Non-alcoholic fatty liver disease (NAFLD) is a public health problem, affecting up to a third of the world’s adult population. Several cohort studies have consistently documented that NAFLD ...(especially in its more advanced forms) is associated with a higher risk of all-cause mortality and that the leading causes of death among patients with NAFLD are cardiovascular diseases (CVDs), followed by extrahepatic malignancies and liver-related complications. A growing body of evidence also indicates that NAFLD is strongly associated with an increased risk of major CVD events and other cardiac complications (ie, cardiomyopathy, cardiac valvular calcification and cardiac arrhythmias), independently of traditional cardiovascular risk factors. This narrative review provides an overview of the literature on: (1) the evidence for an association between NAFLD and increased risk of cardiovascular, cardiac and arrhythmic complications, (2) the putative pathophysiological mechanisms linking NAFLD to CVD and other cardiac complications and (3) the current pharmacological treatments for NAFLD that might also benefit or adversely affect risk of CVD.
NAFLD as a driver of chronic kidney disease Byrne, Christopher D.; Targher, Giovanni
Journal of hepatology,
April 2020, 2020-04-00, 20200401, Letnik:
72, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are worldwide public health problems, affecting up to 25–30% (NAFLD), and up to 10–15% (CKD) of the general population. ...Recently, it has also been established that there is a strong association between NAFLD and CKD, regardless of the presence of potential confounding diseases such as obesity, hypertension and type 2 diabetes. Since NAFLD and CKD are both common diseases that often occur alongside other metabolic conditions, such as type 2 diabetes or metabolic syndrome, elucidating the relative impact of NAFLD on the risk of incident CKD presents a substantial challenge for investigators working in this research field. A growing body of epidemiological evidence suggests that NAFLD is an independent risk factor for CKD and recent evidence also suggests that associated factors such as metabolic syndrome, dysbiosis, unhealthy diets, platelet activation and processes associated with ageing could also contribute mechanisms linking NAFLD and CKD. This narrative review provides an overview of the literature on: a) the evidence for an association and causal link between NAFLD and CKD and b) the underlying mechanisms by which NAFLD (and factors strongly linked with NAFLD) may increase the risk of developing CKD.
NAFLD: A multisystem disease Byrne, Christopher D; Targher, Giovanni
Journal of hepatology,
04/2015, Letnik:
62, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Summary Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries that is predicted to become also the most frequent indication for liver ...transplantation by 2030. Over the last decade, it has been shown that the clinical burden of NAFLD is not only confined to liver-related morbidity and mortality, but there is now growing evidence that NAFLD is a multisystem disease, affecting extra-hepatic organs and regulatory pathways. For example, NAFLD increases risk of type 2 diabetes mellitus (T2DM), cardiovascular (CVD) and cardiac diseases, and chronic kidney disease (CKD). Although the primary liver pathology in NAFLD affects hepatic structure and function to cause morbidity and mortality from cirrhosis, liver failure and hepatocellular carcinoma, the majority of deaths among NAFLD patients are attributable to CVD. This narrative review focuses on the rapidly expanding body of clinical evidence that supports the concept of NAFLD as a multisystem disease. The review discusses the factors involved in the progression of liver disease in NAFLD and the factors linking NAFLD with other extra-hepatic chronic diseases, such as T2DM, CVD, cardiac diseases and CKD. The review will not discuss NAFLD treatments as these are discussed elsewhere in this issue of the Journal. For this review, PubMed was searched for articles using the keywords “non-alcoholic fatty liver disease” or “fatty liver” combined with “diabetes”, “cardiovascular (or cardiac) disease”, “cardiovascular mortality” or “chronic kidney disease” between 1990 and 2014. Articles published in languages other than English were excluded.
Nonalcoholic fatty liver disease (NAFLD) has reached epidemic proportions worldwide. NAFLD and type 2 diabetes mellitus (T2DM) are known to frequently coexist and act synergistically to increase the ...risk of adverse (hepatic and extra-hepatic) clinical outcomes. T2DM is also one of the strongest risk factors for the faster progression of NAFLD to nonalcoholic steatohepatitis, advanced fibrosis or cirrhosis. However, the link between NAFLD and T2DM is more complex than previously believed. Strong evidence indicates that NAFLD is associated with an approximate twofold higher risk of developing T2DM, irrespective of obesity and other common metabolic risk factors. This risk parallels the severity of NAFLD, such that patients with more advanced stages of liver fibrosis are at increased risk of incident T2DM. In addition, the improvement or resolution of NAFLD (on ultrasonography) is associated with a reduction of T2DM risk, adding weight to causality and suggesting that liver-focused treatments might reduce the risk of developing T2DM. This Review describes the evidence of an association and causal link between NAFLD and T2DM, discusses the putative pathophysiological mechanisms linking NAFLD to T2DM and summarizes the current pharmacological treatments for NAFLD or T2DM that might benefit or adversely affect the risk of T2DM or NAFLD progression.
Nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus are common diseases that often coexist and might act synergistically to increase the risk of hepatic and extra-hepatic clinical ...outcomes. NAFLD affects up to 70-80% of patients with type 2 diabetes mellitus and up to 30-40% of adults with type 1 diabetes mellitus. The coexistence of NAFLD and diabetes mellitus increases the risk of developing not only the more severe forms of NAFLD but also chronic vascular complications of diabetes mellitus. Indeed, substantial evidence links NAFLD with an increased risk of developing cardiovascular disease and other cardiac and arrhythmic complications in patients with type 1 diabetes mellitus or type 2 diabetes mellitus. NAFLD is also associated with an increased risk of developing microvascular diabetic complications, especially chronic kidney disease. This Review focuses on the strong association between NAFLD and the risk of chronic vascular complications in patients with type 1 diabetes mellitus or type 2 diabetes mellitus, thereby promoting an increased awareness of the extra-hepatic implications of this increasingly prevalent and burdensome liver disease. We also discuss the putative underlying mechanisms by which NAFLD contributes to vascular diseases, as well as the emerging role of changes in the gut microbiota (dysbiosis) in the pathogenesis of NAFLD and associated vascular diseases.
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There have been many studies of the effects of non-alcoholic fatty liver disease (NAFLD) and the risk of cardiovascular disease (CVD), but these have produced conflicting results. We ...performed a meta-analysis of these studies to quantify the magnitude of the association between NAFLD (and NAFLD severity) and risk of CVD events.
We searched PubMed, Google scholar, and Web of Science databases using terms “NAFLD”, “cardiovascular events”, “cardiovascular mortality”, “prognosis” and their combinations to identify observational studies published through January 2016. We included only observational studies conducted in adults >18years and in which NAFLD was diagnosed on imaging or histology. Data from selected studies were extracted and meta-analysis was then performed using random effects modelling.
A total of 16 unique, observational prospective and retrospective studies with 34,043 adult individuals (36.3% with NAFLD) and approximately 2,600 CVD outcomes (>70% CVD deaths) over a median period of 6.9years were included in the final analysis. Patients with NAFLD had a higher risk of fatal and/or non-fatal CVD events than those without NAFLD (random effect odds ratio OR 1.64, 95% CI 1.26–2.13). Patients with more ‘severe’ NAFLD were also more likely to develop fatal and non-fatal CVD events (OR 2.58; 1.78–3.75). Sensitivity analyses did not alter these findings. Funnel plot and Egger’s test did not reveal significant publication bias.
NAFLD is associated with an increased risk of fatal and non-fatal CVD events. However, the observational design of the studies included does not allow to draw definitive causal inferences.
The data on whether NAFLD by itself is associated with increased cardiovascular events and death remains an issue of debate. The findings of this updated and large meta-analysis of observational studies indicate that NAFLD is significantly associated with an increased risk of fatal and non-fatal cardiovascular events. However, the observational design of the studies included does not allow us to prove that NAFLD causes cardiovascular disease. Clinicians who manage patients with NAFLD should not focus only on liver disease but should also consider the increased risk of cardiovascular disease and undertake early, aggressive risk factor modification.
Non-alcoholic fatty liver disease (NAFLD) is caused by an accumulation of fat in the liver; the condition can progress over time to increase the risk of developing cirrhosis, end-stage liver disease ...and hepatocellular carcinoma. The prevalence of NAFLD is increasing rapidly owing to the global epidemics of obesity and type 2 diabetes mellitus (T2DM), and NAFLD has been predicted to become the most important indication for liver transplantation over the next decade. It is now increasingly clear that NAFLD not only affects the liver but can also increase the risk of developing extra-hepatic diseases, including T2DM, cardiovascular disease and chronic kidney disease (CKD), which have a considerable impact on health-care resources. Accumulating evidence indicates that NAFLD exacerbates insulin resistance, predisposes to atherogenic dyslipidaemia and releases a variety of proinflammatory factors, prothrombotic factors and profibrogenic molecules that can promote vascular and renal damage. Furthermore, communication or 'crosstalk' between affected organs or tissues in these diseases has the potential to further harm function and worsen patient outcomes, and increasing amounts of evidence point to a strong association between NAFLD and CKD. Whether a causal relationship between NAFLD and CKD exists remains to be definitively established.
Several studies have explored the impact of nonalcoholic fatty liver disease (NAFLD) on risk of incident type 2 diabetes. However, the extent to which NAFLD may confer risk of incident diabetes ...remains uncertain. We performed a meta-analysis of relevant studies to quantify the magnitude of the association between NAFLD and risk of incident diabetes.
We collected data using PubMed, Scopus, and Web of Science from January 2000 to July 2017. We included only large (
≥500) observational studies with a follow-up duration of at least 1 year in which NAFLD was diagnosed on imaging methods. Eligible studies were selected according to predefined keywords and clinical outcomes. Data from selected studies were extracted, and meta-analysis was performed using random-effects modeling.
A total of 19 observational studies with 296,439 individuals (30.1% with NAFLD) and nearly 16,000 cases of incident diabetes over a median of 5 years were included in the final analysis. Patients with NAFLD had a greater risk of incident diabetes than those without NAFLD (random-effects hazard ratio HR 2.22, 95% CI 1.84-2.60;
= 79.2%). Patients with more "severe" NAFLD were also more likely to develop incident diabetes; this risk increased across the ultrasonographic scores of steatosis (
= 3 studies), but it appeared to be even greater among NAFLD patients with advanced high NAFLD fibrosis score (
= 1 study; random-effects HR 4.74, 95% CI 3.54-5.94). Sensitivity analyses did not alter these findings. Funnel plot and Egger test did not reveal significant publication bias. Study limitations included high heterogeneity, varying degrees of confounder adjustment across individual studies, and lack of studies using liver biopsy.
NAFLD is significantly associated with a twofold increased risk of incident diabetes. However, the observational design of the eligible studies does not allow for proving causality.
For many years it has been known that high doses of long chain omega-3 fatty acids are beneficial in the treatment of hypertriglyceridaemia. Over the last three decades, there has also been a wealth ...of in vitro and in vivo data that has accumulated to suggest that long chain omega-3 fatty acid treatment might be beneficial to decrease liver triacylglycerol. Several biological mechanisms have been identified that support this hypothesis; notably, it has been shown that long chain omega-3 fatty acids have a beneficial effect: a) on bioactive metabolites involved in inflammatory pathways, and b) on alteration of nuclear transcription factor activities such as peroxisome proliferator-activated receptors (PPARs), sterol regulatory element-binding protein 1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP), involved in inflammatory pathways and liver lipid metabolism. Since the pathogenesis of non alcoholic fatty liver disease (NAFLD) begins with the accumulation of liver lipid and progresses with inflammation and then several years later with development of fibrosis; it has been thought in patients with NAFLD omega-3 fatty acid treatment would be beneficial in treating liver lipid and possibly also in ameliorating inflammation. Meta-analyses (of predominantly dietary studies and small trials) have tended to support the assertion that omega-3 fatty acids are beneficial in decreasing liver lipid, but recent randomised controlled trials have produced conflicting data. These trials have suggested that omega-3 fatty acid might be beneficial in decreasing liver triglyceride (docosahexanoic acid also possibly being more effective than eicosapentanoic acid) but not in decreasing other features of steatohepatitis (or liver fibrosis). The purpose of this review is to discuss recent evidence regarding biological mechanisms by which long chain omega-3 fatty acids might act to ameliorate liver disease in NAFLD; to consider the recent evidence from randomised trials in both adults and children with NAFLD; and finally to discuss key ‘known unknowns’ that need to be considered, before planning future studies that are focussed on testing the effects of omega-3 fatty acid treatment in patients with NAFLD.
Context:
Nonalcoholic fatty liver disease (NAFLD) is increasingly diagnosed worldwide and is the most common chronic liver disease in Western countries. In this review, we discuss the role of NAFLD ...as a novel cardiometabolic risk factor for the development of type 2 diabetes (T2DM) and for the development of major chronic complications and poor glycemic control in people with established T2DM.
Evidence Acquisition:
This is a clinical, narrative review and not a systematic review and meta-analysis. PubMed was extensively searched for articles using the keywords “nonalcoholic fatty liver disease” or “fatty liver” combined with “diabetes risk,” “cardiovascular risk,” “cardiovascular mortality,” “chronic kidney disease,” or “diabetic nephropathy” between 1990 and 2012. Articles published in languages other than English were excluded from the analysis.
Evidence Synthesis:
NAFLD exacerbates hepatic insulin resistance and increases the risk of developing T2DM. Growing evidence also indicates that NAFLD may worsen glycemic control in people with T2DM and may contribute to the development and progression of the most important chronic complications of diabetes, such as cardiovascular disease and chronic kidney disease.
Conclusions:
The adverse impact of NAFLD on risk for T2DM and its major chronic vascular complications deserves particular attention among endocrinologists/cardiologists/hepatologists, in view of the implications for screening and surveillance strategies in the growing number of patients with NAFLD. Clinicians who manage patients with NAFLD should not only focus on liver disease, but should also recognize the increased risk of developing T2DM and its chronic vascular complications and undertake early, aggressive risk factor modification.
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