Advanced fibrosis associates with atherosclerosis in subjects with nonalcoholic fatty liver disease

Chen, Ying; Xu, Min; Wang, Tiange; Sun, Jichao; Sun, Wanwan; Xu, Bo; Huang, Xiaolin; Xu, Yu; Lu, Jieli; Li, Xiaoying; Wang, Weiqing; Bi, Yufang; Ning, Guang

doi:10.1016/j.atherosclerosis.2015.05.002

Cited by 69 publications

(43 citation statements)

References 29 publications

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“…3 In some studies, NAFLD with advanced fibrosis was more M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 13 strongly associated with atherosclerosis than NAFLD without fibrosis. 30,31 In our study, participants with high NAFLD fibrosis or FIB-4 scores had a higher risk of subclinical carotid atherosclerosis development. Participants with NAFLD and elevated baseline GGT, however, showed an increased risk of subclinical carotid atherosclerosis development, and persistently elevated GGT levels were associated with the risk of subclinical carotid atherosclerosis.…”

Section: Discussionmentioning

confidence: 94%

Persistent Nonalcoholic Fatty Liver Disease Increases Risk for Carotid Atherosclerosis

et al. 2016

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Section: Discussionmentioning

confidence: 94%

Persistent Nonalcoholic Fatty Liver Disease Increases Risk for Carotid Atherosclerosis

et al. 2016

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“…The entity of this NAFLD-related proatherogenic risk is probably linked to the severity of hepatic fibrosis[35], the degree of fatty liver[36], or both. More importantly, follow-up studies have consistently shown that CVD is the leading cause of mortality in NAFLD patients[37,38].…”

Section: Nafldmentioning

confidence: 99%

Fatty liver is associated with an increased risk of diabetes and cardiovascular disease - Evidence from three different disease models: NAFLD, HCV and HIV

Lonardo¹,

Ballestri²,

Guaraldi³

et al. 2016

WJG

101

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Fatty liver, which frequently coexists with necro-inflammatory and fibrotic changes, may occur in the setting of nonalcoholic fatty liver disease (NAFLD) and chronic infections due to either hepatitis C virus (HCV) or human immunodeficiency virus (HIV). These three pathologic conditions are associated with an increased prevalence and incidence of cardiovascular disease (CVD) and type 2 diabetes (T2D). In this multidisciplinary clinical review, we aim to discuss the ever-expanding wealth of clinical and epidemiological evidence supporting a key role of fatty liver in the development of T2D and CVD in patients with NAFLD and in those with HCV or HIV infections. For each of these three common diseases, the epidemiological features, pathophysiologic mechanisms and clinical implications of the presence of fatty liver in predicting the risk of incident T2D and CVD are examined in depth. Collectively, the data discussed in this updated review, which follows an innovative comparative approach, further reinforce the conclusion that the presence of fatty/inflamed/fibrotic liver might be a shared important determinant for the development of T2D and CVD in patients with NAFLD, HCV or HIV. This review may also open new avenues in the clinical and research arenas and paves the way for the planning of future, well-designed prospective and intervention studies.

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“…Indeed, the severity of fibrosis in NAFLD is thought to be the most important histological variable for predicting mortality [33,34], including cardiovascular mortality [35]. It has also been linked to increased epicardial fat thickness, and abnormal cardiac geometry and function [36] and markers of subclinical atherosclerosis [37,38].…”

mentioning

confidence: 99%

Opposite associations between alanine aminotransferase and γ-glutamyl transferase levels and all-cause mortality in type 2 diabetes: Analysis of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study

et al. 2016

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Opposite associations between alanine aminotransferase and γ-glutamyl transferase levels and all-cause mortality in type 2 diabetes: analysis of the fenofibrate intervention and event lowering in diabetes (FIELD) study Kathryn H. Williams, David R. Sullivan, Geoffrey C. Nicholson, Jacob George, Alicia J. Jenkins, Andrzej S. Januszewski, Val J. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (2) 9562 5304; E-mail: fieldtrial@ctc.usyd.edu.au. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT3 Abstract AimsReported associations between liver enzymes and mortality may not hold true in type 2 diabetes, owing to a high prevalence of non-alcoholic fatty liver disease, which has been linked to cardiovascular disease and mortality in its own right. Our study aimed to determine whether alanine aminotransferase (ALT) or γ-glutamyl transferase (GGT) levels predict mortality in type 2 diabetes, and to examine possible mechanisms. MethodsData from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study were analysed to examine the relationship between liver enzymes and all-cause and cause-specific mortality over 5 years. ResultsOver 5 years, 679 (6.9%) individuals died. After adjustment, for every standard deviation increase in ALT (13.2U/L), the HR for death on study was 0.85 (95% CI 0.78-0.93), p<0.001.Conversely, GGT >70 U/L, compared with GGT ≤70 U/L, had HR 1.82 (1.48−2.24), p<0.001.For cause-specific mortality, lower ALT was associated with a higher risk of cardiovascular death only, whereas GGT >70 U/L was associated with higher risks of death due to cardiovascular disease, cancer and non-cancer/non-cardiovascular causes. The relationship for ALT persisted after adjustment for indirect measures of frailty but was attenuated by elevated hsCRP. ConclusionsAs in the general population, ALT has a negative, and GGT a positive, correlation with mortality in type 2 diabetes when ALT is less than two times the upper limit of normal. The relationship A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT4 for ALT appears specific for death due to cardiovascular disease. Links of low ALT with frailty, as a potential mechanism for relationships seen, were neither supported nor conclusively refuted by our analysis and other factors are also likely to be important in those with type 2 diabetes.

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Advanced fibrosis associates with atherosclerosis in subjects with nonalcoholic fatty liver disease

Cited by 69 publications

References 29 publications

Persistent Nonalcoholic Fatty Liver Disease Increases Risk for Carotid Atherosclerosis

Persistent Nonalcoholic Fatty Liver Disease Increases Risk for Carotid Atherosclerosis

Fatty liver is associated with an increased risk of diabetes and cardiovascular disease - Evidence from three different disease models: NAFLD, HCV and HIV

Opposite associations between alanine aminotransferase and γ-glutamyl transferase levels and all-cause mortality in type 2 diabetes: Analysis of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study

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