Nonalcoholic fatty liver disease: an independent risk factor for colorectal neoplasia

Stadlmayr, Andreas; Aigner, Elmar; Steger, Bernhard; Scharinger, Ludwig; Lederer, Dieter; Mayr, Alexander; Straßer, Michael; Brunner, Eric J.; Heuberger, A.; Hohla, Florian; Steinwendner, J.; Patsch, Wolfgang; Datz, Christian

doi:10.1111/j.1365-2796.2011.02377.x

Cited by 103 publications

(71 citation statements)

References 35 publications

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“…Studies have shown that NAFLD patients have significantly more colorectal (CR) neoplasia and early CR cancer compared to those without NAFLD (29). We did not have data available on screening for colorectal neoplasia; thus, the potential of underlying gastrointestinal bleed from undetected CR neoplasia may potentially be a cause for ID.…”

Section: Discussionmentioning

confidence: 99%

Iron Deficiency in Patients With Nonalcoholic Fatty Liver Disease Is Associated With Obesity, Female Gender, and Low Serum Hepcidin

Siddique

Nelson

Aouizerat

et al. 2014

Clinical Gastroenterology and Hepatology

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Background & Aims Iron deficiency is often observed in obese individuals. The iron regulatory hormone hepcidin is regulated by iron and cytokines IL6 and IL1β. We examine the relationship between obesity, circulating levels of hepcidin and IL6 and IL1β, and other risk factors in patients with non-alcoholic fatty liver disease (NAFLD) with iron deficiency. Methods We collected data on 675 adult subjects (>18 y old) enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network. Subjects with transferrin saturation <20% were categorized as iron deficient, whereas those with transferrin saturation ≥20% were classified as iron normal. We assessed clinical, demographic, anthropometric, laboratory, dietary, and histologic data from patients, as well as serum levels of hepcidin and cytokines IL6 and IL1β. Univariate and multivariate analysis were used to identify risk factors for iron deficiency. Results One third of patients (231/675; 34%) were iron deficient. Obesity, diabetes, and metabolic syndrome were more common in subjects with iron deficiency (P<.01), compared with those that were iron normal. Serum levels of hepcidin were significantly lower in subjects with iron deficiency (61±45 vs 81±51 ng/mL; P<.0001). Iron deficiency was significantly associated with female sex, obesity, increased body mass index and waist circumference, presence of diabetes, lower alcohol consumption, Black or American Indian/Alaska Native race (P≤.018), and increased levels of IL6 and IL1β (6.6 vs 4.8 for iron normal; P≤.0001 and 0.45 vs 0.32 for iron normal; P≤.005). Conclusion Iron deficiency is prevalent in patients with NAFLD and associated with female sex, increased body mass index, and non-white race. Serum levels of hepcidin were lower in iron-deficient subjects, reflecting an appropriate physiological response to decreased circulating levels of iron, rather than a primary cause of iron deficiency in the setting of obesity and NAFLD.

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Section: Discussionmentioning

confidence: 99%

Iron Deficiency in Patients With Nonalcoholic Fatty Liver Disease Is Associated With Obesity, Female Gender, and Low Serum Hepcidin

Siddique

Nelson

Aouizerat

et al. 2014

Clinical Gastroenterology and Hepatology

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“…The study design and details of the clinical and biochemical work-up of included subjects have been reported previously [23]. Subjects were allocated to one of three groups: (1) lean, healthy control group (n = 53), (2) MetS without iron overload (n = 54) and (3) MetS with iron overload (n = 56).…”

Section: Methodsmentioning

confidence: 99%

Metabolomic profiling identifies potential pathways involved in the interaction of iron homeostasis with glucose metabolism

Stechemesser

Eder

Wagner

et al. 2017

Molecular Metabolism

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ObjectiveElevated serum ferritin has been linked to type 2 diabetes (T2D) and adverse health outcomes in subjects with the Metabolic Syndrome (MetS). As the mechanisms underlying the negative impact of excess iron have so far remained elusive, we aimed to identify potential links between iron homeostasis and metabolic pathways.MethodsIn a cross-sectional study, data were obtained from 163 patients, allocated to one of three groups: (1) lean, healthy controls (n = 53), (2) MetS without hyperferritinemia (n = 54) and (3) MetS with hyperferritinemia (n = 56). An additional phlebotomy study included 29 patients with biopsy-proven iron overload before and after iron removal. A detailed clinical and biochemical characterization was obtained and metabolomic profiling was performed via a targeted metabolomics approach.ResultsSubjects with MetS and elevated ferritin had higher fasting glucose (p < 0.001), HbA1c (p = 0.035) and 1 h glucose in oral glucose tolerance test (p = 0.002) compared to MetS subjects without iron overload, whereas other clinical and biochemical features of the MetS were not different. The metabolomic study revealed significant differences between MetS with high and low ferritin in the serum concentrations of sarcosine, citrulline and particularly long-chain phosphatidylcholines. Methionine, glutamate, and long-chain phosphatidylcholines were significantly different before and after phlebotomy (p < 0.05 for all metabolites).ConclusionsOur data suggest that high serum ferritin concentrations are linked to impaired glucose homeostasis in subjects with the MetS. Iron excess is associated to distinct changes in the serum concentrations of phosphatidylcholine subsets. A pathway involving sarcosine and citrulline also may be involved in iron-induced impairment of glucose metabolism.

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“…As stated previously, patients with NAFLD have reduced levels of protective adipokines and adiponectin. Therefore, common factors among NAFLD, colon polyps and CRC include IR, chronic inflammation, oxidative stress and decreased levels of adiponectin[2,4,147,148,149,150,152]. In recent years, an increasing number of publications have identified NAFLD as an independent risk factor for the development of adenomatous polyps and CRC[147-153].…”

Section: Nonalcoholic Fatty Liver Disease and Colorectal Cancermentioning

confidence: 99%

Nonalcoholic fatty liver disease - A multisystem disease?

Mikolašević

Milić

Wensveen

et al. 2016

WJG

154

155

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Non-alcoholic fatty liver disease (NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome (MetS). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of MetS. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease (CVD), diabetes mellitus type 2 (T2DM) and chronic kidney disease (CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with MetS, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both (sub-) specialists and primary care physicians.

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Nonalcoholic fatty liver disease: an independent risk factor for colorectal neoplasia

Cited by 103 publications

References 35 publications

Iron Deficiency in Patients With Nonalcoholic Fatty Liver Disease Is Associated With Obesity, Female Gender, and Low Serum Hepcidin

Iron Deficiency in Patients With Nonalcoholic Fatty Liver Disease Is Associated With Obesity, Female Gender, and Low Serum Hepcidin

Metabolomic profiling identifies potential pathways involved in the interaction of iron homeostasis with glucose metabolism

Nonalcoholic fatty liver disease - A multisystem disease?

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