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Puri R, Bansal M, Mehta V, Duell PB, Wong ND, Iyengar SS, Kalra D, Nair DR, Nanda NC, Narula J, Deedwania P, Yusuf J, Dalal JJ, Shetty S, Vijan VM, Agarwala R, Kumar S, Vijay K, Khan A, Wander GS, Manoria PC, Wangnoo SK, Mohan V, Joshi SR, Singh B, Kerkar P, Rajput R, Prabhakar D, Zargar AH, Saboo B, Kasliwal RR, Ray S, Bansal S, Rabbani MU, Chhabra ST, Chandra S, Bardoloi N, Kavalipati N, Sathyamurthy I, Mahajan K, Pradhan A, Khanna NN, Khadgawat R, Gupta P, Chag MC, Gupta A, Murugnathan A, Narasingan SN, Upadhyaya S, Mittal V, Melinkeri RP, Yadav M, Mubarak MR, Pareek KK, Dabla PK, Nanda R, Mohan JC. Lipid Association of India 2023 update on cardiovascular risk assessment and lipid management in Indian patients: Consensus statement IV. J Clin Lipidol 2024; 18:e351-e373. [PMID: 38485619 DOI: 10.1016/j.jacl.2024.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Revised: 01/16/2024] [Accepted: 01/25/2024] [Indexed: 06/28/2024]
Abstract
OBJECTIVE In 2016, the Lipid Association of India (LAI) developed a cardiovascular risk assessment algorithm and defined low-density lipoprotein cholesterol (LDL-C) goals for prevention of atherosclerotic cardiovascular disease (ASCVD) in Indians. The recent refinements in the role of various risk factors and subclinical atherosclerosis in prediction of ASCVD risk necessitated updating the risk algorithm and treatment goals. METHODS The LAI core committee held twenty-one meetings and webinars from June 2022 to July 2023 with experts across India and critically reviewed the latest evidence regarding the strategies for ASCVD risk prediction and the benefits and modalities for intensive lipid lowering. Based on the expert consensus and extensive review of published data, consensus statement IV was commissioned. RESULTS The young age of onset and a more aggressive nature of ASCVD in Indians necessitates emphasis on lifetime ASCVD risk instead of the conventional 10-year risk. It also demands early institution of aggressive preventive measures to protect the young population prior to development of ASCVD events. Wide availability and low cost of statins in India enable implementation of effective LDL-C-lowering therapy in individuals at high risk of ASCVD. Subjects with any evidence of subclinical atherosclerosis are likely to benefit the most from early aggressive interventions. CONCLUSIONS This document presents the updated risk stratification and treatment algorithm and describes the rationale for each modification. The intent of these updated recommendations is to modernize management of dyslipidemia in Indian patients with the goal of reducing the epidemic of ASCVD among Indians in Asia and worldwide.
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Affiliation(s)
- Raman Puri
- Chair, FNLA, Sr. Consultant Cardiologist, Cardiac Care Centre, New Delhi, India (Dr Puri).
| | - Manish Bansal
- Co-Chair, Senior Director, Department of Cardiology, Medanta- The Medicity, Gurugram, Haryana, India (Dr Bansal)
| | - Vimal Mehta
- Co-Chair, Director-Professor, Department of Cardiology, G. B. Pant Institute of Postgraduate Medical Education and Research, New Delhi, India (Dr Mehta)
| | - P Barton Duell
- Co-Chair, FNLA, Professor of Medicine, Knight Cardiovascular Institute and Division of Endocrinology Diabetes and Clinical Nutrition, Oregon Health & Science University, Portland, OR, USA (Dr Duell)
| | - Nathan D Wong
- FNLA, Professor & Director Heart Disease Prevention program division of Cardiology, University of California, Irvine School of Medicine, USA (Dr Wong)
| | - S S Iyengar
- Sr. Consultant and Head, Department of Cardiology, Manipal Hospital, Bangalore, Karnataka, India (Dr Iyengar)
| | - Dinesh Kalra
- FNLA, Professor of Medicine, University of Louisville School of Medicine, USA (Dr Kalra)
| | - Devaki R Nair
- Sr. Consultant Department of Lipidology and Chemical pathologist, Royal Free Hospital, London, UK (Dr Nair)
| | - Navin C Nanda
- Professor of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, KY, USA (Dr Nanda)
| | - Jagat Narula
- Executive Vice President and Chief Academic Officer, UT Health, Houston, TX USA (Dr Narula)
| | - P Deedwania
- Professor of Medicine, University of California San Francisco, San Francisco, CA, USA (Dr Deedwania)
| | - Jamal Yusuf
- Director-Professor and Head, Department of Cardiology, G. B. Pant Institute of Postgraduate Medical Education and Research, New Delhi, India (Dr Yusuf)
| | - Jamshed J Dalal
- Sr. Consultant Cardiologist, Kokilaben Dhirubhai Ambani Hospital, Director-Centre for Cardiac Sciences, Mumbai, Maharashtra, India (Dr Dalal)
| | - Sadanand Shetty
- Head, Department of Cardiology, K. J. Somaiya Super Specialty Institute, Sion (East), Mumbai, Maharashtra, India (Dr Shetty)
| | - Vinod M Vijan
- Director, Vijan Hospital & Research Centre, Nashik, Uniqare Hospital, PCMC, Pune, India (Dr Vijan)
| | - Rajeev Agarwala
- Sr. Consultant Cardiologist, Jaswant Rai Specialty Hospital, Meerut, Uttar Pradesh, India (Dr Agarwala)
| | - Soumitra Kumar
- Professor and Head, Department of Cardiology, Vivekananda Institute of Medical Sciences, Kolkata, India (Dr Kumar)
| | - Kris Vijay
- FNLA, Professor of Medicine, Arizona Heart Foundation, University of Arizona, Phoenix, USA (Dr Vijay)
| | - Aziz Khan
- Sr. Consultant cardiologist, Crescent Hospital and Heart Centre, Nagpur, Maharashtra, India (Dr Khan)
| | - Gurpreet Singh Wander
- Professor of Cardiology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India (Dr Wander)
| | - P C Manoria
- Director, Manoria Heart and critical Care Hospital, Bhopal, Madhya Pradesh, India (Dr Manoria)
| | - S K Wangnoo
- Sr. Consultant Endocrinology & Diabetologist, Indraprastha Apollo Hospitals, New Delhi, India (Dr Wangnoo)
| | - Viswanathan Mohan
- Director Madras Diabetic Research foundation and Chairman & chief Diabetology, Dr Mohan Diabetes Specialties Centre, Chennai, India (Dr Mohan)
| | - Shashank R Joshi
- Sr. Consultant Endocrinologist, Lilavati Hospital, Mumbai, Maharashtra, India (Dr Joshi)
| | - Balbir Singh
- Chairman - Cardiac Sciences, Max Hospital Saket, New Delhi, India (Dr Singh)
| | - Prafulla Kerkar
- Sr. Consultant Cardiologist, Asian Heart Institute and Research Centre, Mumbai, India (Dr Kerkar)
| | - Rajesh Rajput
- Professor & Head, Department of Endocrinology, Post Graduate Institute of Medical Sciences, Rohtak, Haryana, India (Dr Rajput)
| | - D Prabhakar
- Sr. Consultant, Department of Cardiology, Apollo Hospitals, Chennai, Tamil Nadu, India (Dr Prabhakar)
| | - Abdul Hamid Zargar
- Medical Director, Centre for Diabetes and Endocrine Care, National Highway, Gulshan Nagar, Srinagar, J&K, India (Dr Zargar)
| | - Banshi Saboo
- Chairman-Diacare- Diabetes Care, and Hormone Clinic, Ahmedabad, India (Dr Saboo)
| | - Ravi R Kasliwal
- Chairman, Division of Clinical & Preventive Cardiology, Medanta- The Medicity, Gurugram, Haryana, India (Dr Kasliwal)
| | - Saumitra Ray
- Director of Intervention Cardiology, AMRI (S), Kolkata, India (Dr Ray)
| | - Sandeep Bansal
- Professor and Head, Dept. of Cardiology, Vardhman Mahavir Medical College & Safdarjung Hospital, New Delhi, India (Dr Bansal)
| | - M U Rabbani
- Professor Dept. of Cardiology, J. N. Medical College, AMU, Aligarh, India (Dr Rabbani)
| | - Shibba Takkar Chhabra
- Professor Dept. of Cardiology, Dayanand Medical College and Hospital, Ludhiana, India (Dr Chhabra)
| | - Sarat Chandra
- Chief Cardiologist, TX Group of Hospitals, Banjara Hills, Hyderabad, India (Dr Chandra)
| | - Neil Bardoloi
- Managing Director and HOD, Cardiology, Excel Care Hospital, Guwahati, Assam, India (Dr Bardoloi)
| | - Narasaraju Kavalipati
- Director of Cardiology and Sr Interventional Cardiologist, Apollo Hospitals, Hyderabad, India (Dr Kavalipati)
| | - Immaneni Sathyamurthy
- Sr. Consultant Cardiologist, Apollo Hospital, Chennai, Tamil Nadu, India (Dr Sathyamurthy)
| | - Kunal Mahajan
- Director Dept. of Cardiology, Himachal Heart Institute, Mandi, Himachal Pradesh, India (Dr Mahajan)
| | - Akshya Pradhan
- Sr. Consultant, Department of Cardiology King George's Medical University, Lucknow, Uttar Pradesh, India (Dr Pradhan)
| | - N N Khanna
- Sr. Consultant, Department of Cardiology, Indraprastha Apollo Hospitals, New Delhi, India (Dr Khanna)
| | - Rajesh Khadgawat
- Professor, Department of Endocrinology and Metabolism, All India Institute of Medical Sciences (AIIMS), New Delhi, India (Dr Khadgawat)
| | - Preeti Gupta
- Associate Professor Dept. of Cardiology, Vardhman Mahavir Medical College & Safdarjung Hospital, New Delhi, India (Dr Gupta)
| | - Milan C Chag
- Sr. Consultant Cardiologist, Marengo CIMS Hospital, Ahmadabad, Gujarat, India (Dr Chag)
| | - Ashu Gupta
- Sr Consultant Cardiologist, Holy Heart Advanced Cardiac Care and Research Centre, Rohtak, Haryana, India (Dr Gupta)
| | - A Murugnathan
- Sr. Consultant Internal Medicine, AG Hospital, Tirupur, Tamil Nadu, India (Dr Murugnathan)
| | - S N Narasingan
- Former Adjunct Professor of Medicine, The Tamil Nadu Dr MGR Medical University & Managing Director, SNN Specialties Clinic, Chennai, India (Dr Narasingan)
| | - Sundeep Upadhyaya
- Sr. Consultant, Department of Rheumatology, Indraprastha Apollo Hospitals, New Delhi, India (Dr Upadhyaya)
| | - Vinod Mittal
- Sr. Consultant Diabetologist and Head, Centre for Diabetes & Metabolic disease Delhi Heart & Lung Institute, Delhi, India (Dr Mittal)
| | - Rashida Patanwala Melinkeri
- Sr. Consultant, Department of Internal Medicine, KEM Hospital and Sahyadri Hospitals, Pune, Maharashtra, India (Dr Melinkeri)
| | - Madhur Yadav
- Director- Professor of Medicine, Lady Harding Medical College, New Delhi, India (Dr Yadav)
| | - M Raseed Mubarak
- Sr. Consultant Cardiologist, Lanka Hospital, Colombo, Sri Lanka (Dr Mubarak)
| | - K K Pareek
- Head, Department of Medicine, S. N. Pareek Hospital, Dadabari, Kota, Rajasthan, India (Dr Pareek)
| | - Pradeep Kumar Dabla
- Professor of Biochemistry, G. B. Pant Institute of Postgraduate Medical Education and Research, New Delhi, India (Dr Dabla)
| | - Rashmi Nanda
- Managing Director, Ashakiran Family Wellness Clinic, Indrapuram, U.P, India (Dr Nanda)
| | - J C Mohan
- Sr. Consultant Cardiologist, Institute of Heart and Vascular Diseases, Jaipur Golden Hospital, New Delhi, India (Dr Mohan)
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Anwar SD, Foster C, Ashraf A. Lipid Disorders and Metabolic-Associated Fatty Liver Disease. Endocrinol Metab Clin North Am 2023; 52:445-457. [PMID: 37495336 DOI: 10.1016/j.ecl.2023.01.003] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/28/2023]
Abstract
Dyslipidemia has been linked metabolic-associated fatty liver disease (MAFLD). Several genes and transcription factors involved in lipid metabolism can increase susceptibility to MAFLD. Multiple parallel 'hits' have been proposed for developing hepatic steatosis, NASH, and MAFLD, including insulin resistance and subsequent free fatty acid excess, de novo lipogenesis, and excessive hepatic triglyceride and cholesterol deposition in the liver. This lead to defective beta-oxidation in the mitochondria and VLDL export and increased inflammation. Given the significant cardiovascular risk, dyslipidemia associated with MAFLD should be managed by lifestyle changes and lipid-lowering agents such as statins, fenofibrate, and omega-3 fatty acids, with judicious use of insulin-sensitizing agents, and adequate control of dysglycemia.
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Affiliation(s)
- Shima Dowla Anwar
- Department of Pediatrics, Boston Children Hospital, Harvard Medical School, Boston, MA, USA
| | - Christy Foster
- University of Alabama at Birmingham, 1601, 4th Avenue South, CPP M 30, Birmingham, AL 35233, USA
| | - Ambika Ashraf
- University of Alabama at Birmingham, 1601, 4th Avenue South, CPP M 30, Birmingham, AL 35233, USA.
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Ramadan OI, Nasr M, El-Hay OMA, Hasan A, Abd-Allah EEE, Mahmoud ME, Abd-Allah FM, Abuamara TMM, Hablas MGA, Awad MMY, Diab M, Taha AM, Radwan MK, Abulkhair NH, Abdel-Hady AA. Potential Protective Effect of Zingiber officinale in Comparison to Rosuvastatin on High-fat diet-induced Non-alcoholic Fatty Liver Disease in Rats. Open Access Maced J Med Sci 2022. [DOI: 10.3889/oamjms.2022.9643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common liver disease affecting nearly 25% of adults worldwide with related risk factors including obesity, metabolic, and inflammatory diseases. Many therapeutic remedies of natural or synthetic properties were used.
AIM: This study aimed to investigate and compare the effects of ginger/rosuvastatin (ROSU) on the liver of rats with induced NAFLD.
MATERIALS AND METHODS: Forty adult male albino rats were used in this study and divided into four equal subgroups, Group I, control received the standard rat chow diet and given normal saline (1 ml/kg/day), Group II, high-fat diet (HFD) group, Group III, received HFD+ ROSU (15 mg/kg/day), and Group IV, HFD+ Zingiber officinale (10% W/V) for 6 weeks. At the end of our experiment, the rats were sacrificed then blood samples were collected for biochemical analysis of lipid profiles and liver enzymes, liver specimen was prepared for light and electron microscopic examination, and measurement of tissue level of malondialdehyde.
RESULTS: NAFLD caused degenerative changes and lipid deposition in liver cells as evidenced by microscopic results and laboratory tests. Treatment with ginger/ROSU alleviated those changes.
CONCLUSION: Ginger and ROSU could ameliorate liver functions in NAFLD and ginger effect is superior to ROSU.
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Pastori D, Pani A, Di Rocco A, Menichelli D, Gazzaniga G, Farcomeni A, D'Erasmo L, Angelico F, Del Ben M, Baratta F. Statin liver safety in non-alcoholic fatty liver disease: A systematic review and metanalysis. Br J Clin Pharmacol 2022; 88:441-451. [PMID: 34133035 PMCID: PMC9290532 DOI: 10.1111/bcp.14943] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 04/27/2021] [Accepted: 05/31/2021] [Indexed: 01/06/2023] Open
Abstract
AIMS Statin liver safety in non-alcoholic fatty liver disease (NAFLD) patients is not well defined. We analysed differences in liver function tests, including alanine transaminase aminotransferase (ALT), aspartate transaminase (AST) and gamma-glutamyl transpeptidase (GGT) in NAFLD patients treated or not treated with statins. METHODS We performed a systematic review of MEDLINE via PubMed and EMBASE databases and metanalysis of clinical studies investigating levels of ALT, AST and GGT in NAFLD according to statin treatment. Mean difference (MD) and percentage MD were calculated between the two groups. RESULTS We included 22 studies with 2345 NAFLD patients. Overall, 16 were before-after interventional, five were cross-sectional and one was combined cross-sectional/interventional study. In all interventional studies, except one, patients had raised ALT, AST and GGT at baseline. Interventional studies showed reduced ALT values with an MD reduction of -27.2 U/L (95% CI -35.25/-19.15) and a percentage MD reduction of -35.41% (95% CI -44.78/-26.04). Also, AST values were reduced after statin treatment in interventional studies with an MD of -18.82 U/L (95% CI -25.63/-12.02) (percentage -31.78%, 95% CI -41.45/-22.11). Similarly, GGT levels were reduced after statin treatment with an MD of -19.93 U/L (95% CI -27.10/-12.77) (percentage -25.57%, 95% CI -35.18/-15.97). Cross-sectional studies showed no difference in AST and GGT values between patients treated with and without statins. CONCLUSION In interventional studies, ALT, AST and GGT were reduced after statin treatment with a percentage mean difference of -35.41%, -31.78% and -25.57%, respectively, while observational studies showed a null effect, suggesting liver safety of statins in NAFLD patients.
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Affiliation(s)
- Daniele Pastori
- Department of Clinical, Internal, Anesthesiological and Cardiovascular SciencesSapienza University of RomeItaly
| | - Arianna Pani
- Clinical Pharmacology UnitASST Grande Ospedale Metropolitano NiguardaMilanItaly
| | - Arianna Di Rocco
- Department of Public Health and Infectious DiseasesSapienza University of RomeRomeItaly
| | - Danilo Menichelli
- Department of Clinical, Internal, Anesthesiological and Cardiovascular SciencesSapienza University of RomeItaly
| | - Gianluca Gazzaniga
- Clinical Pharmacology UnitASST Grande Ospedale Metropolitano NiguardaMilanItaly
| | - Alessio Farcomeni
- Department of Economics and FinanceUniversity of Rome Tor VergataRomeItaly
| | - Laura D'Erasmo
- Department of Translational and Precision MedicineSapienza University of RomeItaly
| | - Francesco Angelico
- Department of Public Health and Infectious DiseasesSapienza University of RomeRomeItaly
| | - Maria Del Ben
- Department of Clinical, Internal, Anesthesiological and Cardiovascular SciencesSapienza University of RomeItaly
| | - Francesco Baratta
- Department of Clinical, Internal, Anesthesiological and Cardiovascular SciencesSapienza University of RomeItaly
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Tzanaki I, Agouridis AP, Kostapanos MS. Is there a role of lipid-lowering therapies in the management of fatty liver disease? World J Hepatol 2022; 14:119-139. [PMID: 35126843 PMCID: PMC8790403 DOI: 10.4254/wjh.v14.i1.119] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 08/30/2021] [Accepted: 12/07/2021] [Indexed: 02/06/2023] Open
Abstract
Atherogenic dyslipidemia is characterized by increased triglyceride-rich lipoproteins and low high-density lipoprotein cholesterol concentrations. It is highly prevalent in non-alcoholic fatty liver disease (NAFLD) and contributes to the increased cardiovascular risk associated with this condition. Alongside insulin resistance it plays an important pathogenetic role in NAFLD/non-alcoholic steatohepatitis (NASH) development and progression. It has been shown that cholesterol-lowering reduces cardiovascular risk more in NAFLD vs non-NAFLD high-risk individuals. This evidence highlights the importance of effective lipid modulation in NAFLD. In this narrative review the effects of the most commonly used lipid-lowering therapies on liver outcomes alongside their therapeutic implications in NAFLD/NASH are critically discussed. Preclinical and clinical evidence suggests that statins reduce hepatic steatosis, inflammation and fibrosis in patients with NAFLD/NASH. Most data are derived from observational and small prospective clinical studies using changes in liver enzyme activities, steatosis/fibrosis scores, and imaging evidence of steatosis as surrogates. Also, relevant histologic benefits were noted in small biopsy studies. Atorvastatin and rosuvastatin showed greater benefits, whereas data for other statins are scarce and sometimes conflicting. Similar studies to those of statins showed efficacy of ezetimibe against hepatic steatosis. However, no significant anti-inflammatory and anti-fibrotic actions of ezetimibe have been shown. Preclinical studies showed that fibrates through peroxisome proliferator-activated receptor (PPAR)α activation may have a role in NAFLD prevention and management. Nevertheless, no relevant benefits have been noted in human studies. Species-related differences in PPARα expression and its activation responsiveness may help explain this discrepancy. Omega-3 fatty acids reduced hepatic steatosis in numerous heterogeneous studies, but their benefits on hepatic inflammation and fibrosis have not been established. Promising preliminary data for the highly purified eicosapentaenoic acid require further confirmation. Observational studies suggest that proprotein convertase subtilisin/kexin9 inhibitors may also have a role in the management of NAFLD, though this needs to be established by future prospective studies.
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Affiliation(s)
- Ismini Tzanaki
- School of Medicine, European University Cyprus, Nicosia, Cyprus, Nicosia 2404, Cyprus
| | - Aris P Agouridis
- School of Medicine, European University Cyprus, Nicosia 2404, Cyprus
| | - Michael S Kostapanos
- General Medicine, Addenbrooke's Hospital, Cambridge University Hospitals, Cambridge CB20QQ, United Kingdom.
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Rhabdomyolysis due to rosuvastatin in a patient with ROHHAD syndrome. J Clin Lipidol 2021; 15:789-792. [PMID: 34600840 DOI: 10.1016/j.jacl.2021.09.002] [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: 05/12/2021] [Revised: 09/01/2021] [Accepted: 09/05/2021] [Indexed: 10/20/2022]
Abstract
We report a 13-year-old female with rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome, panhypopituitarism, dyslipidemia, type 2 diabetes mellitus, and nonalcoholic fatty liver disease, who developed rhabdomyolysis and acute kidney injury, two weeks after switching from lovastatin to rosuvastatin. She had been on lovastatin for eight years without any adverse effects.
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Sandhu N, Navarro V. Drug-Induced Liver Injury in GI Practice. Hepatol Commun 2020; 4:631-645. [PMID: 32363315 PMCID: PMC7193133 DOI: 10.1002/hep4.1503] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Revised: 02/18/2020] [Accepted: 02/24/2020] [Indexed: 12/14/2022] Open
Abstract
Although drug-induced liver injury (DILI) is a rare clinical event, it carries significant morbidity and mortality, leaving it as the leading cause of acute liver failure in the United States. It is one of the most challenging diagnoses encountered by gastroenterologists. The development of various drug injury networks has played a vital role in expanding our knowledge regarding drug-related and herbal and dietary supplement-related liver injury. In this review, we discuss what defines liver injury, epidemiology of DILI, its biochemical and pathologic patterns, and management.
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Affiliation(s)
- Naemat Sandhu
- Division of Digestive Diseases and TransplantationAlbert Einstein Healthcare NetworkPhiladelphiaPA
| | - Victor Navarro
- Division of Digestive Diseases and TransplantationAlbert Einstein Healthcare NetworkPhiladelphiaPA
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Preparation and evaluation of spray dried rosuvastatin calcium-PVP microparticles for the improvement of serum lipid profile. J Drug Deliv Sci Technol 2020. [DOI: 10.1016/j.jddst.2019.101342] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Nascimbeni F, Pellegrini E, Lugari S, Mondelli A, Bursi S, Onfiani G, Carubbi F, Lonardo A. Statins and nonalcoholic fatty liver disease in the era of precision medicine: More friends than foes. Atherosclerosis 2019; 284:66-74. [PMID: 30875495 DOI: 10.1016/j.atherosclerosis.2019.02.028] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2018] [Revised: 02/26/2019] [Accepted: 02/27/2019] [Indexed: 12/12/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) describes a spectrum of alcohol-like hepatic histological changes, which occur in the absence of any competing causes of chronic liver disease, notably including significant alcohol consumption. A close and bi-directional relationship links NAFLD with the metabolic syndrome (MetS), and concurrent MetS will hasten the progression to more severe forms of NAFLD, including cirrhosis and hepatocellular carcinoma (HCC). Patients with NAFLD will typically exhibit atherogenic dyslipidemia and increased cardiovascular risk (CVR). Statins are among the most widely prescribed lipid-lowering drugs. Their use has historically been hampered, in individuals with liver disease, owing to the fear of hepatotoxicity. However, studies suggest that statins are not only effective in reducing cardiovascular events, but may also exert multiple beneficial effects on the liver. CVR in those with NAFLD has extensively been covered by our group and others. This updated clinical narrative review will critically examine the effects of statins on the pathogenesis of NAFLD, including the key elementary pathological lesions of NAFLD, i.e. steatosis, inflammation and fibrosis, and its liver-related complications, i.e. cirrhosis, portal hypertension and HCC.
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Affiliation(s)
- Fabio Nascimbeni
- Operating Unit of Internal and Metabolic Medicine, Azienda Ospedaliero-Universitaria of Modena, Civil Hospital of Baggiovara, Via Giardini 1355, 41126, Modena, Italy.
| | - Elisa Pellegrini
- Operating Unit of Internal and Metabolic Medicine, Azienda Ospedaliero-Universitaria of Modena, Civil Hospital of Baggiovara, Via Giardini 1355, 41126, Modena, Italy
| | - Simonetta Lugari
- Operating Unit of Internal and Metabolic Medicine, Azienda Ospedaliero-Universitaria of Modena and University of Modena and Reggio Emilia, Civil Hospital of Baggiovara, Via Giardini 1355, 41126, Modena, Italy
| | - Alberto Mondelli
- Operating Unit of Internal and Metabolic Medicine, Azienda Ospedaliero-Universitaria of Modena and University of Modena and Reggio Emilia, Civil Hospital of Baggiovara, Via Giardini 1355, 41126, Modena, Italy
| | - Serena Bursi
- Operating Unit of Internal and Metabolic Medicine, Azienda Ospedaliero-Universitaria of Modena and University of Modena and Reggio Emilia, Civil Hospital of Baggiovara, Via Giardini 1355, 41126, Modena, Italy
| | - Giovanna Onfiani
- Operating Unit of Internal and Metabolic Medicine, Azienda Ospedaliero-Universitaria of Modena and University of Modena and Reggio Emilia, Civil Hospital of Baggiovara, Via Giardini 1355, 41126, Modena, Italy
| | - Francesca Carubbi
- Operating Unit of Internal and Metabolic Medicine, Azienda Ospedaliero-Universitaria of Modena and University of Modena and Reggio Emilia, Civil Hospital of Baggiovara, Via Giardini 1355, 41126, Modena, Italy
| | - Amedeo Lonardo
- Operating Unit of Internal and Metabolic Medicine, Azienda Ospedaliero-Universitaria of Modena, Civil Hospital of Baggiovara, Via Giardini 1355, 41126, Modena, Italy
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Khan RA, Bhandari U, Kapur P, Jain A, Farah F. Effects of rosuvastatin (added to hypocaloric diet) on serum periostin, adiponectin, proinflammtory cytokines levels and hepatic steatosis in non-alcoholic fatty liver disease patients with dyslipidemia. CLINICAL EPIDEMIOLOGY AND GLOBAL HEALTH 2019. [DOI: 10.1016/j.cegh.2017.12.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Rattanachaisit P, Susantitaphong P, Thanapirom K, Chaiteerakij R, Komolmit P, Tangkijvanich P, Treeprasertsuk S. Statin use and histopathological change in patients with non-alcoholic fatty liver disease: a systematic review and meta-analysis. ASIAN BIOMED 2018; 12:3-13. [DOI: 10.1515/abm-2018-0026] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2025]
Abstract
Abstract
Background
Non-alcoholic fatty liver disease (NAFLD) is one of the major causes of chronic liver disease. The primary treatment of NAFLD by statins has not been clearly elucidated.
Objectives
To evaluate the effectiveness of statin use in patients with biopsy-proven NAFLD or non-alcoholic steatohepatitis on the change in liver histology.
Methods
We searched MEDLINE, Scopus, Google Scholar, and the Cochrane Central Register of Controlled Trials for clinical trials and observational studies investigating the effects of statins on histological change regardless of type or dosage from inception to December 2015. Random-effect model meta-analyses were used to compute changes in outcomes of interest. The study protocol was registered in advance with the International Prospective Register of Systematic Reviews (PROSPERO 2016 CRD42016033132).
Results
We identified 6 studies (111 patients), representing 5 cohort studies and 1 randomized controlled clinical trial. There was significant decrease in steatosis grading with a standardized mean difference of –2.580 (95% confidence interval [CI] –4.623 to –0.536; P = 0.013) and NAFLD activity score standardized mean difference of –1.488 (95% CI –2.506 to –0.471; P = 0.004). However, there was no significant change in fibrosis stage (0.156; 95% CI –0.553 to 0.865; P = 0.667).
Conclusions
Statin use can possibly reduce the extent of steatohepatitis but not the stage of fibrosis. Further randomized controlled studies to assess histological evidence with adequate sample size and duration are required in order to establish the role of statin as a primary treatment of NAFLD.
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Affiliation(s)
- Pakkapon Rattanachaisit
- Department of Medicine, Division of Gastroenterology, Faculty of Medicine , Chulalongkorn University , Bangkok 10330 Bangkok , Thailand
- The Thai Red Cross Society , Bangkok 10330 Bangkok , Thailand
| | - Paweena Susantitaphong
- Department of Medicine, Division of Nephrology, Faculty of Medicine , Chulalongkorn University , Bangkok 10330 Bangkok , Thailand
- The Thai Red Cross Society , Bangkok 10330 Bangkok , Thailand
| | - Kessarin Thanapirom
- Department of Medicine, Division of Gastroenterology, Faculty of Medicine , Chulalongkorn University , Bangkok 10330 Bangkok , Thailand
- The Thai Red Cross Society , Bangkok 10330 Bangkok , Thailand
| | - Roongruedee Chaiteerakij
- Department of Medicine, Division of Gastroenterology, Faculty of Medicine , Chulalongkorn University , Bangkok 10330 Bangkok , Thailand
- The Thai Red Cross Society , Bangkok 10330 Bangkok , Thailand
| | - Piyawat Komolmit
- Department of Medicine, Division of Gastroenterology, Faculty of Medicine , Chulalongkorn University , Bangkok 10330 Bangkok , Thailand
- The Thai Red Cross Society , Bangkok 10330 Bangkok , Thailand
| | - Pisit Tangkijvanich
- Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine , Chulalongkorn University , Bangkok 10330 Bangkok , Thailand
| | - Sombat Treeprasertsuk
- Department of Medicine, Division of Gastroenterology, Faculty of Medicine , Chulalongkorn University , Bangkok 10330 Bangkok , Thailand
- The Thai Red Cross Society , Bangkok 10330 Bangkok , Thailand
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12
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The impact of non-alcoholic fatty liver disease and metabolic syndrome on the progression of coronary artery calcification. Sci Rep 2018; 8:12004. [PMID: 30104707 PMCID: PMC6089954 DOI: 10.1038/s41598-018-30465-y] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Accepted: 07/26/2018] [Indexed: 12/20/2022] Open
Abstract
It is unclear whether non-alcoholic fatty liver disease (NAFLD) is an independent risk factor for cardiovascular disease. We examined the independent impact of NAFLD on the progression of the coronary artery calcification (CAC) score, a well-known marker of atherosclerosis progression. We examined 1,173 asymptomatic participants who underwent repeated CAC score measurement during routine health examinations. The subjects were categorised into four groups based on the presence (+) or absence (−) of NAFLD and metabolic syndrome (MetS). The progression of CAC score was defined as either incident CAC in a CAC-free population at baseline or an increase of ≥2.5 units between the baseline and the final square roots of the CAC scores of participants with detectable CAC at baseline. CAC progression was seen in 18.6% (98/526), 28.3% (77/272), 29.1% (30/103) and 32.0% (87/272) of the subjects with NAFLD(−)/MetS(−), NAFLD(+)/MetS(−), NAFLD(−)/MetS(+) and NAFLD(+)/MetS(+), respectively. The subjects with NAFLD(+)/MetS(+) and NAFLD(+)/MetS(−) had a significantly higher risk of CAC progression than those with NAFLD(−)/MetS(−) (multivariate-adjusted odds ratio [OR]: 1.76; 95% confidence interval [CI]: 1.18–2.62 and multivariate-adjusted OR: 1.53, 95% CI: 1.05–2.23, respectively). NAFLD is an independent risk factor for CAC progression, irrespective of the presence of MetS.
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Bril F, Portillo Sanchez P, Lomonaco R, Orsak B, Hecht J, Tio F, Cusi K. Liver Safety of Statins in Prediabetes or T2DM and Nonalcoholic Steatohepatitis: Post Hoc Analysis of a Randomized Trial. J Clin Endocrinol Metab 2017; 102:2950-2961. [PMID: 28575232 PMCID: PMC5546850 DOI: 10.1210/jc.2017-00867] [Citation(s) in RCA: 75] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2017] [Accepted: 05/26/2017] [Indexed: 12/28/2022]
Abstract
CONTEXT Patients with nonalcoholic fatty liver disease have a high cardiovascular risk, but statins are rarely prescribed because of fear of hepatotoxicity. OBJECTIVE To prospectively assess the long-term safety of statins in patients with prediabetes/type 2 diabetes mellitus (T2DM) and nonalcoholic steatohepatitis (NASH). DESIGN Post hoc analysis of statin use during a randomized, controlled trial assessing pioglitazone vs placebo for NASH. PATIENTS A total of 101 patients (86 receiving statins) with biopsy-proven NASH and prediabetes/T2DM were followed for up to 36 months. INTERVENTIONS Oral glucose tolerance test and percutaneous liver biopsy (baseline, month 18, and month 36); liver magnetic resonance spectroscopy and euglycemic insulin clamp (baseline and month 18). MAIN OUTCOME MEASURES Histologic and biochemical safety of statin use among patients with NASH. RESULTS Only 37% of patients were receiving statins at enrollment despite their high cardiovascular risk. Statin nonusers had higher plasma alanine aminotransferase levels but similar histologic severity of liver disease at baseline. In both statin users and nonusers, the same number of patients (n = 4) had a twofold or greater increase in plasma aminotransferases during follow-up. One statin nonuser was discontinued from the study because of this elevation. Values returned to normal without any active measure in all other cases. No changes on liver histology or hepatic insulin resistance were observed in patients with NASH newly started on a statin and receiving placebo during the main study. CONCLUSIONS Statin therapy is safe in patients with prediabetes/T2DM and NASH. Given their high cardiovascular risk, statin therapy should be encouraged in this population.
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Affiliation(s)
- Fernando Bril
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida 32610
- Malcom Randall Veterans Affairs Medical Center, Gainesville, Florida 32608
| | - Paola Portillo Sanchez
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida 32610
- Malcom Randall Veterans Affairs Medical Center, Gainesville, Florida 32608
| | - Romina Lomonaco
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida 32610
- Malcom Randall Veterans Affairs Medical Center, Gainesville, Florida 32608
| | - Beverly Orsak
- Division of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229
| | - Joan Hecht
- Audie L. Murphy Veterans Affairs Medical Center, San Antonio, Texas 78229
| | - Fermin Tio
- Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229
| | - Kenneth Cusi
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida 32610
- Malcom Randall Veterans Affairs Medical Center, Gainesville, Florida 32608
- Division of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229
- Audie L. Murphy Veterans Affairs Medical Center, San Antonio, Texas 78229
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Abstract
Objective: To review if utilizing statin therapy in patients with nonalcoholic fatty liver disease (NAFLD) is safe and efficacious. Data Sources: A MEDLINE literature search was performed using the search terms statins, nonalcoholic fatty liver disease, NAFLD, safety, effectiveness, and efficacy. The literature search was not limited to a predetermined set of dates. The literature search included information from 2003 until February 2016. Additional references were identified from a review of literature citations. Study Selection and Data Extraction: All English-language randomized controlled trials, case reports, meta-analyses, and guidelines assessing the use of statins in patients with NAFLD were evaluated. Data Synthesis: Clinical data demonstrate that statins can increase serum transaminases; however, these effects appear to be dose dependent. Data show that statins do not exacerbate liver injury. The Statin Liver Safety Task Force indicates that statins are safe to use in patients with chronic liver diseases and compensated cirrhosis. Studies conducted to determine if statins are efficacious have been limited to small trials or case reports. However, data suggest that statins can reduce elevated serum transaminases and improve liver histology. Conclusions: Guidelines indicate that statins can be used to treat dyslipidemia in patients with NAFLD and nonalcoholic steatohepatitis. Statins may be a viable treatment option for NAFLD in patients who have an increased cardiovascular risk. Additional large, randomized controlled trials need to be conducted in order to confirm the beneficial effects of statins in NAFLD.
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15
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Pravastatin-Induced Hepatotoxicity in a Patient With Fatty Liver Disease: A Case Presentation With Literature Review. J Pharm Pract 2016. [DOI: 10.1177/0897190007303052] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Purpose. To report a case of biopsy-confirmed pravastatin-induced liver injury in a patient with nonalcoholic fatty liver disease (NAFLD). Second, to review the data regarding hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) use in patients with NAFLD and monitoring that may be required for statin therapy. Literature Search. A PubMed search and review of the reference lists of the articles included in the case report was performed to find human studies from 1965 to the present on statin therapy in patients with NAFLD. To the authors' knowledge, there are no other case reports that parallel the one presented here. Case Report. A 71-year-old female with NAFLD, challenged multiple times on different lipid lowering agents, with a history of elevated liver enzymes post statin therapy, developed drug-induced hepatocellular damage following pravastatin therapy. Discussion. Symptomatic liver injury with statin therapy is rare even in patients with NAFLD. To the authors' knowledge, there are no case reports demonstrating statin-induced hepatocellular damage in a patient with NAFLD. Conclusion. Contrary to numerous pilot studies indicating the benefit and safety of statin therapy in patients with NAFLD, the authors report a patient case with underlying NAFLD that developed drug-induced liver injury post statin therapy. This case highlights the importance of identifying when symptoms associated with liver injury are occurring in patients with comorbid NAFLD, instead of solely relying on routine monitoring of transaminase levels. Health care providers need to closely examine and question NAFLD patients who develop liver enzyme elevations while on statin therapy to determine if they are showing signs of significant liver dysfunction and obtain more detailed laboratory assessments such as indirect bilirubin and prothrombin time. If hepatotoxicity occurs, the statin should be stopped immediately and treated with an alternative lipid-lowering agent per the National Lipid Association Statin Safety Assessment Task Force recommendations.
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16
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Lo J, Lu MT, Kim EA, Nou E, Hallett TR, Park J, Hoffmann U, Grinspoon SK. Statin Effects to Reduce Hepatosteatosis as Measured by Computed Tomography in Patients With Human Immunodeficiency Virus. Open Forum Infect Dis 2016; 3:ofw062. [PMID: 27419149 PMCID: PMC4943550 DOI: 10.1093/ofid/ofw062] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2015] [Accepted: 03/18/2016] [Indexed: 12/28/2022] Open
Abstract
Hepatosteatosis is highly prevalent among patients living with human immunodeficiency virus. In a 1-year, randomized, double-blind trial of atorvastatin or placebo, atorvastatin increased liver/spleen ratio among patients with nonalcoholic fatty liver disease, indicating a reduction in hepatosteatosis. This reduction in hepatosteatosis is associated with reduction in low-density lipoprotein cholesterol with statin therapy.
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Affiliation(s)
- Janet Lo
- Department of Medicine, Endocrine Division, Program in Nutritional Metabolism , Massachusetts General Hospital and Harvard Medical School , and
| | - Michael T Lu
- Department of Radiology, Cardiac PET MR CT Program , Massachusetts General Hospital, and Harvard Medical School , Boston
| | - Elli A Kim
- Department of Medicine, Endocrine Division, Program in Nutritional Metabolism , Massachusetts General Hospital and Harvard Medical School , and
| | - Eric Nou
- Department of Medicine, Endocrine Division, Program in Nutritional Metabolism , Massachusetts General Hospital and Harvard Medical School , and
| | - Travis R Hallett
- Department of Radiology, Cardiac PET MR CT Program , Massachusetts General Hospital, and Harvard Medical School , Boston
| | - Jakob Park
- Department of Radiology, Cardiac PET MR CT Program , Massachusetts General Hospital, and Harvard Medical School , Boston
| | - Udo Hoffmann
- Department of Radiology, Cardiac PET MR CT Program , Massachusetts General Hospital, and Harvard Medical School , Boston
| | - Steven K Grinspoon
- Department of Medicine, Endocrine Division, Program in Nutritional Metabolism , Massachusetts General Hospital and Harvard Medical School , and
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Cortese F, Gesualdo M, Cortese A, Carbonara S, Devito F, Zito A, Ricci G, Scicchitano P, Ciccone MM. Rosuvastatin: Beyond the cholesterol-lowering effect. Pharmacol Res 2016; 107:1-18. [PMID: 26930419 DOI: 10.1016/j.phrs.2016.02.012] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Revised: 02/13/2016] [Accepted: 02/14/2016] [Indexed: 12/18/2022]
Abstract
Rosuvastatin is a fully synthetic statin wich acts by interfering with the endogenous synthesis of cholesterol through competitively inhibiting the 3-hydroxy-3-methylglutaryl coenzyme A reductase, a liver enzyme responsible of the rate-limiting step in cholesterol synthesis. When compared to other molecules of the same class, it shows high efficacy in the improvement of lipid profile, and, thanks to its non-cholesterol-lowering actions (anti-inflammatory, antioxidant and antithrombotic), represents a crucial tool for cardiovascular primary and secondary prevention. Moreover, recent data highlight rosuvastatin beneficial effects in several other fields. In this manuscript we analyzed literature sources in order to better define rosuvastatin features and discuss some critical issues.
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Affiliation(s)
- Francesca Cortese
- Cardiovascular Diseases Section, Department of Emergency and Organ Transplantation (DETO), University of Bari, Bari, Italy.
| | - Michele Gesualdo
- Cardiovascular Diseases Section, Department of Emergency and Organ Transplantation (DETO), University of Bari, Bari, Italy
| | - Annamaria Cortese
- Cerebrovascular Diseases and Neurorehabilitation Department, San Camillo Hospital, Venezia Lido, Italy
| | - Santa Carbonara
- Cardiovascular Diseases Section, Department of Emergency and Organ Transplantation (DETO), University of Bari, Bari, Italy
| | - Fiorella Devito
- Cardiovascular Diseases Section, Department of Emergency and Organ Transplantation (DETO), University of Bari, Bari, Italy
| | - Annapaola Zito
- Cardiovascular Diseases Section, Department of Emergency and Organ Transplantation (DETO), University of Bari, Bari, Italy
| | - Gabriella Ricci
- Cardiovascular Diseases Section, Department of Emergency and Organ Transplantation (DETO), University of Bari, Bari, Italy
| | - Pietro Scicchitano
- Cardiovascular Diseases Section, Department of Emergency and Organ Transplantation (DETO), University of Bari, Bari, Italy
| | - Marco Matteo Ciccone
- Cardiovascular Diseases Section, Department of Emergency and Organ Transplantation (DETO), University of Bari, Bari, Italy
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18
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Abstract
Lipid lowering, particularly with 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors ("statins"), reduces the risk of cardiovascular disease. Patients with chronic liver disease present challenges to the use of lipid medications. In the case of most liver disorders, the concern has been one of safety. There is evidence that most lipid-lowering medications can be used safely in many situations, although large outcomes trials are lacking. This review examines lipid physiology and cardiovascular risk in specific liver diseases and reviews the evidence for lipid lowering and the use of statins in chronic liver disease.
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Affiliation(s)
- Cynthia Herrick
- Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, Campus Box 8127, 660 South Euclid, St Louis, MO 63110, USA.
| | - Samira Bahrainy
- VA Medical Center, Puget Sound, 1660 South Columbian Way, Seattle, WA 98104, USA
| | - Edward A Gill
- Harborview Medical Center, University of Washington School of Medicine, 325 Ninth Avenue, Box 359748, Seattle, WA 98104, USA
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19
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Dajani AIM, Abu Hammour AM, Zakaria MA, Al Jaberi MR, Nounou MA, Semrin AIM. Essential phospholipids as a supportive adjunct in the management of patients with NAFLD. Arab J Gastroenterol 2015; 16:99-104. [PMID: 26589371 DOI: 10.1016/j.ajg.2015.09.001] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2015] [Revised: 06/01/2015] [Accepted: 09/13/2015] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND STUDY AIMS Treatment of nonalcoholic fatty liver (NAFLD) is important because NAFLD patients have a 1.7-fold increase in standardised age and gender matched mortality. Currently treatment is based on life style modification and managing comorbid associating disease. Other medications remain experimental. Essential phospholipid (EPL) is a nutrient for the liver, helping to maintain vitality of cell membranes where the vast majority of liver activities are regulated. We performed a randomised open label study to evaluate EPL as an adjuvant nutrient to the treatment of primary NAFLD or NAFLD with comorbid disease. PATIENTS AND METHOD Three groups of NAFLD patients were recruited: lone (n=113), diabetes mellitus type 2 (n=107) and mixed hyperlipidaemia (n=104). Diagnosis was established by excluding other chronic liver diseases. A standard diet and physical activity plan were advised to all patients. 1800mg of EPL a day was given for 24weeks, followed by 900mg for 48weeks. RESULTS Essential phospholipid EPL led to a significant improvement of symptoms and a mean reduction of ALT of 50.8IU and AST of 46.1IU per patient (p<0.01). Abdominal ultrasonography indicated normalisation in 4.6% and a shift from grade II to grade I in 24% of patients. Liver stiffness measurement indicated an improvement in 21.1%, with a mean reduction in the LSM of 3.1K Pascal/patient. Reducing the dosage after six months led to a limited relapse in 43.8-63.2% of patients, for lone and NAFLD with co-morbid conditions. CONCLUSION Essential phospholipid (EPL) as a nutritional supplement resulted in a significant improvement in clinical parameters and transaminases for all NAFLD patients. Ultrasound and LSM revealed modest improvement. There is a need for uninterrupted maintenance to avoid relapse.
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20
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Tziomalos K, Athyros VG, Paschos P, Karagiannis A. Nonalcoholic fatty liver disease and statins. Metabolism 2015; 64:1215-1223. [PMID: 26234727 DOI: 10.1016/j.metabol.2015.07.003] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2015] [Revised: 06/30/2015] [Accepted: 07/06/2015] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Nonalcoholic fatty liver disease (NAFLD) is the most frequent cause of elevated transaminase levels and affects approximately one third of the general population. Patients with NAFLD are at increased risk for cardiovascular events, which represent the leading cause of death in this population. We discuss the safety and efficacy of statins in this population. MATERIALS/METHODS We reviewed the most recent literature on the safety of statins in patients with NAFLD and on their effects on liver histology and cardiovascular events. RESULTS It appears that statins can be safely administered to patients with NAFLD, including those with elevated transaminase levels (<3 times the upper limit of normal). Post-hoc analyses of randomized controlled trials also suggest that statins might reduce cardiovascular morbidity in this population. On the other hand, there are few and controversial data on the effects of statins on liver histology in patients with NAFLD. CONCLUSIONS Statins appear to be safe and might also reduce cardiovascular events in patients with NAFLD. Ongoing and future studies will clarify whether statins might also have a role in the treatment of NAFLD.
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Affiliation(s)
- Konstantinos Tziomalos
- First Propaedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece.
| | - Vasilios G Athyros
- Second Propaedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece
| | - Paschalis Paschos
- Second Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece
| | - Asterios Karagiannis
- Second Propaedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece
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21
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22
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Zhang QQ, Lu LG. Nonalcoholic Fatty Liver Disease: Dyslipidemia, Risk for Cardiovascular Complications, and Treatment Strategy. J Clin Transl Hepatol 2015; 3:78-84. [PMID: 26357637 PMCID: PMC4542078 DOI: 10.14218/jcth.2014.00037] [Citation(s) in RCA: 109] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2014] [Revised: 12/15/2014] [Accepted: 12/22/2014] [Indexed: 12/11/2022] Open
Abstract
Studies have shown that nonalcoholic fatty liver disease (NAFLD) is strongly associated with several metabolic disorders and diseases, such as obesity, type 2 diabetes mellitus, and dyslipidemia. In NAFLD, dyslipidemia is manifested as increased serum triglyceride and low-density lipoprotein cholesterol levels and decreased high-density lipoprotein cholesterol levels, all of which are key risk factors for cardiovascular disease (CVD). CVD is a leading cause of mortality in NAFLD patients. Thus, implementation of an aggressive therapeutic strategy for dyslipidemia with hypolipidemic agents may mitigate the risk for CVD among NAFLD patients. Here, we provide a current review of literature regarding NAFLD, with particular emphasis on dyslipidemia and available treatment options.
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Affiliation(s)
| | - Lun-Gen Lu
- Correspondence to: Lun-Gen Lu, Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, China. Tel: +86-21-63240090, Fax: +86-21-63241377. E-mail:
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23
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Pastori D, Polimeni L, Baratta F, Pani A, Del Ben M, Angelico F. The efficacy and safety of statins for the treatment of non-alcoholic fatty liver disease. Dig Liver Dis 2015; 47:4-11. [PMID: 25224698 DOI: 10.1016/j.dld.2014.07.170] [Citation(s) in RCA: 116] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2014] [Revised: 07/18/2014] [Accepted: 07/24/2014] [Indexed: 12/11/2022]
Abstract
Non-alcoholic fatty liver disease is an emerging liver disease in Western countries and the most frequent cause of incidental elevation of serum liver enzymes. Dyslipidaemia is frequently observed in patients with non-alcoholic fatty liver disease, and treatment of dyslipidaemia plays a critical role in the overall management of these patients. Moreover, coronary artery disease remains the most common cause of death. Statins are effective lipid-lowering agents, associated with a lowering the risk of cardiovascular events in several interventional randomized clinical trials. However, statins are often underused in patients with non-alcoholic fatty liver disease and many physicians are concerned about the prescription of statins to patients with unexplained persistent elevation of liver enzymes or active liver disease. Based on currently available data, statin therapy, at low-to-moderate doses, seems to be safe and has low liver toxicity. Treatment of dyslipidaemia in patients with non-alcoholic fatty liver disease is recommended and may also improve liver function tests. In these patients, the risks of not taking statins could outweigh the risks of taking the drug. Conversely, the usefulness of statins for the treatment of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis is still a matter of debate and randomized clinical trials of adequate size and duration are required.
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Affiliation(s)
- Daniele Pastori
- Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy
| | - Licia Polimeni
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Italy
| | - Francesco Baratta
- Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy
| | - Arianna Pani
- Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy
| | - Maria Del Ben
- Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy
| | - Francesco Angelico
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Italy.
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Lim S, Barter P. Antioxidant effects of statins in the management of cardiometabolic disorders. J Atheroscler Thromb 2014; 21:997-1010. [PMID: 25132378 DOI: 10.5551/jat.24398] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Redox systems are key players in vascular health. A shift in redox homeostasis-that results in an imbalance between reactive oxygen species (ROS) generation and endogenous antioxidant defenses has the potential to create a state of oxidative stress that subsequently plays a role in the pathogenesis of a number of diseases, including those of the cardiovascular and metabolic system. Statins, which are primarily used to reduce the concentration of low-density lipoprotein cholesterol, have also been shown to reduce oxidative stress by modulating redox systems. Studies conducted both in vitro and in vivo support the role of oxidative stress in the development of atherosclerosis and cardiovascular diseases. Oxidative stress may also be responsible for various diabetic complications and the development of fatty liver. Statins reduce oxidative stress by blocking the generation of ROS and reducing the NAD+/NADH ratio. These drugs also have effects on nitric oxide synthase, lipid peroxidation and the adiponectin levels. It is possible that the antioxidant properties of statins contribute to their protective cardiovascular effects, independent of the lipid-lowering actions of these agents. However, possible adverse effects of statins on glucose homeostasis may be related to the redox system. Therefore, studies investigating the modulation of redox signaling by statins are warranted.
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Affiliation(s)
- Soo Lim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine
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25
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Ben MD, Polimeni L, Baratta F, Pastori D, Loffredo L, Angelico F. Modern approach to the clinical management of non-alcoholic fatty liver disease. World J Gastroenterol 2014; 20:8341-8350. [PMID: 25024593 PMCID: PMC4093688 DOI: 10.3748/wjg.v20.i26.8341] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2013] [Revised: 11/05/2013] [Accepted: 03/07/2014] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common and emerging form of chronic liver disease worldwide. It includes a wide spectrum of liver diseases ranging from simple fatty liver to steatohepatitis, which may progress to cirrhosis, liver cancer, and liver mortality. Common metabolic diseases, which are well established cardiovascular risk factors, have been associated to NAFLD and cardiovascular disease is the single most important cause of morbidity and mortality in this patient population. The pathogenesis of NAFLD appears multifactorial and many mechanisms have been proposed as possible causes of fatty liver infiltration. Management of fatty liver has become a major challenge to healthcare systems as the consequence of the increasing rates of obesity worldwide. First-line management focuses on lifestyle modifications. Moderate weight reduction either by dietary restriction or by increased habitual physical activity is safe and highly recommended. Several therapeutic interventions have been proposed. These include insulin sensitizer agents, lipid lowering drugs, antioxidants such as vitamin E and supplementation of vitamin D3. However, therapeutic strategies have been largely empirical so far, and experimental trials have mostly been carried out in uncontrolled settings with small sample sizes. Metabolic conditions such as diabetes mellitus, obesity, hypertension and hyperlipidemia, should be strongly considered and a multidisciplinary approach should be personalized for individual patients. Treatment of co-morbidities should be regarded as of paramount importance in the management of these patients. The purpose of this review is to examine different approaches for the clinical management of non-alcoholic fatty liver disease.
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Kostapanos MS, Rizos CV, Elisaf MS. Benefit-risk assessment of rosuvastatin in the treatment of atherosclerosis and related diseases. Drug Saf 2014; 37:481-500. [PMID: 24788803 DOI: 10.1007/s40264-014-0169-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Rosuvastatin has been marketed for approximately a decade. In this review we critically discuss available evidence on the benefits and risks from its use. In clinical trials using rosuvastatin, 'lowest is best' was relevant for on-treatment low-density lipoprotein cholesterol levels. Targeting levels <50 mg/dl was associated with the greatest decrease in vascular morbidity/mortality in the primary prevention setting. Also, such reduction can induce atherosclerosis regression without increasing the risk of adverse effects. Pooled data suggest that the safety profile of rosuvastatin is not different from that of other statins. It was estimated that rosuvastatin-associated absolute hazards of muscle-, liver- and renal-related adverse effects are lower than the corresponding vascular benefits in moderate vascular risk individuals. However, these data are subject to biases and need confirmation on a prospective basis. Significant liver enzyme elevations are rare. These often imply underlying non-alcoholic fatty liver disease (NAFLD), which is associated with increased vascular risk. Rosuvastatin can improve biochemical biomarkers and histological score of NAFLD. Whether this benefit is associated with vascular risk reduction should be assessed by prospective studies. Both chronic kidney disease and albuminuria independently predict vascular morbidity and mortality. Rosuvastatin improved the estimated glomerular filtration rate and decreased albuminuria in patients with moderately impaired kidney function. Also, vascular morbidity and mortality might be reduced in these patients. The same was not relevant in end-stage renal disease. Rosuvastatin-induced proteinuria appears to be of tubular origin, not relating to kidney injury. Rosuvastatin increases the risk of new-onset diabetes by dose-dependently impairing insulin sensitivity. Obese individuals with prediabetes appear to be predominantly affected. However, absolute vascular benefits of rosuvastatin may counterbalance this risk. Rosuvastatin is effective for the prevention and management of atherosclerotic vascular disease. Individualization of its use can maximize benefits and reduce the risk of adverse effects.
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Affiliation(s)
- Michael S Kostapanos
- Department of Internal Medicine, Medical School, University of Ioannina, St. Niarchou Avenue, 45110, Ioannina, Greece
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Oza N, Takahashi H, Eguchi Y, Kitajima Y, Kuwashiro T, Ishibashi E, Nakashita S, Iwane S, Kawaguchi Y, Mizuta T, Ozaki I, Ono N, Eguchi T, Fujimoto K, Anzai K. Efficacy of ezetimibe for reducing serum low-density lipoprotein cholesterol levels resistant to lifestyle intervention in patients with non-alcoholic fatty liver disease. Hepatol Res 2014; 44:812-7. [PMID: 23721476 DOI: 10.1111/hepr.12176] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2013] [Revised: 05/09/2013] [Accepted: 05/27/2013] [Indexed: 02/08/2023]
Abstract
AIM To investigate the efficacy of ezetimibe and lifestyle intervention for treating patients with non-alcoholic fatty liver disease (NAFLD) and residual dyslipidemia via a combination of ezetimibe and lifestyle intervention. METHODS Patients with NAFLD with residual dyslipidemia after a 6-month lifestyle intervention program were included. After completion of the 6-month program, the patients received p.o. administration of ezetimibe at 10 mg/day, in addition to lifestyle intervention, for 6 months. RESULTS Of the 59 patients with NAFLD who had participated in the 6-month lifestyle intervention program between 2007 and 2012, 21 with residual dyslipidemia (10 males and 11 females) were enrolled. Median age was 58 years (range, 27-75), median bodyweight was 63.0 kg (range, 39.4-109.0), median body mass index was 25.4 kg/m2 (range, 18.2-37.1), median alanine aminotransferase was 23 IU/L (14-73), median high-density lipoprotein (HDL) was 58 mg/dL (range, 37-93), median triglycerides (TG) was 105 mg/dL (range, 42-216) and median low-density lipoprotein (LDL) was 153 (66-209) mg/dL. After 6 months of treatment with ezetimibe, serum LDL levels were improved in 15 of 20 (75%) patients (P = 0.0015), while no improvements were observed in the remaining five patient (25%). Ezetimibe was discontinued in one patient who developed skin rash. CONCLUSION Ezetimibe is effective for treating residual dyslipidemia after lifestyle intervention in patients with NAFLD.
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Affiliation(s)
- Noriko Oza
- Department of Internal Medicine, Saga Medical School, Nabeshima, Japan
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Khullar V, Dolganiuc A, Firpi RJ. Pre-and-post transplant considerations in patients with nonalcoholic fatty liver disease. World J Transplant 2014; 4:81-92. [PMID: 25032097 PMCID: PMC4094954 DOI: 10.5500/wjt.v4.i2.81] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2013] [Revised: 02/17/2014] [Accepted: 03/12/2014] [Indexed: 02/05/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is currently the third most common indication for liver transplantation in the United States. With the growing incidence of obesity, NAFLD is expected to become the most common indication for liver transplantation over the next few decades. As the number of patients who have undergone transplantation for NAFLD increases, unique challenges have emerged in the management and long-term outcomes in patients. Risk factors such as obesity, hypertension, diabetes, and hyperlipidemia continue to play an important role in the pathogenesis of the disease and its recurrence. Patients who undergo liver transplantation for NAFLD have similar long-term survival as patients who undergo liver transplantation for other indications. Research shows that post-transplantation recurrence of NAFLD is commonplace with some patients progressing to recurrent non-alcoholic steatohepatitis and cirrhosis. While treatment of comorbidities is important, there is no consensus on the management of modifiable risk factors or the role of pharmacotherapy and immunosuppression in patients who develop recurrent or de novo NAFLD post-transplant. This review provides an outline of NAFLD as indication for liver transplantation with a focus on the epidemiology, pathophysiology and risk factors associated with this disease. It also provides a brief review on the pre-transplant considerations and post-transplant factors including patient characteristics, role of obesity and metabolic syndrome, recurrence and de novo NAFLD, outcomes post-liver transplantation, choice of medications, and options for immunosuppression.
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Abstract
Lipid lowering, particularly with HMG CoA reductase inhibitors ("statins"), reduces the risk of cardiovascular disease. Patients with chronic liver and kidney disease present challenges to the use of lipid medications. In the case of most liver disorders, the concern has been one of safety. There is evidence that most lipid-lowering medications can be used safely in many situations, although large outcomes trials are not available. In contrast, in chronic kidney disease, dosing of lipid medications may require substantial modification depending on creatinine clearance. There are significant alterations in lipid metabolism in chronic kidney disease with concomitant increases in cardiovascular risk. Some data are available on cardiovascular outcomes with dyslipidemia treatment in renal patients. This review will examine lipid physiology and cardiovascular risk in specific liver and kidney diseases and review the evidence for lipid lowering and the use of statin and non-statin therapies in chronic liver and kidney disease.
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Affiliation(s)
- Cynthia Herrick
- Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, Campus Box 8127, 660 South Euclid, St. Louis, MO 63110, USA.
| | - Marina Litvin
- Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, Campus Box 8127, 660 South Euclid, St. Louis, MO 63110, USA; Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, Campus Box 8127, 660 S. Euclid Ave, St. Louis, MO 63110, USA.
| | - Anne Carol Goldberg
- Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, Campus Box 8127, 660 South Euclid, St. Louis, MO 63110, USA; Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, Campus Box 8127, 660 S. Euclid Ave, St. Louis, MO 63110, USA.
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Eslami L, Merat S, Malekzadeh R, Nasseri‐Moghaddam S, Aramin H, Cochrane Hepato‐Biliary Group. Statins for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Cochrane Database Syst Rev 2013; 2013:CD008623. [PMID: 24374462 PMCID: PMC12050155 DOI: 10.1002/14651858.cd008623.pub2] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are common causes of elevated liver enzymes in the general population. NASH and to some extent NAFLD have been associated with increased liver-related and all-cause mortality. No effective treatment is yet available. Recent reports have shown that the use of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) in patients with elevated plasma aminotransferases may result in normalisation of these liver enzymes. Whether this is a consistent effect or whether it can lead to improved clinical outcomes beyond normalisation of abnormal liver enzymes is not clear. OBJECTIVES To assess the beneficial and harmful effects of statins (that is, lovastatin, atorvastatin, simvastatin, pravastatin, rosuvastatin, and fluvastatin) on all-cause and liver-related mortality, adverse events, and histological, biochemical, and imaging responses in patients with NAFLD or NASH. SEARCH METHODS We performed a computerised literature search in the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded up to March 2013. We did fully recursive searches from the reference lists of all retrieved relevant publications to ensure a complete and comprehensive search of the published literature. We did not apply any restrictions regarding language of publication or publication date. SELECTION CRITERIA All randomised clinical trials using statins as the primary treatment for NAFLD or NASH versus no treatment, placebo, or other hypolipidaemic agents. DATA COLLECTION AND ANALYSIS Data were extracted, and risk of bias of each trial was assessed independently by two or more review authors. Meta-analyses were performed whenever possible. Review Manager 5.2 was used. MAIN RESULTS When the described search method was used and the eligibility criteria of the search results were applied, 653 records were found. Only two of these were randomised clinical trials that were considered eligible for inclusion. We assessed both trials as trials with high risk of bias. One of the trials was a pilot trial in which 16 participants with biopsy-proven NASH were randomised to receive simvastatin 40 mg (n = 10) or placebo (n = 6) once daily for 12 months. No statistically significant improvement in the aminotransferase level was seen in the simvastatin group compared with the placebo group. Liver histology was not significantly affected by simvastatin.The other trial had three arms. The trial compared atorvastatin 20 mg daily (n = 63) versus fenofibrate 200 mg daily (n = 62) versus a group treated with a combination of the two interventions (n = 61). There were no statistically significant differences between any of the three intervention groups regarding the week 54 mean activity levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, and alkaline phosphatase. The triglyceride levels seemed higher in the fenofibrate group compared with the atorvastatin group. Liver histology was not assessed in this trial. The presence of biochemical and ultrasonographic evidence of NAFLD seemed to be higher in the fenofibrate group compared with the atorvastatin group (58% versus 33%). Three patients discontinued treatment due to myalgia and elevated serum creatine kinase activity; one from the atorvastatin group and two from the combination group. Another patient from the atorvastatin group discontinued treatment due to alanine aminotransferase activity that was over three times the upper normal limit.No data for all-cause mortality and hepatic-related mortality were reported in the included trials. AUTHORS' CONCLUSIONS Based on the findings of this review, which included two trials with high risk of bias and a small numbers of participants, it seems possible that statins may improve serum aminotransferase levels as well as ultrasound findings. Neither of the trials reported on possible histological changes, liver-related morbidity or mortality. Trials with larger sample sizes and low risk of bias are necessary before we may suggest statins as an effective treatment for patients with NASH. However, as statins can improve the adverse outcomes of other conditions commonly associated with NASH (for example, hyperlipidaemia, diabetes mellitus, metabolic syndrome), their use in patients with non-alcoholic steatohepatitis may be justified.
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Affiliation(s)
- Layli Eslami
- Golestan University of Medical Science, Taleghani HospitalNorth Khayyam crossroadEast Taleghani AvenueGonbad e KavousGolestan provinceIran49791‐31983
| | - Shahin Merat
- Shariati Hospital, Tehran University of Medical SciencesDigestive Diseases Research CentreNorth Kargar StreetTehranTehranIran14117
| | - Reza Malekzadeh
- Shariati Hospital, Tehran University of Medical SciencesDigestive Diseases Research CentreNorth Kargar StreetTehranTehranIran14117
| | - Siavosh Nasseri‐Moghaddam
- Shariati Hospital, Tehran University of Medical SciencesDigestive Diseases Research CentreNorth Kargar StreetTehranTehranIran14117
| | - Hermineh Aramin
- Shariati Hospital, Tehran University of Medical SciencesDigestive Diseases Research CentreNorth Kargar StreetTehranTehranIran14117
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Oni ET, Sinha P, Karim A, Martin SS, Blaha MJ, Agatston AS, Blumenthal RS, Meneghelo RS, Conceiçao RD, Santos RD, Nasir K. Statin use is not associated with presence of and severity of nonalcoholic fatty liver disease. Arch Med Res 2013; 45:52-7. [PMID: 24333254 DOI: 10.1016/j.arcmed.2013.12.003] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2013] [Accepted: 10/11/2013] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND AIMS There is concern that statin use may exacerbate nonalcoholic fatty liver disease (NAFLD). We aimed to assess the association of statin use with NALFD and severity of liver fibrosis among NAFLD individuals. METHODS We evaluated 6,385 cross-sectional healthy Brazilian subjects (43 ± 10 years, 79% males) without clinical coronary heart disease between November 2008 and July 2010. NAFLD was diagnosed by ultrasound. Severity of liver fibrosis was predicted by fatty liver index and FIB-4. RESULTS NAFLD prevalence was 36% (n = 2310). Overall 552 (9%) individuals were using statins of whom 49% had NAFLD. Statin users were more likely to be men, older age, and have higher burden of risk factors (p <0.05). In age gender adjusted analysis the odds ratio for NAFLD with statin use was 0.87 (0.61-1.25, p = 0.46) in the presence of metabolic syndrome and 1.08 (0.88-1.32, p = 0.56) in its absence. On further adjustment for metabolic risk factors, LDL and smoking the results remained unchanged (OR: 0.89, 95% CI: 0.65-1.32, p = 0.56 and 0.90 (0.69-1.18, p = 0.46). There was no significant association between statin use and fatty liver index in a subanalysis of NAFLD individuals (71 ± 18 vs. 69 ± 23, p = 0.18). Although FIB-4 was mildly elevated with statin use (1.20 ± 0.51 vs. 1.02 ± 0.46, p <0.001), a multivariate analysis adjusted for age, gender and risk factors revealed statin use was not associated with severe fibrosis (FIB >1.45) (OR 0.88, 95% CI: 0.60-1.29, p = 0.50). CONCLUSIONS The results of this study favor statin use in subjects with NAFLD as its use is not associated with the presence of NAFLD or increased fibrosis.
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Affiliation(s)
- Ebenezer T Oni
- Center for Prevention and Wellness Research, Baptist Health Medical Group, Miami Beach, Florida
| | - Pragya Sinha
- Center for Prevention and Wellness Research, Baptist Health Medical Group, Miami Beach, Florida
| | - Adil Karim
- Center for Prevention and Wellness Research, Baptist Health Medical Group, Miami Beach, Florida
| | - Seth S Martin
- The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland
| | - Michael J Blaha
- The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland
| | - Arthur S Agatston
- Center for Prevention and Wellness Research, Baptist Health Medical Group, Miami Beach, Florida; Department of Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida
| | - Roger S Blumenthal
- The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland
| | - Romeu S Meneghelo
- Preventive Medicine Center Hospital Israelita Albert Einstein, Sao Paulo, Brazil
| | - Raquel D Conceiçao
- Preventive Medicine Center Hospital Israelita Albert Einstein, Sao Paulo, Brazil
| | - Raul D Santos
- Lipid Clinic-Heart Institute (InCor) University of São Paulo Medical School Hospital, Sao Paulo-São Paulo, Brazil
| | - Khurram Nasir
- Center for Prevention and Wellness Research, Baptist Health Medical Group, Miami Beach, Florida; The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland; Department of Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida; Department of Epidemiology, Robert Stempel College of Public Health, Florida International University, Miami, Florida.
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Riche DM, Fleming JW, Malinowski SS, Black CA, Miller KH, Wofford MR. Resistant nonalcoholic fatty liver disease amelioration with rosuvastatin and pioglitazone combination therapy in a patient with metabolic syndrome. Ann Pharmacother 2013; 48:137-41. [PMID: 24259612 DOI: 10.1177/1060028013507239] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
OBJECTIVE To report a case describing resolution of persistently elevated aminotransferases in a patient with severe, resistant nonalcoholic fatty liver disease (NAFLD) using combination therapy. CASE SUMMARY A 47-year-old obese male patient presented with a history of elevated aminotransferases and numerous statin intolerances. In addition to worsening control of diabetes and dyslipidemia, severe NAFLD was confirmed. Rosuvastatin was started, which induced short-term elevations in aminotransferases resulting in patient discontinuation. Biochemical markers of NAFLD worsened over time. Therefore, both rosuvastatin 20 mg daily and pioglitazone 15 mg daily were started simultaneously to potentially blunt the early increase in transaminases seen with rosuvastatin. At 2 weeks, the patient's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) had decreased 57% and 56% from baseline, respectively. By 9 months, the patient's ALT and AST serum concentrations had normalized. Repeat liver ultrasound demonstrated improvement in steatosis grading and reduction in liver size. These improvements occurred despite a 4.5-kg weight gain since starting rosuvastatin and pioglitazone. DISCUSSION Pharmacotherapy in NAFLD is not well validated, particularly combination therapy. Medications that target obesity-related consequences are commonly used, although evidence regarding biochemical and histological improvement is inconclusive. Consideration should be given to the use of combination of thiazolidinediones and statins for rapid biochemical improvement and long-term histological impact. CONCLUSIONS The improvement in this patient's biochemical and ultrasonographic markers of resistant, severe NAFLD was rapid and sustained with combination therapy. This case represents a potential solution for initiating or maintaining statin therapy in patients with NAFLD who are at high cardiovascular risk.
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Nseir W, Mahamid M. Statins in nonalcoholic fatty liver disease and steatohepatitis: updated review. Curr Atheroscler Rep 2013; 15:305. [PMID: 23328905 DOI: 10.1007/s11883-012-0305-5] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that refers to the presence of hepatic steatosis without significant intake of alcohol. NAFLD is an asymptomatic disease that can progress to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. The most common cause of mortality in patients with NAFLD or NASH is cardiovascular disease (CVD). Currently, the treatment of NAFLD focuses on gradual weight loss and life style modifications. However, multifactorial treatment of NAFLD or NASH risk factors may be needed to reduce the likelihood of these patients developing CVD. This review discusses the mechanisms that link hyperlipidemia and NAFLD. In addition, the review focuses on the safety and efficacy of statins in patients with NAFLD or NASH, and their effect on the extent of hepatic steatosis and fibrosis based on human studies.
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Affiliation(s)
- William Nseir
- Department of Internal Medicine, Holy Family Hospital, Faculty of Medicine in the Galilee, Bar-Ilan University, Safed Israel, POB 8, Nazareth, 16100, Israel.
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Okada Y, Yamaguchi K, Nakajima T, Nishikawa T, Jo M, Mitsumoto Y, Kimura H, Nishimura T, Tochiki N, Yasui K, Mitsuyoshi H, Minami M, Kagawa K, Okanoue T, Itoh Y. Rosuvastatin ameliorates high-fat and high-cholesterol diet-induced nonalcoholic steatohepatitis in rats. Liver Int 2013; 33:301-11. [PMID: 23295058 DOI: 10.1111/liv.12033] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2012] [Accepted: 10/16/2012] [Indexed: 02/13/2023]
Abstract
BACKGROUND/AIMS Statins, which are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase and inhibit endogenous cholesterol synthesis, possess pleiotropic activities, such as anti-inflammatory, anti-oxidative and antifibrotic effects. Here, we investigated whether statins ameliorate steatohepatitis using a high-fat and high-cholesterol (HFHC) diet-induced rat model. METHODS Eight-week-old male Sprague-Dawley rats were fed control chow or HFHC diet. Half of the HFHC diet-fed rats were orally administered 2 mg/kg/day rosuvastatin for 12 weeks. Hepatic injury, steatosis, fibrosis and markers of lipid peroxidation/oxidant stress were evaluated. RESULTS As previously reported, HFHC diet induced steatohepatitis in rat livers with hypercholesterolaemia. Rosuvastatin decreased Oil Red O stained-positive areas, liver/body weight ratio, serum total cholesterol levels and hepatic free fatty acid contents in HFHC diet-fed rats. Further study revealed that rosuvastatin significantly decreased hepatic mRNA expression of tumour necrosis factor-α and interleukin-6, serum alanine aminotransferase levels and hepatic lobular inflammation grade. Hepatic fibrosis was also ameliorated by rosuvastatin with decreases in hepatic mRNA expression of transforming growth factor-β, connective tissue growth factor and type-1 procollagen. Similarly, hepatic Sirius red stained or α-smooth muscle actin stained-positive areas and expression of markers of lipid peroxidation/oxidant stress [hepatic 8-hydroxy-oxyguanosine and hepatic 4-hydroxy-2-nonenal] were decreased. Interestingly, whereas the expression of carnitine palmitoyltransferase-1 and long-chain acyl-CoA dehydrogenase was not affected, that of catalase and acyl-coA oxidase was restored. CONCLUSIONS These data suggest that rosuvastatin improved not only hepatic steatosis but also hepatic injury and fibrosis via improved peroxisomal β-oxidation in this rat HFHC model.
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Affiliation(s)
- Yoshihisa Okada
- Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
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Malinowski SS, Byrd JS, Bell AM, Wofford MR, Riche DM. Pharmacologic therapy for nonalcoholic fatty liver disease in adults. Pharmacotherapy 2013; 33:223-42. [PMID: 23359475 DOI: 10.1002/phar.1190] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of triglycerides in hepatocytes in the absence of excessive alcohol intake, ranging in severity from simple steatosis to nonalcoholic steatohepatitis (NASH). Nonalcoholic steatohepatitis can ultimately progress to cirrhosis and hepatocellular carcinoma. NAFLD is associated with cardiometabolic risk factors and is the most common chronic liver disease among adults in the Western Hemisphere. Although simple steatosis is generally considered a self-limiting disease, evidence suggests an increased risk of cardiovascular disease, and, less conclusively, mortality, among individuals with NAFLD and/or NASH. The current standard of care for the treatment of patients with NAFLD focuses on lifestyle interventions, particularly diet and exercise. There is a lack of consensus regarding the most effective and appropriate pharmacologic therapy. A PubMed search was conducted using the medical subject heading terms "fatty liver" and "steatohepatitis." This review focuses on the current pharmacologic options available for treating adults with NAFLD and/or NASH. Continued investigation of drugs or combinations that improve NAFLD progression is crucial. Clinicians, particularly pharmacists, must take an active role in identification and appropriate selection of pharmacotherapy for NAFLD.
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Affiliation(s)
- Scott S Malinowski
- Department of Pharmacy Practice, School of Pharmacy, University of Mississippi, Jackson, USA
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Brea A, Puzo J. Non-alcoholic fatty liver disease and cardiovascular risk. Int J Cardiol 2012; 167:1109-17. [PMID: 23141876 DOI: 10.1016/j.ijcard.2012.09.085] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2012] [Revised: 05/26/2012] [Accepted: 09/15/2012] [Indexed: 02/07/2023]
Abstract
The term "Non-alcoholic fatty liver disease" (NAFLD) covers a series of liver lesions similar to those induced by alcohol, but not caused by alcohol use. The importance of NAFLD lies in the high prevalence in Western societies and, from the point of view of the liver, in its progression from steatosis to cirrhosis and liver cancer. More recently, NAFLD has been found to be associated with lipid metabolism disorders, the deposition of fat outside of the adipocytes, insulin resistance and Metabolic Syndrome. Also attributed to NAFLD is a heightened systemic pro-inflammatory state, which accelerates arteriosclerosis, thereby increasing cardiovascular risk and associated cardiovascular events. Here we provide an update to the etiopathogenesis of NAFLD, its influence on cardiovascular disease, and the treatment options.
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Affiliation(s)
- Angel Brea
- Unidad de Lípidos, Servicio de Medicina Interna, Hospital San Pedro, Logroño, Spain
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Nakahara T, Hyogo H, Kimura Y, Ishitobi T, Arihiro K, Aikata H, Takahashi S, Chayama K. Efficacy of rosuvastatin for the treatment of non-alcoholic steatohepatitis with dyslipidemia: An open-label, pilot study. Hepatol Res 2012; 42:1065-72. [PMID: 22583925 DOI: 10.1111/j.1872-034x.2012.01034.x] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
AIM Statins, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, are reported to be useful for the treatment of non-alcoholic steatohepatitis (NASH). Currently, there is no proven therapy for NASH. In this study, we assessed the efficacy of rosuvastatin in NASH patients with dyslipidemia. METHODS Nineteen patients with biopsy-proven NASH with dyslipidemia who agreed to participate in this prospective study were enrolled. The patients were treated for 24 months with 2.5 mg/day rosuvastatin. Clinical and histological alterations were comparatively evaluated before and after treatment. Standard weight-loss counseling was continued during the treatment period. Follow-up liver biopsy was performed in nine patients. RESULTS Twenty-six percent of patients had hyperlipoproteinemia type IIa and 74% had hyperlipoproteinemia type IIb at baseline. Body mass indices were not significantly changed during the treatment. The levels of transaminases were relatively low at the beginning, and were not significantly changed during the treatment. Lipid profiles were significantly improved by the treatment with rosuvastatin for 24 months. While non-alcoholic fatty liver disease activity score and fibrotic stage did not change significantly in all patients, they were improved in 33.3% and 33.3% individual patients, and stayed stable in 33.3% and 55.6%, respectively. CONCLUSION NASH-related metabolic parameters improved with therapy including histology in some patients. However, one of nine patients had progression of fibrosis during the treatment. Our pilot study demonstrated the efficacy of rosuvastatin for the treatment of NASH with dyslipidemia, even if transaminases are not so elevated and controlled trials are needed in the future.
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Affiliation(s)
- Takashi Nakahara
- Departments of Medicine and Molecular Science, Pathology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
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Ono M. Is rosuvastatin effective for non-alcoholic steatohepatitis with dyslipidemia? Hepatol Res 2012; 42:1055-7. [PMID: 23094853 DOI: 10.1111/j.1872-034x.2012.01052.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Nseir W, Mograbi J, Ghali M. Lipid-lowering agents in nonalcoholic fatty liver disease and steatohepatitis: human studies. Dig Dis Sci 2012; 57:1773-1781. [PMID: 22419057 DOI: 10.1007/s10620-012-2118-3] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2011] [Accepted: 02/22/2012] [Indexed: 02/07/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease which refers to the presence of hepatic steatosis without significant intake of alcohol. NAFLD is an asymptomatic disease that can progress to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. NAFLD is currently the most common cause of incidental abnormal liver tests and elevated serum liver enzyme activities in the developed world. Obesity, diabetes, and other components of the metabolic syndrome are frequently associated with the NAFLD. The treatment of NAFLD focuses on life-style modifications. Statins, fibrates, and other lipid-lowering agents have been proposed as effective lipid-lowering treatments in patients with NAFLD/NASH. However, clinicians are concerned that hyperlipidemic patients with NAFLD/NASH who are treated with statins could develop transaminitis. We assessed the efficacy and safety of lipid-lowering agents for NAFLD/NASH by reviewing reports of human studies including pilot, prospective, preliminary, and post hoc analysis studies on online databases during the period of 1980 to December 2012. The results of studies provide compelling evidence that lipid-lowering agents are safe and efficacious in patients with NAFLD/NASH and that some of these agents can induce a reduction in the extent of the hepatic steatosis. Well-designed randomized controlled studies of adequate size and duration with histological endpoints are needed in order to establish a suitable lipid-lowering treatment for hyperlipidemic patients with NAFLD/NASH, and for nonhyperlipidemic patients with NAFLD/NASH with a high risk for cardiovascular disease.
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Affiliation(s)
- William Nseir
- Department of Internal Medicine, Holy Family Hospital, Nazareth, Israel.
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40
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Miura K, Ohnishi H. Nonalcoholic fatty liver disease: from lipid profile to treatment. Clin J Gastroenterol 2012; 5:313-21. [DOI: 10.1007/s12328-012-0315-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2012] [Accepted: 05/24/2012] [Indexed: 02/06/2023]
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Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of non-alcoholic fatty liver disease: Practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Am J Gastroenterol 2012; 107:811-26. [PMID: 22641309 DOI: 10.1038/ajg.2012.128] [Citation(s) in RCA: 303] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Naga Chalasani
- Indiana University School of Medicine, Indianapolis, 46202, USA.
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42
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Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 2012; 55:2005-23. [PMID: 22488764 DOI: 10.1002/hep.25762] [Citation(s) in RCA: 2602] [Impact Index Per Article: 200.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Affiliation(s)
- Naga Chalasani
- Indiana University School of Medicine, Indianapolis, IN, USA.
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43
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Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology 2012; 142:1592-609. [PMID: 22656328 DOI: 10.1053/j.gastro.2012.04.001] [Citation(s) in RCA: 1346] [Impact Index Per Article: 103.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2012] [Indexed: 02/06/2023]
Affiliation(s)
- Naga Chalasani
- Indiana University School of Medicine, Indianapolis, IN 46202, USA.
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44
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Li JJ, Lu ZL, Kou WR, Bolli R, Chen Z, Wu YF, Yu XH, Zhao YC. Impact of long-term Xuezhikang therapy on cardiovascular events in high-risk patients with nonspecific, preexisting abnormal liver tests: a post-hoc analysis from Chinese Coronary Secondary Prevention Study (CCSPS). Int J Cardiol 2012; 154:362-365. [PMID: 22133469 DOI: 10.1016/j.ijcard.2011.11.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2011] [Accepted: 11/04/2011] [Indexed: 11/24/2022]
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Abstract
Patients with nonalcoholic fatty liver disease (NAFLD) often have dyslipidemia along with other features of metabolic syndrome such as obesity, diabetes mellitus, and hypertension. The dyslipidemia in NAFLD is characterized by increased serum triglycerides, increased small, dense low-density lipoprotein (LDL nontype A) particles, and low high-density lipoprotein (HDL) cholesterol. The pathogenesis of dyslipidemia in NAFLD is not well understood, but it is likely related to hepatic overproduction of the very low-density lipoprotein particles and dysregulated clearance of lipoproteins from the circulation. There is unequivocal evidence that cardiovascular disease is the most common cause of mortality in patients with NAFLD. Aggressive treatment of dyslipidemia plays a critical role in the overall management of patients with NAFLD. Statins are the first-line agents to treat high cholesterol and their dosage should be adjusted based on achieving therapeutic targets and tolerability. Although all statins appear to be effective in improving cholesterol levels in patients with NAFLD, there is more experience with atorvastatin in patients with NAFLD; furthermore, it is the only statin to date to show a reduced cardiovascular morbidity in patients with NAFLD. The risk for serious liver injury from statins is quite rare and patients with NAFLD are not at increased risk for statin hepatotoxicity. Omega-3 fatty acids are perhaps the first choice to treat hypertriglyceridemia because of their safety, tolerability, and efficacy in improving serum triglycerides, as well as their potential to improve liver disease.
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Affiliation(s)
- Hemant Chatrath
- Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana
| | - Raj Vuppalanchi
- Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana
| | - Naga Chalasani
- Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana
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46
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Nobili V, Sanyal AJ. Treatment of nonalcoholic fatty liver disease in adults and children: a closer look at the arsenal. J Gastroenterol 2012; 47:29-36. [PMID: 21983927 DOI: 10.1007/s00535-011-0467-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2011] [Accepted: 07/28/2011] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease encompasses a spectrum of disease from asymptomatic steatosis, with or without elevated aminotransferases, to cirrhosis with relative complications and hepatocellular carcinoma. Owing to the increasing prevalence of nonalcoholic fatty liver disease and the potential for nonalcoholic steatohepatitis to progress to cirrhosis and liver-related mortality, more research has been focused on therapy of this important liver disease over the last two decades. To date, weight loss and physical activity represent the cornerstone of treatment, with interventions being limited to subjects at risk of disease progression, but the type of treatment remains a matter of debate. A few medications have shown promising results in preliminary pilot studies, but few agents have been tested rigorously. Today, multiple therapeutic approaches are considered the way to go in treating nonalcoholic steatohepatitis patients. In this paper we review the status of current and emerging therapeutic strategies for children and adult patients with nonalcoholic steatohepatitis.
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Affiliation(s)
- Valerio Nobili
- Unit of Metabolic and Autoimmune Liver Diseases, Pediatric Hospital Bambino Gesù, IRCCS, Square S. Onofrio 4, 00165, Rome, Italy.
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47
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Nseir W, Shalata A, Marmor A, Assy N. Mechanisms linking nonalcoholic fatty liver disease with coronary artery disease. Dig Dis Sci 2011; 56:3439-3449. [PMID: 21655948 DOI: 10.1007/s10620-011-1767-y] [Citation(s) in RCA: 67] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2011] [Accepted: 05/18/2011] [Indexed: 02/08/2023]
Abstract
The most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD) is coronary artery disease (CAD), not chronic liver disease. Fatty liver increases cardiovascular risk by classical (dyslipidemia, hypertension, diabetes) and by less conventional mechanisms. Common pathways involved in the pathogenesis of fatty liver and CAD includes hepatic insulin resistance and sub clinical inflammation. The hepatic insulin resistance state of fatty liver infiltration is characterized by increased FFA, which causes lipotoxicity and impairs endothelium-dependent vasodilatation, increases oxidative stress, and has a cardio toxic effect. Additional metabolic risk factors include leptin, adiponectin, pro inflammatory cytokines [such as IL-6, C-reactive protein and plasminogen activator inhibitor-1 (PAI-1)], which together lead to increased oxidative stress and endothelial dysfunction, finally promoting coronary artery disease (CAD). When classical risk factors are superimposed on fatty liver accumulation, they may further increase the new metabolic risk factors, exacerbating CAD. The clinical implication is that patients with NAFLD are at higher risk (steatohepatitis, diabetes, obesity, atherogenic dyslipidemia) and should undergo periodic cardiovascular risk assessment including the Framingham score, cardiac effort test, and measurement of intimae-media thickening of the carotids arteries. This may improve risk stratification for CAD.
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Affiliation(s)
- W Nseir
- Department of Internal Medicine, Holy Family Hospital, Nazareth, Israel
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48
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Hyogo H, Ikegami T, Tokushige K, Hashimoto E, Inui K, Matsuzaki Y, Tokumo H, Hino F, Tazuma S. Efficacy of pitavastatin for the treatment of non-alcoholic steatohepatitis with dyslipidemia: An open-label, pilot study. Hepatol Res 2011; 41:1057-65. [PMID: 21951922 DOI: 10.1111/j.1872-034x.2011.00849.x] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
AIM Non-alcoholic fatty liver disease (NAFLD) that encompasses a spectrum of liver disorders characterized by simple steatosis, non-alcoholic steatohepatitis (NASH) through cirrhosis, is becoming an important chronic liver disease in Japan. Currently, there is no proven therapy for NASH. In this study, we assessed the efficacy of statin therapy in NASH patients with dyslipidemia. METHODS Twenty patients with biopsy-proven NASH with dyslipidemia who agreed to participate in this multicentric prospective study were enrolled. The patients were treated for 12 months with pitavastatin 2 mg/day. Clinical and histological alterations were comparatively evaluated before and after treatment. Standard weight loss counseling was continued during the treatment period. Follow-up liver biopsy was performed in 13 patients. RESULTS Twenty-five percent of patients had hyperlipoproteinemia type IIa and 75% had hyperlipoproteinemia type IIb at baseline. The levels of alanine aminotransferase, γ-glutamyl transpeptidase and lipid profiles were significantly improved by the treatment with pitavastatin for 12 months. Especially, these improvements were prominent in NASH patients with hyperlipoproteinemia type IIb. While non-alcoholic fatty liver disease activity score and fibrosis stage did not change significantly in all patients, they did improve in 54% and 42% in individual patients, respectively. CONCLUSION NASH-related metabolic parameters improved with therapy including histology in some patients. However, three of 13 patients had progression of fibrosis during the treatment. Our pilot study demonstrated the efficacy of pitavastatin for the treatment of NASH with dyslipidemia, especially with hyperlipoproteinemia type IIb and controlled trials are needed in the future.
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Affiliation(s)
- Hideyuki Hyogo
- Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University Department of Gastroenterology and Hepatology, Hiroshima General Hospital Department of Gastroenterology and Hepatology, Onomichi General Hospital Department of General Medicine, Hiroshima University Graduate School of Medical Science, Programs of Applied Medicine, Clinical Pharmacotherapy, Hiroshima Division of Gastroenterology and Hepatology, Tokyo Medical University, Ibaraki Department of Internal Medicine and Gastroenterology, Tokyo Women's Medical University, Tokyo Department of Internal Medicine, Second Teaching Hospital, Fujita Health University School of Medicine, Aichi, Japan
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49
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Tzefos M, Olin JL. 3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitor use in chronic liver disease: A therapeutic controversy. J Clin Lipidol 2011; 5:450-9. [DOI: 10.1016/j.jacl.2011.06.013] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2011] [Revised: 06/19/2011] [Accepted: 06/21/2011] [Indexed: 02/07/2023]
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50
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Darwish IA, Al-Obaid ARM, Al-Malaq HA. Validated enzyme-linked immunosorbent assay for determination of rosuvastatin in plasma at picogram level. Drug Test Anal 2011; 5:334-9. [DOI: 10.1002/dta.328] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2011] [Revised: 06/17/2011] [Accepted: 06/17/2011] [Indexed: 11/12/2022]
Affiliation(s)
- Ibrahim A Darwish
- Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO Box 2457, Riyadh, 11451, Saudi Arabia.
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