with a hazard ratio of 0.920 (95% confidence interval 0.0.897-0.943) for mortality. After risk-set matching, each year of statin exposure among new initiators was associated with a hazard ratio of 0.913 (95% confidence interval 0.890-0.937) for mortality. CONCLUSIONS In a retrospective cohort study of veterans with a new diagnosis of cirrhosis, we associated hypercholesterolemia with well-preserved hepatic function and decreased mortality. Nonetheless, each cumulative year of statin exposure was associated with an independent 8.0%-8.7% decrease of mortality of patients with cirrhosis of Child-Turcotte-Pugh classes A and B.
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Affiliation(s)
- David E Kaplan
- Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania; Division of Gastroenterology and Hepatology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
| | - Marina A Serper
- Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania; Division of Gastroenterology and Hepatology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Rajni Mehta
- VA Connecticut Healthcare System, West Haven, Connecticut
| | - Rena Fox
- San Francisco VA Medical Center, San Francisco, California
| | - Binu John
- Hunter Holmes McGuire VA Medical Center, Richmond, Virginia
| | - Ayse Aytaman
- VA New York Harbor Health Care System, Brooklyn, New York
| | | | - Kristel Hunt
- James J. Peters VA Medical Center, Bronx, New York
| | | | - Basile Njei
- VA Connecticut Healthcare System, West Haven, Connecticut
| | - Tamar H Taddei
- VA Connecticut Healthcare System, West Haven, Connecticut
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Hung TH, Tsai CC, Lee HF. Statin use in cirrhotic patients with infectious diseases: A population-based study. PLoS One 2019; 14:e0215839. [PMID: 31017946 PMCID: PMC6481830 DOI: 10.1371/journal.pone.0215839] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Accepted: 04/09/2019] [Indexed: 12/13/2022] Open
Abstract
Background Recent studies have shown benefits of statins in patients with liver cirrhosis. However, it is still unknown if statins have a beneficial effect on the mortality of cirrhotic patients with bacterial infections. Methods The Taiwan National Health Insurance Database was searched, and 816 cirrhotic patients receiving statins with bacterial infections hospitalized between January 1, 2010 and December 31, 2013 were included in the study. A one-to-four propensity score matching was performed to select a comparison group based on age, sex, and comorbid disorders. Results The overall 30-day mortalities in statin and non-statin group were 5.3% and 9.8%, respectively (P = 0.001). After Cox regression modeling adjusting for age, sex, and comorbid disorders, the hazard ratio (HR) of statin use on 30-day mortality was 0.52 (95% confidence interval [CI]: 0.38–0.72, P<0.001). In subgroup analysis, the 30-day mortality effect of statin use was more pronounced in patients with pneumonia (HR = 0.34; 95% CI: 0.19–0.59; P<0.001) and bacteremia (HR = 0.55; 95% CI: 0.35–0.85; P = 0.008). Atovastatin (HR = 0.59; 95% CI: 0.37–0.93) and rosuvastatin (HR = 0.59; 95% CI: 0.36–0.98) were associated with a decreased 30-day mortality risk compared to patients not taking statins. Conclusions Statin use decreases the 30-day mortality of cirrhotic patients with bacteremia and pneumonia.
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Affiliation(s)
- Tsung-Hsing Hung
- Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Chih-Chun Tsai
- Department of Mathematics, Tamkang University, Tamsui, Taiwan
| | - Hsing-Feng Lee
- Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
- * E-mail:
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Effects of Atorvastatin Alongside Conventional Medical Treatment on Liver Fibrosis and Dysfunction in Patients with Chronic Hepatitis B: A Double-Blinded Clinical Trial. HEPATITIS MONTHLY 2019. [DOI: 10.5812/hepatmon.84656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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Cho Y, Kim MS, Nam CM, Kang ES. Statin Use is Associated with Decreased Hepatocellular Carcinoma Recurrence in Liver Transplant Patients. Sci Rep 2019; 9:1467. [PMID: 30728421 PMCID: PMC6365496 DOI: 10.1038/s41598-018-38110-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Accepted: 11/28/2018] [Indexed: 12/16/2022] Open
Abstract
Statins have been reported to prevent the development of hepatocellular carcinoma (HCC). We examined whether statin therapy is associated with decreased HCC recurrence in patients who underwent liver transplantation for HCC. Three hundred forty-seven patients ≥ 20 years old who underwent liver transplantation for HCC from 2006 to 2016 were enrolled in this study. Statin therapy was defined as the administration of statins for more than 30 days after liver transplantation. One hundred twelve (32.3%) patients treated with statins over 30 days were defined as the statin group, and the remaining 235 (67.7%) were defined as the non-statin group. Several risk factors reported to be associated with HCC recurrence, such as proportion of underlying liver disease, above Milan criteria, differentiation of HCC, vascular invasion, and preoperative alpha-fetoprotein level were not different between the two groups. Time-dependent Cox regression analysis showed that statin treatment was associated with significantly lower recurrence risk of HCC after adjusting for other risk factors (hazard ratio = 0.32, 95% CI = 0.11-0.89).
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Affiliation(s)
- Yongin Cho
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Myoung Soo Kim
- Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Chung Mo Nam
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Health Services Research, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Eun Seok Kang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
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Pose E, Trebicka J, Mookerjee RP, Angeli P, Ginès P. Statins: Old drugs as new therapy for liver diseases? J Hepatol 2019; 70:194-202. [PMID: 30075229 DOI: 10.1016/j.jhep.2018.07.019] [Citation(s) in RCA: 103] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Revised: 07/17/2018] [Accepted: 07/23/2018] [Indexed: 12/19/2022]
Abstract
In addition to lowering cholesterol levels, statins have pleiotropic effects, particularly anti-inflammatory, antiangiogenic, and antifibrotic, that may be beneficial in some chronic inflammatory conditions. Statins have only recently been investigated as a potential treatment option in chronic liver diseases because of concerns related to their safety in patients with impaired liver function. A number of experimental studies in animal models of liver diseases have shown that statins decrease hepatic inflammation, fibrogenesis and portal pressure. In addition, retrospective cohort studies in large populations of patients with cirrhosis and pre-cirrhotic conditions have shown that treatment with statins, with the purpose of decreasing high cholesterol levels, was associated with a reduced risk of disease progression, hepatic decompensation, hepatocellular carcinoma development, and death. These beneficial effects persisted after adjustment for disease severity and other potential confounders. Finally, a few randomised controlled trials have shown that treatment with simvastatin decreases portal pressure (two studies) and mortality (one study). Statin treatment was generally well tolerated but a few patients developed severe side effects, particularly rhabdomyolysis. Despite these promising beneficial effects, further randomised controlled trials in large series of patients with hard clinical endpoints should be performed before statins can be recommended for use in clinical practice.
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Affiliation(s)
- Elisa Pose
- Liver Unit, Hospital Clinic, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain
| | - Jonel Trebicka
- Department of Internal Medicine I, University of Bonn, Germany; European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain; Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Institute for Bioengineering of Catalonia, Barcelona, Spain
| | | | - Paolo Angeli
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine - DIMED, University of Padova, Padova, Italy
| | - Pere Ginès
- Liver Unit, Hospital Clinic, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain; Centro de Investigaciones Biomédicas en Red Enfermedades Hepáticas y Digestivas, Catalonia, Spain.
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