Efficacy of statins in treatment and development of non-alcoholic fatty liver disease and steatohepatitis: A systematic review and meta-analysis

Fatima, Kaneez; Moeed, Abdul; Waqar, Eisha; Atif, Abdul Raafe; Kamran, Alishba; Rizvi, Hura; Suri, Noor Fatima; Haider, Hoorain; Shuja, Syed Hasan; Khalid, Mariam; Minhas, Abdul Mannan Khan

doi:10.1016/j.clinre.2021.101816

Cited by 29 publications

(26 citation statements)

References 32 publications

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“…While maintaining a healthy lifestyle should always be a cornerstone in the management of patients with NAFLD, those with the lipid-liver phenotype could most benefit from novel therapies targeting cholesterol and liver physiology. [15][16][17] The average phenotype was the most frequent. This signals a group of patients with NAFLD who should be carefully monitored, though, perhaps, not with the same frequency or intensity as for the other phenotypes in which risk factors levels were higher and had higher all-cause mortality risk.…”

Section: Resultsmentioning

confidence: 99%

“…9 Despite this high disease burden, there are no specific treatments for NAFLD other than managing the underlying conditions such as obesity or T2DM together with recommendations for healthy lifestyles. [10][11][12][13][14] Consistent with the global call for precision medicine and public health, a way to maximise the benefits of available and forthcoming [15][16][17] treatments for NAFLD, could be to identify phenotypes in patients with NAFLD. Therefore, specific management plans can be proposed according to the underlying profile of each phenotype.…”

Section: Introductionmentioning

confidence: 99%

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Phenotypes of non-alcoholic fatty liver disease (NAFLD) and all-cause mortality: unsupervised machine learning analysis of NHANES III

et al. 2022

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ObjectivesNon-alcoholic fatty liver disease (NAFLD) is a non-communicable disease with a rising prevalence worldwide and with large burden for patients and health systems. To date, the presence of unique phenotypes in patients with NAFLD has not been studied, and their identification could inform precision medicine and public health with pragmatic implications in personalised management and care for patients with NAFLD.DesignCross-sectional and prospective (up to 31 December 2019) analysis of National Health and Nutrition Examination Survey III (1988–1994).Primary and secondary outcomes measuresNAFLD diagnosis was based on liver ultrasound. The following predictors informed an unsupervised machine learning algorithm (k-means): body mass index, waist circumference, systolic blood pressure (SBP), plasma glucose, total cholesterol, triglycerides, liver enzymes alanine aminotransferase, aspartate aminotransferase and gamma glutamyl transferase. We summarised (means) and compared the predictors across clusters. We used Cox proportional hazard models to quantify the all-cause mortality risk associated with each cluster.Results1652 patients with NAFLD (mean age 47.2 years and 51.5% women) were grouped into 3 clusters: anthro-SBP-glucose (6.36%; highest levels of anthropometrics, SBP and glucose), lipid-liver (10.35%; highest levels of lipid and liver enzymes) and average (83.29%; predictors at average levels). Compared with the average phenotype, the anthro-SBP-glucose phenotype had higher all-cause mortality risk (aHR=2.88; 95% CI: 2.26 to 3.67); the lipid-liver phenotype was not associated with higher all-cause mortality risk (aHR=1.11; 95% CI: 0.86 to 1.42).ConclusionsThere is heterogeneity in patients with NAFLD, whom can be divided into three phenotypes with different mortality risk. These phenotypes could guide specific interventions and management plans, thus advancing precision medicine and public health for patients with NAFLD.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Phenotypes of non-alcoholic fatty liver disease (NAFLD) and all-cause mortality: unsupervised machine learning analysis of NHANES III

et al. 2022

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Section: Interventions To Prevent Nafld/nash-associated Hccmentioning

confidence: 99%

“…Statins: Two recent meta-analyses of observational and interventional studies have confirmed liver safety for statin use in patients with NAFLD and even a reduction of transaminases levels[ 197 , 198 ]. Moreover, the meta-analysis by Fatima et al [ 198 ], which also analyzed the liver histology outcomes, reported a significant reduction of steatosis grade, necro-inflammatory stage, and of significant fibrosis but not the fibrosis stage. Several meta-analyses (mostly of observational studies) have consistently reported reduced risk of HCC in statin users (RRs/ORs/HR between 0.52-0.75 for all statins), with some indication of differences between them[ 199 - 208 ].…”

Section: Interventions To Prevent Nafld/nash-associated Hccmentioning

confidence: 99%

Screening and interventions to prevent nonalcoholic fatty liver disease/nonalcoholic steatohepatitis-associated hepatocellular carcinoma

Onişor¹

2023

World J Gastroenterol

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Liver cancer is the sixth most commonly diagnosed cancer worldwide, with hepatocellular carcinoma (HCC) comprising most cases. Besides hepatitis B and C viral infections, heavy alcohol use, and nonalcoholic steatohepatitis (NASH)-associated advanced fibrosis/cirrhosis, several other risk factors for HCC have been identified ( i.e. old age, obesity, insulin resistance, type 2 diabetes). These might in fact partially explain the occurrence of HCC in non-cirrhotic patients without viral infection. HCC surveillance through effective screening programs is still an unmet need for many nonalcoholic fatty liver disease (NAFLD) patients, and identification of pre-cirrhotic individuals who progress to HCC represents a substantial challenge in clinical practice at the moment. Patients with NASH-cirrhosis should undergo systematic HCC surveillance, while this might be considered in patients with advanced fibrosis based on individual risk assessment. In this context, interventions that potentially prevent NAFLD/ NASH-associated HCC are needed. This paper provided an overview of evidence related to lifestyle changes ( i.e. weight loss, physical exercise, adherence to healthy dietary patterns, intake of certain dietary components, etc. ) and pharmacological interventions that might play a protective role by targeting the underlying causative factors and pathogenetic mechanisms. However, well-designed prospective studies specifically dedicated to NAFLD/NASH patients are still needed to clarify the relationship with HCC risk.

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“…In a study using data from the National Health Information database of South Korea, statin treatment decreased not only the risk of NAFLD occurrence but also the development of fibrosis attributed to NAFLD, regardless of diabetes mellitus [ 173 ]. A meta-analysis by Fatima et al [ 174 ] reported that statin treatment reduced the risk of NAFLD development (OR, 0.69; 95% CI, 0.57–0.84; I 2 =36%; P =0.0002); ALT and GGT levels; and histologic grades with steatosis, inflammation, and fibrosis. There was also a report that statin treatment reduced the HCC risk in patients with NAFLD (HR, 0.47; 95% CI, 0.36–0.60) [ 175 ].…”

Section: Statinmentioning

confidence: 99%

Therapeutic mechanisms and beneficial effects of non-antidiabetic drugs in chronic liver diseases

et al. 2022

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The global burden of chronic liver disease (CLD) is substantial. Due to the limited indication of and accessibility to antiviral therapy in viral hepatitis and lack of effective pharmacological treatment in nonalcoholic fatty liver disease, the beneficial effects of antidiabetics and non–antidiabetics in clinical practice have been continuously investigated in patients with CLD. In this narrative review, we focused on non-antidiabetic drugs, including ursodeoxycholic acid, silymarin, dimethyl4,4’-dimethoxy-5,6,5’,6’-dimethylenedixoybiphenyl-2,2’-dicarboxylate, L-ornithine L-aspartate, branched chain amino acids, statin, probiotics, vitamin E, and aspirin, and summarized their beneficial effects in CLD. Based on the antioxidant, anti-inflammatory properties, and regulatory functions in glucose or lipid metabolism, several non–antidiabetic drugs have shown beneficial effects in improving liver histology, aminotransferase level, and metabolic parameters and reducing risks of hepatocellular carcinoma and mortality, without significant safety concerns, in patients with CLD. Although the effect as the centerpiece management in patients with CLD is not robust, the use of these non-antidiabetic drugs might be potentially beneficial as an adjuvant or combined treatment strategy.

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Efficacy of statins in treatment and development of non-alcoholic fatty liver disease and steatohepatitis: A systematic review and meta-analysis

Cited by 29 publications

References 32 publications

Phenotypes of non-alcoholic fatty liver disease (NAFLD) and all-cause mortality: unsupervised machine learning analysis of NHANES III

Phenotypes of non-alcoholic fatty liver disease (NAFLD) and all-cause mortality: unsupervised machine learning analysis of NHANES III

Screening and interventions to prevent nonalcoholic fatty liver disease/nonalcoholic steatohepatitis-associated hepatocellular carcinoma

Therapeutic mechanisms and beneficial effects of non-antidiabetic drugs in chronic liver diseases

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