Efficacy of long-term ezetimibe therapy in patients with nonalcoholic fatty liver disease

Park, Hyohun; Shima, Toshihide; Yamaguchi, Kanji; Mitsuyoshi, Hironori; Minami, Masahito; Yasui, Kohichiroh; Itoh, Yoshito; Yoshikawa, Toshikazu; Fukui, Michiaki; Hasegawa, Goji; Nakamura, Naoto; Ohta, Mitsuhiro; Obayashi, Hiroshi; Okanoue, Takeshi

doi:10.1007/s00535-010-0291-8

Cited by 170 publications

(131 citation statements)

References 46 publications

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“…Third, the average serum aminotransferase levels were lower than those in previous studies [9,10], and most of the patients had mild steatosis, fibrosis and lower NAS at baseline before ezetimibe treatment. Serum ALT levels did not decrease with ezetimibe treatment in the present study, in contrast to the significant improvement reported previously [9,10]. And finally, secondary outcomes are always at risk of false-positive associations.…”

Section: Discussionmentioning

confidence: 62%

“…Indeed, a 6 month duration may be too short a period to expect improvement of fibrosis, which is a slowly ND, not determined progressive process [40]. Third, the average serum aminotransferase levels were lower than those in previous studies [9,10], and most of the patients had mild steatosis, fibrosis and lower NAS at baseline before ezetimibe treatment. Serum ALT levels did not decrease with ezetimibe treatment in the present study, in contrast to the significant improvement reported previously [9,10].…”

Section: Discussionmentioning

confidence: 89%

“…Indeed, ezetimibe improves liver steatosis and insulin resistance in mice [7] and Zucker obese fatty rats [8], although the beneficial effects of ezetimibe are observed only when the animals are fed a high-fat diet. Ezetimibe can also ameliorate liver pathology in patients with NAFLD [9,10]; however, these studies lack a control group, which precludes meaningful conclusions as liver pathology can improve over the natural course of the disease or with tight glycaemic control in some NAFLD patients [1]. In the present study, we investigated the efficacy of ezetimibe treatment in patients with NAFLD for 6 months in an open-label randomised control study by examining liver pathology, as well as hepatic enzymes, glucose metabolism, hepatic fatty acid composition and hepatic gene expression profiles.…”

Section: Introductionmentioning

confidence: 99%

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The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism: a randomised controlled trial

et al. 2014

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Aims/hypothesis The cholesterol absorption inhibitor ezetimibe has been shown to ameliorate non-alcoholic fatty liver disease (NAFLD) pathology in a single-armed clinical study and in experimental animal models. In this study, we investigated the efficacy of ezetimibe on NAFLD pathology in an open-label randomised controlled clinical trial. Methods We had planned to enrol 80 patients in the trial, as we had estimated that, with this sample size, the study would have 90% power. The study intervention and enrolment were discontinued because of the higher proportion of adverse events (significant elevation in HbA 1c ) in the ezetimibe group than in the control group. Thirty-two patients with NAFLD were enrolled and randomised (allocation by computer program). Ezetimibe (10 mg/day) was given to 17 patients with NAFLD for 6 months. The primary endpoint was change in serum aminotransferase level. Secondary outcomes were change in liver histology (12 control and 16 ezetimibe patients), insulin sensitivity including a hyperinsulinaemic-euglycaemic clamp study (ten control and 13 ezetimibe patients) and hepatic fatty acid composition (six control and nine ezetimibe patients). Hepatic gene expression profiling was completed in 15 patients using an Affymetrix gene chip. Patients and the physician in charge knew to which group the patient had been allocated, but people carrying out measurements or examinations were blinded to group. Results Serum total cholesterol was significantly decreased in the ezetimibe group. The fibrosis stage and ballooning score were also significantly improved with ezetimibe treatment. However, ezetimibe treatment significantly increased HbA 1c and was associated with a significant increase in hepatic longchain fatty acids. Hepatic gene expression analysis showed coordinate downregulation of genes involved in skeletal muscle development and cell adhesion molecules in the ezetimibe treatment group, suggesting a suppression of stellate cell development into myofibroblasts. Genes involved in the L-carnitine pathway were coordinately downregulated by ezetimibe treatment and those in the steroid metabolism pathway upregulated, suggestive of impaired oxidation of long-chain fatty acids. Conclusions/interpretation Ezetimibe improved hepatic fibrosis but increased hepatic long-chain fatty acids and HbA 1c in patients with NAFLD. These findings shed light on previously unrecognised actions of ezetimibe that should be examined further in future studies.

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

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The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism: a randomised controlled trial

et al. 2014

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“…77,101 The newer agent ezetimibe, which acts through inhibiting cholesterol absorption, has shown promising effects, especially in association with acarbose, but further results are needed in order to enable its use to be validated as a current recommendation. [111][112][113][114] There is a lack of conclusive evidence supporting the use of ursodeoxycholic acid, N-3 polyunsaturated fatty acids, angiotensin receptor blockers, probiotics and synbiotics as validated treatment options for NAFLD.…”

Section: 107-110mentioning

confidence: 99%

Nonalcoholic fatty liver disease and bariatric surgery: a comprehensive review

2017

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CONTEXT AND OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) has been increasingly diagnosed worldwide and is now recognized as a source of public health concern. It comprises a wide spectrum of histological features that range from simple steatosis to severe forms of fibrosis, steatohepatitis and even cirrhosis. The impact of bariatric surgery on the course of NAFLD in individuals with obesity has been extensively studied. DESIGN AND SETTING: Narrative review; public university hospital. METHODS: A comprehensive review was conducted based on an online search on the electronic databases MEDLINE and LILACS using the MeSH terms "fatty liver" and "bariatric surgery". RESULTS:The exact mechanisms that lead to improvement in NAFLD following bariatric surgery are not completely understood. Since Roux-en-Y gastric bypass (RYGB) is the bariatric surgical procedure most performed worldwide, it is also the one from which the effects on NAFLD have been most studied, although there is also consistent evidence regarding the effects from gastric banding, sleeve gastrectomy and biliopancreatic diversions. CONCLUSION: According to the currently available evidence, bariatric surgery leads to significant improvement in NAFLD. Further research, especially by means of randomized controlled trials enrolling larger cohorts of individuals, is needed to determine the optimal procedure for this group of subjects. RESUMO CONTEXTO E OBJETIVO:A doença hepática gordurosa não alcoólica (DHGNA) tem sido diagnosticada com maior frequência em todo o mundo na atualidade, sendo agora reconhecida como motivo de preocupação em saúde pública. Abrange um amplo espectro de alterações histológicas que variam desde a simples esteatose até formas graves de fibrose, esteato-hepatite e até cirrose. O impacto da cirurgia bariátrica sobre o curso da DHGNA em indivíduos com obesidade tem sido profundamente estudado. TIPO DE ESTUDO E LOCAL: Revisão narrativa; hospital universitário público. MÉTODOS: Uma revisão abrangente da literatura foi conduzida baseada na pesquisa on-line nas bases de dados eletrônicas MEDLINE e LILACS por meio dos termos MeSH "fígado gorduroso" e "cirurgia bariátrica". RESULTADOS: Os mecanismos exatos que levam à melhora da DHGNA após a cirurgia bariátrica não são completamente conhecidos. Como o bypass gástrico em Y de Roux é a cirurgia bariátrica mais realizada em todo o mundo, é também o procedimento cujos efeitos sobre DHGNA foram mais estudados, embora haja também evidências consistentes sobre os efeitos de banda gástrica, gastrectomia vertical e derivações biliopancreáticas. CONCLUSÃO: De acordo com as evidências atualmente disponíveis, a cirurgia bariátrica leva à melhora significativa da DHGNA. Mais estudos, especialmente por meio de ensaios clínicos randomizados e controlados, recrutando coortes maiores de indivíduos, são necessários para determinar o melhor procedimento para esse grupo de pacientes.

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“…Studies have explored ezetimbe monotherapy or in combination with other agents such as statins and acarbose, which in general, showed improvement in aminotransaminases and lipid profile and NAS on histology. However, there was no significant effect on fibrosis [76,77]. A subsequent and only RCT to date that evaluated ezetimibe in NAFLD with post treatment histology reported significant improvement in histological ballooning and fibrosis from baseline, but there were no significant histological differences compared to placebo.…”

Section: Lipid Lowering Agentsmentioning

confidence: 97%

Pharmacologic Management of Non-Alcoholic Fatty Liver Disease

Goh¹,

Dasarathy²,

McCullough³

2014

Adv Pharmacoepidemiol Drug Saf

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Background: Non-alcoholic fatty liver disease (NAFLD) is a common complex chronic liver disease that encompasses a spectrum of disease from simple steatosis to non-alcoholic steatohepatitis (NASH). NASH has the potential to progress to advanced fibrosis and cirrhosis and is associated with increased morbidity and mortality. Currently, there are no definitive universally accepted treatment options available for NASH. Most pharmacological agents that have been investigated are limited by inconsistent efficacy or side effects. We reviewed the current literature on the principle drugs that have been tested for NAFLD in the adult population, with special emphasis on clinical data and safety profiles. Methods:A comprehensive PUBMED/MEDLINE search was conducted to identify principal therapeutic intervention studies for NAFLD, from which a summary of the studies were formulated in this review. Results:A variety of studies, including retrospective, open-label and randomised controlled trials were reviewed in terms of clinical efficacy and side effect profiles. In addition to the most commonly studied therapeutic agents (insulin sensitizers, vitamin E, pentoxifylline, UDCA, PUFA, statins and ezetimibe), emerging pharmacologic agents showing potential efficacy in NAFLD were also explored. Conclusion:Based on risk-benefit profiles, pentoxifylline seems to have the best treatment outcomes currently, with significant improvement in histology while having minimal tolerable side effects. Further clinical research is warranted to understand and improve our repertoire of treatment options, including potential combination therapy, towards this complex disease.

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Efficacy of long-term ezetimibe therapy in patients with nonalcoholic fatty liver disease

Abstract: The results in this study suggest that the long-term EZ therapy can lead to improvement in metabolic, biochemical, and histological abnormalities of NAFLD. Therefore, EZ may be a promising agent for treatment of NAFLD.

Cited by 170 publications

References 46 publications

The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism: a randomised controlled trial

The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism: a randomised controlled trial

Nonalcoholic fatty liver disease and bariatric surgery: a comprehensive review

Pharmacologic Management of Non-Alcoholic Fatty Liver Disease

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