Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis

Targher, Giovanni; Byrne, Christopher D.; Lonardo, Amedeo; Zoppini, Giacomo; Barbui, Corrado

doi:10.1016/j.jhep.2016.05.013

Cited by 1,102 publications

(943 citation statements)

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“…Our findings showing an association between NAFLD and cardiovascular disease are consistent with a recent systematic review and meta-analysis of data from 16 prospective and retrospective studies that were not limited to people with diabetes (11). The meta-analysis included 34,043 people among whom 36% had NAFLD identified by imaging or biopsy and approximately 2,600 CVD outcomes occurred over a median of almost seven years of follow-up.…”

Section: Discussionsupporting

confidence: 89%

“…It will only be possible to estimate the size of this presumed bias when there are robust ways of identifying people with all levels of severity of liver disease and their risk of outcomes of interest at a population level. Our estimates of the strength of the association between NAFLD and mortality or CVD are consistent with those of other studies that included people with the whole spectrum of NAFLD and in which there are fewer concerns about ascertainment and misclassification bias (11,17,18). This suggests that the opposing effect of the different biases in the way we have identified the NAFLD and comparison groups are approximately balanced, but this hypothesis clearly requires testing when suitable data are available.…”

Section: Discussionsupporting

confidence: 85%

“…Despite the concerns about potential bias in our study noted above the association between NAFLD and incident/recurrent CVD that we describe was similar to that reported in a meta-analysis of studies that included people without diabetes and used other ways of identifying NAFLD (11). These findings suggest that liver disease per se may influence risk of CVD although it remains possible that common risk factors underlie risk of both liver disease and CVD.…”

Section: Discussionsupporting

confidence: 82%

“…The absolute risks of the outcomes of interest in this sub-group of people who, in general, have less severe liver disease are expected to be intermediate between people without liver disease and people with severe liver disease who are likely to form the majority of our population of people with a record of hospital admission with liver disease (11,12). Consequently, we expect that the relative risks describing the association between severe liver disease and outcomes of interest would be larger than we have reported if we had been able to exclude people with liver disease from the comparison group.…”

Section: Discussionmentioning

confidence: 99%

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Cardiovascular Disease, Cancer, and Mortality Among People With Type 2 Diabetes and Alcoholic or Nonalcoholic Fatty Liver Disease Hospital Admission

et al. 2017

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OBJECTIVE To describe associations between alcoholic fatty liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD) hospital admission and cardiovascular disease (CVD), cancer, and mortality in people with T2DM. RESEARCH DESIGN AND METHODSWe performed a retrospective cohort study using linked population-based routine data from the diabetes register, hospital, cancer and death records for people aged 40-89 years, diagnosed with T2DM in Scotland 2004-2013 who had one or more hospital admission records. Liver disease and outcomes were identified using International Classification of Diseases codes.We estimated hazard ratios from Cox proportional hazards models, adjusted for key risk factors (aHRs). RESULTS

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 85%

Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

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Cardiovascular Disease, Cancer, and Mortality Among People With Type 2 Diabetes and Alcoholic or Nonalcoholic Fatty Liver Disease Hospital Admission

et al. 2017

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“…NAFLD is commonly associated with components of metabolic syndrome2 and is an independent risk factor for cardiovascular disease 3, 4…”

Section: Introductionmentioning

confidence: 99%

Natural history of nonalcoholic fatty liver disease: A prospective follow‐up study with serial biopsies

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Ignatova

Kechagias

et al. 2017

Hepatology Communications

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Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in the world. The complete natural history of NAFLD is unknown because few high‐quality follow‐up studies have been conducted. Our aim was to find variables predicting disease severity through an extended follow‐up with serial biopsies. In a prospective cohort study, 129 patients who enrolled between 1988 and 1993 were asked to participate in a follow‐up study on two occasions; biochemical, clinical, and histologic data were documented. The mean time between biopsies was 13.7 (±1.7) and 9.3 (±1.0) years, respectively. At the end of the study period, 12 patients (9.3%) had developed end‐stage liver disease and 34% had advanced fibrosis. Out of the 113 patients with baseline low fibrosis (<3), 16% developed advanced fibrosis. Fibrosis progression did not differ among the different stages of baseline fibrosis (P = 0.374). Fifty‐six patients (43%) had isolated steatosis, of whom 9% developed advanced fibrosis (3 patients with biopsy‐proven fibrosis stage F3‐F4 and 2 patients with end‐stage liver disease). Fibrosis stage, ballooning, and diabetes were more common in patients who developed end‐stage liver disease; however, there were no baseline clinical, histologic, or biochemical variables that predicted clinical significant disease progression. Conclusion: NAFLD is a highly heterogeneous disease, and it is surprisingly hard to predict fibrosis progression. Given enough time, NAFLD seems to have a more dismal prognosis then previously reported, with 16% of patients with fibrosis stage <3 developing advanced fibrosis and 9.3% showing signs of end‐stage liver disease. (Hepatology Communications 2018;2:199–210)

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Association of Weight Loss Interventions With Changes in Biomarkers of Nonalcoholic Fatty Liver Disease

et al. 2019

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IMPORTANCE Nonalcoholic fatty liver disease (NAFLD) affects about 25% of adults worldwide and is associated with obesity. Weight loss may improve biomarkers of liver disease, but its implications have not been systematically reviewed and quantified. OBJECTIVE To estimate the association of weight loss interventions with biomarkers of liver disease in NAFLD. DATA SOURCES MEDLINE, Embase, PsycINFO, CINAHL, Cochrane, and Web of Science databases along with 3 trial registries were searched from inception through January 2019. STUDY SELECTION Randomized clinical trials of people with NAFLD were included if they compared any intervention aiming to reduce weight (behavioral weight loss programs [BWLPs], pharmacotherapy, and surgical procedures) with no or lower-intensity weight loss intervention. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. DATA EXTRACTION AND SYNTHESIS Two independent reviewers screened the studies, extracted the data, and assessed the risk of bias using the Cochrane tool. Pooled mean differences or odds ratios (ORs) were obtained from random-effects meta-analyses. MAIN OUTCOMES AND MEASURES Blood, radiologic, and histologic biomarkers of liver disease. RESULTS Twenty-two studies with 2588 participants (with a mean [SD] age of 45 [14] years and with approximately 66% male) were included. Fifteen studies tested BWLPs, 6 tested pharmacotherapy, and 1 tested a surgical procedure. The median (interquartile range) intervention duration was 6 (3-8) months. Compared with no or lower-intensity weight loss interventions, more-intensive weight loss interventions were statistically significantly associated with greater weight change (-3.61 kg; 95% CI,-5.11 to-2.12; I 2 = 95%). Weight loss interventions were statistically significantly associated with improvements in biomarkers, including alanine aminotransferase (-9.81 U/L; 95% CI,-13.12 to-6.50; I 2 = 97%), histologically or radiologically measured liver steatosis (standardized mean difference:-1.48; 95% CI,-2.27 to-0.70; I 2 = 94%), histologic NAFLD activity score (-0.92; 95% CI,-1.75 to-0.09; I 2 = 95%), and presence of nonalcoholic steatohepatitis (OR, 0.14; 95% CI, 0.04-0.49; I 2 = 0%). No statistically significant change in histologic liver fibrosis was found (-0.13; 95% CI,-0.54 to 0.27; I 2 = 68%). Twelve studies were at high risk of bias in at least 1 domain. In a sensitivity analysis of the 3 trials at low risk of bias, the estimates and precision of most outcomes did not materially change. CONCLUSIONS AND RELEVANCE The trials, despite some heterogeneity, consistently showed evidence of the association between weight loss interventions and improved biomarkers of liver disease in NAFLD in the short to medium term, although evidence on long-term health outcomes was limited. These findings appear to support the need to change the clinical guidelines and to recommend formal weight loss programs for people with NAFLD.

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Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis

Cited by 1,102 publications

References 51 publications

Cardiovascular Disease, Cancer, and Mortality Among People With Type 2 Diabetes and Alcoholic or Nonalcoholic Fatty Liver Disease Hospital Admission

Cardiovascular Disease, Cancer, and Mortality Among People With Type 2 Diabetes and Alcoholic or Nonalcoholic Fatty Liver Disease Hospital Admission

Natural history of nonalcoholic fatty liver disease: A prospective follow‐up study with serial biopsies

Association of Weight Loss Interventions With Changes in Biomarkers of Nonalcoholic Fatty Liver Disease

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