Extrahepatic morbidities and mortality of <scp>NAFLD</scp>: an umbrella review of meta‐analyses

Yi, Mengshi; Peng, Wei; Feng, Xi; Teng, Fei; Tang, Youyin; Kong, Qingyan; Chen, Zheyu

doi:10.1111/apt.17165

Cited by 30 publications

(28 citation statements)

References 69 publications

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“…This is in striking contrast with HCC where the most advanced stages of liver fibrosis are associated with an increasing risk of disease [20,21]. Finally, an umbrella meta-analysis by Yi et al [22] based on the scrutiny of 39 published meta-analyses results found that individuals with NAFLD exhibited an increased risk of the following extra-hepatic cancers: thyroid, extra-hepatic and intra-hepatic cholangiocarcinoma, pancreatic, esophago-gastric, urinary tract, breast, and lung. The entity of this risk, however, ranged, based on various cancer types, from hazard ratio (HR) 1.25 for lung cancer to HR 2.63 for thyroid cancer.…”

Section: Methods Findings Conclusionmentioning

confidence: 98%

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Extra-hepatic cancers in metabolic fatty liver syndromes

Lonardo

2023

Explor Dig Dis

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The liver operates an array of vital digestive, metabolic, immunological, and purificatory physiological functions including synthesis of albumin, regulation of glucose and lipid homeostasis, detoxification of ammonia and xenobiotics, choleresis and production of hepatokines and hormones [1]. However, in healthy states, it is not involved in the storage of fatty substrates and, whenever the normal liver threshold is exceeded, accumulated triglycerides will impair whole-body insulin sensitivity, trigger sterile low-grade hepatic metaflammation, and promote the progression of the fibrosing process that will eventually conduce to cirrhosis in a subset of individuals [2,3]. While the histopathological cascade described above was first recognized in the 1800s by distinguished liver pathologists, such as Addison, Rokitansky, Pepper, and Bartolow, until the years 1958-1971 the debate, with the contributions by Zelman and Thaler, mainly focused on such hepato-histopathological changes being indistinguishable irrespective of the inciting triggers: alcohol, obesity, and diabetes [4]. From the perspective of clinical nosography, this finding eventually led to coining the innovative definitions of "nonalcoholic steatohepatitis (NASH)" and "nonalcoholic fatty liver disease (NAFLD)" in the 1980s. "Nonalcoholic" is a composite word that, at least in the spelling used by Ludwig et al., and by Schaffner and Thaler; does not require any hyphens [4] at variance with the use that is sometimes encountered in contemporary literature ("non-alcoholic").To convert a "negative" definition (i.e., nonalcoholic) into a positive diagnosis highlighting the pathogenic (dysmetabolic) origin, while also avoiding stigmatizing alcohol consumption, a panel of international experts have proposed renaming NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD). Although endorsed to an unprecedented extent [5], MAFLD retains some elements of ambiguity and amplifies NAFLD's heterogeneity, therefore creating major implications for research arena and clinical practice [6,7].Compared to the history of NAFLD briefly summarized above, the notions that NAFLD and NAFLD-related metabolic conditions could also be a risk factor for the development of primary liver cancer (PLC) in a limited proportion of individuals are more recent (Table 1) [8-13].While it is logical and somewhat foreseeable that PLC may eventually develop in some individuals with NAFLD, more recent observations substantiate the probably unexpected theory that, further to PLCs, NAFLD

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Section: Methods Findings Conclusionmentioning

confidence: 98%

“…Principal modifiers and putative pathomechanisms involved in the association of NAFLD and MAFLD with extra-hepatic cancers. This illustration, based on published studies[18,19,[22][23][24][29][30][31][32], highlights the knowns of this topic. However, our understanding of this complex scenario is far from complete…”

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confidence: 87%

Extra-hepatic cancers in metabolic fatty liver syndromes

Lonardo

2023

Explor Dig Dis

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“…A recent umbrella review examined the associations of NAFLD with the risk of developing CKD stage ≥3 and other extrahepatic adverse outcomes [ 41 ]. Notably, the authors reported a hazard risk for incident CKD (pooled random-effects HR, 1.42; 95% CI 1.33–1.52) that was identical to that reported by the meta-analysis by Mantovani et al [ 37 ].…”

Section: Epidemiologymentioning

confidence: 99%

Nonalcoholic Fatty Liver Disease and Chronic Kidney Disease: Epidemiology, Pathogenesis, and Clinical and Research Implications

Lonardo

Mantovani

Targher

et al. 2022

IJMS

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Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide, affecting up to ~30% of adult populations. NAFLD defines a spectrum of progressive liver conditions ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma, which often occur in close and bidirectional associations with metabolic disorders. Chronic kidney disease (CKD) is characterized by anatomic and/or functional renal damage, ultimately resulting in a reduced glomerular filtration rate. The physiological axis linking the liver and kidneys often passes unnoticed until clinically significant portal hypertension, as a major complication of cirrhosis, becomes apparent in the form of ascites, refractory ascites, or hepatorenal syndrome. However, the extensive evidence accumulated since 2008 indicates that noncirrhotic NAFLD is associated with a higher risk of incident CKD, independent of obesity, type 2 diabetes, and other common renal risk factors. In addition, subclinical portal hypertension has been demonstrated to occur in noncirrhotic NAFLD, with a potential adverse impact on renal vasoregulation. However, the mechanisms underlying this association remain unexplored to a substantial extent. With this background, in this review we discuss the current evidence showing a strong association between NAFLD and the risk of CKD, and the putative biological mechanisms underpinning this association. We also discuss in depth the potential pathogenic role of the hepatorenal reflex, which may be triggered by subclinical portal hypertension and is a poorly investigated but promising research topic. Finally, we address emerging pharmacotherapies for NAFLD that may also beneficially affect the risk of developing CKD in individuals with NAFLD.

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“…Due to the similarity in pathogenesis, MAFLD is often associated with other lifestyle-related disorders such as hypertension, dyslipidemia, and most importantly T2DM, which significantly increases cardiovascular disease (CVD). MAFLD has also been found to be associated with excess risk of extrahepatic cancers, gallstones, gastro-oesophageal reflux disease, hypothyroidism, urolithiasis, chronic kidney disease (CKD), depression and worse maternal and foetal outcomes during pregnancy[ 2 ]. MAFLD is also associated with a substantial increase in cardiovascular morbidity and mortality, with a 3.5 times higher risk of heart failure and 1.93 times excess risk of all-cause CVD mortality as per recent study data in patients with T2DM[ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Management of metabolic-associated fatty liver disease: The diabetology perspective

Jeeyavudeen¹,

Khan²,

Fouda³

et al. 2023

World J Gastroenterol

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The metabolic syndrome as a consequence of the obesity pandemic resulted in a substantial increase in the prevalence of metabolic-associated fatty live disease (MAFLD) and type 2 diabetes mellitus (T2DM). Because of the similarity in pathobiology shared between T2DM and MAFLD, both disorders coexist in many patients and may potentiate the disease-related outcomes with rapid progression and increased complications of the individual diseases. In fact, awareness about this coexistence and the risk of complications are often overlooked by both hepatologists and diabetologists. Management of these individual disorders in a patient should be addressed wholistically using an appropriate multidisciplinary team approach involving both the specialists and, when necessary, liaising with dieticians and surgeons. This comprehensive review is to compile the current evidence from a diabetologist's perspective on MAFLD and T2DM and to suggest optimal management strategies.

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Extrahepatic morbidities and mortality of NAFLD: an umbrella review of meta‐analyses

Cited by 30 publications

References 69 publications

Extra-hepatic cancers in metabolic fatty liver syndromes

Extra-hepatic cancers in metabolic fatty liver syndromes

Nonalcoholic Fatty Liver Disease and Chronic Kidney Disease: Epidemiology, Pathogenesis, and Clinical and Research Implications

Management of metabolic-associated fatty liver disease: The diabetology perspective

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